**Omega-3 Polyunsaturated Fatty Acids in Blood Pressure Control and Essential Hypertension**

GianLuca Colussi, Cristiana Catena, Marileda Novello and Leonardo A. Sechi

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/63501

#### **Abstract**

Hypertension is a worldwide problem that affects up to 22% of adults and contributes to the global burden of disability due to cardiovascular disease. Several factors influence blood pressure and participate to the development of hypertension. Among these factors, polyunsaturated fatty acids of the omega-3 family (omega-3 PUFA) are effective hypotensive agents. Through their anti-inflammatory and antioxidant properties, omega-3 PUFA can improve cardiac hemodynamics and vascular function and potentially reduce arterial stiffness and atherosclerotic damage. However, despite this promising evidence many meta-analyses on the cardiovascular effect of omega-3 PUFA were inconclusive. The choice of the omega-3 PUFA sources, baseline tissue content of these fatty acids, and individual compliance to their intake can be reasons for such a discrepancy between studies. Basic and clinical research on these fatty acids docu‐ ments interesting mechanisms through which these molecules could be useful in the treatment of hypertension and its related organ damage. The role of the maternal dietary habit during pregnancy and the quality of prenatal growth on the effect of omega-3 PUFA in cardiovascular system need further investigations. This chapter summarizes the literature of the past 30 years on the antihypertensive effects of this family of essential fatty acids.

**Keywords:** Omega-3 fatty acids, Cardiovascular disease, Atherosclerosis, Vascular function, Oxidative stress

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

## **1. Introduction**

Worldwide, hypertension affects more than one billion people and about 22% of individuals older than 18 years suffer from this disease. Untreated hypertension increases the risk and mortality for myocardial infarction and stroke, as well as it is responsible for chronic invalid‐ ating disorders such as coronary and peripheral vascular diseases, heart and renal failure, and visual impairment, all problems that heavily impact the individual's quality of life [1]. Al‐ though a descending trend of blood pressure levels has been observed in the past decades [2], hypertension remains the most underdiagnosed, undertreated, and uncontrolled problem [3] among the noncommunicable diseases. For these reasons, the prevention of hypertension is one of the main goals of the global healthcare system.

Primary or essential hypertension is diagnosed when secondary causes of high blood pressure are excluded [4]. Therefore defined, essential hypertension is a modifiable cardiovascular risk factor often associated with several inappropriate conditions related to lifestyle habits, such as overweight/obesity, excess of alcohol consumption, and high salt intake. Lifestyle changes have proven to reduce blood pressure and are highly recommended as the first step to treat hypertensive disease in all affected patients [4]. Among these changes, dietary habits have a primary role because food quantity affects directly body weight and food quality can modulate some minerals and nutrients associated with blood pressure regulation. For example, low salt and low alcohol intake, and increased consumption of polyunsaturated fatty acids of the omega-3 family (omega-3 PUFA) have shown to reduce blood pressure levels and in some cases to reduce the cardiovascular risk [5]. In this chapter, we present evidence of the beneficial effects of omega-3 PUFA on blood pressure and hypertension-related organ complications.

## **2. Biochemistry and physiology of the omega-3 PUFA**

Long-chain PUFA are present in all tissues of mammals; tough mammals cannot directly synthesize these fatty acids because they lack enzymes to make double bonds at some position in the fatty acid chain. Therefore, long-chain PUFA need to be consumed with diet and for that reason they are "essential" fatty acids. Essential PUFA are those of the omega-6 and omega-3 families, whereas nonessential are those of the omega-7 and omega-9. Nonessential PUFA families can be synthesized directly from endogenous saturated fatty acids. The "omega" letter indicates the last methyl carbon opposed to the carboxyl group of the acyl chain and the expression of "minus 6" or "minus 3" indicates the position of the first double bond from the last methyl group. Fatty acids are abbreviated with the C letter standing for "carbon" followed by the number of carbons in the molecule, the number of double bonds separated by colon, and the PUFA family name [6].

Linoleic acid (C18:2, LA) is the precursor of long-chain omega-6 PUFA that is abundant in vegetable oils such as those derived from soybean, corn, and rapeseed and in some species of insects. The omega-6 arachidonic acid (C20:4, AA) derives from LA through elongation and desaturation of the acyl chain (**Figure 1**) and it is involved in important cellular processes including eicosanoids and endocannabinoids production, inflammation, and hemostasis. The content of AA in vegetables is poor and its main source is animal-derived food. Alpha linolenic acid (C18:3, ALA), an analog of LA with one more double bond, is the precursor of long-chain omega-3 PUFA. By elongation and desaturation of its acyl chain, it is converted into the two principal long-chain omega-3 PUFA, the eicosapentaenoic acid (C20:5, EPA) and the docosa‐ hexaenoic acid (C22:6, DHA). ALA is from plant origin where it is abundant in seeds and vegetable oils, whereas EPA and DHA are mainly from marine source. In particular, fish directly synthesize EPA and DHA by ingesting phytoplankton enzymes. Since in humans the rate of conversion of ALA in EPA and DHA is relatively slow, the main source of omega-3 PUFA is seafood (**Table 1**). Enrichment in omega-3 PUFA content of cell membranes can be reached by omega-3 consumption for a relatively short time (days or weeks) [7].

**1. Introduction**

50 Update on Essential Hypertension

of the main goals of the global healthcare system.

**2. Biochemistry and physiology of the omega-3 PUFA**

and the PUFA family name [6].

Worldwide, hypertension affects more than one billion people and about 22% of individuals older than 18 years suffer from this disease. Untreated hypertension increases the risk and mortality for myocardial infarction and stroke, as well as it is responsible for chronic invalid‐ ating disorders such as coronary and peripheral vascular diseases, heart and renal failure, and visual impairment, all problems that heavily impact the individual's quality of life [1]. Al‐ though a descending trend of blood pressure levels has been observed in the past decades [2], hypertension remains the most underdiagnosed, undertreated, and uncontrolled problem [3] among the noncommunicable diseases. For these reasons, the prevention of hypertension is one

Primary or essential hypertension is diagnosed when secondary causes of high blood pressure are excluded [4]. Therefore defined, essential hypertension is a modifiable cardiovascular risk factor often associated with several inappropriate conditions related to lifestyle habits, such as overweight/obesity, excess of alcohol consumption, and high salt intake. Lifestyle changes have proven to reduce blood pressure and are highly recommended as the first step to treat hypertensive disease in all affected patients [4]. Among these changes, dietary habits have a primary role because food quantity affects directly body weight and food quality can modulate some minerals and nutrients associated with blood pressure regulation. For example, low salt and low alcohol intake, and increased consumption of polyunsaturated fatty acids of the omega-3 family (omega-3 PUFA) have shown to reduce blood pressure levels and in some cases to reduce the cardiovascular risk [5]. In this chapter, we present evidence of the beneficial effects of omega-3 PUFA on blood pressure and hypertension-related organ complications.

Long-chain PUFA are present in all tissues of mammals; tough mammals cannot directly synthesize these fatty acids because they lack enzymes to make double bonds at some position in the fatty acid chain. Therefore, long-chain PUFA need to be consumed with diet and for that reason they are "essential" fatty acids. Essential PUFA are those of the omega-6 and omega-3 families, whereas nonessential are those of the omega-7 and omega-9. Nonessential PUFA families can be synthesized directly from endogenous saturated fatty acids. The "omega" letter indicates the last methyl carbon opposed to the carboxyl group of the acyl chain and the expression of "minus 6" or "minus 3" indicates the position of the first double bond from the last methyl group. Fatty acids are abbreviated with the C letter standing for "carbon" followed by the number of carbons in the molecule, the number of double bonds separated by colon,

Linoleic acid (C18:2, LA) is the precursor of long-chain omega-6 PUFA that is abundant in vegetable oils such as those derived from soybean, corn, and rapeseed and in some species of insects. The omega-6 arachidonic acid (C20:4, AA) derives from LA through elongation and desaturation of the acyl chain (**Figure 1**) and it is involved in important cellular processes

**Figure 1.** Biosynthesis of long-chain omega-6 and omega-3 polyunsaturated fatty acids from precursor essential fatty acids. The same elongase and desaturase enzymes act on linoleic and alpha-linolenic acids to produce omega-6 arachi‐ donic acid and omega-3 eicosapentaenoic and docosahexaenoic acids, respectively. Only the last step of the biosynthet‐ ic pathway is located in peroxisomes where the beta-oxidation of 24-carbon long-chain fatty acids produce the final 22 carbon chains.


Data from the National Nutrient Database for Standard Reference 28 (2015). United States Department of Agriculture.

PUFA, polyunsaturated fatty acids; LA, linolenic acid; AA, arachidonic acid; ALA, alpha-linolenic acid; EPA, eicosapentaenoic acid; and DHA, docosahexaenoic acid.

**Table 1.** Polyunsaturated fatty acids and cholesterol composition of the major edible sources of omega-3 polyunsaturated fatty acids.

Fatty acids are quickly incorporated in phospholipids of plasma, platelets, neutrophil, and red blood cells, whereas enrichment of other tissues takes longer time. Omega-3 PUFA accumulate especially in cerebral cortex, retina, testes, muscle, and liver; omega-6 are ubiquitous in all tissues. The process of elongation and desaturation of precursors of PUFA is competitive because the synthesis of omega-6 and omega-3 PUFA utilizes the same enzymatic pathway. Despite that, ALA is a more affine substrate for desaturases and conversion of ALA into longchain omega-3 PUFA is more efficient than that of LA into AA. Therefore, increased ALA availability reduces AA formation and the balance between omega-6 and omega-3 PUFA content in cell membranes can be modulated by changing the dietary habit. Accordingly, it has been shown that populations that live in regions with higher seafood consumption have lower omega-6 to omega-3 PUFA ratio than populations that live in farming-prevalent regions with a lower omega-3 PUFA consumption. Interestingly, the former populations are those with the lowest risk for cardiovascular mortality [8].

**Source Total**

52 Update on Essential Hypertension

Mackerel, Atlantic, cooked, dry heat

Herring, Atlantic, cooked, dry heat

Salmon, Atlantic, farmed, cooked, dry heat

Tuna, fresh, bluefin,

Tuna, fresh, yellowfin,

Trout, mixed species, cooked, dry heat

Halibut, Atlantic and Pacific, cooked, dry heat

Cod, Atlantic, cooked,

polyunsaturated fatty acids.

eicosapentaenoic acid; and DHA, docosahexaenoic acid.

cooked, dry heat

cooked, dry heat

dry heat

**PUFA (g/100g)**  **LA (g/100g)** 

**AA (g/ 100g)** 

Salmon oil 40.324 1.543 0.675 1.061 13.023 18.232 3 485 Menhaden oil 34.197 2.154 1.169 1.490 13.168 8.562 5 521 Sardine oil 31.867 2.014 1.756 1.327 10.137 10.656 5 710 Cod liver oil 22.541 0.935 0.935 0.935 6.898 10.968 6 570 Herring oil 15.604 1.149 0.289 0.763 6.273 4.206 7 766 Flaxseed oil 67.849 14.327 0 53.368 0 0 2 0

**ALA (g/100g)** 

4.300 0.147 0.051 0.113 0.504 0.699 83 75

2.735 0.167 0.077 0.132 0.909 1.105 50 77

4.553 0.666 1.273 0.113 0.690 1.457 47 63

1.844 0.068 0.055 - 0.363 1.141 66 49

0.175 0.023 0.018 0.002 0.015 0.105 833 47

1.922 0.224 0.242 0.199 0.259 0.677 107 63

0.352 0.041 0.017 0.013 0.080 0.155 425 60

0.292 0.006 0.028 0.001 0.004 0.154 633 55

Flaxseeds 28.730 5.903 0 22.813 0 0 4 0

PUFA, polyunsaturated fatty acids; LA, linolenic acid; AA, arachidonic acid; ALA, alpha-linolenic acid; EPA,

**Table 1.** Polyunsaturated fatty acids and cholesterol composition of the major edible sources of omega-3

Data from the National Nutrient Database for Standard Reference 28 (2015). United States Department of Agriculture.

**EPA (g/100g)** 

**DHA (g/100g)** 

**Amount (g) to provide about 1 g of omega-3 PUFA** 

**Cholesterol (mg/100g)**

> Deficiency of PUFA is rare in humans, because normal diet contains an adequate amount of omega-6 and omega-3 PUFA. However, signs of severe PUFA deficiency have been docu‐ mented in premature infants with limited lipid stores or when these infants were fed with low lipid formulas; such signs were severe skin rash, loss of hair, and irritability. Several clinical conditions may also be associated with PUFA deficiency [9]. Clinical manifestations associated with PUFA deficiency consist of dermatitis, increased skin-water permeability, susceptibility to infection, higher sensitivity to radiation damage, impaired wound healing, hematological abnormalities, and fatty liver disease. Biochemically, PUFA deficiency is associated with an increased eicosatrienoic acid (C20:3 omega-9) to AA ratio (Holman index) because mammals can use oleic acid (C18:1 omega-9) as a precursor of long-chain PUFA only in the absence of the other families [10].

