**1. Introduction**

By definition, hypertension is a chronic condition characterised by persistent elevated blood pressure [1]. Traditionally, the term hypertension has been used to describe a condition in which systolic BP (SBP) is equal or above 140 mm Hg and/ or a diastolic BP (DBP) is equal or above 90 mm Hg [2]. The term Systolic-diastolic hypertension (SDH) is slowly replacing 'hypertension' in this regard as the latter becomes a broader term describing a large number of classes/categories of persistent high BP [3–5]. Thus hypertension can be divided into several types based on several criteria which may or may not overlap.

European Society of Cardiology/European Society of Hypertension (ESC/ESH) criteria for the classification of participants according to office (conventional) BP measurement [4].


The America College of cardiology/American Heart Society (ACC/AHA) has more stringent criteria for conventional BP diagnosis of the hypertension categories.


The advent of ambulatory BP monitoring (ABPM) has revealed much about other subtypes of hypertension in everyday environments; in fact, some developed countries have called for the application of ABPM as a routine tool in clinical practice [6–9]. The superiority of this technique over office BP measurement has been well documented, particularly with respect to the prediction of cardiovascular events and target organ damage [10, 11]. Another benefit of this method is that it minimises the interference of false BP elevations/reductions that may be influenced by clinical settings or other stimuli, as the case may be with white coat hypertension or masked hypertension [10, 12].

The ABPM technique has been instrumental in the understanding of circadian rhythm of haemodynamics, in particular the phenomena of night-time BP dipping or rising, the early morning BP surge [13] as well as BP variability [8, 12]. In light of all these advantages, it is not surprising that ambulatory techniques are now considered the gold standard in hypertension diagnosis and out of office BP measurement [9, 14]. In fact, the ESH and ESC guidelines recommend that wherever possible this method be used as the basis for hypertension diagnosis [2].

The ESC/ESH and ACC/AHA thresholds for hypertension diagnosis according to ABPM [2, 15].


Using the above ambulatory blood pressure thresholds, the following subtypes of hypertension have been identified:

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on target organs.

*Ambulatory Isolated Systolic Hypertension and Cardiovascular Target Organ Damage in People…*

**Hypertension subtype Day BP (mm Hg) Nigh BP (mm Hg)** Isolated Nocturnal Hypertension < 135/85 ≥ 120/70 Isolated Daytime Hypertension ≥ 135/85 < 120/70 Sustained 24-hour Hypertension ≥ 135/85 ≥ 120/70

Ambulatory BP has also allowed identification of two abnormal night-time blood pressure patterns. The first one is an attenuated decline in nocturnal BP. Blood pressure varies over 24 hours, it is high during the day and low during the night. Normally, BP decreases by 10% to 20% during the night. Individuals that lack this decline in nocturnal BP are classified as non-dippers. A large body of evidence exists around the strong association between a non-dipping profile and target organ damage at a vascular, cardiac and cerebrovascular level**.** Another variant BP pattern that is opposite to non-dipping has been identified with ambulatory BP monitoring. Individuals who present with this condition have an abnormally high night-time BP that rises above the daytime BP values. This condition known as reverse dipping has also been associated with cardiovascular

Isolated Systolic Hypertension is a form of hypertension characterised by elevated SBP ≥ 140 mm Hg and often normal or low DBP < 90 mm Hg [16]. As a result of this, ISH is associated with increased pulse pressure (PP), which is the difference between SBP and DBP [16, 17]. Previous studies of ISH date as far back as 1970 [18], with interest in the subject increasing around the 1980's [19–22]. Most of these earlier studies identified ISH as a disease of the elderly, stemming from the "normal" physiological processes associated with ageing [20, 22, 23]. More recent studies have revealed that ISH does in fact also exist in younger individuals [24–27]. In either age group the condition can have detrimental effects on the cardiovascular

Systolic BP and PP are both increased in ISH, and are major predictors of heart disease. These haemodynamic parameters are associated with increased risk of myocardial infarction, left ventricular hypertrophy (LVH), renal dysfunction, stroke and cardiovascular mortality to a greater extent than DBP [29–31]. Some data from clinical trials suggest that even small elevations of SBP confer a significant risk of coronary heart disease [32]. The low DBP associated with ISH may lead to impaired tissue perfusion, particularly of the heart itself [29, 31]. In fact, ISH, which was long believed to be a normal and physiologically harmless state associated with the ageing process [30] has been shown to be a stronger predictor of cerebrovascular and cardiovascular events [32] as well as renal disease [29] than elevated DBP. A thorough understanding of the pathophysiology of ISH is necessary in order to manage the condition effectively and possibly reduce its negative effects

Systolic BP has been shown to increase with age [33], a phenomenon that has been attributed to "natural" changes occurring in the arterial walls as the body ages. For this reason, most of the physiological mechanisms that are believed to be responsible for ISH are associated with the vascular ageing process [34]. This involves an interplay of several processes typically culminating in increased stiff-

As the vascular system ages - usually from about the age of 50 [17, 30], the arterial walls experience fatigue and the elastin fibres therein begin to fragment. This

*DOI: http://dx.doi.org/10.5772/intechopen.96521*

target organ damage.

