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Previous Volume 354:1264-1272 March 23, 2006 Number 12 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Editorial by Tall, A. R. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background A low plasma level of low-density lipoprotein (LDL) cholesterol is associated with reduced risk of coronary heart disease (CHD), but the effect of lifelong reductions in plasma LDL cholesterol is not known. We examined the effect of DNA-sequence variations that reduce plasma levels of LDL cholesterol on the incidence of coronary events in a large population.

Methods We compared the incidence of CHD (myocardial infarction, fatal CHD, or coronary revascularization) over a 15-year interval in the Atherosclerosis Risk in Communities study according to the presence or absence of sequence variants in the proprotein convertase subtilisin/kexin type 9 serine protease gene (PCSK9) that are associated with reduced plasma levels of LDL cholesterol.

Results Of the 3363 black subjects examined, 2.6 percent had nonsense mutations in PCSK9; these mutations were associated with a 28 percent reduction in mean LDL cholesterol and an 88 percent reduction in the risk of CHD (P=0.008 for the reduction; hazard ratio, 0.11; 95 percent confidence interval, 0.02 to 0.81; P=0.03). Of the 9524 white subjects examined, 3.2 percent had a sequence variation in PCSK9 that was associated with a 15 percent reduction in LDL cholesterol and a 47 percent reduction in the risk of CHD (hazard ratio, 0.50; 95 percent confidence interval, 0.32 to 0.79; P=0.003).

Conclusions These data indicate that moderate lifelong reduction in the plasma level of LDL cholesterol is associated with a substantial reduction in the incidence of coronary events, even in populations with a high prevalence of non–lipid-related cardiovascular risk factors.

Source Information

From the Donald W. Reynolds Cardiovascular Clinical Research Center (J.C.C., H.H.H.), the Center for Human Nutrition (J.C.C.), the Departments of Internal Medicine (J.C.C., H.H.H.) and Molecular Genetics (H.H.H.), and the Howard Hughes Medical Institute (H.H.H.), University of Texas Southwestern Medical Center, Dallas; the Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston (E.B.); and the Department of Medicine, University of Mississippi Medical Center, Jackson (T.H.M.).

Address reprint requests to Dr. Hobbs at the Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas TX 75390-9046, or at helen.hobbs{at}utsouthwestern.edu.

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