## **3. Effects of omega-3 PUFA on blood pressure regulation**

Arterial blood pressure is the product of cardiac output and peripheral vascular resistance to blood flow. Cardiac output results from the stroke volume times the heart rate, whereas the vascular resistance to blood flow depends on the vascular function. Regulation of arterial blood pressure derives from a complex interaction between cardiovascular cell components with autocrine, paracrine, and endocrine factors and the involvement of the nervous and immune systems. Many physiologic systems are involved in blood pressure regulation such as that of baroreceptor signals, natriuretic peptides, renin-angiotensin-aldosterone, kinin-kallikrein, and catecholamine. In addition, several genetic, anthropometric, and dietetic factors can influence blood pressure, such as family history, age, gender, body mass index, and consump‐ tion of salt. Classically, hypertension is a multifactorial complex disease mainly related to an initial abnormality in the kidney that leads to inappropriate tubular sodium retention, intravascular volume expansion, cardiac overload, vascular dysfunction, and sustained high blood pressure levels [11].

Arterial hypertension is defined in adults when systolic (SBP) and diastolic (DBP) blood pressure levels persist over 140 or 90 mm Hg, respectively [4]. In fact, over these thresholds lowering blood pressure is protective for the occurrence of organ damage and cardiovascular events. Reducing blood pressure by a few mm Hg in hypertensive patients can significantly decrease the incidence of stroke and coronary events [12] independently of the class of drug used [13]. Omega-3 PUFA intake has shown to reduce blood pressure especially in hyperten‐ sive patients by interacting with several mechanisms of blood pressure regulation (**Table 2**).

#### **Mechanisms of blood pressure regulation**


#### **Mechanisms of hypertension-related organ damage protection**


**Table 2.** Mechanisms by which omega-3 polyunsaturated fatty acids can modulate blood pressure levels and protect from the hypertension-related organ damage.

#### **3.1. Effects of omega-3 PUFA on cardiac function and hemodynamics**

Omega-3 PUFA can influence blood pressure by acting on the cardiac hemodynamics. In particular, the influence of omega-3 PUFA on the electrophysiological properties of cardio‐ myocytes can account for the reduced heart rate and the antiarrhythmic effect of these molecules [14]. Mozaffarian et al. [15] published a meta-analysis on the effects of omega-3 PUFA on resting heart rate demonstrating that fish oil treatment can reduce the heart rate by few beats per minute with respect to placebo. Omega-3 PUFA have shown also to improve heart rate variability, heart rate response during exercise, and heart rate post-exercise recovery by modulating the vagal tone [16, 17].

Influences of omega-3 PUFA on heart rate and peripheral vascular resistance may explain the effects of these fatty acids on the left ventricular function. Studies on nonhuman primates firstly showed that fish oil consumption can enhance left ventricular diastolic filling by improving left ventricular diastolic volume, stroke volume, and myocardial efficiency [18, 19]. In addition, other experimental studies demonstrated that omega-3 PUFA can blunt the hypertrophic response of the left ventricle to the pressure overload and prevent the abnormal gene expres‐ sion of cardiomyocytes [20, 21]. Evidence for hemodynamic effects of omega-3 PUFA in humans was also reported. In a parallel double-blind randomized controlled trial (RCT) in 224 young-adult and middle-aged healthy men, 4 g/day of ethyl ester DHA reduced the heart rate of 2.2 bpm with respect to placebo without affecting blood pressure levels. In another study, a small group of about 50 men taking omega-3 PUFA improved left ventricular diastolic filling assessed by echocardiography when compared to controls [22]. In a cross-sectional study, an increased intake of non-fried fish (tuna or other broiled or backed fish) was associated with lower blood pressure, lower heart rate, lower systemic vascular resistances, greater stroke volume, and better ventricular diastolic function. Conversely, fried fish intake was associated with worse cardiac function [23].

#### **3.2. Effects of omega-3 PUFA on vascular function**

lowering blood pressure is protective for the occurrence of organ damage and cardiovascular events. Reducing blood pressure by a few mm Hg in hypertensive patients can significantly decrease the incidence of stroke and coronary events [12] independently of the class of drug used [13]. Omega-3 PUFA intake has shown to reduce blood pressure especially in hyperten‐ sive patients by interacting with several mechanisms of blood pressure regulation (**Table 2**).

**Mechanisms of blood pressure regulation**

54 Update on Essential Hypertension

**•** Reduction of stroke volume and heart rate

**•** Improvement of left ventricle diastolic filling

**•** Reduction of peripheral vascular resistances

∎ Stimulation of nitric oxide production

∎ Relaxation of vascular smooth muscle cells

∎ Metabolic effects on perivascular adipocytes

∎ Reduction of endothelin-1

∎ Endothelial regeneration

**•** Reduction of arterial stiffness

° Improvement of endothelial-dependent and -independent vasodilation

∎ Reduction of the asymmetric di-methyl-arginine (ADMA)

**Mechanisms of hypertension-related organ damage protection**

**•** Anti-inflammatory, antioxidant, and antithrombotic effects

**•** Effects on atherosclerotic plaque progression and stability

from the hypertension-related organ damage.

by modulating the vagal tone [16, 17].

**•** Experimental effects on left ventricular hypertrophy and abnormal gene expression

**3.1. Effects of omega-3 PUFA on cardiac function and hemodynamics**

**Table 2.** Mechanisms by which omega-3 polyunsaturated fatty acids can modulate blood pressure levels and protect

Omega-3 PUFA can influence blood pressure by acting on the cardiac hemodynamics. In particular, the influence of omega-3 PUFA on the electrophysiological properties of cardio‐ myocytes can account for the reduced heart rate and the antiarrhythmic effect of these molecules [14]. Mozaffarian et al. [15] published a meta-analysis on the effects of omega-3 PUFA on resting heart rate demonstrating that fish oil treatment can reduce the heart rate by few beats per minute with respect to placebo. Omega-3 PUFA have shown also to improve heart rate variability, heart rate response during exercise, and heart rate post-exercise recovery Vascular function results from a complex interaction between neurohormonal signaling, circulating cells, immune system, and different components of the vascular wall. These components consist of endothelial cells, vascular smooth muscle cells, extracellular matrix, and perivascular adipocytes. There is a clear relationship between inflammation, oxidation, thrombosis, and endothelial dysfunction, conditions continuously interacting in a vicious circle that promote high blood pressure and the atherosclerotic process. Omega-3 PUFA have shown to modulate vascular resistance and blood pressure by acting on several determinants of the vascular function.

## *3.2.1. Omega-3 PUFA in inflammation and thrombosis*

Omega-3 PUFA affect several mechanisms of the inflammatory process [24]. The intake of omega-3 PUFA increases these fatty acids in phospholipids of cells involved in inflammation at the expenses of omega-6 PUFA. Since AA is the precursor of the pro-inflammatory and prothrombotic eicosanoids (prostaglandins, leukotrienes, and thromboxanes), the reduction of AA by increasing omega-3 PUFA decreases the amount of AA-derived eicosanoids. In addition, EPA competes with AA for cyclooxygenase and lipoxygenase enzymes generating eicosanoid derivatives that are less pro-inflammatory and pro-thrombotic than those derived from AA.

Omega-3 PUFA are involved in the production of "specialized pro-resolving mediators" (SPMs) from EPA and DHA through the activity of cyclooxygenase and lipoxygenase enzymes. These molecules include resolvins (E- and D-series), protectins, and maresins. Their amount increases in plasma of subjects with a high intake of omega-3 PUFA and can be found in human milk during the first month of lactation. These molecules are actively involved in the termi‐ nation (resolution) of an acute inflammatory process by activating local resolution programs that include inhibition of trans-endothelial neutrophil migration, reduced pro-inflammatory cytokines production, limitation of leukocyte recruitment, enhancement of macrophage uptake of debris, bacteria and apoptotic cells, and tissue repair [25].

Omega-3 PUFA exert their anti-inflammatory properties also by inhibiting other pro-inflam‐ matory mediators (platelet-activating factor, PAF; interleukin (IL)-1, -2, -6, and -8; tumor necrosis factor alpha) and several pro-inflammatory transcription factors (activator protein-1, AP-1; nuclear factor kappa-light-chain-enhancer of activated B cells, nuclear factor (NF)-κB) [26, 27]. EPA and DHA can disrupt the small heterogeneous membrane microdomains (lipid raft) of inflammatory cells by changing their lipid composition. In these microdomains, several important processes for the cell take place, especially the activation of the pro-inflammatory NF-κB [28].

In addition, omega-3 PUFA can modulate the activity of inflammasomes. Inflammasomes are a group of sensor and receptor proteins of the innate immunity assembled in an intracyto‐ plasmic complex in response to harmful stimuli [29]. These stimuli consist of exogenous product such as bacterial or endogenous advanced glycation end products (AGEs), cholesterol crystals in atherosclerotic lesions, and oxidized low-density lipoproteins (ox-LDL) [30]. EPA and DHA can inhibit the inflammasome activation through the G-protein receptor (GPR)120/ beta-arrestin2-dependent pathway by suppressing the nuclear translocation of the NF-κB [31] and by stimulating inflammasome autophagy [32].

## *3.2.2. Omega-3 PUFA in mechanisms of endothelial dysfunction*

Several experimental and human studies have demonstrated that omega-3 PUFA can improve endothelial function in both normal and damaged endothelium. In endothelial cells, the incubation with EPA stimulates the production of nitric oxide (NO) through the activation and translocation of the endothelial nitric oxide synthase (eNOS) from caveolae (a special type of cell membrane lipid raft) to the cytoplasm [33]. In experimental studies, NO produced via eNOS after EPA stimulation induced endothelial-dependent vasodilation of arteries [33, 34]. Omega-3 PUFA enhance endothelial-dependent vasodilation also in arteries with a damaged endothelium [35], by reducing plasma levels of the asymmetric dimethylarginine (ADMA), a potent endogenous inhibitor of the eNOS activity [36].

Other mechanisms by which omega-3 PUFA can improve endothelial dysfunction are antioxidation [37], reduction of the vasoconstrictive endothelin-1 (ET-1) [38], and the genera‐ tion of omega-3 PUFA-derived epoxides from the metabolic pathway of the cytochrome P450 epoxygenases [39]. Recently, Hoshi et al. elucidated with an elegant work that DHA can directly induce relaxation of the vascular smooth muscle cells (VSMCs) and acutely reduce blood pressure in anesthetized mice. This effect was mediated by a direct hyperpolarization of the VSMC induced by DHA through the stimulation of the large-conductance calcium- and voltage-activated potassium channels (BK channels) [40]. The activation of BK channels by DHA depends from the activity of cytochrome P450 epoxygenase, since its selective inhibition abolishes the effect [41].

Omega-3 PUFA can modulate endothelial function also by regulating the endocrine activity of the perivascular adipose cells. Experimentally, ALA stimulates the release of adiponectine, an anti-inflammatory, insulin sensitizer, and vasodilating adipokine, from mature adipocytes by inhibiting calcium current through the calcium-permeable nonselective cationic channels [42]. Other metabolic important effects of omega-3 PUFA on the adipose cells are increased sensitivity to insulin through PPAR-gamma and GPR120 stimulation [28, 43] and increased production of anti-inflammatory endocannabinoids [44].

Omega-3 PUFA demonstrate an important endothelium protective and reparative effect. The treatment with EPA partially repairs endothelial damage induced by hyperlipidemia in rabbits [45]. Reparative effects of omega-3 PUFA can be mediated by their capacity to stimulate endothelial progenitor cells availability and by promoting endothelial regeneration and neoangiogenesis in damaged vessels. These effects have been observed in experimental model of diabetic retinopathy [46] and cerebrovascular ischemia [47], and also in healthy individuals [48]. Recently, an endothelial regenerative effect of omega-3 PUFA has been demonstrated in low cardiovascular risk patients. In these patients, omega-3 PUFA promoted the production of endothelial progenitor cells and reduced the presence of endothelial cell-damaged micro‐ particles [49].

#### *3.2.3. Omega-3 PUFA in endothelial dysfunction in human studies*

that include inhibition of trans-endothelial neutrophil migration, reduced pro-inflammatory cytokines production, limitation of leukocyte recruitment, enhancement of macrophage

Omega-3 PUFA exert their anti-inflammatory properties also by inhibiting other pro-inflam‐ matory mediators (platelet-activating factor, PAF; interleukin (IL)-1, -2, -6, and -8; tumor necrosis factor alpha) and several pro-inflammatory transcription factors (activator protein-1, AP-1; nuclear factor kappa-light-chain-enhancer of activated B cells, nuclear factor (NF)-κB) [26, 27]. EPA and DHA can disrupt the small heterogeneous membrane microdomains (lipid raft) of inflammatory cells by changing their lipid composition. In these microdomains, several important processes for the cell take place, especially the activation of the pro-inflammatory

In addition, omega-3 PUFA can modulate the activity of inflammasomes. Inflammasomes are a group of sensor and receptor proteins of the innate immunity assembled in an intracyto‐ plasmic complex in response to harmful stimuli [29]. These stimuli consist of exogenous product such as bacterial or endogenous advanced glycation end products (AGEs), cholesterol crystals in atherosclerotic lesions, and oxidized low-density lipoproteins (ox-LDL) [30]. EPA and DHA can inhibit the inflammasome activation through the G-protein receptor (GPR)120/ beta-arrestin2-dependent pathway by suppressing the nuclear translocation of the NF-κB [31]

Several experimental and human studies have demonstrated that omega-3 PUFA can improve endothelial function in both normal and damaged endothelium. In endothelial cells, the incubation with EPA stimulates the production of nitric oxide (NO) through the activation and translocation of the endothelial nitric oxide synthase (eNOS) from caveolae (a special type of cell membrane lipid raft) to the cytoplasm [33]. In experimental studies, NO produced via eNOS after EPA stimulation induced endothelial-dependent vasodilation of arteries [33, 34]. Omega-3 PUFA enhance endothelial-dependent vasodilation also in arteries with a damaged endothelium [35], by reducing plasma levels of the asymmetric dimethylarginine (ADMA), a

Other mechanisms by which omega-3 PUFA can improve endothelial dysfunction are antioxidation [37], reduction of the vasoconstrictive endothelin-1 (ET-1) [38], and the genera‐ tion of omega-3 PUFA-derived epoxides from the metabolic pathway of the cytochrome P450 epoxygenases [39]. Recently, Hoshi et al. elucidated with an elegant work that DHA can directly induce relaxation of the vascular smooth muscle cells (VSMCs) and acutely reduce blood pressure in anesthetized mice. This effect was mediated by a direct hyperpolarization of the VSMC induced by DHA through the stimulation of the large-conductance calcium- and voltage-activated potassium channels (BK channels) [40]. The activation of BK channels by DHA depends from the activity of cytochrome P450 epoxygenase, since its selective inhibition

uptake of debris, bacteria and apoptotic cells, and tissue repair [25].

and by stimulating inflammasome autophagy [32].

