NEED FOR MORE AGGRESSIVE STATIN USE IN VARIOUS ETHNIC GROUPS: LATINO, ASIAN, AND AFRICAN AMERICAN POPULATIONS
Overview
Cardiovascular disease (CVD) is the leading cause of death among all ethnic
groups. Recent data suggest that certain ethnic groups, such as Latinos, African
Americans, and Asians (especially South Asian Indians), experience a disproportionately
greater burden of CVDs, such as heart disease, stroke, and hypertension. Ironically,
these minority populations are consistently under-represented in major clinical
trials. Long overdue, several randomized trials of statin therapy among ethnic
groups are now underway. The results of these trials will shape future treatment
strategy.
Latino
Populations
Heart disease is the leading cause of death for Hispanic men and women.
It kills more people than all forms of cancer. People of Latino ancestry
are the second largest and fastest growing racial and ethnic minority group
in the United States. CVD, overall, accounted for 27.3% of Hispanic male
deaths and 33.1% of Hispanic female deaths in 2000. Among Mexican American
adults, 28.8% of men and 26.6% of women have CVD. Recent studies indicate
that Mexican American women are at greater risk for CVD than are non-Latino
white women of comparable socioeconomic status. Even though the data from
the 1998 National Health Interview Survey showed that Hispanic people had
somewhat lower rates of CVD than did non-Hispanic whites or African Americans,
CVD remains the number one killer among Hispanic people. CVD mortality rates
among Hispanic groups are highest for Puerto Ricans. In Hispanic populations,
the risk of stroke is 1.3 times higher than in non-Hispanic populations,
and 48% of Hispanic women older than 65 years have hypertension. Hypertension
is present but undiagnosed in as many as 50% of Puerto Rican and Mexican
American people.
Several studies have shown that Latino persons have high cholesterol levels
in ranges that increase their risk for developing CVD. In addition, Latino
persons have higher cholesterol levels than whites and African Americans.
The STARSHIP trial (Study Assessing Rosuvastatin
in the Hispanic Population), currently underway,
is designed to assess the efficacy of rosuvastatin and atorvastatin in lowering
low-density lipoprotein cholesterol (LDL-C) levels in Hispanic populations.
Hispanic people have an adverse cardiovascular risk profile with an increased
risk of metabolic syndrome. Further clarification of the role of lipid-lowering
therapy in Latinos is greatly needed, and results from the STARSHIP trial may
have important treatment implications for this high-risk population. Until
the results of this specific trial are published, current data for the treatment
of patients with metabolic syndrome (common in Hispanic people) indicate the
need for more aggressive cholesterol reduction in this subpopulation.
South
Asian – Asian Indian Populations
The death rates from CVD among South Asian Americans of Indian ancestry
have been reported to be 50-300% higher than those of whites, irrespective
of sex, religion, or social class. The rates are much lower for persons of
East Asian descent (eg, Chinese, Japanese). Among persons younger than 30
years, the CVD mortality among Asian Indians is 3 times higher than that
among whites in the United Kingdom and 10 times higher than the CVD mortality
rate among Chinese persons in Singapore. The disease tends to be more aggressive
and manifests at a younger age than it does in white or East Asian persons.
Approximately 50% of myocardial infarctions among Asian Indians occur in
persons younger than 55 years and 25% occur in persons younger than 40 years.
The Coronary Artery Disease in Asian Indians (CADI) Study was the major study
of Asian Indians in the United States. The CADI Study participants were highly
educated persons of Asian Indian origin with ready access to medical care
in the United States. This study showed that diabetes (which is 2-3 times
more common among Asian Indians than among white persons), combined with
a higher prevalence of metabolic syndrome, may account for a third of the
excess burden of CVD in this subpopulation.
