Coronary Artery Disease In African Americans Research Articles

Relation of Plasma Lipoprotein(a) to Subclinical Coronary Plaque Volumes, Three-Vessel and Left Main Coronary Disease, and Severe Coronary Stenoses in Apparently Healthy African-Americans With a Family History of Early-Onset Coronary Artery Disease

Serum lipoprotein(a) [Lp(a)] is a coronary artery disease (CAD) risk factor in persons of European ancestry. Levels are twofold to threefold higher in African-Americans (AAs), but reported associations with CAD have been inconsistent. The relation of Lp(a) with the extent and severity of subclinical coronary plaque has not been described in AAs. We screened 269 apparently healthy AAs for risk factors and coronary plaque using advanced coronary computed tomographic angiography. Total coronary plaque (TCP), noncalcified coronary plaque, and calcified coronary plaque volumes (mm(3)) were quantified using a validated automated method. Lp(a) was measured by ELISA. Multivariable modeling was performed with adjustment for traditional CAD risk factors and intrafamilial correlations. Mean age was 51 ± 11years and 64% were female. Plaque was present in 41%. Lp(a) was independently associated with TCP volume [log(TCP+ 1)] (p= 0.04), 3-vessel and/or left main involvement (p= 0.04), and at least 1 stenosis >50% (p= 0.006). Best-fit regression analyses showed that subjects with Lp(a) >40mg/dl were threefold more likely to have 3-vessel and/or left main disease (95% confidence interval 1.4 to 6.8, p= 0.005) and fourfold more likely to have stenosis >50% (95% confidence interval 1.3 to 15.0, p= 0.02). In subjects with plaque (n= 110), multivariable models showed the Lp(a) level was significantly and independently associated with TCP (p= 0.009), noncalcified coronary plaque (p= 0.01), and calcified coronary plaque (p= 0.003) and affected vessel length (p= 0.01). In conclusion, high Lp(a) is strongly associated with coronary plaque volumes, extent, and severity in apparently healthy AAs. High levels of Lp(a) may be particularly important in the pathogenesis of CAD in AAs.

Vitamin D Deficiency is Associated With the Development of Subclinical Coronary Artery Disease in African Americans With HIV Infection

BackgroundPremature coronary artery disease (CAD) is a major concern in human immunodeficiency virus (HIV)-infected African Americans. The objectives of the study were to estimate the incidence of subclinical CAD, defined...

Genetic contribution of the leukotriene pathway to coronary artery disease.

We evaluated the genetic contribution of the leukotriene (LT) pathway to risk of coronary artery disease (CAD) in 4,512 Caucasian and African American subjects ascertained through elective cardiac evaluation. Of the three previously associated variants, the shorter “3” and “4” alleles of a promoter repeat polymorphism in ALOX5 increased risk of CAD in African Americans (OR = 1.4, 95% CI 1.0–1.9; p = 0.04), whereas a haplotype of LTA4H (HapK) was associated with CAD in Caucasians (OR = 1.2, 95% CI 1.01–1.4; p = 0.03). In Caucasians, first-stage analysis of 254 haplotype-tagging SNPs in 15 LT pathway genes with follow-up of 19 variants in stage 2 revealed an LTA4H SNP (rs2540477) that increased risk of CAD (OR = 1.2, 95% CI 1.1–1.5; p = 0.003) and a PLA2G4A SNP (rs12746200) that decreased risk of CAD (OR = 0.7, 95% CI 0.6–0.9; p = 0.0007). The PLA2G4A rs12746200 variant also decreased risk of experiencing a major adverse cardiac event (MACE = myocardial infarction, stroke, or death) over 3 years of follow-up (HR = 0.7, 95% CI 0.5–0.9; p = 0.01), consistent with its cardioprotective effect. Functional experiments demonstrated that stimulated monocytes from carriers of LTA4H variants HapK or rs2540477 had 50% (p = 0.002) and 33% (p = 0.03) higher LTB4 production, respectively, compared to non-carriers. These ex vivo results are consistent with LTB4 being the direct product of the reaction catalyzed by LTA4H and its role in promoting monocyte chemotaxis to sites of inflammation, including the artery wall of atherosclerotic lesions. Taken together, this study provides additional evidence that functional genetic variation of the LT pathway can mediate atherogenic processes and the risk of CAD in humans.Electronic supplementary materialThe online version of this article (doi:10.1007/s00439-011-0963-3) contains supplementary material, which is available to authorized users.