*3.2.2. Omega-3 PUFA in mechanisms of endothelial dysfunction*

potent endogenous inhibitor of the eNOS activity [36].

abolishes the effect [41].

NF-κB [28].

56 Update on Essential Hypertension

Endothelial cell function can be indirectly assessed *in vivo* in humans by stimulating endothe‐ lial NO production with pharmacological or mechanical stimuli (endothelial-dependent vasodilation) and comparing the induced vasodilatory response with that induced by an exogenous nitrate-donor compounds (endothelial-independent vasodilation) [50]. The difference between endothelial-dependent and -independent vasodilation is proportional to the extent of endothelial dysfunction [51]. Endothelial dysfunction assessed with these techniques is an independent predictor of cardiovascular events and mortality [52]. Omega-3 PUFA have shown to improve endothelial-dependent vasodilation in several RCTs. The results of these studies were summarized in two recent systematic reviews and meta-analyses [53, 54]. In the first were included 16 RCTs involving 901 participants who took a dose of omega-3 PUFA ranging from 0.45 to 4.5 g/day for a mean of 56 days. Omega-3 PUFA slightly improved the flow-mediated vasodilation (FMD) of the brachial artery in treated patients. The effect was present especially in patients affected by a pathological condition respect to healthy subjects and was greater with a higher dose of omega-3 PUFA [53]. In the second meta-analysis were included 23 studied with 1385 participants. The source of omega-3 PUFA was fish oil with a dose ranging from 0.45 to 4.53 g/day and a treatment duration from 2 to 52 weeks. Again, the FMD response of the brachial artery was slightly better in treated patients. However, an inverse association between study quality and the improvement of FMD due to fish oil supplemen‐ tation was observed and when authors considered only high-quality RCTs (19 studies) no overall effect was observed anymore [54]. Recently, many RCTs of different quality on the effect of omega-3 PUFA on endothelial-dependent vasodilation have been published. How‐ ever, results of these studies are conflicting and again a final conclusion cannot be drawn [55– 59].

## **4. Effects of omega-3 PUFA on hypertension and hypertensive-related organ damage**

The first evidence of the hypotensive effect of omega-3 PUFA was observed more than 30 years ago and was summarized in two seminal systematic reviews and meta-analyses about 10 years later. The first meta-analysis selected 17 controlled clinical trials including 728 normotensive healthy individuals and 291 untreated hypertensive patients without any other comorbidity. The analysis showed a significant blood pressure reduction for SBP and DBP only in hyper‐ tensive patients. The omega-3 PUFA-lowering effect was directly related to the baseline levels of blood pressure [60]. The second meta-analysis included 31 controlled clinical trials with 1356 participants who were healthy or at risk for cardiovascular disease. The mean dose of omega-3 PUFA used was of 4.8 g/day as fish or fish oil for 3–24 weeks of treatment. Again, omega-3 PUFA reduced SBP and DBP only in hypertensive patients. Importantly, there was a total doseresponse effect of −0.66/−0.35 mm Hg/g assumed of omega-3 PUFA [61]. Thereafter, many meta-analyses on the effect of omega-3 PUFA on blood pressure have been published [62–66] and are summarized in **Table 3**. All these meta-analyses confirmed a significant although small hypotensive effect of these fatty acids especially in hypertensive patients who are not taking any antihypertensive drugs. Evidence from observational prospective studies suggests also that baseline omega-3 PUFA intake can be associated with the occurrence of future develop‐ ment of hypertension [67].



PUFA, polyunsaturated fatty acids; EPA, eicosapentaenoic acid; DHA, docosahexaenoic acid; CI, confidence intervals.

\* Studies included in subgroup analysis were not specified; therefore, no median dose and treatment duration can be calculated.

**Table 3.** Principal meta-analytical studies on the effects of omega-3 polyunsaturated fatty acids on blood pressure levels in healthy subjects and hypertensive patients.

Another source of omega-3 PUFA, flaxseeds or flaxseed-derived oil, showed anti-inflamma‐ tory, antioxidant, and blood pressure-lowering effects in animals and cardiovascular risk patients. Flaxseed is the seed of *Linum usitatissimum*, the richest source of ALA. A recent metaanalysis by Khalesi et al. [68] on 14 trials demonstrated a significant lowering effect on SBP (1.77 mm Hg; 95% confidence interval (CI): −3.45 to −0.09, *P* = 0.04) and DBP (1.58 mm Hg; 95% CI: −2.64 to −0.52, *P* = 0.003) of flaxseeds or flaxseed oil intake. An interesting mechanism suggested for blood pressure reduction of flaxseed was the inhibition of the epoxide hydrolase by ALA that reduced the production of vasoconstrictive oxylipins [69].

#### **4.1. Studies with ambulatory blood pressure monitoring**

**4. Effects of omega-3 PUFA on hypertension and hypertensive-related**

**Populations EPA+DHA**

**(median, g/day)**

Apple, 1993 [60] 11 (728) Healthy subjects 3.35 5 −1.0 (−2.0 to 0.0) −0.5 (−1.2 to 0.2)

Morris, 1993 [61] 8 (569) Healthy subjects 4.3 6 −0.4 (−1.6 to 0.8) −0.7 (−1.5 to 0.1)

23 (760) With hypertension – – −3.97 (−5.66 to

**Duration (median, weeks)**

5 8 −5.5 (−8.1 to

4.75 6 −3.4 (−5.9 to

– – −1.03 (−2.40 to

4.5 11 −2.3 (−4.3 to

2.55 12 −0.50 (−1.44 to

3.4 11 −2.56 (−4.53 to

**Effect on SBP (mm Hg, 95% CI)** 

−2.9)

−0.9)

0.14)

−2.15)

−0.2)

0.45)

−0.58)

**Effect on DBP (mm Hg, 95%**

−3.5 (−5.0 to −2.1)

−2.0 (−3.3 to −0.7)

−1.17 (−1.91 to −0.43)

−2.46 (−3.44 to −1.47)

−2.2 (−4.0 to −0.4)

−0.53 (−1.24 to 0.19)

−1.47 (−2.53 to −0.41)

**CI)**

The first evidence of the hypotensive effect of omega-3 PUFA was observed more than 30 years ago and was summarized in two seminal systematic reviews and meta-analyses about 10 years later. The first meta-analysis selected 17 controlled clinical trials including 728 normotensive healthy individuals and 291 untreated hypertensive patients without any other comorbidity. The analysis showed a significant blood pressure reduction for SBP and DBP only in hyper‐ tensive patients. The omega-3 PUFA-lowering effect was directly related to the baseline levels of blood pressure [60]. The second meta-analysis included 31 controlled clinical trials with 1356 participants who were healthy or at risk for cardiovascular disease. The mean dose of omega-3 PUFA used was of 4.8 g/day as fish or fish oil for 3–24 weeks of treatment. Again, omega-3 PUFA reduced SBP and DBP only in hypertensive patients. Importantly, there was a total doseresponse effect of −0.66/−0.35 mm Hg/g assumed of omega-3 PUFA [61]. Thereafter, many meta-analyses on the effect of omega-3 PUFA on blood pressure have been published [62–66] and are summarized in **Table 3**. All these meta-analyses confirmed a significant although small hypotensive effect of these fatty acids especially in hypertensive patients who are not taking any antihypertensive drugs. Evidence from observational prospective studies suggests also that baseline omega-3 PUFA intake can be associated with the occurrence of future develop‐

**organ damage**

58 Update on Essential Hypertension

ment of hypertension [67].

**Included studies (individuals)**

6 (291) Untreated

9 (415) Hypertensive

8 (375) Hypertensive

9 (1049) Normotensive

8 (475) Hypertensive

27 (1354) Without

hypertensive patients

patients

patients

subjects

patients

hypertension

**First author, publication year**

**[Ref.]**

Geleijnse\*

Dickinson, 2006 [63]

Campbell, 2013 [64]

[62]

, 2002

Ambulatory blood pressure monitoring (ABPM) evaluates blood pressure levels over 24 h giving information on daytime and nighttime blood pressure profiles and their circadian variations. ABPM is a useful tool for the diagnosis of hypertension and for definition of the full-day efficacy of antihypertensive treatments. Several observational and interventional studies have evaluated the effect of omega-3 PUFA on ABPM, though with inconsistent results [70, 71]. We followed up a group of uncomplicated hypertensive patients who were advised to take a diet rich of PUFA by assuming a fish meal three times a week for 6 months. ABPM parameters and omega-3 PUFA enrichment of red blood cell plasma membranes were evaluated at baseline and at the end of the study. Twenty-four-hour and nighttime SBP/DBP were reduced only in patients that increased omega-3 PUFA in cell membranes and the effect was more pronounced in patients with a lower baseline omega-3 PUFA content [72]. Our findings underline the importance of the baseline omega-3 PUFA status in cell membranes as a determinant of the hypotensive effect of these fatty acids. Also, our observation might explain the discrepancy observed among previous studies that did not assess the compliance to dietary prescriptions.

The different effect of EPA and DHA on blood pressure was evaluated by Mori et al. in a small RCT of overweight mild hyperlipidemic men. Specifically, at the end of the follow-up only DHA treatment reduced 24 h and daytime ambulatory SBP/DBP with respect to placebo (5.8/3.3 and 3.5/2.0 mm Hg, respectively). Also, DHA treatment was effective to reduce 24-h, daytime, and nighttime heart rate [73].

## **4.2. Arterial stiffness**

Arterial stiffening is caused by the loss of vascular elasticity due to factors such as aging and atherosclerosis. It depends from the structural properties of the arterial wall that affect the manner in which pressure, blood flow, and arterial diameter change within each heartbeat. Arterial stiffness depends from the balance between extracellular proteins and their distribu‐ tion along the arterial wall. An increased arterial stiffness is associated with hypertension and it is an independent direct predictor of cardiovascular events. The measurement of velocity of the pulse-wave propagation (pulse-wave velocity, PWV) between two vascular points is an accepted method to assess arterial stiffness [74]. Pase et al. summarized in a systematic review the effect of omega-3 PUFA supplementation on PWV and other indexes of arterial stiffness. Ten trials met the inclusion criteria with 550 participants randomized to take a dose of omega-3 PUFA ranging from 0.64 to 3.00 g/day or placebo for a period of 6–105 weeks. Studies involved healthy subjects and patients with overweight, diabetes, hypertension, and dyslipidemia. The treatment with omega-3 PUFA improved arterial stiffness and the effect was independent of changes in blood pressure, heart rate, or body mass index. Neither significant heterogeneity nor publication bias was detected [75]. The same author showed recently in a new larger RCT on healthy subjects that a high dose of fish oil (6 g/day) but not a low dose (3 g/day) could reduce aortic pulse pressure and aortic augmentation pressure, two indirect measures of central blood pressure and arterial stiffness, respectively [76].

The reasons for improvement of arterial stiffness with the use of omega-3 PUFA can be related to the hypotensive, anti-inflammatory, and antioxidative effects of these fatty acids, as well as to their ability to improve endothelial cell function. A low maternal habit in fish consumption during pregnancy is an independent predictor of arterial stiffness later in the childhood life but not of elevated blood pressure [77]. The inverse association between maternal omega-3 PUFA intake and arterial stiffness persists with child aging and it is independent of the individual's fish consumption [77, 78]. Additional evidence of the beneficial effect of omega-3 PUFA on the vascular structure comes from the inverse association between omega-3 PUFA intake and the cross-sectional diameter of arteries. It was demonstrated that a larger brachial artery diameter is a significant independent predictor of future cardiovascular events [79, 80]. Accordingly, we and other authors have reported an inverse association between the brachial artery cross-sectional diameter and the consumption of fish or the concentration of circulatory omega-3 PUFA [81, 82]. We reported also that the membrane content of omega-3 PUFA is directly associated with the extent of the vasodilatory response to sublingual nitrate admin‐ istration, supporting the evidence of a beneficial effect of these fatty acids on the vascular wall [82].

Since aging is another important determinant of arterial stiffening and hypertension, it is interesting to note that blood levels of omega-3 PUFA are inversely related with telomere shortening, a marker of cell senescence, in patients with coronary heart disease [83]. Telomere shortening reflects the generation of oxidative stress and inflammation that characterizes cellular ageing, and omega-3 PUFA might protect cells and slow this process. In a group of overweight patients, supplemental intake of omega-3 PUFA for 4 months increased omega-3 to omega-6 ratio in plasma phospholipids and this ratio was associated with telomeres length of leukocytes. In this study, omega-3 PUFA reduced also the proportion of plasma F2 isoprostanes, a marker of lipid peroxidation and oxidative stress [84]. Similar results were reported in elderly individuals with mild cognitive impairment [85].

