**1. Introduction**

Cardiovascular diseases – the main result of the generalized atherosclerosis are the leading cause of global mortality all over the world [1,2]. The number of atherosclerotic diseases - an ischemic stroke, coronary heart disease and peripheral artery disease increases every year [1]. Possibly, due to increase in the population age, better health care and improved survival the prevalence of heart diseases is still so high [3]. The cardiovascular mortality in the most developed countries also is very high [2,3]. About half of all deaths occures due to cardiovascular diseases, it's an over 4,35 million deaths each year in the 53 member states of the World Health Organization European Region and more than 1,9 million deaths each year in the European Union [2]. Moreover there is a 35 billion euros damage due to working people production loss regarding to cardiovascular morbidity and mortality [2]. The cardiovascular mortality is still a problem not only in the European Union, but in the other developed countries as well. Atherosclerotic coronary artery disease was the most common cause of death in the United States in 2004. Men were more often affected, than women by a ratio of 4:1 and after age of 70 by ratio 1:1 [4]. In 2000 about 37 % of death in Canada were due to cardiovascular diseases [3]. They are still the main cause of mortality in Lithuania, as in the older Western European countries as well [5,6]. At the last decade, cardiovascular morbidity and mortality in Lithuania has not declined (Figure 1) [7,8].

In 2008 in Lithuania standartized cardiovascular mortality rate was 520,1 per 100 000 population (Figure 2) [8]. Although in the last years cardiovascular mortality has a tendency to decrease, it's still very high [7]. Lithuanian mortality from coronary artery disease rate in 2008 was 321,29 per 100 000 population (Figure 3) [7,8]. By the statistic data from the Lithuanian Institute of Hygiene, in 2011 56,3% of the people have died from cardiovascular

© 2012 Umbrasiene et al., licensee InTech. This is an open access chapter 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. © 2012 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.

disease in Lithuania. In 2011, 20944 men and 20093 women have died, 47,7% and 62,7% due to coronary artery disease respectively [9].

The main cardiovascular disease - coronary heart disease - highly associated with an increased cardiovascular mortality, hospitalisation and patients disability, significantly raising the cost of medical care [6]. In 2009 it was 4283,39 per 100 000 population hospital discharge for cardiovascular diseases and 1311,8 for coronary artery disease in Lithuania (Figure 4,5) [8].

In 2000 in Canada 7,3 billion dollars (17%) of total direct health care costs and 12,3 billion (14,5%) dollars of total indirect health care costs for all disease categories were attributed to cardiovascular diseases [3]. In the European Union, the economic cost of cardiovascular diseases in direct and indirect healthcare goes to 192 billion euros annually [1]. A total annual cost for person is vary from 50 euros in Malta to 600 euros in Germany, and 372 euros in average [2].

SDR – standartized death rate

**Figure 1.** Age standartized cardiovascular mortality rate for Baltic States and all European Region dynamic.

SDR – standartized death rate

174 Lipoproteins – Role in Health and Diseases

(Figure 4,5) [8].

euros in average [2].

SDR – standartized death rate

dynamic.

to coronary artery disease respectively [9].

disease in Lithuania. In 2011, 20944 men and 20093 women have died, 47,7% and 62,7% due

The main cardiovascular disease - coronary heart disease - highly associated with an increased cardiovascular mortality, hospitalisation and patients disability, significantly raising the cost of medical care [6]. In 2009 it was 4283,39 per 100 000 population hospital discharge for cardiovascular diseases and 1311,8 for coronary artery disease in Lithuania

In 2000 in Canada 7,3 billion dollars (17%) of total direct health care costs and 12,3 billion (14,5%) dollars of total indirect health care costs for all disease categories were attributed to cardiovascular diseases [3]. In the European Union, the economic cost of cardiovascular diseases in direct and indirect healthcare goes to 192 billion euros annually [1]. A total annual cost for person is vary from 50 euros in Malta to 600 euros in Germany, and 372