An excess prevalence or activation of the so-called “thrifty” or “pig-out” gene
(ie, 825T allele of the B3 subunit of the heteromeric G-protein [GNB3])
is associated with the development of obesity and metabolic syndrome in the
absence of adequate regular exercise. The worldwide prevalence of the 825T
allele is highest in people of African descent (80-90%), followed by people
of Asian descent (50%), and lowest in whites (30%). In addition, environmental
changes such as urbanization, westernization, and cross-country migration
cause changes in lifestyle. These changes increase body mass index, serum
cholesterol, triglycerides, blood glucose, and blood pressure while reducing
high-density lipoprotein cholesterol (HDL-C) in a syndrome known as metabolic
syndrome. Furthermore, the high prevalence of small dense lipoprotein (a)
adds to this atherogenic lipoprotein phenotype, contributing to the excess
risk of CVD.
Randomized trial data in the therapeutic arena for this high-risk subpopulation
are lacking. The database to support treatment recommendations is derived primarily
from studies of white populations. For any given level of risk factors, the
CVD risk among Asian Indians is at least double that of whites. Therefore,
the threshold of intervention and treatment goals may need to be lower in Asian
Indians than in whites by at least 20% (similar to the recommended threshold
for patients with diabetes). In the National Cholesterol Education Program
Adult Treatment Panel III (NCEP ATP III), diabetes is regarded as a CVD risk
equivalent, with an LDL goal of less than 100 mg/dL, irrespective of the presence
or absence of CVD. Those who already have CVD require even more aggressive
treatment to lower LDL to less than 80 mg/dL (cholesterol <150 mg/dL), especially
if they also have high levels of lipoprotein (a).
Asian Indians at high risk of developing premature CVD can be identified
by early determination of emerging risk factors along with conventional risk
factors. Individuals identified as high risk should be targeted for institution
of aggressive therapeutic lifestyle change (TLC) beginning at an earlier
age. Important modifications include adopting an exercise regimen involving
at least 45 minutes of exercise daily; avoiding smoking; and monitoring weight,
cholesterol intake, caloric intake, and waistline circumference. The earlier
the cholesterol level is lowered, the greater the benefit. For example, a
10% lowering of cholesterol at age 40 years results in a 50% reduction in
the risk of CVD versus a 20% reduction in risk if cholesterol is lowered
by 10% at age 70 years. Consequently, the benefit of lowering cholesterol
level at age 20 years should be even greater. Since the average reduction
in LDL with diet is 5-10%, most individuals with suboptimal levels of various
lipoproteins require medication. Therefore, lipid-lowering therapy with statins
should be considered as a first line of treatment rather than as a last resort.
A long overdue randomized trial of lipid reduction in this population, called
the IRIS (Investigation of Rosuvastatin in South-Asian
Subjects) trial, is currently underway. It will assess the comparative efficacy
and safety of rosuvastatin and atorvastatin in Americans of South Asian origin
who have hypercholesterolemia and provide further insight into formulating
adequate risk management strategies in this high-risk subpopulation. On a cautionary
note, persons of Asian Indian descent tend to have twice the drug level compared
to whites on an equivalent dose of statins, especially rosuvastatin. Therefore,
these medications should be started at a lower dose in Asian Indians. A recent
FDA advisory suggests starting treatment with a 5-mg daily dose and avoiding
a 40-mg daily dose to minimize the risk of rhabdomyolysis. The dose should
also be lowered in elderly patients and in those with renal insufficiency.
In addition to statins, fibrates and niacin frequently provide added benefit
in this subpopulation with higher prevalence of metabolic syndrome. The benefits
of glitazones are theoretically positive but are currently unproven, pending
larger randomized studies.
African
American Populations
African Americans have higher CVD and stroke death rates than whites. Approximately
40% of African American men and women older than 20 years have CVD. According
to the American Heart Association, 45% of African Americans have elevated
LDL-C levels. This is a major risk factor for CVD, which claims more than
100,000 African American lives each year. Additionally, the Risk Factor
Surveillance System of the National Center for Chronic Disease Prevention
and Health Promotion reports that about 26% of African Americans have never
had their cholesterol levels checked. Despite the increased rate of CVD,
African Americans remain less likely than whites to receive lipid reduction
treatments. Again, data specific to this population are lacking due to under-representation
in clinical trials.
