Dyslipidemia and Cardiovascular Disease: an assessment of risk factors

Background: Dyslipidemia was identified as one of the risk factors for cardiovascular diseases, and knowing its prevalence in the population, ensures proper planning of health care both at primary and secondary level.

Objectives: To estimate the prevalence of Dyslipidemia among adult population.

Limitation: HDL and LDL cholesterol were not performed due the high cost of laboratory reagents.

Abstract

In a testing of 300 subjects, men were 114 making 38% of those tested, while women were 186 making 62% of the population tested. The prevalence of hypercholesterolemia in men was 42.1%, while that of women recorded 46.8% respectively. The prevalence of hypertriglyceridemia of men amounted to 8.8%, while that of women was 3.2%. Hypercholesterolemia was age dependent in women and not in men, the age group older than 66 years old in women classes, recorded the prevalence of 63.0% of hypercholesterolemia. Hypertriglyceridemia do not show any definite pattern that was statistically significant.

In conclusion, the prevalence of hypercholesterolemia in this region is high; therefore balanced diet, physical exercise, medication, and physician- close to the community relationship must be enhanced.

Keywords: Dyslipidemia, Serum lipids, Cholesterol, Triglycerides, Cardiovascular

Introduction

The term lipid is used to include all fats and substances of a fat –like nature. There are four kinds of lipid in the plasma and they are as follows; Fatty acids, triglycerides, phospholipids and cholesterol.

Fatty acids

They are straight- chain carbon compounds of differing lengths. They may be saturated containing no double bonds, monounsaturated with one or polyunsaturated with more than one, double bonds. Fatty acids may be esterified with glycerol to form triglycerides or be nonesterified or free in nature. Plasma free fatty acids liberated from adipose tissue are transported, mainly attached to albumin, to the liver and muscle, where they are metabolized.

Triglycerides

They are fatty acid esters of glycerol, each containing three different fatty acids. They are transported from the intestine and the liver to various tissues, such as adipose tissue, as lipoproteins. When hydrolyzed, fatty acids are taken up, re-esterified and stored as triglycerides. Plasma triglyceride values rise after taken a fatty meal and remain elevated for many hours.

Phospholipids

These are complex forms of lipid, resembling triglycerides, but containing phosphate and a nitrogenous base in place of one of the fatty acids. They are very essential components of cell membranes and lipoproteins, maintaining the soluble nature of non- polar lipids and cholesterol.

Cholesterol

This is a steroid, precursor to many physiologically important steroids, such as bile acids and steroid hormones. Cholesterol synthesis initially involves the conversion of acetate to mevalonic acid through enzymatic processes, the activity of which is controlled by negative feedback mechanism by the intracellular cholesterol concentration. About two-thirds of the plasma cholesterol is esterified with fatty acids to form cholesterol esters. Routine biochemical assays in use, measure the total plasma cholesterol concentration and do not differentiate between the unesterified and esterified forms. Unlike that of triglycerides, plasma concentrations of cholesterol do not rise after a fatty meal.

Plasma lipids are derived from food (exogenous) or are synthesized in the body (endogenous). Lipids are relatively insoluble in water and are carried in the body fluids as soluble protein complexes called lipoproteins. Lipoproteins are classified by their density which, in turn, reflects size. The greater the lipid/ protein ratio in the complex, the larger it is and lower is its density. They five main classes of lipoproteins- triglycerides- rich substances include:

• Chylomicrons, which has the role of transporting exogenous lipid from the intestine to all cells.

• Very Low Density Lipoproteins (VLDL), with a role of transporting endogenous lipid from the liver to the cells.

• Intermediate Density Lipoproteins (IDL), which are usually undetectable in normal plasma. It is normally a transient intermediate lipoprotein formed during the conversion process of VLDL to Low Density Lipoprotein (LDL); it contains both cholesterol and endogenous triglycerides. IDL remains undetectable in normal plasma biochemical assay.

Because of their large size, these particles reflect light and plasma containing a high concentration appears turbid or milky (lipemia). Two smaller lipoproteins which contain mainly cholesterol are: LDL (Low Density Lipoproteins,) formed from VLDL and transport cholesterol to cells, and HDL (High Density Lipoproteins), are involved in the transport of cholesterol from cells to the liver.

