Ph.D., Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, 2008. / In many developing countries with advanced stages of the nutrition transition, the
burden of coronary artery disease (CAD) has shifted from the rich to the poor. Much of
this transition is caused by changes in lifestyle, in particular: dietary changes, an
increase in weight and obesity, a decrease in physical activity, high levels of stress, and
increasing tobacco and alcohol consumption. However, we have come to appreciate a
prominent role for inflammation in atherosclerosis and its complications.
Globalization, urbanization and Westernization of lifestyle will increase the socioeconomic
burden posed by non-communicable diseases in middle-to-low-income
countries. In South Africa, it is mainly the African population that is experiencing rapid
urbanization and the nutrition transition.
Reliable ischaemic heart disease (IHD) mortality data are not available for the black
population of South Africa.
The purpose of this thesis was: to determine whether factors such as inflammation,
postprandial lipaemia and hyperglycaemia are important determinants in black patients
with documented CAD (with no previous known history of diabetes mellitus) and their
age matched controls; to assess the prevalence of the metabolic syndrome (MS) in black
patients and abnormal glucose regulation on black patients with CAD; and to compare
the metabolic syndrome prevalence rates using the National Cholesterol Education
Program Adult Treatment III (NCEP: ATP III) and International Diabetes Federation
(IDF) definitions.
Socio-economic status, anthropometric data, glucometabolic variables, LDL particles
and MS prevalence rates were measured using 40 patients and 20 controls. The patients
were selected consecutively on the basis of a coronary angiogram performed during the
preceding 24 months. All subjects had significant CAD, which was defined as more
than 50% lesions in one or more major coronary arteries. Subjects with severe
hypercholesterolaemia, defined as an untreated total cholesterol level over 7.5 mmol/l,
were excluded from the study. Those subjects with diabetes mellitus or HIV/AIDS were
excluded from the study.
Paper 1, titled ‘Metabolic syndrome, undiagnosed diabetes mellitus and insulin
resistance are highly prevalent in urbanized South African blacks with coronary artery
disease’, demonstrated a high prevalence of MS in black patients with established CAD.
To our knowledge, this is the first report from South Africa that documents the
prevalence of the syndrome in black patients with CAD. Almost all of our patients had
previously diagnosed hypertension (95%). The second most frequent risk factor was an
elevated glucose concentration, which was seen in half the patient cohort. The
importance of obesity, particularly abdominal obesity expressed as waist circumference
(WC), is well documented as a risk factor for MS. An unexpected outcome of our study
was that half of the patients had abnormal glucose regulation, despite the exclusion of
previously diagnosed DM. This high prevalence was revealed by the oral glucose
tolerance test (OGTT).
Paper 2 compares the MS prevalence estimates, as defined by NCEP: ATP III and IDF,
amongst urbanized black South Africans with CAD. The IDF proposed a single
unifying definition in 2005, as different definitions used different sets of criteria; this
led to confusing and inconsistent estimations of MS prevalence. The new definition
standardizes the criteria for the diagnosis of MS and offers a fresh assessment of the
syndrome. The main findings that arose from the study were that both definitions
generated similar prevalence estimates of MS and the two definitions similarly
identified the presence or absence of MS in more than 80% of patients. This study
demonstrated that postprandial lipaemia and hyperglycemia were common in black
CAD patients. Small dense LDL particles were highly associated with CAD. Fasting
triglyceride concentrations was the strongest determinant. Prolonged exposure of the
endothelium to TG–rich atherogenic remnant particles might be the reason why
postprandial increases in TG account for greater CAD risk.
Paper 3 assessed postprandial lipaemia in black CAD patients with and without
metabolic syndrome. This study was the first to contribute information about
postprandial lipaemia and hyperglycaemia in urbanized South African blacks with
CAD. Fasting lipid profiles and postprandial responses to the oral fat load were similar in patients with and without metabolic syndrome. A possible explanation might be that
because patients in both groups had established CAD, they exhibited some of the
underlying features of CAD, such as atherogenic dyslipidaemia. The main finding was
that postprandial lipaemia was common in black CAD patients, including patients with
metabolic syndrome. Fasting triglycerides concentration was the strongest determinant.
Small, dense LDL particles were highly associated with CAD.
Paper 4 reports on the assessment of postprandial hyperglycaemia in urbanized blacks
with and without CAD. Results showed that glucose AUC was significantly higher in
the patients than in control subjects and 120 min. glucose, followed by 0 min. glucose
concentration, were the strongest determinants of postprandial hyperglycaemia. Our
study demonstrated that as glucose tolerance declined across the normal glucose
tolerance, impaired glucose tolerance and diabetes mellitus categories, peak glucose
concentrations occurred later in the oral glucose tolerance test; insulin and proinsulin responses were also delayed. A comparison between CAD patients and control subjects
drawn from the same ethnic population verified that abnormal glucose tolerance and
insulin resistance were more prevalent in the patients with CAD.
Paper 5 aimed at investigating whether carotid intima-media thickness (CIMT) is a
predictor of CAD in South African black patients. The results showed that CIMT
correlated with evidence of angiographically proven CAD. The findings of this study
need to be considered within the context of its limitations, i.e. the low number of
women and some bias towards only hospital referred CAD patients. It was not our
intention to recruit more men than women, but because CAD is more prevalent in men,
the majority of participants happened to be male. Performance of the OGTT and
hyperinsulinaemic euglycaemic clamp technique is time consuming and requires
considerable laboratory resources; therefore a relatively small number of patients and
control subjects were studied. These limitations do not detract from the overall
conclusions.
Paper 6 evaluated markers of inflammation in black CAD patients, some of whom had
MS. Leptin was the only marker that increased with additional MS criteria. Elevated hs-
CRP concentrations indicated an inflammatory state in CAD patients. Association of leptin with BMI, waist circumference (WC) and hs-CRP revealed a close link with MS,
obesity and inflammation in urban black South African CAD patients.
Paper 7 investigated the role of diet, socio-demographics and physical activity in a
black South African population with CAD, compared to a healthy control group. While
diet is known to be affected by urbanisation, differences in dietary intake were observed
between the two urban groups, despite the similarity in their socio-demographic profile.
The study highlighted the clinical relevance of MS, its likely impact on morbidity and
mortality, and that its identification is, therefore, important in risk assessment of
patients with CAD. Increasing recognition of MS is, therefore, an initial step in
addressing the metabolic problems associated with the syndrome. Furthermore, it was
shown that a preponderance of small, dense LDL particles was highly associated with
CAD in black patients. Although CAD prevalence is still low at this stage, it is likely to
increase rapidly among urban dwellers as they adopt a Western lifestyle.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/7356 |
| Date | 14 October 2009 |
| Creators | Ntyintyane, Lucas Mthetheli |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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