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Dyslipidemia and Cardiovascular Disease: an assessment of risk factors




Enviado por Dr. Peter Ubah Okeke



  1. Abstract
  2. Introduction
  3. Metabolism of Lipoproteins
  4. Literature Review
  5. Materials and Methods
  6. Results
  7. Discussion
  8. Conclusion
  9. References

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:

Pipette into curvettes

Standard

Reagent

Reagent Blank

Control Pathologic

Control Normal

Sample

Standard

10&µl

Control P

10&µl

Control N

10&µl

Sample

10&µl

Reagent

1000&µl

1000&µl

1000&µl

1000&µl

1000&µl

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.

Age in years

Total

n

Hyper

Cholesterolemia (%)

Hyper
triglyceridemia

(%)

18 – 45

43

17 (39.5)

5 (11.6)

46 – 55

27

15 (55.6)

5 (18.5)

56 – 65

14

6 (42.9)

0 –

=66

30

10 (33.3)

0 –

Total

114

48 (42.1)

10 (8.8)

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

Age in years

Total

n

Hyper Cholesterolemia
(%)

Hyper
triglyceridemia

(%)

18 – 45

59

17 (28.8)

1 (1.7)

46 – 55

39

16 (41.0)

0 –

56 – 65

26

15 (57.7)

0 –

= 66

62

39 (63.0)

5 (8.1)

Total

186

87 (46.8)

6 (3.2)

  • 3. Percentage distribution of
    serum Total cholesterol.

Serum cholesterol

Men %

Women %

= 200

57.9

53.2

201 – 240

19.3

32.8

241 – 280

15.8

9.7

= 281

7.0

4.3

  • 4. Percentage distribution of
    serum triglycerides

Serum Triglyceride

Men %

Women %

=200

91.2

96.8

201 -240

4.4

1.6

241 -280

0.88

0.5

= 281

3.51

1.1

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

 

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