ARIES (African American Rosuvastatin Investigation
of Efficacy and Safety), a 6-week, randomized,
controlled, open-label, multicenter trial, compared the efficacy of rosuvastatin
and atorvastatin in 774 African Americans with hypercholesterolemia following
a 6-week dietary lead-in. The results, presented at the 2004 American Heart
Association meeting, showed that rosuvastatin at 10- and 20-mg dosages reduced
LDL-C by 37% and 46% respectively, compared to 32% and 39% reduction with atorvastatin
(P < .017). Rosuvastatin seemed to be better than atorvastatin
at increasing HDL, reducing total cholesterol, and achieving NCEP (ATP III)
LDL-C goals. The triglyceride-lowering effects of rosuvastatin and atorvastatin
were equal. This is the first trial to demonstrate the superiority of rosuvastatin
compared to equal doses of atorvastatin in lowering LDL-C in African Americans.
The benefits of such aggressive therapy need to be demonstrated in a larger,
randomized trial. Until then, a more aggressive cholesterol-reduction strategy
in this high-risk population should be pursued.
Emerging
Data Encourage Further Trials
Latino persons, Asian Indians, and African Americans are rapidly growing
minority groups in the United States currently at high risk for developing
CVD that is often more aggressive and tends to occur at an earlier age than
in whites. It is heartening to see a number of randomized trials beginning
to address this issue. So far, the emerging data indicate the need for more
aggressive treatment goals for cholesterol reduction in these high-risk populations
than the current recommendations of the NCEP (ATP III).
References
American Heart
Association. (2005). Heart disease and stroke statistics—2005 update.
http://www.americanheart.org/downloadable/heart/1105390918119HDSStats2005Update.pdf
American Heart Association. (2003). Hispanics and cardiovascular disease.
http://www.americanheart.org/
Chandalia M, Deedwania PC. Coronary heart disease and risk factors in Asian
Indians. Adv Exp Med Biol. 2001;498:27-34.
Gillum RF. The epidemiology of cardiovascular disease in Black Americans. N
Engl J Med 1996; 335:1597-1599.
Gupta R, Gupta VP. Urban-rural differences in coronary risk factors
do not fully explain greater urban coronary heart disease prevalence. J
Assoc Physicians India 1997;45:683-686.
Hong, B, and Bayat, N. (1999). National Asian American and Pacific
Islander cardiovascular health action plan: Eliminating racial and
ethnic disparities in cardiovascular health: Improving the cardiovascular
health of Asian American and Pacific Islander populations in the United
States. http://www.apiahf.org/
Kraus JF, Borhani NO, Frant CE. Socioeconomic status, ethnicity, and
risk of coronary heart disease. Am J Epidemiol; 1980;111:407-414.
McKeigue PM, Miller GJ, Marmot MG. Coronary heart disease in South
Asians overseas: a review. J Clin Epidemiol 1989; 42:597-609.
Perez-Stable E. Cardiovascular Disease. In: Molina CW, Molina-Aguirre
M, eds. Latino Health in the US: A Growing Challenge. Washington,
DC: American Public Health Association; 1994. 247-278.
Pleis JR, Coles R. Summary health statistics for U.S. adults: National
Health Interview Survey, 1998. National Center for Health Statistics.
Vital Health Stat 10(209). 2002.
Singh, VN: Commentary on "Race and Gender in Coronary Heart Disease." ACP
J Club Nov-Dec: 1993 (Ann Int Med 119: suppl 3). Commentary
on: Keil JE, Sutherland SE, Knapp RG, et al: Mortality rates and risk
factors for coronary disease in black as compared with white men and
women. N
Engl J Med 329:73-78,1993.
Tamir, A, and Cachola, S. (1994). Hypertension and other cardiovascular
risk factors. In Zane, NWS, Takeuchi, DT, and Young, KNJ, eds. Confronting
critical health issues of Asian and Pacific Islander Americans. Thousand
Oaks, CA: Sage, pp. 209–246. |