#### **4.3. Atherosclerotic lesions**

(5.8/3.3 and 3.5/2.0 mm Hg, respectively). Also, DHA treatment was effective to reduce 24-h,

Arterial stiffening is caused by the loss of vascular elasticity due to factors such as aging and atherosclerosis. It depends from the structural properties of the arterial wall that affect the manner in which pressure, blood flow, and arterial diameter change within each heartbeat. Arterial stiffness depends from the balance between extracellular proteins and their distribu‐ tion along the arterial wall. An increased arterial stiffness is associated with hypertension and it is an independent direct predictor of cardiovascular events. The measurement of velocity of the pulse-wave propagation (pulse-wave velocity, PWV) between two vascular points is an accepted method to assess arterial stiffness [74]. Pase et al. summarized in a systematic review the effect of omega-3 PUFA supplementation on PWV and other indexes of arterial stiffness. Ten trials met the inclusion criteria with 550 participants randomized to take a dose of omega-3 PUFA ranging from 0.64 to 3.00 g/day or placebo for a period of 6–105 weeks. Studies involved healthy subjects and patients with overweight, diabetes, hypertension, and dyslipidemia. The treatment with omega-3 PUFA improved arterial stiffness and the effect was independent of changes in blood pressure, heart rate, or body mass index. Neither significant heterogeneity nor publication bias was detected [75]. The same author showed recently in a new larger RCT on healthy subjects that a high dose of fish oil (6 g/day) but not a low dose (3 g/day) could reduce aortic pulse pressure and aortic augmentation pressure, two indirect measures of

The reasons for improvement of arterial stiffness with the use of omega-3 PUFA can be related to the hypotensive, anti-inflammatory, and antioxidative effects of these fatty acids, as well as to their ability to improve endothelial cell function. A low maternal habit in fish consumption during pregnancy is an independent predictor of arterial stiffness later in the childhood life but not of elevated blood pressure [77]. The inverse association between maternal omega-3 PUFA intake and arterial stiffness persists with child aging and it is independent of the individual's fish consumption [77, 78]. Additional evidence of the beneficial effect of omega-3 PUFA on the vascular structure comes from the inverse association between omega-3 PUFA intake and the cross-sectional diameter of arteries. It was demonstrated that a larger brachial artery diameter is a significant independent predictor of future cardiovascular events [79, 80]. Accordingly, we and other authors have reported an inverse association between the brachial artery cross-sectional diameter and the consumption of fish or the concentration of circulatory omega-3 PUFA [81, 82]. We reported also that the membrane content of omega-3 PUFA is directly associated with the extent of the vasodilatory response to sublingual nitrate admin‐ istration, supporting the evidence of a beneficial effect of these fatty acids on the vascular wall

Since aging is another important determinant of arterial stiffening and hypertension, it is interesting to note that blood levels of omega-3 PUFA are inversely related with telomere shortening, a marker of cell senescence, in patients with coronary heart disease [83]. Telomere shortening reflects the generation of oxidative stress and inflammation that characterizes

daytime, and nighttime heart rate [73].

central blood pressure and arterial stiffness, respectively [76].

**4.2. Arterial stiffness**

60 Update on Essential Hypertension

[82].

Omega-3 PUFA have shown to modulate atherosclerotic plaque formation and stability. The carotid intima-media thickness (cIMT) is an early marker of atherosclerotic damage that precedes plaque formation and is easily assessed in humans by ultrasonography. We have recently demonstrated that a diet rich of fish for 1 year can reduce cIMT of patients with uncomplicated hypertension. This effect was observed only in those patients who were compliant with dietary prescription [86]. Similar findings on early atherosclerotic lesions were reported in other studies with different populations [87–89], but not in all those that have investigated this problem [90]. Interesting observation by Skilton and coworkers might help to explain these discrepancies. These authors demonstrated that a factor, which significantly affects the benefit of PUFA supplementation to slow cIMT progression, is the presence of an impaired prenatal growth [91]. As a consequence, dietary omega-3 PUFA supplementation in children with a history of impaired prenatal growth is protective from subsequent carotid wall thickening [92].

In addition to their preventive effect on the formation of atherosclerotic plaques, omega-3 PUFA could stabilize existing plaques. In patients with carotid stenosis, fish oil supplemen‐ tation increases omega-3 PUFA content of plaques. This was associated with a thickening fibrous cup and reduction of intra-plaque inflammation and macrophage infiltration [93]. Similar results were obtained in another group of patients awaiting endarterectomy in which omega-3 PUFA supplementation reduced the intra-plaque content of foam cells and Tlymphocytes and lowered the expression of metalloproteinases, interleukins, and intracellular adhesion molecules [94]. Omega-3 PUFA supplementation can act favorably also on less critical plaques, as those not responsible for an acute coronary syndrome (non-culprit lesions) [95]. Although the beneficial effects of omega-3 PUFA on atherosclerotic plaques are mainly attributed to their anti-inflammatory and antioxidant properties, it was shown that these fatty acids increase the amount of cholesterol of high-density lipoprotein (HDL) [96–98] and reduce plasma levels of lipoprotein(a) [99, 100]. Finally, some studies have shown that omega-3 PUFA intake can enhance the beneficial effects of cardio-protective drugs such as statins and the acetylsalicylic acid [101–104].

Despite the evidence of many effects of omega-3 PUFA in opposing the atherosclerotic process, meta-analytical studies on their use in primary and secondary cardiovascular prevention provided inconclusive results [5].

## **5. Conclusions**

This chapter has analyzed the effects of omega-3 PUFA on blood pressure and their potential benefit for the treatment of hypertension and its related organ damage. Substantial evidence supports the existence of a small hypotensive effect of these fatty acids in hypertensive patients that appears more related to the use of DHA and dietary compliance. Evidence in support of a protective effect of omega-3 PUFA on hypertension-related organ damage is much weaker. Lack of a clear benefit from marine food or other sources of these fatty acids in cardiovascular prevention has limited their use in the clinical practice. Nonetheless, a regular fish intake remains recommended by international guidelines.

Research on omega-3 PUFA has provided many interesting results in the cardiovascular field, but new areas need to be explored. Although effective in hypertensive patients, no studies have evaluated the effects of omega-3 PUFA on specific types of hypertension-related organ damage such as left ventricular hypertrophy, nephroangiosclerosis, and retinopathy. The role of omega-3 PUFA during pre-natal development and potential effects on post-natal cardio‐ vascular outcomes will also need further investigation.

## **Author details**

GianLuca Colussi\* , Cristiana Catena, Marileda Novello and Leonardo A. Sechi

\*Address all correspondence to: gianluca.colussi@uniud.it

Division of Internal Medicine, Department of Experimental and Clinical Medical Sciences, University of Udine, Udine, Italy

## **References**


[4] Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension. *Eur Heart J* 2013; 31: 1281–1357.

**5. Conclusions**

62 Update on Essential Hypertension

**Author details**

GianLuca Colussi\*

**References**

2224–2260.

92: 10–19C.

University of Udine, Udine, Italy

remains recommended by international guidelines.

vascular outcomes will also need further investigation.

\*Address all correspondence to: gianluca.colussi@uniud.it

This chapter has analyzed the effects of omega-3 PUFA on blood pressure and their potential benefit for the treatment of hypertension and its related organ damage. Substantial evidence supports the existence of a small hypotensive effect of these fatty acids in hypertensive patients that appears more related to the use of DHA and dietary compliance. Evidence in support of a protective effect of omega-3 PUFA on hypertension-related organ damage is much weaker. Lack of a clear benefit from marine food or other sources of these fatty acids in cardiovascular prevention has limited their use in the clinical practice. Nonetheless, a regular fish intake

Research on omega-3 PUFA has provided many interesting results in the cardiovascular field, but new areas need to be explored. Although effective in hypertensive patients, no studies have evaluated the effects of omega-3 PUFA on specific types of hypertension-related organ damage such as left ventricular hypertrophy, nephroangiosclerosis, and retinopathy. The role of omega-3 PUFA during pre-natal development and potential effects on post-natal cardio‐

, Cristiana Catena, Marileda Novello and Leonardo A. Sechi

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## **Psychiatric Comorbidity in Essential Hypertension**

*(Pattern, Prevalence of Psychiatric Comorbidity and Quality of Life in Subjects with Essential Hypertension)*

Aborlo Kennedy Nkporbu and Princewill Chukwuemeka Stanley

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/64104

#### **Abstract**

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The prevalence of essential hypertension has continued to increase worldwide, and its consequences have remained a growing concern. A number of sociodemographic and clinical variables may however serve as key determinants of the extent to which it is associated with psychiatric comorbidity as well as impairment of quality of life. The aim of this study, therefore, was to determine the sociodemographic and clinical factors that may influence the level of psychiatric comorbidity and quality of life associated with persons with essential hypertension attending the general outpatient clinic of the University of Port Harcourt Teaching Hospital (UPTH). Following ethical approval and informed consent from the participants, 360 subjects making up the study group were recruited based on the study's inclusion and exclusion criteria. A pilot study was carried out. Subjects were further administered with the study's instruments including the socio-demographic/clinical questionnaire, GHQ-12, WHO Composite International Diagnostic Interview (WHOCIDI) and the WHOQOL-Bref. The data were analysed using the Statistical Package for Social Sciences version 16 statistical package. Confi‐ dence interval was set at 95%, while p-value of less than 0.05 was considered statisti‐ cally significant. The study found a prevalence of psychiatric comorbidity of 64.4% among the hypertensives. Among the study group, there was no significant relation‐ ship between the presence of psychiatric comorbidity and age class (p = 0.350), gender (p = 0.22), level of education (p = 043), income class (p = 0.81) and occupation. Persons who were married were significantly more likely to have a psychiatric comorbidity (p = 0.001). There was also no significant relationships between age of onset of illness (p = 0.60), duration of illness (p = 0.73), duration of treatment (p = 0.82) and self-stigma (p = 0.15). The findings of this study support the impression that essential hypertension is a chronic debilitating illness, associated with psychiatric comorbidity and reduced quality of life, that is largely significantly influenced by a number of sociodemograph‐ ic and clinical factors. The results support the call that the management of patients with

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

essential hypertension should include attention to the mental health status of the sufferers.

**Keywords:** pattern and prevalence, essential hypertension, psychiatric comorbidity, QOL, UPTH

## **1. Introduction**

There is a growing population of persons with essential hypertension (HT) worldwide despite all efforts at increasing education and awareness about it [1–19]. World Health Organization (WHO) estimates that non-communicable diseases like hypertension and other heart diseases, stroke, depression and cancers will increase by 60% by 2020 and are likely to triple in Nigeria and other sub-Saharan African countries in the next 50 years. According to the World Health Report, non-communicable diseases including diabetes mellitus, arthritis and cardiovascular diseases make up to about 22% of all deaths in the region in the year 2000; cardiovascular diseases alone accounted for 9.2% of the total deaths [20]. Indeed, it has already been projected that up to three quarters of the world's hypertensive population will be in economically developing countries by the year 2025 [7]. With increased prevalence rates and the resultant greater economic and health burden [8–10], nations like China and Nigeria will feel the impact mostly due to their population size.

Hypertension constitutes a greater percentage of all the referrals from other nonpsychiatric units seeking for psychiatric evaluation in the University of Port Harcourt Teaching Hospital (UPTH) [21]. Essential hypertension runs the features of chronicity, with subsequent need for long-term medications, adverse effects on the central nervous system (CNS), high rate of mortality and morbidity [10, 22, 23] and impact on emotion [24, 25] (the component that is often neglected). In addition, patients with hypertension need extensive education, attitudinal change, coping and healthy lifestyle, including diet and exercise. The need for these adjust‐ ments is imperative considering the immediate changes that usually accompany the diagnosis of the condition. They include burden of the diseases, regular hospital visits, complications arising from the primary illness and job adjustment. For these reasons, together with their direct effects on the central nervous system (CNS), no doubt, the patients commonly present with varying degrees of psychopathology [26–30]. Psychopathology is the inward or outward manifestation of a disordered psychic system.

Essential hypertension is a severe, chronic systemic disease and is becoming increasingly associated with psychiatric comorbidity, as high as 30–60% at present [31–36]. It carries enormous burden on both the patients and the caregivers [37, 8–10]. Unfortunately, there appears to be a general under-recognition or late recognition of, and in some cases poor attention to, the psychiatric component by clinicians [38–42] particularly in this environment [43]. This is often accompanied by increased severity and clinical deterioration of these illnesses, poor management and prognosis with eventual high mortality rates. Late recognition of mental disorders in hypertensive patients is related, among others, with diminished coping capacity at diagnosis, failure at primary prevention, poor antihypertensive adherence [44–47], impairment in quality of life (QOL) [48–56], greater social burden, overall increases in healthcare costs [57–59], and also higher mortality [8]. Also, psychological distress and lifestyle variables among patients with hypertension are equally associated with noncompliance.

To further compound the problem is the co-existence of other medical conditions like diabetes and obesity, with hypertension. Their presence further worsens the clinical outlook, compli‐ cates treatment and causes noncompliance [60]. Hypertension can, either singly or in associ‐ ation with other adverse psychosocial and clinical factors, predispose to psychiatric disorders. Furthermore, some of the medications employed in the management of these conditions have been associated with inherent neuropsychiatric complications [61, 62] either as direct side effects, from drug interactions with psychoactive substances, from multiple drug therapy or with other concomitantly administered drugs for other comorbid conditions.