Usefulness of Apolipoprotein B/Apolipoprotein A-I Ratio to Predict Coronary Artery Disease Independent of the Metabolic Syndrome in African Americans

Studies have demonstrated that the apolipoprotein B/apolipoprotein A-I (apoB/apoA-I) ratio predicts cardiovascular risk better than any of the cholesterol indexes. A number of factors that define the metabolic syndrome (MS) differ across African-American and European-American ethnicities. We assessed the relation of the apoB/apoA-I ratio to MS and coronary artery disease (CAD) in 224 African Americans and 304 European Americans. The MS was defined using the revised National Cholesterol Education Program Adult Treatment Panel III criteria, and CAD was assessed as ≥50% stenosis or a continuous cardiovascular score (0 to 75). The European Americans had a greater apoB/apoA-I ratio than the African Americans (1.15 vs 1.07, p = 0.008). The apoB/apoA-I ratio was associated with presence of the MS in both European Americans (odds ratio 5.9, 95% confidence interval 2.53 to 13.57, p <0.001) and African Americans (odds ratio 8.3, 95% confidence interval 3.52 to 19.25, p <0.001) and was greater in subjects with the MS than in those without the MS (1.21 vs 1.04, p <0.001, for European Americans and 1.20 vs 0.94, p <0.001, for African Americans). A stepwise increase was seen in the prevalence of the MS across the apoB/apoA-I ratio tertiles in both ethnic groups (chi-square = 13.1, p <0.001, for European Americans and chi-square = 19.6, p <0.001, for African Americans). On multiple regression analyses, the apoB/apoA-I ratio independently predicted CAD in African Americans (β = 0.242, p = 0.011). The cardiovascular score was significantly increased across the apoB/apoA-I ratio tertiles in the European-American subjects with the MS (p = 0.001). However, this association was seen in the African-American subjects without the MS (p = 0.023). In conclusion, the apoB/apoA-I ratio differed across ethnicities and was associated with presence of the MS in both groups. Among African Americans, an elevated apoB/apoA-I ratio independently predicted a greater risk of CAD.

Association of lipoprotein-associated phospholipase A2 with coronary artery disease in African-Americans and Caucasians.

Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is bound predominately to low-density lipoprotein and has been implicated as a risk factor for coronary artery disease (CAD). We investigated the association between Lp-PLA(2) and CAD in a biethnic African-American and Caucasian population. Lp-PLA(2) mass, activity, and index, an integrated measure of mass and activity, and other cardiovascular risk factors were determined in 224 African-Americans and 336 Caucasians undergoing coronary angiography. We assessed the distribution of Lp-PLA(2) levels and determined the predictive role of Lp-PLA(2) as a risk factor for CAD. Levels of Lp-PLA(2) mass and activity were higher among Caucasians compared with African-Americans (293 +/- 75 vs. 232 +/- 76 ng/ml, P < 0.001 for mass and 173 +/- 41 vs. 141 +/- 39 nmol/min/ml, P < 0.001 for activity, respectively). However, Lp-PLA(2) index was similar in the two groups (0.61 +/- 0.17 vs. 0.64 +/- 0.19, P = NS). In both ethnic groups, Lp-PLA(2) activity and index was significantly higher among subjects with CAD. African-American subjects with CAD had significantly higher Lp-PLA(2) index than corresponding Caucasian subjects (0.69 +/- 0.20 vs. 0.63 +/- 0.18, P = 0.028). In multivariate regression analyses, after adjusting for other risk factors, Lp-PLA(2) index was independently (odds ratio 6.7, P = 0.047) associated with CAD in African-Americans but not Caucasians. Lp-PLA(2) activity and index was associated with presence of CAD among African-Americans and Caucasians undergoing coronary angiography. The findings suggest an independent impact of vascular inflammation among African-Americans as contributory to CAD risk and underscore the importance of Lp-PLA(2) as a cardiovascular risk factor.

