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HYPERCHOLESTEROLEMIA IN AFRICAN AMERICAN PATIENTS
Keith C. Ferdinand, MD, FACC
African Americans, when compared to the general population and other racial/ethnic minorities in the United States, have the highest overall rate of coronary heart disease mortality, sudden cardiac death, and incidence of several comorbid conditions. Particularly, there is a greater prevalence of type 2 diabetes and multiple coronary heart disease risk factors, including hypertension, renal insufficiency, and obesity, especially in African American females. Therefore, it would be expected that a larger proportion of African American patients require increased intensive low-density-lipoprotein (LDL)–cholesterol lowering to achieve NCEP Adult Treatment Panel III (ATP III) goals as compared with the general population.1 However, this population has been underrepresented in cardiovascular clinical endpoint studies, including statin trials.
The relationship between elevated cholesterol and coronary heart disease risk appears to be similar in African Americans and the general population. Results of the National Health & Nutrition Examination Survey III (NHANES III) indicate that 45% of black men and 46% of black women have total cholesterol greater than 200 mg/dL. Moreover, patients with total cholesterol greater than or equal to 240 mg/dL represent 15% and 18% of black men and women, respectively.2,3 African American men have mean high-density-lipoprotein (HDL)-cholesterol levels that appear somewhat higher than those in white men, but this does not appear to be protective. The HDL-C levels are similar in African American women and in white men. Triglyceride levels appear to be lower in African American men and women vs. white men and women. In addition, there is an increased level of lipoprotein (a) in African Americans, both men and women. However, it is not known whether this is predictive of an increase in cardiac risk in African Americans.3,4
It is more probable that the increase in cardiovascular morbidity and mortality in African Americans is related to risk factor clustering the increased prevalence and severity of hypertension and its consequences, including: target organ damage in the form of left ventricular hypertrophy; obesity, which is twice as common in African American women vs. white women; and type 2 diabetes, which is more common in both African American men and women. African Americans, therefore, are 1.5 times more likely to have multiple risk factors than whites. The combination of multiple risk factors with less intense use of lipid lowering therapy may explain higher levels of morbidity and mortality.5
The provision of appropriate lipid-lowering therapy in African Americans remains a challenge because of barriers, including diminished access due to lower socioeconomic status and less insurance coverage for medications. Black patients may be less likely than whites to receive lipid-lowering medications at the time of hospital discharge after acute myocardial infarction. In addition, African Americans have been underrepresented in the major cardiovascular trials of lipid-lowering agents covering more than 450,000 patients over the last three decades. In these trials black patients have accounted for no more than 5.1 percent of the population studied. The largest trial with a significant African American cohort was the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), with non-Hispanic blacks accounting for 35 percent of the greater than 10,000 patients in the lipid lowering arm. Interestingly, in that particular trial, black patients in the pravastatin group, unlike non-black patients, experienced significantly reduced coronary heart disease events compared to usual care, relative risk 0.73 (P value 0.03) vs. 1.02 in the general population.6 Unfortunately, this benefit may have been due to the underuse of lipid-lowering therapy in the usual care cohort of black patients vs. those randomized to pravastatin 40 mg.
Considering that prior statin trials of efficacy and safety underrepresented African Americans, better documentation of the response to lipid-lowering treatment in this high risk population is necessary. The failure to include adequate numbers of blacks in landmark statin trials and in trials of safety and efficacy has left open the question of precisely what benefit these agents confer.
The ARIES (African American Rosuvastatin Investigation of Efficacy and Safety) trial7 was designed to document clinical response to statins. It is the first-ever, large-scale, prospective trial exclusively intended to compare the effects of statins in African Americans, who have generally been underrepresented and underserved in clinical trials. Data from this trial were most recently presented at the American Heart Association’s Annual Scientific Sessions in New Orleans, Louisiana, in 2004. This study of 774 enrolled African Americans successfully captured efficacy and safety information, demonstrating greater efficacy of milligram-equivalent doses of 2 statins (rosuvastatin 10 mg and 20 mg vs atorvastatin 10 mg and 20 mg). In ARIES, rosuvastatin significantly lowered low-density lipoprotein (LDL) cholesterol, total cholesterol, and non-HDL cholesterol versus mg equivalent doses of atorvastatin. Furthermore, rosuvastatin 10 mg increased HDL cholesterol more than atorvastatin 20 mg. This trial was also very significant because it demonstrated the ability to successfully enroll a large number of African Americans in a clinical trial. There were no cases of myopathy (CK >10X normal), liver disease (ALT >3X normal), or deaths.
In conclusion, the ARIES trial examines in a randomized study the efficacy and safety of a charged potent statin drug, rosuvastatin, when compared to atorvastatin in an African American cohort. This type of information may give clinicians greater confidence that African Americans will have equal benefit from effective medical care with statin therapy. It is hoped that socioeconomic barriers will be limited in the future so that lipid-lowering therapy, especially statins, will be more widely available and affordable.
References
1. Ferdinand KC. Coronary heart disease and lipid-modifying treatment in African American patients. Am Heart J. 2004;147:774-782.
2. American Heart Association. 2003 heart and stroke statistical update. Dallas, Tex: American Heart Association; 2002.
3. Third National Health and Nutrition Examination Survey (NHANES III, 1988-94). CDC/NCHS Web site. Available at: http://www.cdc.gov/nchs/nhanes.htm
4. Asher CR, Topol EJ, Moliterno DJ. Insight into the pathphysiology of atherosclerosis and prognosis of black Americans with acute coronary syndromes. Am Heart J. 1999;138:1073-1081.
5. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:2486-2497.
6. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). JAMA. 2002;288:2998-3007.
7. Ferdinand KC. Presented at: American Heart Association Scientific Sessions 2004; November 7–10, 2004; New Orleans, Louisiana. Abstract 1224.
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