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(Circulation. 2002;105:1424.)
© 2002 American Heart Association, Inc.

Coronary Heart Disease in Patients With Low LDL-Cholesterol

Benefit of Pravastatin in Diabetics and Enhanced Role for HDL-Cholesterol and Triglycerides as Risk Factors

Frank M. Sacks, MD; Andrew M. Tonkin, MD; Timothy Craven, MSPH; Marc A. Pfeffer, MD PhD; James Shepherd, MD; Anthony Keech, MD; Curt D. Furberg, MD PhD; Eugene Braunwald, MD

From Harvard School of Public Health (F.M.S.), Harvard Medical School and Brigham and Women’s Hospital (F.M.S., E.B., M.A.P.), Boston, Mass; National Heart Foundation (A.M.T.), Melbourne, Australia; University of Sydney (A.K.), Sydney, Australia; Wake Forest University (T.C., C.D.F.), Winston-Salem, NC; and University of Glasgow (J.S.), Glasgow, Scotland.

Correspondence to Dr F.M. Sacks, Nutrition Department, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115. E-mail fsacks{at}hsph.harvard.edu

Background— In two large secondary prevention trials of pravastatin, risk reduction was not significant in participants who had low baseline LDL-C concentrations (that is, <125 mg/dL). We conducted exploratory analyses of participant characteristics, lipid risk factors, and risk reduction in this group.

Methods and Results— Among 13 173 participants with coronary heart disease (CHD), 2607 had baseline LDL-C <125 mg/dL. Those with LDL-C <125 compared with 125 mg/dL were more likely to be diabetic (15% versus 9%), hypertensive (46 versus 41%), and male (89% versus 83%); they had higher triglycerides (169 versus 154 mg/dL), lower HDL-C (36.5 versus 38 mg/dL), and similar body mass index (27 kg/m²); and pravastatin lowered their LDL-C by 36 mg/dL (32%) versus 45 mg/dL (29%). During 5.8-year (mean) follow-up, HDL-C and triglycerides were both significantly stronger predictors of recurrent CHD events in participants with LDL-C <125 than 125 mg/dL. In diabetic participants with low LDL-C, pravastatin decreased CHD events from 34% to 22% (relative risk, 0.56; 95% CI, 0.37 to 0.83; P=0.004), significantly different from the effect in nondiabetic participants with low LDL-C (P interaction, 0.005) (event rate, 21%; relative risk, 1.06 [95% CI, 0.89 to 1.27]). There were trends toward risk reduction in smokers and in those with low HDL-C, <40 mg/dL.

Conclusions— Among patients with CHD who have low LDL-C, diabetics have much higher subsequent CHD event rates than do nondiabetics. Pravastatin reduced the event rate in diabetics to that of nondiabetic participants. The results also suggest enhanced therapeutic potential for improving HDL-C and triglycerides in patients with CHD who have low LDL-C concentrations.

Key Words: cholesterol • coronary disease • diabetes mellitus • lipoproteins • drugs

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