Apart from the above aetiological links, a common pathway—sympathetic pathway [63–66] —seems to mediate both essential hypertension and most anxiety disorders. It is equally important to note that baseline adverse psychosocial factors, psychological distress or clearly identified psychiatric conditions have been implicated as predictors of hypertension [67–72]. In light of the foregoing, there appears to be a bidirectional relationship between associated psychiatric disorders and hypertension. This propensity to be associated with emotional disturbances, with tendency to either predispose to or comorbid with psychiatric disorders, has further increased the degree to which they affect the psychological well-being and quality of life of the sufferers [73–80]. The focus of medical practice has always tended towards relieving physical symptoms, in this case hypertension, which often neglects the huge impact on the psychological well-being, psychiatric comorbidity and the overall quality of life of the sufferers, often occasioning monumental health consequences [81, 82].

A prompt multidisciplinary approach involving evaluation, counselling and treatment of mental disorders in hypertensive patients is becoming more important [83]. Therefore, the determination of the nature and magnitude of psychiatric comorbidity, the additive effects on psychological well-being and quality of life and emphasis on the need for mental health component in the management of essential hypertension and other chronic medical conditions form the areas of concern of this study.

## **2. Overview of hypertension**

essential hypertension should include attention to the mental health status of the

**Keywords:** pattern and prevalence, essential hypertension, psychiatric comorbidity,

There is a growing population of persons with essential hypertension (HT) worldwide despite all efforts at increasing education and awareness about it [1–19]. World Health Organization (WHO) estimates that non-communicable diseases like hypertension and other heart diseases, stroke, depression and cancers will increase by 60% by 2020 and are likely to triple in Nigeria and other sub-Saharan African countries in the next 50 years. According to the World Health Report, non-communicable diseases including diabetes mellitus, arthritis and cardiovascular diseases make up to about 22% of all deaths in the region in the year 2000; cardiovascular diseases alone accounted for 9.2% of the total deaths [20]. Indeed, it has already been projected that up to three quarters of the world's hypertensive population will be in economically developing countries by the year 2025 [7]. With increased prevalence rates and the resultant greater economic and health burden [8–10], nations like China and Nigeria will feel the impact

Hypertension constitutes a greater percentage of all the referrals from other nonpsychiatric units seeking for psychiatric evaluation in the University of Port Harcourt Teaching Hospital (UPTH) [21]. Essential hypertension runs the features of chronicity, with subsequent need for long-term medications, adverse effects on the central nervous system (CNS), high rate of mortality and morbidity [10, 22, 23] and impact on emotion [24, 25] (the component that is often neglected). In addition, patients with hypertension need extensive education, attitudinal change, coping and healthy lifestyle, including diet and exercise. The need for these adjust‐ ments is imperative considering the immediate changes that usually accompany the diagnosis of the condition. They include burden of the diseases, regular hospital visits, complications arising from the primary illness and job adjustment. For these reasons, together with their direct effects on the central nervous system (CNS), no doubt, the patients commonly present with varying degrees of psychopathology [26–30]. Psychopathology is the inward or outward

Essential hypertension is a severe, chronic systemic disease and is becoming increasingly associated with psychiatric comorbidity, as high as 30–60% at present [31–36]. It carries enormous burden on both the patients and the caregivers [37, 8–10]. Unfortunately, there appears to be a general under-recognition or late recognition of, and in some cases poor attention to, the psychiatric component by clinicians [38–42] particularly in this environment [43]. This is often accompanied by increased severity and clinical deterioration of these illnesses, poor management and prognosis with eventual high mortality rates. Late recognition of mental disorders in hypertensive patients is related, among others, with diminished coping

sufferers.

72 Update on Essential Hypertension

QOL, UPTH

mostly due to their population size.

manifestation of a disordered psychic system.

**1. Introduction**

Hypertension is defined as a persistent elevation in blood pressure (BP) over an acceptable upper limit of normal values of systolic and diastolic blood pressures [84]. Objectively, hypertension is blood pressure persistently equal to or greater than 140/90 mmHg [85]. The systolic pressure is the pressure at the peak of the heart's contraction, while diastolic blood pressure is the pressure when the heart relaxes. Blood pressure varies from moment to moment and has a diurnal variation, being highest at 10 am and lowest at 3 am [86]. Hypertension may be of unknown cause called essential hypertension or hyperpiesia [87] or may have an underlying cause when it is known as secondary hypertension. Hypertension has been classified by the World Health Organization/International Society of Hypertension into mild, moderate, severe and high normal [83].

Hypertension is a non-communicable chronic disease, often requiring long-term treatment. The incidence may be on the increase as a result of increasing urbanisation and changing lifestyles in the world [88–92]. Hypertension is regarded a major public health problem [29], and it is an important threat to the health of adults in sub-Saharan Africa [93, 94].

Secondary hypertension indicates that the high blood pressure (HBP) is a result of another underlying condition, such as kidney disease or tumours (adrenal adenoma or phaeochromo‐ cytoma). The pathogenesis of essential hypertension is not clearly understood [95, 96]. However, different investigators have proposed the kidney, peripheral resistance vessels and the sympathetic nervous system as the seat of the primary abnormality [97]. In reality, the problem is probably multifactorial. On the other hand, most mechanisms leading to secondary hypertension are well understood [97]. Some studies have tried to implicate genetic and environmental aetiologies to hypertension [98–101]. Disorder of the autonomic system, as in the case of sympathetic nervous system overactivity and others include imbalance in the reninangiotensin-aldosterone system, chronic exposure to stress, chronic use of alcohol and other associated medical diseases like diabetes.

## **3. Epidemiology of hypertension**

The prevalence of hypertension is probably on the increase in developing countries, including Nigeria, where adoption of western lifestyles and the stress of urbanisation, both of which are expected to increase the morbidity associated with unhealthy lifestyles, are not on the decline [102, 103]. The prevalence of hypertension depends on both racial composition of the popu‐ lation of the study and the criteria for defining the condition [104]. In Nigeria, it is the com‐ monest non-communicable disease; over 4.3 million Nigerians above the age of 15 years are classified as being hypertensives [105, 106].

Risk factors have equally become important in the aetiology of hypertension. A study found that as high as 62% of the total population of hypertensive lived with at least two risk factors, mainly diabetes mellitus and alcohol use. Several other studies both in Nigeria and elsewhere have also implicated diabetes, calcium salt and fat intake from consumption of processed food [91], participating in jobs with minimal activities, obesity [92], consumption of caffeine [89, 108, 109] and alcohol [107], smoking and hypercholesterolemia [110, 111]. A proportion of the diabetic population (20%) suffered from isolated systolic hypertension [106]. In a meta-analysis of nine studies carried out in Nigeria with similar methodology, the authors [93, 112–115] summarised the prevalence of hypertension in population of Nigeria for a 20-year period (1990–2009), in which two reviewers, independently, were used during the selection process, so as to reduce bias as much as possible.

In spite of the peculiarities found in studies on hypertension in different parts of the world, it is important to note that in all areas, hypertension (HT) or high blood pressure (HBP) is a heterogeneous set of disorders. Social and cultural factors have a direct aetiologic effect on hypertension, and these factors are responsible for most of the differences in disease prevalence in different parts of the world. High blood pressure is a mass phenomenon responsible for high morbidity and mortality affecting millions of people the world over [30], and with the notable exception of a few non–salt-eating primitive societies, it occurs everywhere. Diseases of the cardiovascular system are among the most important causes of morbidity in the industrialised world [30, 116, 117], accounting for over one-third of all deaths in the United States [118, 119]. A study [7] estimates a worldwide prevalence of between 10 and 15% of adult populations to have high blood pressure which also agrees with findings in Africa [120]. However, other studies have reported a worldwide prevalence of 15–30% in adults [121]. Studies from the Western world identified five factors associated with hypertension: increasing age, obesity, elevated pressure in blood relative, environment and race [116].

## **4. Hypertension and psychopathology**

classified by the World Health Organization/International Society of Hypertension into mild,

Hypertension is a non-communicable chronic disease, often requiring long-term treatment. The incidence may be on the increase as a result of increasing urbanisation and changing lifestyles in the world [88–92]. Hypertension is regarded a major public health problem [29],

Secondary hypertension indicates that the high blood pressure (HBP) is a result of another underlying condition, such as kidney disease or tumours (adrenal adenoma or phaeochromo‐ cytoma). The pathogenesis of essential hypertension is not clearly understood [95, 96]. However, different investigators have proposed the kidney, peripheral resistance vessels and the sympathetic nervous system as the seat of the primary abnormality [97]. In reality, the problem is probably multifactorial. On the other hand, most mechanisms leading to secondary hypertension are well understood [97]. Some studies have tried to implicate genetic and environmental aetiologies to hypertension [98–101]. Disorder of the autonomic system, as in the case of sympathetic nervous system overactivity and others include imbalance in the reninangiotensin-aldosterone system, chronic exposure to stress, chronic use of alcohol and other

The prevalence of hypertension is probably on the increase in developing countries, including Nigeria, where adoption of western lifestyles and the stress of urbanisation, both of which are expected to increase the morbidity associated with unhealthy lifestyles, are not on the decline [102, 103]. The prevalence of hypertension depends on both racial composition of the popu‐ lation of the study and the criteria for defining the condition [104]. In Nigeria, it is the com‐ monest non-communicable disease; over 4.3 million Nigerians above the age of 15 years are

Risk factors have equally become important in the aetiology of hypertension. A study found that as high as 62% of the total population of hypertensive lived with at least two risk factors, mainly diabetes mellitus and alcohol use. Several other studies both in Nigeria and elsewhere have also implicated diabetes, calcium salt and fat intake from consumption of processed food [91], participating in jobs with minimal activities, obesity [92], consumption of caffeine [89, 108, 109] and alcohol [107], smoking and hypercholesterolemia [110, 111]. A proportion of the diabetic population (20%) suffered from isolated systolic hypertension [106]. In a meta-analysis of nine studies carried out in Nigeria with similar methodology, the authors [93, 112–115] summarised the prevalence of hypertension in population of Nigeria for a 20-year period (1990–2009), in which two reviewers, independently, were used during the selection process,

In spite of the peculiarities found in studies on hypertension in different parts of the world, it is important to note that in all areas, hypertension (HT) or high blood pressure (HBP) is a heterogeneous set of disorders. Social and cultural factors have a direct aetiologic effect on

and it is an important threat to the health of adults in sub-Saharan Africa [93, 94].

moderate, severe and high normal [83].

74 Update on Essential Hypertension

associated medical diseases like diabetes.

**3. Epidemiology of hypertension**

classified as being hypertensives [105, 106].

so as to reduce bias as much as possible.

The relationship between hypertension and emotional disturbance or psychiatric morbidity could be described as bidirectional, or better still, as taking the form of a vicious cycle. Apart from the genetic components, persistent environmental stressors are well-known triggers for hypertension [25, 31, 122]. They reset and over amplify the sympathetic outflow [62–65, 123]. The neurotransmitter that fuels the sympathetic pathway, noradrenaline, is consequently overelaborated and becomes hyperactive. This causes both hypertension and anxiety disorders including generalised anxiety disorder (GAD), panic disorder, acute stress disorder and PTSD. On the other hand, the presence of anxiety alone can cause hypertension in predisposed individuals [49, 50]. The chronicity of hypertension, persistent and recurrent symptoms, impairment in functioning capacity, other adverse and enduring environmental psychosocial burdens and even the thought of these can also in turn cause anxiety and may also quickly drive the patient into depression, suicidal ideation or attempt and ultimately suicide. Longstanding untreated depression in hypertensive patients can be complicated with psychosis [23]. Also, hypertension can be complicated with cerebrovascular accident (CVA), with its attendant neuropsychiatric sequelae including depression, anxiety, mild-to-severe cognitive impairment, personality changes, vascular dementia and psychosis.

Lishman identified the interest of psychiatry in hypertension, besides the obvious consequen‐ ces of its central nervous system effects and noted:


He suggested possible explanations including drugs taken, feeling ill and attendance to hospital per se and possibly more pre-morbidly neurotic individuals becoming hypertensive patients. Other various writers have also looked in depth at purely psychological attributes in hypertensive subjects either causally or effectually [106, 124]. Fundamental advances in the understanding of hypertension from then have coincided with theories of anxiety states and affective disorders suggesting catecholamines as mediators. These find common ground in suggested mechanisms for producing increased arterial pressure [62–65, 123].

Studies have shown that stress-related situations, issue of job loss and unemployment [24], prolonged difficulties, being under stress and people at war front were shown to have elevated blood pressures [25, 31, 122]. It has been found that stress increases the level of cortisol which causes increased deposition of arteriosclerotic deposits in the intima of blood vessels. These depositions gradually narrow the lumen of the vessels, which in turn increases arterial pressure resulting into hypertension. The same elevated cortisol has been implicated in depression and also explains the high rate of depression associated with disorders that primarily involve cortisol-like Cushing's syndrome [125, 126]. It has also been suggested that hypertensive individuals exhibit more aggressive traits than others and that these may be hidden or suppressed, becoming manifest by abnormal elevation of blood pressure [127].

Psychosocial stressors, especially job-related stressors, predicted hypertension more strongly in men than in women in these data as in those of other investigators [50]. Other potential hypertension risk factors included social alienation and low level of education and ethnicity, which are independent predictors of hypertension. Indicators of subjective distress and low educational status, on the other hand, appeared more predictive of hypertension in women than in men. The excess impact of psychosocial stress on the development of hypertension in men compared with women may be related to sex differences in reactions to cardiovascular stress reactivity [127].