Lipoproteins of smaller size do not scatter light; even very high concentrations in plasma do not produce lipemia. Although, the classification of lipoproteins is based on their densities, determined by ultracentrifugation, the lipoprotein composition of plasma can usually be inferred from simple lipid profile assays. Plasma samples taken from a fasting patient contains only, LDL, VLDL, and HDL in normal persons, and in many cases of hyperlipidemia.

However, due to 70% of plasma cholesterol is incorporated in LDL, and only 20% in HDL, the measured plasma total cholesterol concentration basically reflects LDL concentration and the plasma triglyceride concentration, reflects that of VLDL. In some cases of hyperlipidemia, the lipoprotein pattern may be defined according to its electrophoretic mobility.

Metabolism of Lipoproteins

Lipoproteins are synthesized in the liver or intestines. After secretion, they are modified by enzyme- catalyzed reactions and the remnants are taken up by receptors on cell surfaces. These processes are regulated by the protein component of the particles , the apolipoproteins.

Apolipoproteins are classified into different groups such as apo A and apo B. Some of them are incorporated into the lipoprotein structure, but others, such as apo C and apo E, interchange freely between lipoproteins. The lipoproteins have several target functions. They are involved in normal lipid secretion by cells; apo A-I and apo C-II activate enzymes responsible for lipid metabolism. Apo B and apo E, recognize receptors involved in cellular uptake of the lipoprotein particles.

Exogenous lipid pathways

Fatty acids and cholesterol, released by digestion of dietary fat together with cholesterol from bile are absorbed into intestinal mucosal cells where they are re-esterified to form triglycerides and cholesterol esters.

Endogenous lipid pathways

The liver is the main source of endogenous lipids. Triglycerides are synthesized from glycerol and fatty acids, which may reach the liver from the fat stores or from glucose. Hepatic cholesterol may be synthesized locally or be derived from lipoproteins such as, Chylomicron remnants, after taken up by liver cells.

Lipids and cardiovascular disease

When lipid levels in the bloodstream are too high or low, this is called Dyslipidemia. The most common form of Dyslipidemia is;

• High levels of Low Density Lipoprotein(LDL or bad) Cholesterol

• Low levels of High Density Lipoprotein(HDL or good) Cholesterol

• High levels of triglycerides

Fatty deposits in arterial walls are the most important manifestation of lipid disorders. Cholesterol deposits and its associated cellular proliferation and fibrous tissue formation produce atheromatous plaques. The lipoproteins, LDL and IDL are atherogenic in nature. Overtime, plaques narrow the arteries, producing atherosclerosis, and this is the main cause of heart disease, heart attacks, peripheral artery disease (reduced blood flow to the lower limbs, usually the legs) and could cause a fatal condition called stroke. Lowering high plasma LDL cholesterol levels reduces the risk of cardiovascular disease. Hypercholesterolemia is one of the major risks of cardiovascular disease; others include smoking and hypertension.

Low levels of HDL and hypertriglyceridemia can also increase fat build-up in the arteries. High levels of HDL cholesterol, protects the heart by helping to remove the build –up of LDL from the arterial walls.

Our basic medical knowledge of the clinical effects of Dyslipidemia is based on plasma total or LDL or HDL- cholesterol determination, but the disorders of lipoproteins could be discussed based on;

• Hypercholesterolemia

• Hypertriglyceridemia

• Mixed hyperlipidemia

Hypercholesterolemia associated with little or no elevation of plasma triglyceride levels is almost always due to a raised plasma LDL levels. Hypercholesterolemia may be primary or secondary in nature. The primary type deals with the familial incidence of hypercholesterolemia, which also could be monogenic pattern and or polygenic pattern of familial hypercholesterolemia. The secondary type of hypercholesterolemia is due to other prevailing disorders of; Endocrine defects, diabetes, nephritic defects, metabolic syndrome, cushing disease, polycystic ovary syndrome etc.

Hypertriglyceridemia is always secondary to other diseases, while mixed hyperlipidemia involves both raised plasma cholesterol and triglycerides.

Literature Review

Dyslipidemia has been closely linked to the patho-physiology of heart disease and it is a key independent modifiable risk factor for cardiovascular disease, Haffnar M (1999). The rate of Dyslipidemia is high and increasing in most developed countries reported by Wetlisbach,V et al (1984-1993), but this increase is not only seen in developed countries, it is now seen in most developing countries as a result of the occidentalization of diet and other lifestyle changes, Yamada M et al (1997).

