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Originally published In Press as doi:10.1194/jlr.M300520-JLR200 on February 16, 2004

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Journal of Lipid Research, Vol. 45, 948-953, May 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

A prospective study of HDL-C and cholesteryl ester transfer protein gene mutations and the risk of coronary heart disease in the elderly

J. D. Curb1,*,{dagger},§, R. D. Abbott*,**, B. L. Rodriguez*,{dagger},§, K. Masaki*,{dagger},§, R. Chen*, D. S. Sharp{dagger}{dagger} and A. R. Tall§§

* Pacific Health Research Institute, Honolulu, HI
{dagger} Honolulu Heart Program, Kuakini Medical Center, Honolulu, HI
§ John A. Burns School of Medicine, Departments of Health Science and Epidemiology, Geriatric Medicine, and Medicine, University of Hawaii at Manoa, Honolulu, HI
** Division of Biostatistics and Epidemiology, University of Virginia School of Medicine, Charlottesville, VA
{dagger}{dagger} National Institute for Occupational Safety and Health, Health Effects Laboratory Division, Morgantown, WV
§§ Columbia University, New York, NY

1 To whom correspondence should be addressed. e-mail: jdcurb{at}phrihawaii.org

High density lipoprotein cholesterol (HDL-C) levels are inversely associated with the incidence of coronary heart disease (CHD) in middle-aged individuals; in the elderly, the association is less clear. Genetic factors, including variations in the cholesteryl ester transfer protein (CETP) gene, play a role in determining HDL-C levels. Controversy remains about whether CETP deficiency and the resultant rise in HDL-C are antiatherogenic, or whether CETP has the opposite effect due to its role in reverse cholesterol transport. In a seven-year follow-up of 2,340 men aged 71–93 in the Honolulu Heart Program, the age-adjusted CHD incidence rates were significantly lower in men with high versus low HDL-C levels. After adjustment for age, hypertension, smoking, and total cholesterol, the relative risk of CHD for those with HDL-C levels >=60 mg/dl, compared with those with HDL-C levels <40 mg/dl, was 0.6. Men with a CETP mutation had the lowest rates of CHD, although this was not statistically significant.

These data indicate that HDL-C remains an important risk factor for CHD in the elderly. Whether a CETP mutation offers additional protection against CHD warrants further investigation.

Abbreviations: BMI, body mass index; CETP, cholesteryl ester transfer protein; CHD, coronary heart disease; CVD, cardiovascular disease; HDL-C, high density lipoprotein cholesterol; HHP, Honolulu Heart Program; LDL-C, low density lipoprotein cholesterol; MI, myocardial infarction

Supplementary key words epidemiology • risk factors • high density lipoprotein cholesterol


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