**1.1 Isolated systolic hypertension**

system and other vital organs [12, 26, 28].

ness of the central arteries [30, 31, 35, 36].

*Ambulatory Isolated Systolic Hypertension and Cardiovascular Target Organ Damage in People… DOI: http://dx.doi.org/10.5772/intechopen.96521*


Ambulatory BP has also allowed identification of two abnormal night-time blood pressure patterns. The first one is an attenuated decline in nocturnal BP. Blood pressure varies over 24 hours, it is high during the day and low during the night. Normally, BP decreases by 10% to 20% during the night. Individuals that lack this decline in nocturnal BP are classified as non-dippers. A large body of evidence exists around the strong association between a non-dipping profile and target organ damage at a vascular, cardiac and cerebrovascular level**.** Another variant BP pattern that is opposite to non-dipping has been identified with ambulatory BP monitoring. Individuals who present with this condition have an abnormally high night-time BP that rises above the daytime BP values. This condition known as reverse dipping has also been associated with cardiovascular target organ damage.

#### **1.1 Isolated systolic hypertension**

Isolated Systolic Hypertension is a form of hypertension characterised by elevated SBP ≥ 140 mm Hg and often normal or low DBP < 90 mm Hg [16]. As a result of this, ISH is associated with increased pulse pressure (PP), which is the difference between SBP and DBP [16, 17]. Previous studies of ISH date as far back as 1970 [18], with interest in the subject increasing around the 1980's [19–22]. Most of these earlier studies identified ISH as a disease of the elderly, stemming from the "normal" physiological processes associated with ageing [20, 22, 23]. More recent studies have revealed that ISH does in fact also exist in younger individuals [24–27]. In either age group the condition can have detrimental effects on the cardiovascular system and other vital organs [12, 26, 28].

Systolic BP and PP are both increased in ISH, and are major predictors of heart disease. These haemodynamic parameters are associated with increased risk of myocardial infarction, left ventricular hypertrophy (LVH), renal dysfunction, stroke and cardiovascular mortality to a greater extent than DBP [29–31]. Some data from clinical trials suggest that even small elevations of SBP confer a significant risk of coronary heart disease [32]. The low DBP associated with ISH may lead to impaired tissue perfusion, particularly of the heart itself [29, 31]. In fact, ISH, which was long believed to be a normal and physiologically harmless state associated with the ageing process [30] has been shown to be a stronger predictor of cerebrovascular and cardiovascular events [32] as well as renal disease [29] than elevated DBP. A thorough understanding of the pathophysiology of ISH is necessary in order to manage the condition effectively and possibly reduce its negative effects on target organs.

Systolic BP has been shown to increase with age [33], a phenomenon that has been attributed to "natural" changes occurring in the arterial walls as the body ages. For this reason, most of the physiological mechanisms that are believed to be responsible for ISH are associated with the vascular ageing process [34]. This involves an interplay of several processes typically culminating in increased stiffness of the central arteries [30, 31, 35, 36].

As the vascular system ages - usually from about the age of 50 [17, 30], the arterial walls experience fatigue and the elastin fibres therein begin to fragment. This

is associated with increased calcium deposition and subsequent media calcification [17]. In addition to this, more collagen fibres are deposited into this fragile wall. There is an accumulation of Advanced Glycation End products (AGEs), which progressively and irreversibly interlink with collagen and elastin fragments to form a complex matrix [36, 37]. Local inflammation occurs, characterised by the release of pro-inflammatory cytokines and enzymes including some metalloproteases which inhibit the production of Nitric Oxide (NO) an influential vasodilator substance, leading to endothelial dysfunction [35, 36, 38].

The pathophysiology of ISH in young individuals is thought to differ at least to some extent from the mechanisms described for the older population [24, 28]. In some young people, ISH develops following a hyperkinetic pre-hypertensive state which is associated with an increase in sympathetic stimulation. This is associated with adrenergic activation with the release of norepinephrine. In these individuals, an increase in resting heart rate and cardiac output leads to an acceleration of arterial stiffness with an isolated increase of SBP [28]. The findings of McEniery et al. [39] in a study of individuals between 17 and 27 suggest that indeed aortic stiffness is associated with ISH in young people, having similar pathophysiological implications as it does in the elderly. Some researchers have shown that an increase in stroke volume in certain young individuals is the major contributor to an elevated PP leading to premature aortic stiffening [26, 27, 28, 39]. Increased body fat in obese young adults could also be a contributing factor to isolated elevation of SBP as the former has been shown to be a strong predictor of aortic stiffness [24].