In 2002, the World Health Organization (WHO) reported that Dyslipidemia is associated with more than half of the global cause of ischemic heart diseases. Therefore, estimation of the prevalence of Dyslipidemia ensures proper health control planning actions for all health sectors for the prevention of cardiovascular diseases.

Khader et al (2010) studied 1121 subjects in Jordan and reported 75.7% cases with Dyslipidemia, with men greatly affected with hypertriglyceridemia than women. This work stated that age and diabetes mellitus was associated with hypertriglyceridemia.

Dyslipidemia was implicated as one of the four major established conventional risk factors for coronary heart disease, besides cigarette smoking, diabetes and high blood pressure (HBP), Verschuren WM et al (1995).

Detection and treatment of lipid disorders is a key to the prevention and management of clinical outcomes of chronic non- transmissible diseases, and lipid disorders are the most common cardiovascular risk factors among Mexican adults, Barquera S et al (2007). The large percentage of the Mexican population affected by lipid abnormalities involves the interaction of genetic and environmental factors. The risk allelemorphic genes for having either hypertriglyceridemia or hypoalphalipoproteinemia have an intense frequency among the people of Mexico compared to other population, Aguilar-Salinas CA et al (2009).

The work of Enas EA et al (2007) noted that South Asians around the globe have the highest rates of coronary artery disease. According to the research done by the National commission on macroeconomics and health, India, by 2015, 62 million people in India will present coronary artery disease and out of these populations, 23 million will be patients younger than 40 years of age, Indrayan A (2005).

Dr. Sawant and co-workers (2008) revealed that the increased prevalence of dyslipidemia was high among age group 31 to 40 years in men in Mumbai, India, suggesting that this class is at increased risk of developing coronary artery disease leading to young people developing infarcts.

The influence of diet on Dyslipidemia was analyzed on Canadian population by Dr. David et al (2003), where 3 groups of control, a group on statin and a group on dietary modification were studied. A drastic reduction in lipid levels was observed in statin group and group on dietary modifications. Frick et al (1987) demonstrated that lowering cholesterol in apparently healthy adults reduces the chances of developing risk factors associated with coronary artery disease.

Estari M et al (2009) observed Dyslipidemia in 52.7% men against 42.9% in women; once again, men living in Warangal- India have higher prevalence of Dyslipidemia than women living in the same area. Petrella RJ et al (2007) expressed high prevalence of Dyslipidemia in Canadian Primary health care, and despite clinical evidence and treatment guidelines, Dyslipidemia is largely untreated in family practice, suggesting a gap in health care.

Wu Z et al (2001) predict that over the next 20 years, cardiovascular disease morbidity and mortality in China has been projected to increase both in absolute number and as a proportion of total disease burden. The marked increase in cardiovascular diseases in economically developing countries has resulted from the economic growth and its associated sociodemographic changes that have occurred over the recent decades. During this period, the burden of illness from infectious disease has fallen. However, changes in life style and diet have led to an increase in life expectancy and a greatly increased burden of cardiovascular disease and other chronic diseases ensued.

Wang S et al (2011) presented 56 % of Dyslipidemia in Beijing-China, and they associated their findings with increasing age, gender factor, higher income, hyperglycemia, hypertension and smoking. According to Dr. Wang, the population studied showed that treatment rate of Dyslipidemia was 24% with about 60% of the treated subjects still having uncontrolled Dyslipidemia.

Dr. Jia WP et al (2002) reported a rapid increase in total serum cholesterol level in those resident in Shanghai-China, but there are differences in dietary nutrient intake between north and south as well as between rural China and urban China and has significantly contributed to the observed regional differences in serum lipid levels. The prevalence of Dyslipidemia is significantly higher in urban cities than in rural areas.

Atherosclerotic vascular disease is a major cause of morbidity and mortality in diabetic patients. Insulin resistance type 2 diabetes frequently occurs with a variety of cardiovascular risk factors, obesity, hypertension, Dyslipidemia and inactivity physical. The role of Dyslipidemia as a causal agent in vascular disease associated with diabetes was not previously regarded because of frequent normal or minimally elevated values of cholesterol, but recently, it has been clarified that lipid modification is an important factor in decreasing cardiovascular risk in type 2 diabetes, Farmer JA (2007).

