**1. Introduction**

302 Dyslipidemia - From Prevention to Treatment

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associated with myocardial infarctin in 52 countries (the INTERHEART study):

Four non-communicable diseases (NCDs) including cardiovascular disease (CVD), cancer, chronic respiratory disease, and diabetes were announced by World Health Organization (WHO) as the major causes of mortality in the world in 2008(Alwan, 2008). According to WHO prediction, in the next 10 years, mortality rate caused by NCDs will increase by 17 percent with the highest mortality rate in the regions of Africa (27 percent) and Eastern Mediterranean (EMRO, 25 percent) (Alwan, 2008). Fortunately more than 80 percent of heart disease, stroke, and type 2 diabetes mellitus incidence and almost one third of cancers could be prevented with appropriate interventions to reduce the effect of risk factors (Alwan, 2008).

Dyslipidemia, as a risk factor of CVD, is manifested by elevation or attenuation of plasma concentration of lipoproteins. Several methods have been used to classify the lipoproteins in respect to their density, physical, and chemical properties. Based on these classifications, different types of lipoproteins, including chylomicrones, IDL1, VLDL2, LDL3, and HDL4, and apolipoproteins (Apo), including Apo A, Apo B, Apo C, and Apo E, have been introduced. Generally, dyslipidemia is defined as the total cholesterol, LDL, triglycerides, apo B or Lp (a) levels above the 90th percentile or HDL and apo A levels below the 10th percentile of the general population (Dobsn et al., 1996).

CVD is the most common health problem worldwide. This disease is often manifested as coronary heart disease (CHD). According to the international reports, mortality of CHD in the developed countries is expected to reach almost 29 percent in women and 48 percent in men in years 1990-2020. These figures have been estimated to increase by 120 percent in women and 137 percent in men (Thom et al., 1998) in the developing countries.

Atherosclerosis is the most common cause of CHD. According to recent epidemiological studies, hypercholesterolemia and possibly coronary atherosclerosis are suggested as the sole risk factors of ischemic stroke. The results of a meta-analysis of 10 large cohort studies (Law et al., 1994) showed that for each 0.6 mmol/l reduction in serum cholesterol levels in

<sup>1</sup> Intermediate Density Lipoprotein

<sup>2</sup> Very Low Density Lipoprotein

<sup>3</sup> Low Density Lipoprotein

<sup>4</sup> High Density lipoprotein

Dyslipidemia and Cardiovascular Disease 305

and severity of fibroid plaques and calcified lesions as signs of CVD were significantly lower in Asia, underdeveloped countries and consumers of Mediterranean diet (Eggen et al.,

Two decades after World War II, large population studies had been performed in different countries in order to determine risk factors of heart disease. The most famous studies include the Framingham Study, Chicago and Tecumseh in USA (Butler et al., 1985; Dawber et al., 1951; Dyer et al., 1981; Keys, 1970) and Seven Country Studies including studies in England, Sweden and Norway (Fager et al., 1981; Keys et al., 1984; Miller et al., 1977) in European countries. The major finding of these cohort studies was that in addition to serum cholesterol levels, other factors also are involved in development of coronary heart disease. Among the main risk factors, dyslipidemia, especially increase in LDL levels and decrease in HDL concentrations were considered as the important factors. Table-1 demonstrates the Population Attributable Factors (PARs) with its 99 percent confidence interval (CI) associated with lipids by sex and geographic region (Labarthe, 2011; Yusuf et al., 2004). In some countries, PAR estimation in women is based on small numbers which makes them

**% (CI 99%)** 

**West Europe** 36.7 (10.7-73.8) 47.9 (20.3-76.8) 44.6 (23.5-67.8) **Central & eastern Europe** 38.7 (20.0-61.4) 26.8 (5.9-68.2) 35.0 (19.2-54.9) **Middle East** 72.7 (58.8-83.2) 63.3 (32.0-86.3) 70.5 (57.8-80.7) **Africa** 73.7 (55.2-86.4) 74.6 (49.1-90.0) 74.1 (59.7-84.6) **South Asia** 60.2 (42.5-75.6) 52.1 (19.0-83.5) 58.7 (42.7-73.1) **China** 41.3 (32.4-50.7) 48.3 (36.9-59.9) 43.8 (36.7-51.2) **Southeast Asia and Japan** 68.7 (51.2-82.1) 64.5 (29.5-88.7) 67.7 (52.0-80.2) **Australia & New Zealand** 48.7 (17.5-80.9) 14.9 (0.0-99.6) 43.4 (16.0-75.6) **South America** 41.6 (20.2-66.6) 59.3 (30.5-82.9) 47.6 (29.6-66.2) **North America** 60.0 (22.2-88.8) 32.2 (1.1-95.1) 50.5 (18.2-82.4)

Table 1. Population Attributable Factors (PARs) associated with lipids in men & women by

**Lipids in women % (CI 99%)** 

53.8 (48.3-59.2) 52.1 (44.0-60.2) 54.1 (49.6-58.6)

49.5 (43.0-55.9) 47.1 (37.4-57.0) 49.2 (43.8-54.5)

**Lipids in both sexes % (CI 99%)** 

1964).

less reliable.

**Overall adjusted for age,** 

**Overall adjusted for risk** 

Legend: CI: Confidence Interval.

**sex & smoking** 

geographic region.

**factors** 

**2.1 Total and LDL cholesterol** 

**Region Lipids in men** 

those aged 60 years, the risk of CHD decreased by 27 percent, which manifested a calculated relative risk of 0.73. With three times reduction in serum cholesterol (1.80 mmol/l or 70mg/dl), the relative risk of CHD was 0.39 (0.73)3 and risk reduction reached to 61 percent. The expected benefits of total cholesterol and LDL reduction seem to be in both primary and secondary prevention of CHD. Protective effects of HDL against initial coronary events in secondary prevention (Barter et al., 2007; Rosenson, 2007) was even observed in levels of higher than 75 mg/dl with long lifetime protection (Longevity Syndrome) and emancipation of the relative risk of coronary disease. Based on these observations, current attempt for stroke prevention is mostly focused on intensive treatment with lipid-lowering drugs (Gorelick et al., 1997).

In spite of a decline in cardiac events and coronary mortality rates, many people who are under appropriate treatment are still exposed to these events. In a population-based study regarding hypercholesterolemia awareness (Nieto et al., 1995), only 42% of population were informed of their hypercholesterolemia and only 4% were under lipid-lowering drug treatment. Need assessment to better understand the role of lipids and its subgroups including; VLDL, Small dense LDL, lipoprotein (a), and subgroups of HDL in pathogenesis of CVD calls for a general awareness regarding these topics. In this context, the major challenges would be: 1 – to identify those who need treatment (with or without past history of coronary artery disease), 2 – to develop more effective treatment strategies for patients with coronary artery disease (whether individuals were treated with lipid-lowering drugs or people who have not received adequate treatment), 3 – to adequately treat other high risk individuals such as diabetic, hypertensive, and old subjects.