Some other studies that have examined the association of hypertension with psychological distress, such as anxiety and depressive symptoms, have produced mixed findings. Several studies have reported positive associations [128, 129], whereas others have observed weak or no associations. Other numerous studies have produced evidence that patients with depres‐ sion have an increased risk of developing cardiovascular disease [48]. Also, depression in untreated hypertension might increase risk of developing cardiovascular disease. There is even some evidence to suggest lower blood pressure (BP) in participants with depressive or anxiety disorders. These areas of uncertainty call for further research (longitudinal) to evaluate the true associations between mental disorders and hypertension.

The findings of other studies that depressive disorder was associated with lower *s*ystolic blood pressure (SBP), although the use of tricyclic antidepressants was associated with greater risk of hypertension, may simply correspond with increased risk of weight gain associated with these agents [130]. Similar findings have been made with psychotropic medications. These studies are limited by their cross-sectional design, which made it difficult to infer causality or determine the direction of the observed relationship between hypertension and psychological distress. A related issue is the effect of labelling patients as hypertensive. Several studies have suggested that individuals 'labelled' as hypertensive might adopt a sick role that can nega‐ tively affect quality of life [74–79]. For this reason, the association between hypertension and psychological distress may be because of a direct effect of the BP itself, adverse effects of treatment or the consequences of labelling.

Another study also found that health-related quality of life, including physical functioning, vitality, mental health and pain thresholds, was better in unaware compared with aware hypertensive participants [78]. Several mechanisms have been postulated to explain the effects of labelling. Some evidence suggests that the act of labelling somebody as hypertensive can cause increases in sympathetic activity during mental stress [123], which might partly explain the reason for the poor mental health of patients with hypertension. In a study of 214 normo‐ tensive and mildly hypertensive participants, the perception of being hypertensive was associated with greater anxiety during clinic BP measurement and may be due to the white coat effect [131].

Another study also observed direct associations between the use of alcohol (daily >14 g intake of ethanol) and kola nut consumption in men and isolated systolic hypertension [124]. The survey showed that over 10% of the population taking kola nuts (at least one in 2 days) and/or alcohol is hypertensive. Caffeine has been identified as a significant cause of hyper‐ tension [79]. The authors [79] therefore concluded that programmes to improve treatment of hypertension should not only focus on lifestyle variables like smoking and alcohol, but they should also include the identification and treatment of substance abuse and dependence disorders.

Besides anxiety and depression, a range of other psychiatric problems may occur following cerebrovascular accident resulting from hypertension. They include cognitive disorders and personality changes [127], especially with the involvement of the right hemisphere. In fact, untreated hypertension can equally cause cognitive impairment, which is commonly seen in organic psychiatry [97]. A study done in two communities in Ibadan metropolis, Nigeria, by Ogunniyi and Baiyewu found a high rate of incident (vascular) dementia with psychological and behavioural components as complications of hypertension [43]. Studies have also found out the association between hypertension and erectile dysfunction in men. A study noted 1% of psychogenic impotence and 1% secondary to the effect of some antihypertensive drugs like methyldopa and reserpine [29].

This study was therefore designed to evaluate the sociodemographic and clinical correlates of psychiatric comorbidity in hypertensive patients. This, no doubt, would be of immense relevance to the practice of consultation liaison psychiatry in the West African subregion and contribute to the corpus of knowledge on chronic medical conditions and aid care/service providers to plan better management strategies that will also accord premium to the psycho‐ logical component and well-being of these patients. Impairments, disabilities and handicaps from chronic conditions may thus be limited and patients' dignity and functional capacity enhanced.

## **5. Aim**

hypertensive subjects either causally or effectually [106, 124]. Fundamental advances in the understanding of hypertension from then have coincided with theories of anxiety states and affective disorders suggesting catecholamines as mediators. These find common ground in

Studies have shown that stress-related situations, issue of job loss and unemployment [24], prolonged difficulties, being under stress and people at war front were shown to have elevated blood pressures [25, 31, 122]. It has been found that stress increases the level of cortisol which causes increased deposition of arteriosclerotic deposits in the intima of blood vessels. These depositions gradually narrow the lumen of the vessels, which in turn increases arterial pressure resulting into hypertension. The same elevated cortisol has been implicated in depression and also explains the high rate of depression associated with disorders that primarily involve cortisol-like Cushing's syndrome [125, 126]. It has also been suggested that hypertensive individuals exhibit more aggressive traits than others and that these may be hidden or suppressed, becoming manifest by abnormal elevation of blood pressure [127].

Psychosocial stressors, especially job-related stressors, predicted hypertension more strongly in men than in women in these data as in those of other investigators [50]. Other potential hypertension risk factors included social alienation and low level of education and ethnicity, which are independent predictors of hypertension. Indicators of subjective distress and low educational status, on the other hand, appeared more predictive of hypertension in women than in men. The excess impact of psychosocial stress on the development of hypertension in men compared with women may be related to sex differences in reactions to cardiovascular

Some other studies that have examined the association of hypertension with psychological distress, such as anxiety and depressive symptoms, have produced mixed findings. Several studies have reported positive associations [128, 129], whereas others have observed weak or no associations. Other numerous studies have produced evidence that patients with depres‐ sion have an increased risk of developing cardiovascular disease [48]. Also, depression in untreated hypertension might increase risk of developing cardiovascular disease. There is even some evidence to suggest lower blood pressure (BP) in participants with depressive or anxiety disorders. These areas of uncertainty call for further research (longitudinal) to evaluate the

The findings of other studies that depressive disorder was associated with lower *s*ystolic blood pressure (SBP), although the use of tricyclic antidepressants was associated with greater risk of hypertension, may simply correspond with increased risk of weight gain associated with these agents [130]. Similar findings have been made with psychotropic medications. These studies are limited by their cross-sectional design, which made it difficult to infer causality or determine the direction of the observed relationship between hypertension and psychological distress. A related issue is the effect of labelling patients as hypertensive. Several studies have suggested that individuals 'labelled' as hypertensive might adopt a sick role that can nega‐ tively affect quality of life [74–79]. For this reason, the association between hypertension and psychological distress may be because of a direct effect of the BP itself, adverse effects of

true associations between mental disorders and hypertension.

treatment or the consequences of labelling.

suggested mechanisms for producing increased arterial pressure [62–65, 123].

stress reactivity [127].

76 Update on Essential Hypertension

The study was to determine the pattern and prevalence of psychiatric comorbidity and quality of life in subjects with essential hypertension.

## **6. Methodology**

In this cross-sectional study, following ethical approval from the hospital and informed consent from the participants, 360 subjects making up the study group were recruited based on the study's inclusion and exclusion criteria, after a pilot study for both groups. In addition, the hypertensives were screened for human immunodeficiency virus (HIV) infection. Subjects were further administered with the study's instruments including the sociodemographic questionnaire, General Health Questionnaire, version 12 (GHQ-12), World Health Organiza‐ tion Composite International Diagnostic Interview (WHOCIDI) and the brief version of the WHO Quality of Life (WHOQOL-Bref) instrument. Severity of hypertension was determined using the modern classification by the WHO/International Society of Hypertension into mild, moderate and severe. Those considered suitable for the study were patients who had been seen and diagnosed as having essential hypertension by the consultant family physicians and internists.

The hypertensive patients have all had basic investigations: i.e. full blood count, blood urea and electrolytes estimation and urinalysis, in most cases. In addition, some had electrocardio‐ grams (ECG), chest X-rays, serum cholesterol, uric acid, creatinine and creatinine clearance estimations. Investigation results were all recorded in the case notes. Hypertensive patients with primary myocardial or valvular disease, cardiac failure or renal failure or who had a stroke or coronary heart disease, diabetes, asthma or other chronic illnesses or those found to be acutely ill were excluded. Patients were required to have been diagnosed for at least the past 1 year and have had at least 6 months of treatments. The data were analysed using the Statistical Package for Social Sciences version 16 statistical package. Confidence interval was set at 95%, while p-value of less than 0.05 was considered statistically significant.

## **7. Study instruments**

The following instruments were used in this study:


## **8. Results**

#### **8.1. Sociodemographic and clinical correlates of psychiatric morbidity in study group**

Out of the 360 subjects with essential hypertension who fulfilled the inclusion criteria, 141 (39.2%) were males and 219 (60.8%) females. The mean age for the study group (hypertensives)


was 45.57 years. More than half of all the subjects 257 (71.4%) were married. The majority (78.0%) had attained at least a secondary level of education.

**6. Methodology**

78 Update on Essential Hypertension

internists.

**7. Study instruments**

**8. Results**

The following instruments were used in this study:

**•** General Health Questionnaire, version 12 (GHQ-12)

**•** Sociodemographic/clinical questionnaire

In this cross-sectional study, following ethical approval from the hospital and informed consent from the participants, 360 subjects making up the study group were recruited based on the study's inclusion and exclusion criteria, after a pilot study for both groups. In addition, the hypertensives were screened for human immunodeficiency virus (HIV) infection. Subjects were further administered with the study's instruments including the sociodemographic questionnaire, General Health Questionnaire, version 12 (GHQ-12), World Health Organiza‐ tion Composite International Diagnostic Interview (WHOCIDI) and the brief version of the WHO Quality of Life (WHOQOL-Bref) instrument. Severity of hypertension was determined using the modern classification by the WHO/International Society of Hypertension into mild, moderate and severe. Those considered suitable for the study were patients who had been seen and diagnosed as having essential hypertension by the consultant family physicians and

The hypertensive patients have all had basic investigations: i.e. full blood count, blood urea and electrolytes estimation and urinalysis, in most cases. In addition, some had electrocardio‐ grams (ECG), chest X-rays, serum cholesterol, uric acid, creatinine and creatinine clearance estimations. Investigation results were all recorded in the case notes. Hypertensive patients with primary myocardial or valvular disease, cardiac failure or renal failure or who had a stroke or coronary heart disease, diabetes, asthma or other chronic illnesses or those found to be acutely ill were excluded. Patients were required to have been diagnosed for at least the past 1 year and have had at least 6 months of treatments. The data were analysed using the Statistical Package for Social Sciences version 16 statistical package. Confidence interval was

set at 95%, while p-value of less than 0.05 was considered statistically significant.

**•** World Health Organization Composite International Diagnostic Interview (WHOCIDI)

**8.1. Sociodemographic and clinical correlates of psychiatric morbidity in study group**

Out of the 360 subjects with essential hypertension who fulfilled the inclusion criteria, 141 (39.2%) were males and 219 (60.8%) females. The mean age for the study group (hypertensives)



**Variables Essential hypertensive** 

80 Update on Essential Hypertension

**Average monthly income** X2

**Reaction to diagnosis** X2

**Mode of getting drugs** X2

**Source of support** X2

**Domestic situation** X2

**Blood pressure** X2

**Occupation** X2

Low 83 54 (24.8%) 29 (24.2%) Average 159 104 (47.7%) 54 (45.0) High 97 60 (27.5%) 37(30.8)

Normal 38 18 (7.6%) 20 (16.1%) Sad 175 101 (42.8%) 74 (59.7%) Very sad 146 116 (49.2%) 30 (24.2%) Wish to die 1 1 (0.4%) 0 (0.0%)

From the government 106 42 (11.7%) 64 (17.8%) Self-purchase 202 146 (40.6%) 56 (15.6%) Both 52 35 (9.7%) 17 (4.7%)

Charity organisation 14 9 (2.5%) 5 (1.4%) Fiends 36 27 (7.5%) 9 (2.5%) Relatives 92 60 (16.7%) 32 (8.9%) None 218 143 (39.8%) 75 (20.8%)

Partner 37 22 (6.1%) 15 (4.2%) Family 307 213 (59.2%) 94 (26.1%) Friends 7 3 (0.8%) 4 (1.1%) None 9 5 (1.4%) 4 (1.1%)

BP within normal range 0 0 (0%) 0 (0%) Mild hypertension 119 49 (13.7%) 70 (19.4%) Moderate hypertension 161 114 (31.7%) 47 (13.1%) Severe hypertension 80 73 (20.3%) 7 (1.9%)

Managers 5 3 (1.3%) 2 (1.6%) Professionals 15 5 (2.0%) 10 (2.8%)

**Total Psychiatric diagnosis No psychiatric diagnosis Statistical analysis** 

 = 23.86 df = 3 p < 0.001

 = 14.41 df = 10 p = 0.16

 = 13.09 df = 3 p = 0.57

 = 15.06 df = 3 p = 0.33

 = 12.41 df = 3 p = 0.51

 = 16.40 df = 3 p = 0.001

 = 17.63 df = 10 p = 0.82

**Table 1.** Sociodemographic variables and psychiatric comorbidity among hypertensives.

More than one quarter of all the subjects, 241 (66.9%), were within low to average income range of less than 10,000–30,000 naira monthly. The majority, 169 (46.9%), had their onset of illness at the age range of 40–49 years. Persons who were married were significantly more likely to have a psychiatric comorbidity (p < 0.001). Also, those who reacted with either 'very sad' or a 'wish to die' when they received the diagnosis of the medical conditions were more likely to have psychiatric comorbidity (p = 0.001). See **Table 1**.

#### **8.2. Pattern and prevalence of psychiatry morbidity in subjects with essential hypertension**

A total of 232 (64.4%) subjects had associated psychiatric comorbidity, while 128 (35.5%) had no psychiatric diagnosis. Out of the total number with psychiatric comorbidity, 106 (29.4%) had a depressive illness, generalised anxiety disorder (GAD) was diagnosed in 58 (16.2%) patients, 32 (9.3%) patients had sexual dysfunction out of which 27 (7.5%) had male erectile dysfunction, while 5 (1.4%) had hyposexual dysfunction and was diagnosed all in females (see **Figure 1**).