Dr. Goldberg (2001) identified four key features of diabetic Dyslipidemia to be; hypertriglyceridemia, high LDL, Low HDL and postprandial lipemia. Plasma LDL levels per se is not usually higher than those of non diabetic people. A cascade of pathogenic steps resulting from insulin resistance together with dysfunction of the enzyme lipoprotein lipase (LPL) could result for most of these disorders. Insulin resistance in adipocytes allows exuberant lipolysis stimulated by hormone sensitive lipase resulting in excessive free fatty acid release into the blood stream.

Dr. Elisabeth Steinhagen Thiessen et al (2008) documented a prevalence of Dyslipidemia of 76.4% in Germany, using European society of Cardiology guidelines. A number of secondary prevention trials have shown the benefit of lipid lowering in patients with pre-existing cardiovascular disease. However, because of a high baseline risk in these patients, the benefit of pharmacotherapy translates into a high absolute risk reduction and in these patients; statins are highly cost effective drugs. It is the apparent focus in primary care setting in Germany as patients with cardiovascular risk factors like type 2 diabetes or pre existing cardiovascular and organ damage are diagnosed, treated and controlled to a higher extent than patients without.

Myung Ha Lee et al (2012) postulated that, the prevalence of Dyslipidemia were gradually increased between 1988 to 2001, and suggested intensive efforts by the health authorities on prevention and treatment strategies of Dyslipidemia in Koran region.

Okayama A et al (1993) considered Japan to have decreased chronic artery disease mortality despite an increasing trends in serum total cholesterol, this is attributable to better control mechanism of other risk factors such as hypertension and smoking.

Corti MC et al (1995) suggested that a low HDL cholesterol level is a more specific and powerful predictor of risk for coronary death than total cholesterol. High rates of Dyslipidemia is seen among Brazilian population, Gigante et al (2006), conducted research experiments on 49,395 adults living in the state capitals and federal districts and reported 16.5% cases of Dyslipidemia. Hence, Dyslipidemia pose a challenge to the Brazilian public health officers in monitoring this problem in the affected areas. The insufficient practice of physical exercise is also a risk factor for the development of the clinical features of Dyslipidemia and atherosclerosis.

Lipids are important substrates for energy production during physical exercise and studies confirmed that physically active adults have higher levels of plasma HDL- cholesterol, Lower levels of LDL- cholesterol and lower levels of triglycerides, when compared to physically sedentary or inactive adults, Guedes& Gonçalves (2007). Recent studies reviewed that the practice of physical activities in childhood and adolescence, more than those practiced in adulthood, is an important parameter and determinant in the occurrence of outcomes such as hypertension, type2 diabetes mellitus and Dyslipidemia at adult age Fernandes & Zanesco (2010).

The primary goal of treating Dyslipidemia is to reduce the risk of cardiovascular disease and diabetes. This includes quitting smoking and reducing LDL cholesterol, blood pressure, and glucose to recommended levels. Lifestyle changes also help reduce the metabolic risk factors: losing weight, eating a healthy diets and increase physical activities.

Materials and Methods

A total of 300 subjects aged 18 to 94 years old were bled after fasting for about 10 hours. The laboratory analyses were done within the period of 4 months, covering September to December, 2012, and the subjects were randomly selected. The lipid profiles of total Cholesterol and triglycerides were determined in all samples within about 1 hour of blood collection. The principal apparatus used was Humalyser 3000 produced by Human, Germany.

Total Cholesterol and triglycerides determination were performed by enzymatic methods by technique of micro pipetting.

Micro Technical scheme used were as follows:

Mix, incubate for 5 minutes at 370c, Measure the absorbance of standard, sample, control s, against the reagent blank or distilled water within 30 minutes and record all results. Laboratory local reference values of total cholesterol and triglycerides in Porto Novo region of Cape Verde is 200mg/dl. Data analysis was obtained using statistical package for social sciences software (SPSS) version 15.

Results

They results of a total of 300 subjects (114 were men while 186 were women) aged 18 to 94 years old, showed that prevalence of hypercholesterolemia in was 42.1%, while that of women was 46.8%. Hypertriglyceridemia in men category was 8.8%, while that of women recorded 3.2% respectively. Furthermore, they results stated that in men classes aged 46 to 55 years old, hypercholesterolemia was 55.6%, while in this vein, aged = 66 years presented 33.3%. In all classes of men, hypertriglyceridemia do not show any definite pattern.

