Influence of Genetic Risk Factors on Coronary Heart Disease Occurrence in Afro-Caribbeans.

BACKGROUND: Despite excessive rates of cardiovascular risk factors such as hypertension, diabetes, and obesity, Afro-Caribbeans have lower mortality rates from coronary heart disease (CHD) than do whites. This study evaluated the association of genetic risk markers previously identified in whites and CHD in Afro-Caribbeans. METHODS: We studied 537 Afro-Caribbean individuals (178 CHD cases and 359 controls) who were genotyped for 19 CHD-related single-nucleotide polymorphisms (SNPs). A genetic risk score (GRS) incorporating the 19 SNPs was calculated. These participants were compared with 1360 white individuals from the Second Northwick Park Heart Study. RESULTS: In Afro-Caribbeans, patients with CHD had higher rates of hypertension (78.7% vs 30.1%), hypercholesterolemia (52.8% vs 15.0%), and diabetes (53.9% vs 14.8%) and were more often men (64.0% vs 43.7%) and smokers (27.5% vs 13.4%) compared with non-CHD controls (all P < 0.001). The GRS was higher in Afro-Caribbeans with CHD than in those without CHD (13.90 vs 13.17; P < 0.001) and was significantly associated with CHD after adjustment for cardiovascular risk factors, with an odds ratio of 1.40 (95% confidence interval, 1.09-1.80) per standard deviation change. There were significant differences in allelic distributions between the 2 ethnic groups for 14 of the 19 SNPs. The GRS was substantially lower in Afro-Caribbean controls compared with white controls (13.17 vs 16.59; P < 0.001). CONCLUSIONS: This study demonstrates that a multilocus GRS composed of 19 SNPs associated with CHD in whites is a strong predictor of the disease in Afro-Caribbeans. The differences in CHD occurrence between Afro-Caribbeans and whites might be a result of significant discrepancies in common gene variant distribution.

Distribution of coronary artery disease severity and risk factors in Afro-Caribbeans.

BACKGROUND: Traditional risk factors are strong predictors of the incidence of coronary artery disease (CAD), but their association with disease severity remains controversial and could differ across ethnic groups. AIMS: In this study, we assessed the prevalence of cardiovascular risk factors (CRFs) in Afro-Caribbean patients with documented CAD, and sought to identify which of these factors are related to disease severity. METHODS: We retrospectively studied 420 consecutive patients with CAD. Disease severity was determined from the results of invasive coronary angiography, based on the presence or absence of multiple (two or three) diseased vessels and the myocardial jeopardy (MJ) score. RESULTS: In the studied population (mean age 64.7 ± 12.4 years), hypertension, diabetes and dyslipidaemia were the most frequent modifiable CRFs, present in 75.9, 47.8 and 37.8% of patients, respectively. Multiple logistic regression analysis showed that diabetes, male sex and personal cardiovascular history significantly increased the risk of multivessel CAD: odds ratios (ORs) of 1.53 (1.01-2.33; P=0.048), 1.61 (1.02-2.55; P=0.043) and 1.68 (1.11-2.56; P=0.015), respectively. Obesity was an independent negative predictor, with an OR of 0.48 (0.29-0.79; P=0.004). Other traditional CRFs (hypertension, dyslipidaemia, smoking, age and family history of vascular disease) were not associated with CAD severity. For high-risk lesions (MJ score ≥8), both diabetes and hypertension were independent predictors of disease severity, whereas obesity was no longer a protective factor. CONCLUSION: Diabetes emerged as the strongest modifiable risk factor predictor of multivessel disease in Afro-Caribbean patients, whereas obesity was an independent protective factor. The underlying mechanisms of these associations should be relevant to disease prevention.

Association of 2238T>C polymorphism of the atrial natriuretic peptide gene with coronary artery disease in Afro-Caribbeans with type 2 diabetes.

BACKGROUND: The atrial natriuretic peptide (ANP) is known mainly for its effects on kidney function and blood pressure homeostasis. We investigated the association between two ANP polymorphisms and pre-existing coronary artery disease (CAD) in patients of African descent with type 2 diabetes (T2D). METHODS: We conducted a cross-sectional and retrospective study of 218 volunteer Afro-Caribbean patients with T2D. Two polymorphisms (rs5064, 708C>T; and rs5065, 2238T>C) of ANP were genotyped using PCR-restriction fragment length polymorphism analysis. ANCOVA, χ2-test, and logistic regression were used for statistical analysis. RESULTS: Among these patients (92 men; 128 women), 67 (30.7%) had CAD, of whom 75% had had myocardial infarction. The frequency of rs5065-C carriers (TC/CC) was significantly lower in patients with CAD than in those without CAD (24 vs. 41%, P = 0.01). The frequency of hypertension did not differ significantly according to genotype. Univariate logistic regression revealed that male sex, age, dyslipidemia, hypertension, and rs5065-C carrier status were associated significantly with CAD. After adjustment for the variables of interest, the odds ratio (ORs) of CAD for rs5065-C carriers (TC/CC) was 0.50 (0.26-0.96; P = 0.038). No association was found between the rs5064 (708C>T) single-nucleotide polymorphisms (SNPs) and pre-existing CAD or cardiovascular risk factors. CONCLUSIONS: The ANP rs5065 (2238T>C) C allele seems to exert a protective effect against CAD in T2D patients of African descent. The relevance of ANP polymorphisms for CAD should be determined in different populations.