**Figure 1.** Bar chart showing the pattern and prevalence of psychiatric morbidity among persons with essential hyper‐ tension.

It is important to note that 20 (5.6%) patients were diagnosed with more than one condition. Erectile dysfunction and substance abuse were diagnosed in one patient; one respondent had GAD, substance abuse and erectile dysfunction; five respondents had GAD and hyposexual dysfunction; six had GAD and male erectile dysfunction, two had mixed anxiety and depression and male erectile dysfunction; and five had depressive illness and male erectile dysfunction. This accounted for the excess above 590 patients if the total diagnoses are summed up (see **Table 2**).


More than one quarter of all the subjects, 241 (66.9%), were within low to average income range of less than 10,000–30,000 naira monthly. The majority, 169 (46.9%), had their onset of illness at the age range of 40–49 years. Persons who were married were significantly more likely to have a psychiatric comorbidity (p < 0.001). Also, those who reacted with either 'very sad' or a 'wish to die' when they received the diagnosis of the medical conditions were more likely to

**8.2. Pattern and prevalence of psychiatry morbidity in subjects with essential hypertension**

A total of 232 (64.4%) subjects had associated psychiatric comorbidity, while 128 (35.5%) had no psychiatric diagnosis. Out of the total number with psychiatric comorbidity, 106 (29.4%) had a depressive illness, generalised anxiety disorder (GAD) was diagnosed in 58 (16.2%) patients, 32 (9.3%) patients had sexual dysfunction out of which 27 (7.5%) had male erectile dysfunction, while 5 (1.4%) had hyposexual dysfunction and was diagnosed all in females (see

**Figure 1.** Bar chart showing the pattern and prevalence of psychiatric morbidity among persons with essential hyper‐

It is important to note that 20 (5.6%) patients were diagnosed with more than one condition. Erectile dysfunction and substance abuse were diagnosed in one patient; one respondent had GAD, substance abuse and erectile dysfunction; five respondents had GAD and hyposexual dysfunction; six had GAD and male erectile dysfunction, two had mixed anxiety and depression and male erectile dysfunction; and five had depressive illness and male erectile dysfunction. This accounted for the excess above 590 patients if the total diagnoses are summed

have psychiatric comorbidity (p = 0.001). See **Table 1**.

**Figure 1**).

82 Update on Essential Hypertension

tension.

up (see **Table 2**).

**Table 2.** Pattern and prevalence of psychiatry morbidity in subjects with essential hypertension.

## **9. Association of psychiatric comorbidity with quality of life in persons with essential hypertension**

From the study, psychiatric comorbidity was negatively statistically significantly associated with QOL in all domains except in General Health Facet in both medical conditions. Among the hypertensives patients, those with psychiatric comorbidity performed better on psycho‐ logical and social domains (see **Table 3**).


**Table 3.** Association of psychiatric morbidity with quality of life in persons with essential hypertension.

## **10. Discussion**

The study on the psychiatric comorbidities associated with essential hypertension was conceptualised mainly from the observation of the relatively high frequency with which requests for psychiatric consultation were being received over time from other clinical departments in UPTH, particularly internal medicine. The observation was later confirmed by a study [43]. The study was, thus, started with the main objectives of determining the pattern and prevalence of psychiatric morbidity among persons with essential hypertension attending the outpatients clinic of UPTH. A cross-sectional design was adopted, with a sequential use of four study instruments, followed by analysis of data using the various statistical methods.

From the study, the prevalence of essential hypertension was noted to be increasing with age and was about twice higher, in the age groups 40–49 and 50 and above, compared to age group of 30–39, and about six times higher compared with age group 20–29. This result is consistent with earlier studies which reported that about 4.3 million Nigerians above the age of 15 years are classified as being hypertensive. Furthermore, the prevalence has been said to be related to age, particularly in females, with a substantial increase occurring after the age of 50 [36].

Though essential hypertension commonly starts in middle age, the illness may progressively become worse with attendant incapacitating symptoms that may infringe on the functional capacity of the individual and thereby lowering the quality of life. Africans usually seek medical attention mostly when illness has worsened with disabling symptoms, and in most cases late, in spite of awareness of the diagnosis. This is particularly more so for essential hypertension. Moreover, cultural factors, poverty and inaccessibility to healthcare facilities often contribute to this delay. This could also explain the over-representation of the older age group in the hypertensive patients in this study, who are more superstitious, poor and with low-income capacity and hence unable to seek health care, particularly timely. Furthermore, essential hypertension is a chronic disease, and most of the respondents diagnosed over 5–10 years ago are still on maintenance antihypertensive therapy.

**Domains of QOL** 

84 Update on Essential Hypertension

Psychological domain

Environment domain

General health facet

**10. Discussion**

**Quality of life of all hypertensive patients** 

**Psychiatric comorbidity** 

**Quality of life in persons with essential hypertension** 

54.20 ± 22.186 56.60 ± 24.914 61.05 ± 13.362 t = −4.35 df = 358 p < 0.001

50.01 ± 16.91 44.95 ± 14.831 59.62 ± 16.503 t = −8.57 df = 358 p < 0.001

49.34 ± 22.44 47.98 ± 21.896 51.91 ± 23.319 t = −1.58 df = 358 p < 0.001

Physical domain 50.97 ± 14.671 45.98 ± 13.064 60.46 ± 12.788 t = −10.07 df = 358 p < 0.001

Social domain 54.51 ± 26.13 48.06 ± 26.114 66.80 ± 21.378 t = − 6.87 df = 358 p < 0.001

The study on the psychiatric comorbidities associated with essential hypertension was conceptualised mainly from the observation of the relatively high frequency with which requests for psychiatric consultation were being received over time from other clinical departments in UPTH, particularly internal medicine. The observation was later confirmed by a study [43]. The study was, thus, started with the main objectives of determining the pattern and prevalence of psychiatric morbidity among persons with essential hypertension attending the outpatients clinic of UPTH. A cross-sectional design was adopted, with a sequential use of four study instruments, followed by analysis of data using the various statistical methods.

From the study, the prevalence of essential hypertension was noted to be increasing with age and was about twice higher, in the age groups 40–49 and 50 and above, compared to age group of 30–39, and about six times higher compared with age group 20–29. This result is consistent with earlier studies which reported that about 4.3 million Nigerians above the age of 15 years are classified as being hypertensive. Furthermore, the prevalence has been said to be related to age, particularly in females, with a substantial increase occurring after the age of 50 [36].

Though essential hypertension commonly starts in middle age, the illness may progressively become worse with attendant incapacitating symptoms that may infringe on the functional capacity of the individual and thereby lowering the quality of life. Africans usually seek medical attention mostly when illness has worsened with disabling symptoms, and in most cases late, in spite of awareness of the diagnosis. This is particularly more so for essential hypertension. Moreover, cultural factors, poverty and inaccessibility to healthcare facilities often contribute to this delay. This could also explain the over-representation of the older age group in the hypertensive patients in this study, who are more superstitious, poor and with

**Table 3.** Association of psychiatric morbidity with quality of life in persons with essential hypertension.

**No psychiatric comorbidity**  **Statistical analysis** 

On the other hand, the rising prevalence of hypertension with age could be a reflection of exposure to enduring stressors, poor dietary habit, lack of exercise and other culturally permissible hazardous lifestyle [36].

The most prevalent age of onset of hypertension was ages 40–49, with 169 respondents or 46.9%. This was in agreement with other studies, which had established that the illness is commonest after 40 years. It is interesting to note that the number of patients steadily increased with increasing age of onset of illness with a sharp decrease after the age of 50. Hypertension beginning after the age of 50 years is most likely to be secondary hypertension [23]. This result is therefore in consonant with the methodology adopted in this study, where all those with any other concurrent medical illnesses were excluded in other not to introduce bias. However, it was difficult for most of the respondents to know exactly the age of onset of disease since majority only became aware of the diagnosis during their first or routine hospital visits.

Females predominated in the study with 60.8%, and although essential hypertension is more common in males, females may have been over-represented in this study due to two reasons. First, African females tend to have lower blood pressure than males early in life with a reversal of the trend after the ages 45–50 years [35, 36]. This may be due to hormonal changes associated with the preparation for or actual menopause occurring in this age group, coupled with the increasing family and domestic (stressors) responsibilities shouldered by married females in this age group. Interestingly, in this study, there was high prevalence of the married females in both groups. Another probable reason for the predominance of females in this study is that females are more willing and likely to volunteer their symptoms easier than males and consequently tend to have better health-seeking behaviours.

The married group was over-represented in the study (71.4%). This preponderance might be due to low rates of divorce and separation, which may reflect a dominance of Christianity in the study environment. Furthermore, widows constituted a significant percentage (15%) among the hypertensives, next to the married group. Widowhood, no doubt, hurts and often results in severe emotional trauma, particularly when it is sudden and early in life. More than half of the subjects who were single (10.6%) were above the age of 30 years, many of whom were unemployed. In Africa, due to sociocultural values, a female not yet married at the age of 30 years and above calls for concern not only to her but also to her family members. Majority of the separated group were females. Although lower rates of psychiatric comorbidities were found among these categories, both separation and divorce are capable of impacting enormous psychological trauma in affected individuals.

Also from the study, it was found that more of each of the categories—married, separated and widowed—had more psychiatric comorbidity among patients with hypertension. A possible explanation could be that in hypertension, marital difficulties, separation and even widow‐ hood may serve as baseline psychosocial factors that may act either singly or in synergy with the medical stressor (hypertension) to cause psychiatric comorbidity. The presence of these psychosocial stressors alone can equally predispose to hypertension. Thus, in hypertension, psychological stressors are both causal and effectual.

Most of the subjects in this study had attained various levels of formal education especially secondary and tertiary. Perhaps the influence of westernisation and urbanisation in Rivers State, Niger Delta and Nigeria might have played an important role. Furthermore, the cosmopolitan nature of Port Harcourt, domiciling majority of ethnic groups in Nigeria, with over 50% of Nigeria's oil and gas business, makes education a priority. A good number (39%) of the subjects with hypertension had tertiary education. The fact that they were educated may have increased their chances of employment and possibly ability to seek quality health care and timely, too. It is equally important to note that perhaps the older one becomes, and probably with more education, the more his or her socioeconomic and family responsibilities, with their accompanying stressors.

A number of studies have implicated environmental stressors as important aetiological factors in high blood pressure, particularly in already genetically predisposed individuals [82]. Occupational environments in Nigeria had remained stressful due to lack of job security and poor wages and remunerations, confronting countless demands from members of the family in a poverty-ravaged economy such as ours. This is supported by the fact that the percentage of females with tertiary education was significantly less compared to other educational levels. The incidence of psychiatric comorbidity was lowest among those with tertiary education. Hence, education tended to have some protective influence on the psyche of the study subjects. Expectedly, those with higher level of education were more likely to secure better employment, earn better income and have better access to quality health care. Thus, in this study, results showed that being employed correlated positively, while unemployment correlated negatively with occurrence of psychiatric comorbidity.

From the study, essential hypertension was associated more with low income. Stable income, no doubt, is an important stabilising factor for any chronic illness. In this study, income level negatively correlated with psychiatric comorbidity in hypertension. The higher the income level, the lower the prevalence of psychiatric illness in hypertension. Among the hypertensives, there was preponderance of older adults; however, as it has to do with income level, it appears to be a combined effect of both income and age in the study.

African extended family may also be contributory. Sharing the burden of disease by relatives in the African extended family system may be an advantage to the outcome of chronic illnesses like hypertension, as it tends to distribute responsibility from such patients to other family members. This was evident from this study where 85% of hypertensives live with their supportive family members. Adequate social support has been identified as a key factor in relieving or decreasing psychosocial burden associated with chronic medical conditions.

Expectedly, the longer the duration of these illnesses, the more likelihood of developing psychopathology. Interestingly, however, the reverse was observed in this study, as psychi‐ atric comorbidity steadily decreased with increasing duration of illness. This might suggest that with the passage of time, one tended to absorb the initial shock of diagnosis and had adequately readjusted to the medical condition. Secondly, they might have stabilised on medications. The high rate of psychiatric illnesses among those in treatment between 1 and 5 years could probably reflect an over-representation of subjects in this category ab initio. Also, the effect of advancing age might have played a role as many would have died from compli‐ cations of the illness. This was reflected in this study as subjects in the category of duration of treatment greater than 10 years were fewer. Mortality rates in this medical condition have remained high [93].

psychosocial stressors alone can equally predispose to hypertension. Thus, in hypertension,

Most of the subjects in this study had attained various levels of formal education especially secondary and tertiary. Perhaps the influence of westernisation and urbanisation in Rivers State, Niger Delta and Nigeria might have played an important role. Furthermore, the cosmopolitan nature of Port Harcourt, domiciling majority of ethnic groups in Nigeria, with over 50% of Nigeria's oil and gas business, makes education a priority. A good number (39%) of the subjects with hypertension had tertiary education. The fact that they were educated may have increased their chances of employment and possibly ability to seek quality health care and timely, too. It is equally important to note that perhaps the older one becomes, and probably with more education, the more his or her socioeconomic and family responsibilities,

A number of studies have implicated environmental stressors as important aetiological factors in high blood pressure, particularly in already genetically predisposed individuals [82]. Occupational environments in Nigeria had remained stressful due to lack of job security and poor wages and remunerations, confronting countless demands from members of the family in a poverty-ravaged economy such as ours. This is supported by the fact that the percentage of females with tertiary education was significantly less compared to other educational levels. The incidence of psychiatric comorbidity was lowest among those with tertiary education. Hence, education tended to have some protective influence on the psyche of the study subjects. Expectedly, those with higher level of education were more likely to secure better employment, earn better income and have better access to quality health care. Thus, in this study, results showed that being employed correlated positively, while unemployment correlated negatively

From the study, essential hypertension was associated more with low income. Stable income, no doubt, is an important stabilising factor for any chronic illness. In this study, income level negatively correlated with psychiatric comorbidity in hypertension. The higher the income level, the lower the prevalence of psychiatric illness in hypertension. Among the hypertensives, there was preponderance of older adults; however, as it has to do with income level, it appears

African extended family may also be contributory. Sharing the burden of disease by relatives in the African extended family system may be an advantage to the outcome of chronic illnesses like hypertension, as it tends to distribute responsibility from such patients to other family members. This was evident from this study where 85% of hypertensives live with their supportive family members. Adequate social support has been identified as a key factor in relieving or decreasing psychosocial burden associated with chronic medical conditions.