Susceptibility locus for clinical and subclinical coronary artery disease at chromosome 9p21 in the multi-ethnic ADVANCE study

A susceptibility locus for coronary artery disease (CAD) at chromosome 9p21 has recently been reported, which may influence the age of onset of CAD. We sought to replicate these findings among white subjects and to examine whether these results are consistent with other racial/ethnic groups by genotyping three single nucleotide polymorphisms (SNPs) in the risk interval in the Atherosclerotic Disease, Vascular Function, and Genetic Epidemiology (ADVANCE) study. One or more of these SNPs was associated with clinical CAD in whites, U.S. Hispanics and U.S. East Asians. None of the SNPs were associated with CAD in African Americans although the power to detect an odds ratio (OR) in this group equivalent to that seen in whites was only 24-30%. ORs were higher in Hispanics and East Asians and lower in African Americans, but in all groups the 95% confidence intervals overlapped with ORs observed in whites. High-risk alleles were also associated with increased coronary artery calcification in controls and the magnitude of these associations by racial/ethnic group closely mirrored the magnitude observed for clinical CAD. Unexpectedly, we noted significant genotype frequency differences between male and female cases (P = 0.003-0.05). Consequently, men tended towards a recessive and women tended towards a dominant mode of inheritance. Finally, an effect of genotype on the age of onset of CAD was detected but only in men carrying two versus one or no copy of the high-risk allele and presenting with CAD at age >50 years. Further investigations in other populations are needed to confirm or refute our findings.

Usefulness of an abnormal ankle-brachial index to predict presence of coronary artery disease in African-Americans

We sought to determine the role of an abnormal ankle-brachial index (ABI) in an African-American population with suspected coronary artery disease (CAD) referred for diagnostic coronary angiography. In this population, an ABI ≤0.90 predicted the presence of ≥3-vessel or left main CAD with a sensitivity of 85% and specificity of 77%. However, a normal ABI did not predict absence of 1- or 2-vessel CAD. These results suggest that in this population, the ABI can be used to increase the pretest probability of severe CAD.

High levels of Lp(a) with a small apo(a) isoform are associated with coronary artery disease in African American and white men.

Elevated levels of lipoprotein(a) [Lp(a)] and the presence of small isoforms of apolipoprotein(a) [apo(a)] have been associated with coronary artery disease (CAD) in whites but not in African Americans. Because of marked race/ethnicity differences in the distribution of Lp(a) levels across apo(a) sizes, we tested the hypothesis that apo(a) isoform size determines the association between Lp(a) and CAD. We related Lp(a) levels, apo(a) isoforms, and the levels of Lp(a) associated with different apo(a) isoforms to the presence of CAD (>/=50% stenosis) in 576 white and African American men and women. Only in white men were Lp(a) levels significantly higher among patients with CAD than in those without CAD (28.4 versus 16.5 mg/dL, respectively; P:=0.004), and only in this group was the presence of small apo(a) isoforms (<22 kringle 4 repeats) associated with CAD (P:=0.043). Elevated Lp(a) levels (>/=30 mg/dL) were found in 26% of whites and 68% of African Americans, and of those, 80% of whites but only 26% of African Americans had a small apo(a) isoform. Elevated Lp(a) levels with small apo(a) isoforms were significantly associated with CAD (P:<0.01) in African American and white men but not in women. This association remained significant after adjusting for age, diabetes mellitus, smoking, hypertension, HDL cholesterol, LDL cholesterol, and triglycerides. We conclude that elevated levels of Lp(a) with small apo(a) isoforms independently predict risk for CAD in African American and white men. Our study, by determining the predictive power of Lp(a) levels combined with apo(a) isoform size, provides an explanation for the apparent lack of association of either measure alone with CAD in African Americans. Furthermore, our results suggest that small apo(a) size confers atherogenicity to Lp(a).