Another type of ISH is observed in young active, particularly athletic adults. In this group, the SBP and PP elevations are often isolated to the peripheral arteries (especially in the upper limbs), while central haemodynamics remain normal [28, 40]. This phenomenon has been attributed to the effects of exercise-related bradycardia on stroke volume; which is thought to increase PP by exaggerating the amplification of the pressure wave [28, 40, 41]. This type of ISH is arguably considered spurious and somewhat 'non-detrimental' by most researchers [28, 42–44] since most risk is often associated with central rather than peripheral abnormalities [27].

#### **1.2 Ambulatory isolated systolic hypertension**

Early studies into ambulatory ISH seemed to suggest that ISH was a form of "white coat" hypertension that was not sustained during day to day activities outside a clinical setting [45, 46]. The work of Staessen et al. [10] compared the predictive ability of ABPM over conventional BP measurement in older ISH patients, and found that ambulatory SBP was a more superior predictor of cardiovascular risk than conventional SBP. Later research using improved technology for ABPM showed that while this may be true to some extent, sustained and masked forms of ISH are also prevalent, particularly in the elderly population [47]. Over time, ABPM became more useful in investigating ISH from several angles. It has been used to investigate postprandial hypotension in elderly ISH patients [48]. Saladini et al. [49] investigated the future risk of sustained hypertension in young, sporty ISH patients diagnosed by ABPM. These studies either used ABPM in people already diagnosed with ISH using conventional BP monitoring or diagnosed ISH with ABPM using only 24-hour BP. None these studies identified the ambulatory ISH subtypes. Therefore, a possibility exists that with ambulatory BP monitoring, different types of ISH can be identified.

With this gap in the current literature, we designed a study using ambulatory BP monitoring, with the aim of identifying different ambulatory ISH subtypes,

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*Ambulatory Isolated Systolic Hypertension and Cardiovascular Target Organ Damage in People…*

determining their prevalence and investigating whether these subtypes are associated with preclinical cardiovascular pathology in a population of African ancestry.

Participants of African ancestry were recruited from Soweto, a township in the southwest of Johannesburg. The lower age limit for the participants was 18 years and there was no upper age limit. Based on their conventional and ambulatory BP

i.Normotensives (NT). Those with normal daytime and normal nighttime ambulatory BP (daytime BP < 135/85 mm Hg and nighttime

ii.Hypertensives (HT). Those with increased daytime BP and increased nighttime BP (daytime BP ≥ 135/85 mm Hg and night-time BP ≥ 120/70 mm Hg).

iii.Conventional isolated systolic hypertensives (ISHC). Those with increased conventional systolic BP and normal conventional diastolic BP (systolic

iv.Twenty four-hour ambulatory isolated systolic hypertension (ISH24). Those with increased 24-hour systolic BP and normal 24-hour diastolic BP (24-hour

v.Night-time isolated systolic hypertensives (ISHN). Those with increased night-time systolic BP and normal night-time diastolic BP (night-time

vi.Daytime isolated systolic hypertensives (ISHD). Those with increased daytime systolic BP and normal daytime diastolic BP (daytime systolic

Participants were invited to visit the Human Nutrition Clinic at the School of Physiology, Wits Medical School where conventional BP was measured using an automated pressure monitor (Omron, Kyoto, Japan) after they were allowed to rest for 10 minutes. Twenty four-hour ambulatory BP was measured using a 24-hour BP monitor (Spacelab, model 91207). Monitors were set to measure BP every 15 minutes from 06:00–22:00 and every 30 minutes thereafter until 06:00 the next morning. On average, participant bedtime was 19:00 and wake up time was 05:00. Based on this, the 09:00–19:00 and 23:00–05:00 intervals were used to define daytime and

Anthropometric measurements were taken while the participants were barefoot and wearing lightweight indoor robes. Weight was measured using a floor scale

systolic BP ≥ 130 mm Hg and 24-hour diastolic BP < 80 mm Hg).

systolic BP ≥ 120 and night-time diastolic BP < 70 mm Hg).

BP ≥ 135 mm Hg and daytime diastolic BP < 85 mm Hg).

*DOI: http://dx.doi.org/10.5772/intechopen.96521*

BP < 120/70 mm Hg).

**2.2 Blood pressure measurement**

night time respectively.

**2.3 Anthropometric measurements**

measurements were divided into the following six groups:

BP ≥ 140 mm Hg and diastolic BP < 90 mm Hg).

**2. Methods**

**2.1 Study group**

*Ambulatory Isolated Systolic Hypertension and Cardiovascular Target Organ Damage in People… DOI: http://dx.doi.org/10.5772/intechopen.96521*

determining their prevalence and investigating whether these subtypes are associated with preclinical cardiovascular pathology in a population of African ancestry.
