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conferring an excess risk for death of 26%. In contrast, investigators studying 9,105 middle-aged men at high baseline risk for CHD from the Multiple Risk Factor Intervention Trial could not replicate a significant hazard ratio for CHD mortality, death from an acute myocardial infarction, or death from any cardiovascular cause when comparing individuals with and without hyperuricemia.225 A significant hazard for death from CHD among patients with gout, however, was reported. Gender differences in the strength of these associations are not completely defined at this moment, although they seem to be more pronounced for women.
2.5 DETERMINANTS OF CAROTID INTIMA MEDIA THICKNESS
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accumulation of LDL in the arterial wall.230 Keidar et al demonstrated that hypertension may be related to increased ox-LDL by showing increased in vitro oxidizability of LDL in patients with essential hypertension.231
In addition to increases in LDL cholesterol being implicated in atherosclerosis, a decrease in high density lipoprotein (HDL) cholesterol also increases atherosclerotic risk.227, 232
Triglycerides are also important in CVD because they have been found to contribute to dyslipidemia.233 Boquist et al reported that the TG response after an oral fat load related to CIMT independently of clinical risk factors and plasma LDL-C and HDL-C levels and accounted for a substantial proportion of the between-individual variation in CIMT.234 In addition, although the mechanisms are not known, increased triglyceride concentrations are often associated with decreased HDL cholesterol concentrations while it increases the remnant lipoproteins and small dense LDL, these effects would induce thrombogenesis, intimal proliferation and promote atherosclerosis.235 Most importantly, the risk of atherosclerosis increases as total cholesterol and LDL cholesterol increases even if the levels are not high enough to be considered dyslipidemia. This is because the classical LDL receptor pathway which sought to demonstrate how LDL-C uptake promotes atherosclerosis cannot sufficiently result in appreciable cholesterol accumulation because the LDL receptor is subject to feedback inhibition by the intracellular cholesterol content.
However, modified forms of LDL-C, such as oxidized LDL (not routinely measured), are taken up by the scavenger receptor mechanism, resulting in cholesterol accumulation and subsequent foam cell formation, since the scavenger receptor is not regulated by the cholesterol content within the cell.236
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Although there is no doubt that cholesterol is an important factor in determining CIMT, it is generally thought that serum cholesterol levels are low in Nigerians because a nationwide survey for non-communicable diseases showed the prevalence of hyperlipidaemia to be low at 4.0%.237 However, urbanization, increased consumption of western diets, and improved socio-economic activities coupled with changing population dynamics are expected to influence the incidence pattern and prevalence of non-communicable diseases including hyperlipidaemia.238,239 Its therefore not surprising that in a population survey carried out in Port Harcourt by Akpa et. al. among apparently healthy adult subjects the prevalence rate of hypercholesterolemia was found to be 31.52%.240 The investigators reported a mean total cholesterol level of 4.77± 1.06mmol/L which was however, lower than the Caucasian value of 5.41mmol/L reported by Fugerbery et. al 241 The question therefore arises as to whether factors such as triglycerides, HDL cholesterol, LDL cholesterol, and total cholesterol contribute towards increases in CIMT in populations of African ancestry.
2.5.2 Effects of high blood pressure on CIMT
Although vascular damage in the cerebral, renal, and other peripheral circulations represents common complications of hypertension, relatively little is known of the in vivo structure or function of the arterial circulation in patients with uncomplicated hypertension. Roman et al. documented the existence of highly significant structural remodeling characterized by both wall thickening and luminal dilatation of the common carotid artery in patients with essential hypertension.242
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Carotid wall thickness was significantly increased on average in the hypertensive group and fell above the 95th percentile of values in normal subjects in 28% of the patients. The increase in wall thickness was disproportionate to that in internal dimension such that carotid relative wall thickness was also significantly increased.243
Crouse et al244 and Rubens et al245 found hypertension to be independently and positively related to a score that summated maximal wall thicknesses of the internal, external, and common carotid arteries in patients hospitalized to undergo coronary angiography. In a study by Prati et al. involving subjects aged 40 years and above, systolic blood pressure, the number of cigarette packs smoked during the subject's lifetime, and lifetime alcohol intake were significantly and independently associated with the severity of atherosclerotic lesions (plaques and stenosis) after adjustment for age and sex.246
Increased systolic blood pressure (SBP) causes structural arterial wall changes which lead to an increased CIMT. The potential explanation is that high blood pressure causes thickening of large elastic and muscular fibers; as well as remodeling (hypertrophy) of small muscular arteries thus resulting in increased wall to lumen ratio.247 The above mentioned changes cause the CIMT to increase due to the increase in collagen fibers which may lead to arterial stiffening. In addition, high blood pressure is known to enhance oxidation of LDL cholesterol and decrease endothelial function.
The relevance of detecting carotid artery disease in asymptomatic individuals, and in hypertensive patients in particular, is double. First, the presence of atherosclerotic lesions at this site is an important factor for the development of stroke. Second, such lesions are good predictors of coronary artery disease as well.248, 249
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CHAPTER 3
MATERIALS AND METHODS 3.1 Study site
The medical and general out-patient clinics of the University of Port Harcourt Teaching Hospital were the sites from which the study subjects were recruited.
This hospital has 600 in-patient beds and serves as the main tertiary referral center for Rivers State and the neighboring south-south states of the Niger Delta. Rivers State has a heterogeneous population (5.1 million people as at
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the 2006 National population census) consisting of several local tribes as well as foreigners involved in the various economic activities in the area, mainly the oil and gas sector. The medical out-patient clinic sees an average of two-thousand one hundred and fifty patients per year, while the general out-patient clinic sees an average of thirty-three thousand six hundred and eighty patients per year.