**Figure 1.** Age standartized cardiovascular mortality rate for Baltic States and all European Region

**Figure 2.** Age standartized cardiovascular mortality rate per 100 000 population, 2008.

SDR – standartized death rate

**Figure 3.** Age standartized mortality rate for coronary artery disease per 100 000 population, 2008.

**Figure 4.** Hospital discharges for the patients with cardiovascular diseases in 2009, per 100 000 population.

**Figure 5.** Hospital discharges for the patients with coronary artery disease in 2009, per 100 000 population.

Epidemiological studies have evaluated a number of important risk factors for coronary artery disease, such as positive family history, particulary in the age less than 40 for men, and 50 for women, age, male gender, blood lipids abnormalities, diabetes, hypertension, loss of physical activity, smoking and others, not so substantial (high sensitivity Creactive protein, hyperfibrinogenemia etc.) [4,6,10-12]. Reducing one or more of these risk factors reduces the risk of major cardiac event accordingly [4]. There are a lot of evidence that lipoprotein disorder is the main pathogenesis of atherosclerosis. This relationship that was estimated century ago by Anitschkow is still important today [3,13]. Variuos epidemiological studies demonstrated a strong association between dyslipoproteinemia and coronary heart disease. There is a strong relation between serum cholesterol concentration level and the coronary heart disease risk [14]. The Multiple Risk Factor Intervention Trial (MRFIT) in USA with 356222 men with different cardiovascular risk factors and 6-year follow-up period have shown that elevated total cholesterol blood concentration significantly increases cardiovascular risk [14,15]. In 2008, the authors published the report about the continuous follow-up for 25 years. The main finding was that total cholesterol is continuous and strong independent predictor for cardiovascular mortality. Estimated increased cardiovascular mortality risk at every total cholesterol level from 160 mg/dl (about 4,14 mmol/l) and higher [15]. Abnormal lipids metabolism or excessive intake of cholesterol especially with a genetic predisposition, initiates the atherosclerosis. A lot of clinical studies established total cholesterol and low density lipoprotein cholesterol are associated with a great risk of coronary heart disease. The reduce of total cholesterol by 10% decreasing the risk of ischemic heart disease by 25% within 5 years [16]. Low density lipoprotein cholesterol reduction not only decreases cardiovascular events, but reduce total mortality as well [3,17]. Furthermore, large randomized controlled clinical trials established the low density lipoprotein cholesterol lowering benefits [10]. It is proved, the reduce of low density lipoprotein cholesterol by 1 mmol/l, decreasing the risk of acute cardiac events by 20%, cardiovascular mortality by 22% [1,11,16-18]. Treatment of lipoproteins disorder also decrease the development of new lesion, regenerates endothelial function and signally reduce cardiovascular events in treated patients [4]. However, the data based on the National Health And Nutrition Examination Survey (NHANES) study from 2005-2008 have estimated that 71 million adults (33,5%) in the USA had elevated low density lipoprotein cholesterol level, but only 34 million (48,1%) were treated and 23 million (33,2%) had reached target low density lipoprotein value. Though, comparing this data to the data from NHANES study in 1999-2002, the number of people with elevated low density lipoprotein level treated with lipids-lowering medications increased from 28,4% to 48,1% between 1999- 2002 and 2005-2008 periods. The prevalence of controled low density lipoprotein increased from 14,6% to 33,2% [17]. Although, statins significantly reduce low density lipoprotein cholesterol and coronary heart disease risk, substantial residual cardiovascular risk remains, even with very aggressive low density lipoprotein cholesterol values reduction [11,19,20]. However, atherosclerosis pathogenesis is multiple. It depends not only on low density lipoprotein cholesterol level, but also on genetic, environmental factors, infections, lifestyle factors and other diseases or condition [10-12]. More than a hundred different risk factors for atherosclerosis are estimated today. Although it is known many risk factors for coronary heart disease, the most of them are modifiable. Such as smoking cessation, treatment of dyslipidaemia, lowering of blood pressure can prevent the progression of atherosclerosis and major cardiovascular events [4]. One of the most important mechanisms of the atherosclerosis pathogenesis is Endothelial dysfunction [21]. In the early stages of atherosclerosis endothelian-dependent vasorelaxation disturbes due to oxidative stress and reduced nitric oxide bioavailability. Monocytes and T-lymphocytes adhesion occures. These inflammatory cells penetrate the cell wall, as well as lipid accumulation in the walls of blood vessels takes place. The inflammation and lipids accumulation make a plaque unstable, so it may occlude the vessel. Endothelial dysfunction is observed not only in the initial stage, but also in all other stages of atherosclerosis as well [21-23]. However, the main risk factors still

178 Lipoproteins – Role in Health and Diseases

population.