Diagnosis and Therapeutic Intervention in the Management of Coronary Artery Disease in African Americans

Coronary artery disease (CAD) is the leading cause of death in African Americans, despite the lower prevalence of anatomic coronary atherosclerosis in this group. Risk factors for CAD in African Americans are considerable; however, the specific role of these risk factors in the excess mortality rates as compared with that of whites is not clarified. Factors such as differences in vascular pathobiology may be important in determining the cause of the excess mortality. The higher prevalence of normal coronary angiograms in African Americans with angina may be caused by pathobiology related to microvascular function and reserve. When access is available, the initial approach to diagnoses and management of coronary artery disease in African Americans is no different from that in other populations. Diagnostic approaches and therapeutic interventions are needed to identify the cause and modify the effects of the excess risks from coronary artery disease in African Americans.

No association between plasma lipoprotein(a) concentrations and the presence or absence of coronary atherosclerosis in African-Americans.

Elevated plasma concentrations of lipoprotein(a) [Lp(a)] are associated with coronary atherosclerosis in Caucasians. Although African-Americans have a higher median plasma Lp(a) concentration than Caucasians, they do not have a greater incidence of coronary atherosclerosis. This study was performed to determine whether the plasma concentration of Lp(a) is associated with coronary atherosclerosis in African-Americans. The fasting plasma concentrations of Lp(a) and lipoproteins were measured in 140 African-American subjects (62 men, 78 women, aged 31 to 80 years) 18 +/- 16 months (mean +/- SD) after they underwent coronary angiography: 72 had angiographically normal coronary arteries and 68 had > 70% luminal diameter narrowing of one or more major epicardial coronary arteries. The groups were similar in age, sex, and other risk factors for atherosclerosis. The subjects with coronary artery disease had higher plasma concentrations of total cholesterol, triglycerides, and VLDL and LDL cholesterol (P = .04) and lower concentrations of HDL cholesterol (P = .0001) than subjects without coronary artery disease, but there was no significant difference in the plasma concentration of Lp(a). The distribution of apolipoprotein(a) alleles by size was also not significantly different between the two groups. These results suggest that the plasma concentration of Lp(a) is not an independent risk factor for coronary artery disease in African-Americans.

Body mass index and coronary artery disease in African-Americans.

There are limited data available concerning the influence of obesity, a major cardiovascular disease risk factor, in relationship to coronary artery disease (CAD). This is of considerable importance to African-Americans since African-Americans have one of the world's highest CAD mortality rates coupled with the fact that obesity is extremely prevalent in this population. The present study assessed the relationship between body mass index and CAD in African-Americans undergoing coronary angiography. Eight hundred sixty-six available cardiac catheterization reports between the years 1983 through 1990 were retrospectively reviewed at Howard University Hospital in Washington, D.C. CAD was prevalent in 59.6% and 41.2%, males and females, respectively. Among the males overweight and obesity were found in 22.4% and 20.9%, respectively, compared to 39.6% and 30.6% for females. An upside-down U-shaped relationship between BMI and CAD was found. The interpretation of this finding is that being overweight is associated with increased risk of CAD compared to the lean and obese.

Coronary artery disease in African-Americans.

Contrary to opinions generally accepted in the past, CHD is very common in both African-American men and women, with incidence rates approaching those of US Caucasians. Higher prevalence of hypertension, diabetes, cigarette smoking, and obesity all contribute to the high level of CHD in African-Americans. Additional research is needed about the interrelations and management of various risk factors for CHD in African-Americans outside of the sudden death of African-Americans outside of the hospital is urgent, and special attention should be given to accessibility and use of health services by minority populations.