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A Prospective Study

Andrew G. Bostom, MD, MS; L. Adrienne Cupples, PhD; Jennifer L. Jenner, MS; Jose M. Ordovas, PhD; Leo J. Seman, MD, PhD; Peter W. F. Wilson, MD; Ernst J. Schaefer, MD; William P. Castelli, MD

JAMA. 1996;276(7):544-548.

Abstract
Objective.
—To establish whether elevated lipoprotein(a) [Lp(a)], detected as a sinking pre-β-lipoportein band on electrophoresis of fresh plasma, is an independent risk factor for the development of premature coronary heart disease (CHD) in men.

Design and Setting.
—Prospective study of the Framingham offspring cohort.

Participants.
—A total of 2191 men aged 20 to 54 years old who were free of cardiovascular disease when they were examined between 1971 and 1975.

Main Outcome Measures.
—Incident CHD (myocardial infarction, coronary insufficiency, angina pectoris, or sudden cardiac death) occurring by age 55 years.

Results.
—After a median follow-up of 15.4 years, there were 129 CHD events. The relative risk (RR) estimates (with 95% confidence intervals [Cls]) for premature CHD derived from a proportional hazards model that included age, body mass index, and the dichotomized risk factor covariables elevated plasma Lp(a) level, total cholesterol level of 6.2 mmol/L (240 mg/dL) or more, high-density lipoprotein (HDL) level less than 0.9 mmol/L (35 mg/dL), smoking, glucose intolerance, and hypertension were as follows: elevated Lp(a) level, RR, 1.9 (95% CI, 1.2-2.9), prevalence, 11.3%; total cholesterol level of 6.2 mmol/L or more, RR, 1.8 (95% CI, 1.2-2.7), prevalence, 14.3%; HDL level of less than 0.9 mmol/L, RR, 1.8 (95% CI, 1.2-2.6), prevalence, 19.2%; smoking, RR, 3.6 (95% CI, 2.2-5.5), prevalence, 46.7%; glucose intolerance, RR, 2.7 (95% CI, 1.4-5.3), prevalence, 2.6%; hypertension, RR, 1.2 (95% CI, 0.8-1.8), prevalence, 26.3%.

Conclusions.
—Elevated plasma Lp(a) is an independent risk factor for the development of premature CHD in men, comparable in magnitude and prevalence (ie, attributable risk) to a total cholesterol level of 6.2 mmol/L (240 mg/dL) or more, or an HDL level less than 0.9 mmol/L (35 mg/dL).

Author Affiliations
From the Framingham Study, Epidemiology and Biometry Program, Framingham, Mass (Drs Bostom, Wilson, and Castelli); the Department of Epidemiology and Biostatistics, Boston University School of Public Health, Boston, Mass (Dr Cupples); and the Lipid Metabolism Laboratory, Jean Mayer US Dept of Agriculture Human Nutrition Research Center on Aging at Tufts New England Medical Center, Boston, Mass (Ms Jenner and Drs Ordovas, Seman, and Schaefer).

Footnotes
Presented in part at the American Heart Association 36th Annual Conference on Cardiovascular Disease Epidemiology and Prevention, San Francisco, Calif, March 8, 1996.

Reprints: Andrew G. Bostom, MD, MS, Vitamin Bioavailability Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts New England Medical Center, 711 Washington St, Boston, MA 02111 (e-mail: bostom vb@hnrc.tufts.edu).

References 13, 25, 26, 32, 37, 38, 41-43, 45, 46.

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