However, in women classes, hypercholesterolemia is age dependent, and aged = 66 years registered 63.0%, more than the rest in the classification.

• 1. The prevalence of Hypercholesterolemia and hypertriglyceridemia concentrations according to sex and age (%) in men category, research of 2013.

• 2. The prevalence of hypercholesterolemia and hypertriglyceridemia concentrations according to sex and age (%) in women category, research of 2013.

• 3. Percentage distribution of serum Total cholesterol.

• 4. Percentage distribution of serum triglycerides

Discussion

The burden of dislipidemia is alarming when considered by the perspective of morbidity, mortality and its high medical bills. Stamler J et al (1993) considered Dyslipidemia as one of the four established conventional risk factors for cardiovascular diseases besides, cigarette smoking, diabetes, and high blood pressure (HBP). All risk factors and their associated clinical features are largely controllable using a healthy lifestyle.

They results recorded in this study showed that Dyslipidemia is high among the people of Porto Novo in Cape Verde. Hypercholesterolemia of 46.8% in women and 42.1% in men, confirms that, the people of this region, needs to change their attitude as regards to the risk factors of cardiovascular diseases. In women group studied, hypercholesterolemia increases with age and those with more than 66 years old recorded 63.0%. In men groups, aged 46 to 55 years old presented 55.6%, and those more than 66 years old were 33.3%. This proves that in men, hypercholesterolemia is not directly age related.

Khader et al (2010) reported 48.8% of hypercholesterolemia among Jordan adults , and 43.6% was obtained by Dr. Carlos Aguilar Salinas et al(2010) on Mexican adults. The Porto Novo adult experiment of hypercholesterolemia was quite similar and related to that already stated.

However, the work of Dr. Romulo Araujo Fernandes et al (2011) registered 12.2% of hypercholesterolemia among Londrina adults of Brazil; the present study on Porto Novo is totally in contrast with that of Londrina- Brazil.

The insufficient practice of physical exercise is also a risk factor for the development of the clinical symptoms of Dyslipidemia and atherosclerosis. They adolescence should involve in physical exercise, while the aged should practice ordinary walking exercise. A study conducted in Saudi Arabia revealed that overweight and obesity were not significant risk factors for hypercholesterolemia, Al – Nuaim AR et al (1997).

Diet with high fat and calorie intake could be a major contributing factor of Dyslipidemia in this study; others could result from diabetes, those with hypertension, and those on drugs to lower hypercholesterolemia which was not taken note of, in this work. So the present findings must be interpreted within the context of a number of potential strengths and weaknesses.

The people of this locality enjoy diets rich in saturated fats, such diets include; meat from pigs, frozen chicken without removing its skin cover, overcooking of food which destroys the nutrients and folates. Deep frying and refrying in the same oil leading to Trans fatty acids formation which contributes to the increase of Dyslipidemia. Most people here consume less fruits, but eat more on local diets called KACHUPA which is normally fried with fatty substances before consumption; most families could afford this local Cape Verdean diet.

Even though the benefit of treatment of individuals with hypercholesterolemia for primary coronary artery disease prevention is controversial, health education and serious campaigns to lower fat and cholesterol intake in the population of the region must be instituted.

Conclusion

• Dyslipidemia recorded in this study was high, so long term medical follow up is necessary to determine the impact of hypercholesterolemia on the risk of heart diseases and death.

• Doctor – community approximation intervention is imperative to decrease the levels of Dyslipidemia and other contributing risk factors in this region.

• Physical exercise, balanced diets, stop smoking campaign or slogans, and treatment of all people with hypercholesterolemia should be encouraged.

• Qualified nutritionist should always be incorporated in controlling hypercholesterolemia.

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About the Author

Peter Ubah Okeke is a Medical Laboratory Scientist by profession, a graduate of Ahmadu Bello University, Nigeria. He later earned master and doctorate degree in health Science, from the school of science and engineering, Atlantic International University, Hawaii, USA. He is also an associate member, medical laboratory science council of Nigeria, affiliateship British society for Hematology, American counseling Association (counselor education & supervision), and member, Order of medical technologist and public health, Cape Verde.

Autor:

Dr. Peter Ubah Okeke