Expectedly, the longer the duration of these illnesses, the more likelihood of developing psychopathology. Interestingly, however, the reverse was observed in this study, as psychi‐ atric comorbidity steadily decreased with increasing duration of illness. This might suggest that with the passage of time, one tended to absorb the initial shock of diagnosis and had adequately readjusted to the medical condition. Secondly, they might have stabilised on

psychological stressors are both causal and effectual.

with their accompanying stressors.

86 Update on Essential Hypertension

with occurrence of psychiatric comorbidity.

to be a combined effect of both income and age in the study.

The reduced rate of psychiatric comorbidity among the category that has had treatment for 6 years and above could suggest that most of the medications being used in these clinics in the treatment of patients with essential hypertension even though they potentially may be associated with neuropsychiatric side effects [82] were cautiously used and properly moni‐ tored. This might have resulted into minimal rate of psychiatric side effects even with prolonged use.

From the results of this present study, the prevalence of psychiatric morbidity in the hyper‐ tensives was 64.4%. This was slightly higher than results from previous studies [62]. Ohene, in his study in Benin City, found a prevalence of 35% psychiatric morbidity among persons with essential hypertension [62]. Although these results seem to be far apart, the difference might reflect the increasing environmental stressors and economic hardship, increasing spate of insecurity in Nigeria and particularly in the Niger Delta, which has significantly worsened over the last 10 years.

Hypertension alone can present with psychiatric morbidity, and this may be aggravated by adverse environmental factors. Adverse environmental factors can in turn predispose to essential hypertension and mental illness. Indeed, this relationship describes a sustained vicious circle. Another possible reason for the observed difference was that in the study by Ohene [62], GHQ-30 was used which is a less-sensitive version when compared with GHQ-12 (used in this study). Thirdly, the sample size was smaller, i.e. 40 patients compared with 360 hypertensives used in this study. The higher the sample size, the higher the likelihood of diagnosis of psychiatric morbidity. Furthermore, several studies have suggested that hospitalbased treatment of hypertensives tends to be associated with higher neuroticism and levels of psychiatric morbidity than their counterparts on community-based treatment. Another plausible reason could be the use of some antihypertensive particularly calcium channel blockers and α-methyldopa, implicated recently in psychiatry comorbidity among patients on treatment for hypertension.

Out of the total number with psychiatric illness, 232 (64.4%), depression was significantly the commonest with 29.4% as against 16% in Ohene's study [62]. Depression was mostly the mild and moderate types with few cases presenting with psychotic features which were mostly mood congruent. This might also be due to reasons earlier given for overall psychiatric disorders. Hypertension presents with very disabling symptoms, which could impair the functional capability of the sufferer. This, coupled with other adverse depressogenic environ‐ mental factors, might predispose the patient to depressive illness. There was significant predominance of females with depression. This finding, which is consistent with the gender distribution of depression, may equally reflect the willingness of the female gender to volunteer information on their health, hence, better health-seeking behaviour. Hypertensive disease, which carries the risk of both physical and emotional burden, is likely to affect the mood-regulating centre of the brain, i.e. the limbic system.

The prevalence of generalised anxiety disorder was 16.1% in this study. Previous study had found 12%. This could possibly be more frequent. The effect of propranolol and benzodiaze‐ pines (bromazepam and diazepam), which are commonly used medications in the General Outpatient Department, may have been responsible for the relatively low prevalence. Males were 48.2% and females 51.8%. Again, the observed gender bias is in line with existing literature. Earlier studies have suggested that hypertensives were more neurotic, more insecure, more conservative and more tense.

Hypertension and generalised anxiety disorder are somewhat similar illnesses, sharing common pathway—the sympathetic pathway. It is for this reason that medications like beta blockers such as propranolol and some benzodiazepine that act by dampening the activity of the sympathetic pathway have comparable usefulness in both disease conditions. Another reason to 'drive home' the relationship between hypertension and anxiety is that fundamental advances in the understanding of hypertension have coincided with the theories of anxiety states and affective disorders, suggesting catecholamines—particularly known here is noradrenaline [11].

This finds common ground in suggested mechanism for producing increased arterial pressure and neurotic states [11]. This is also consistent with the study by Kidson [94], who argued that higher neurotic scores of his hypertensive outpatients were due to a 'reactive state' occurring in them contrary to other study [113], which reported the absence of neuroticism among newly hypertensives and suggested that drug treatment could cause the observed neurosis. However, in this study, the inclusion criteria of 1 year duration of illness stand to disprove this, and it also appears that most of the hypertensives with diagnosis of anxiety were not due to their medication, and most were having one psychosocial stressor or the other that may either be responsible for or worsen the hypertension, anxiety or even both.

Panic disorder was diagnosed in 1.1% of hypertensive patients in this study. Many workers have consistently established that most of the major deleterious effects of high blood pressure are in the heart, blood vessels, kidneys and brain [11]. Therefore, with the strong connection between the heart and cardiovascular system, hypertension and the psyche, diagnosis of panic disorder in hypertensive subjects might not be a surprising finding. In fact, other names that have been given to anxiety neurosis (now obsolete) include cardiac neurosis, irritable heart syndrome, soldier's heart, nervous tachycardia, vasomotor neurosis, vasoregulatory asthenia and disordered action of heart, among others. Strikingly, these names mainly further imply the close and strong association between the heart or cardiovascular system and anxiety states.

Considering the fact that psychiatric morbidity was most prevalent in the unemployed, elementary and low-income workers, separated and divorced, all baseline psychosocial factors, capable of causing depressive illness, anxiety disorders and other mental illnesses, hypertension is commonly associated with stressful conditions. This is in line with findings from other studies which also showed that some common aetiological factors like stress-related situations, issues of job loss and unemployment, prolonged difficulties and people at war front were shown to have hypertension and anxiety [100]. It has been found that stress, which potentially causes anxiety, also increases the level of cortisol which in turn causes increased deposition of arteriosclerotic deposits in the intima of blood vessels [11]. These deposits gradually narrow the lumen of the vessels. This in turn increases arterial pressure resulting in hypertension [11].

disease, which carries the risk of both physical and emotional burden, is likely to affect the

The prevalence of generalised anxiety disorder was 16.1% in this study. Previous study had found 12%. This could possibly be more frequent. The effect of propranolol and benzodiaze‐ pines (bromazepam and diazepam), which are commonly used medications in the General Outpatient Department, may have been responsible for the relatively low prevalence. Males were 48.2% and females 51.8%. Again, the observed gender bias is in line with existing literature. Earlier studies have suggested that hypertensives were more neurotic, more

Hypertension and generalised anxiety disorder are somewhat similar illnesses, sharing common pathway—the sympathetic pathway. It is for this reason that medications like beta blockers such as propranolol and some benzodiazepine that act by dampening the activity of the sympathetic pathway have comparable usefulness in both disease conditions. Another reason to 'drive home' the relationship between hypertension and anxiety is that fundamental advances in the understanding of hypertension have coincided with the theories of anxiety states and affective disorders, suggesting catecholamines—particularly known here is

This finds common ground in suggested mechanism for producing increased arterial pressure and neurotic states [11]. This is also consistent with the study by Kidson [94], who argued that higher neurotic scores of his hypertensive outpatients were due to a 'reactive state' occurring in them contrary to other study [113], which reported the absence of neuroticism among newly hypertensives and suggested that drug treatment could cause the observed neurosis. However, in this study, the inclusion criteria of 1 year duration of illness stand to disprove this, and it also appears that most of the hypertensives with diagnosis of anxiety were not due to their medication, and most were having one psychosocial stressor or the other that may either be

Panic disorder was diagnosed in 1.1% of hypertensive patients in this study. Many workers have consistently established that most of the major deleterious effects of high blood pressure are in the heart, blood vessels, kidneys and brain [11]. Therefore, with the strong connection between the heart and cardiovascular system, hypertension and the psyche, diagnosis of panic disorder in hypertensive subjects might not be a surprising finding. In fact, other names that have been given to anxiety neurosis (now obsolete) include cardiac neurosis, irritable heart syndrome, soldier's heart, nervous tachycardia, vasomotor neurosis, vasoregulatory asthenia and disordered action of heart, among others. Strikingly, these names mainly further imply the close and strong association between the heart or cardiovascular system and anxiety states.

Considering the fact that psychiatric morbidity was most prevalent in the unemployed, elementary and low-income workers, separated and divorced, all baseline psychosocial factors, capable of causing depressive illness, anxiety disorders and other mental illnesses, hypertension is commonly associated with stressful conditions. This is in line with findings from other studies which also showed that some common aetiological factors like stress-related situations, issues of job loss and unemployment, prolonged difficulties and people at war front

responsible for or worsen the hypertension, anxiety or even both.

mood-regulating centre of the brain, i.e. the limbic system.

insecure, more conservative and more tense.

noradrenaline [11].

88 Update on Essential Hypertension

Sexual dysfunction was diagnosed in 9.0% of hypertensive patients. Of this, 84% had male erectile dysfunction, while 16% who were all females had hyposexual dysfunction. Hyposex‐ ual desire disorder (HSDD) is sexual dysfunction with decreased libido, lack of sexual motivation and decreased sexual fantasies. Some studies have found associations between hypertension and erectile dysfunction in men, while others have implicated effects of some antihypertensive drugs like methyldopa and reserpine [50, 62], in addition to psychogenic impotence. However, in this study no patient was being treated with reserpine, and of the 27 males with erectile dysfunction, only negligible three subjects were on methyldopa.

Another diagnosis that was made among eight of the hypertensives was substance abuse. More than 80% of them had alcohol-related disorder with the male-to-female ratio of 7:1. Although the gender gap was wide, substance abuse generally is commoner among males than females. There is a bidirectional relationship between substance abuse and hypertension, i.e. substance abuse particularly alcohol can cause hypertension while hypertension, on the other hand, can precipitate substance abuse due to frustration [70, 71]. People with hypertension tend to abuse substance mainly to self-medicate their depression or to abate the many anxiety or anxietylike symptoms that characterised hypertension, hence the use of propranolol and diazepam which have anxiolytic effects.

Personality disorder was seen in 5% of the hypertensive subjects. The concept of type A behaviour pattern (TABP), also referred to as type A personality, which appears fairly well established as a strong correlate of coronary heart disease (CHD), strongly supports a rela‐ tionship between hypertension and personality disorder [93]. High blood pressure (HBP) is identified as major risk factor to CHD, which is reported to be on the increase in Nigeria. However, the present study found a low rate of personality disorder.

Hypertensive subjects with more than one psychiatric morbidity were seen in this study. Twelve percent had both GAD and sexual dysfunction, while 8% had both major depression and sexual dysfunction. This equally agrees with the multifactorial aetiological basis of essential hypertensive with environmental stressors playing as much significant role as genetic factors.

For quality of life among patients with hypertension, studies in western countries have shown inconsistent findings. There are no local studies to compare with the present study where both psychiatric comorbidity and QOL were studied together. However, a study that compared QOL of epileptics, schizophrenics and hypertensives found that the last fared poorly on all domains except on overall quality of life where they all faired equally. Some authors have opined that quality of life will be poor in the developing countries like Nigeria where factors of finances, social relationships, health and personal safety are considered to be poor. Hyper‐ tension in adults has a high impact on the economy and with consequent low quality of life of individuals. The results in this study are consistent with many studies elsewhere [27]. It also agrees with a population-based study, which found a lower health status in the hypertensives compared with individuals free from hypertension. This finding varied a little from previous studies where all domains of QOL except domain 4 (environment) and health satisfaction were affected by psychiatric comorbidity.

## **11. Conclusion/recommendations**

The findings of this study support the impression that essential hypertension is a chronic debilitating illness, associated with psychiatric comorbidity. In both groups, being divorced was associated with lower QOL in some domains. The results support the call that the management of patients with hypertension should include attention to their mental health status and subjective quality of life in order to enhance the quality of care.

## **Author details**

Aborlo Kennedy Nkporbu\* and Princewill Chukwuemeka Stanley

\*Address all correspondence to: nakpigi2008@yahoo.com

Department of Neuropsychiatry, University of Port Harcourt Teaching Hospital, Port Harcourt, Nigeria

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The findings of this study support the impression that essential hypertension is a chronic debilitating illness, associated with psychiatric comorbidity. In both groups, being divorced was associated with lower QOL in some domains. The results support the call that the management of patients with hypertension should include attention to their mental health

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**11. Conclusion/recommendations**


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