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Circulation
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Circulation. 2001;104:3046-3051
doi: 10.1161/hc5001.100624
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(Circulation. 2001;104:3046.)
© 2001 American Heart Association, Inc.


Clinical Investigation and Reports

Influence of Low High-Density Lipoprotein Cholesterol and Elevated Triglyceride on Coronary Heart Disease Events and Response to Simvastatin Therapy in 4S

Christie M. Ballantyne, MD; Anders G. Olsson, MD; Thomas J. Cook, MS; Michele F. Mercuri, MD; Terje R. Pedersen, MD; John Kjekshus, MD, for the Scandinavian Simvastatin Survival Study (4S) Group

From the Department of Medicine, Baylor College of Medicine, Houston, Tex (C.M.B.); the Department of Internal Medicine, Linköping University Hospital, Linköping, Sweden (A.G.O.); Merck Research Laboratories, Rahway, NJ (T.J.C., M.F.M.); and the Medical Clinic, Aker Hospital (T.R.P.), and Department of Medicine, Rikshospitalet (J.K.), Oslo, Norway.

Correspondence to Christie M. Ballantyne, MD, Baylor College of Medicine, 6565 Fannin, MS A-601, Houston, TX 77030. E-mail cmb{at}bcm.tmc.edu

Background Patients with low HDL cholesterol (HDL-C) and elevated triglyceride had an increased risk for coronary heart disease (CHD) events and received the greatest benefit with fibrate therapy in substudy analyses of the Helsinki Heart Study and the Bezafibrate Infarction Prevention Study.

Methods and Results In this post hoc analysis of the Scandinavian Simvastatin Survival Study, which enrolled patients with elevated LDL cholesterol (LDL-C) and CHD, subgroups defined by HDL-C and triglyceride quartiles were compared to examine the influence of HDL-C and triglyceride on CHD events and response to therapy. Patients in the lowest HDL-C (<1.00 mmol/L [39 mg/dL]) and highest triglyceride (>1.80 mmol/L [159 mg/dL]) quartiles (lipid triad; n=458) had increased proportions of other features of the metabolic syndrome (increased body mass index, hypertension, diabetes), men, prior myocardial infarction, prior revascularization, and ß-blocker use than patients in the highest HDL-C (>1.34 mmol/L [52 mg/dL]) and lowest triglyceride (<1.11 mmol/L [98 mg/dL]) quartiles (isolated LDL-C elevation; n=545). The major coronary event rate was highest in lipid triad patients on placebo (35.9%), and this subgroup had the greatest event reduction (relative risk 0.48, 95% CI 0.33 to 0.69); a significant treatment-by-subgroup interaction (P=0.03) indicated a greater treatment effect in the lipid triad subgroup than the isolated LDL-C elevation subgroup.

Conclusions Patients with elevated LDL-C, low HDL-C, and elevated triglycerides were more likely than patients with isolated LDL-C elevation to have other characteristics of the metabolic syndrome, had increased risk for CHD events on placebo, and received greater benefit with simvastatin therapy.


Key Words: lipids • statins • trials




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