This proposal will examine whether differences exist between asymptomatic white and African American people known to be at high risk for premature coronary artery disease (CAD) in risk factor distributions, prevalence of occult CAD, and mechanisms of CAD expression. We hypothesize that increased platelet activation and coronary artery vasoconstriction exist in African Americans, due to greater vascular endothelial dysfunction, heightened adrenergic drive, and greater vascular reactivity, resulting in excess sudden death and the occurrence of myocardial infarction in people with less severe angiographic CAD. The study population will consist of asymptomatic siblings, 30-59 years of age, of patients with documented CAD prior to age 60, identified in the Johns Hopkins Hospital or the East Baltimore Community. 0ur studies over the past 9 years have demonstrated high prevalences of CAD risk factors and occult CAD in this sibling population. We will recruit 325 African American and 325 white siblings, equally divided between men and women, to come for a one day screening, with measurement of CAD risk factors (blood pressure, smoking, lipid profile, apolipoproteins B and A1, lipoprotein(a), blood glucose, insulin, and fibrinogen), and a maximal treadmill test with tomographic thallium imaging to identify occult CAD. Platelet function will be assessed by spontaneous in-vitro aggregation, activated IIa/IIIb receptor density, and serum thromboxane B2 concentration. Factors contributing to sudden cardiac death will be assessed by an echocardiogram for left ventricular mass, ECG for QRS late potentials, and 24 hour ECG monitoring for ventricular arrhythmias, episodes of silent ischemia, and heart rate variability (to assess adrenergic drive). Vascular reactivity will be characterized by heart rate and blood pressure changes during Stroop color card and cold pressor testing. Siblings with an abnormal exercise ECG and/or thallium scan will be offered coronary arteriography to assess the severity of angiographic CAD and the vasomotor responses to isometric handgrip and intracoronary acetylcholine, an endothelium-dependent vasodilator. In coronary arteries with minimal angiographic disease, changes in coronary vascular resistance during handgrip and acetylcholine will also be measured with a doppler flow velocity catheter and the proximal arteries will be imaged with intravascular ultrasound. This study will provide important new information about possible racial differences in CAD mechanisms, including atherosclerotic and thrombotic risk factors and their relationship to occult CAD, platelet activation, coronary vasoconstriction and factors associated with sudden cardiac death in a relatively large, racially balanced group of individuals at high risk for a premature CAD event.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL049762-02
Application #
3368782
Study Section
Special Emphasis Panel (ZHL1 (01))
Project Start
1992-09-30
Project End
1996-08-31
Budget Start
1993-09-30
Budget End
1994-08-31
Support Year
2
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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Kral, B G; Becker, L C; Yook, R M et al. (2001) Racial differences in low-density lipoprotein particle size in families at high risk for premature coronary heart disease. Ethn Dis 11:325-37

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