**Figure 5.** Hospital discharges for the patients with coronary artery disease in 2009, per 100 000

Epidemiological studies have evaluated a number of important risk factors for coronary artery disease, such as positive family history, particulary in the age less than 40 for men, and 50 for women, age, male gender, blood lipids abnormalities, diabetes, hypertension, loss of physical activity, smoking and others, not so substantial (high sensitivity Creactive protein, hyperfibrinogenemia etc.) [4,6,10-12]. Reducing one or more of these risk factors reduces the risk of major cardiac event accordingly [4]. There are a lot of evidence that lipoprotein disorder is the main pathogenesis of atherosclerosis. This relationship that was estimated century ago by Anitschkow is still important today [3,13]. Variuos epidemiological studies demonstrated a strong association between dyslipoproteinemia and coronary heart disease. There is a strong relation between serum cholesterol concentration

are male gender and older age (more common in women in menopause), heredity, hypertension, diabetes, smoking, stress, obesity, lack of physical activity, elevated low density lipoprotein cholesterol and total cholesterol and decrease high density lipoprotein cholesterol levels [6,10-12]. Numerous epidemiological studies have found reduced high density lipoprotein cholesterol as an independent risk factor for cardiovascular disease [24]. The Framingham study evaluated 43-44% increasing coronary events in patients with high density lipoprotein cholesterol < 40 mg/dL (1,03 mmol/l) [25]. Patients whose high density lipoprotein cholesterol less than 0,9 mmol/l (35 mg/dL) have 8 times higher risk of cardiovascular disease, versus those, whose high density lipoprotein cholesterol more than 1,68 mmol/l (65 mg/dL) [26]. Studies demonstrates that declined high density lipoprotein cholesterol levels are relatively common in general population. 16-18% of men and 3-6% of women have a high density lipoprotein cholesterol level less than 0,9 mmol/l (35 mg/dL) [20]. Moreover, the reduced high density lipoprotein cholesterol level is a component of the metabolic syndrome – the great predictor of high cardiovascular risk. Experimental studies have found high density lipoprotein cholesterol as a potential antiatherogenic by following characteristics. Estimated high density lipoprotein cholesterol facilitates reverse cholesterol transport and delivers cholesterol from the smooth muscles into hepatic cholesterol uptake. So, harmfull atherogenic cholesterol parts, such as low density lipoprotein cholesterol, are catabolized and neutralized [27-29]. High density lipoprotein cholesterol acts as an antioxidant, reducing vascular oxidative stress and has anti-inflammatory properties, reducing vascular inflammation due to atherosclerosis. There are evidence high density lipoprotein cholesterol has a vasoprotective effect, facilitates blood vessel relaxation, play an important role in the inhibition of white blood cells chemotaxis and adhesion. Also it is known about an anti-apoptotic effect of high density lipoprotein cholesterol on endothelial cells. High density lipoprotein cholesterol enhances the proliferation and migration of Endothelial cells and endothelial progenitor cells and thereby promotes the restoration of the endothelium's integrity. Finally, it has an antiplatelet/profibrinolitic effect, in this way reducing platelet aggregation and inactivating coagulation cascade [20,27-29]. Despite the evidence that reduced high density lipoprotein cholesterol is associated with an increased cardiovascular morbidity and mortality, the major guidelines in cardiology still do not recommend to initiate the treatment of dyslipidemia on high density lipoprotein cholesterol.

So, dyslipoproteinemia is a major risk factor for atherosclerosis and coronary artery disease. Its' proper recognition and management can significantly reduce cardiovascular and total mortality rates [12]. Follow the American Heart Association and the National Heart, Lung and Blood Institute and the Adult Treatment Panel III guidelines it is recommended to start treat from the low density lipoprotein cholesterol. Recent clinical studies provide supporting evidence for low density lipoprotein cholesterol target values of less than 2,5 mmol/l (< 100 mg/dl) for the prevention of coronary artery disease for the high cardiovascular risk patients and less thant 1,8 mmol/l (< 70 mg/dl) for the very high cardiovascular risk patients [1]. Studies demonstrate the significant decrease of atherosclerosis with aggressive reduction of low density lipoprotein cholesterol level in patients with coronary artery disease [3]. Only achieved target low density lipoprotein cholesterol value it is recommended to take care of high density lipoprotein cholesterol. Studies evaluated, that high density lipoprotein cholesterol level more than 60 mg/dl (about 1,5 mmol/l) significantly reduce cardiovascular risk and can be named as "inverse risk factor" [21]. The target high density lipoprotein cholesterol is over 1,03 mmol/l (40 mg/dL) for men and more than 1,29 mmol/l (50 mg/dL) for women [20].
