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Paul M Ridker, MD; Nader Rifai, PhD; Nancy R. Cook, ScD; Gary Bradwin, BS; Julie E. Buring, ScD

JAMA. 2005;294:326-333.

Context  Current guidelines for cardiovascular risk detection are controversial with regard to the clinical utility of different lipid measures, non–high-density lipoprotein cholesterol (non–HDL-C), lipid ratios, apolipoproteins, and C-reactive protein (CRP).

Objective  To directly compare the clinical utility of total cholesterol, low-density lipoprotein cholesterol (LDL-C), HDL-C, non–HDL-C, apolipoproteins A-I and B₁₀₀, high-sensitivity CRP, and the ratios of total cholesterol to HDL-C, LDL-C to HDL-C, apolipoprotein B₁₀₀ to apolipoprotein A-I, and apolipoprotein B₁₀₀ to HDL-C as predictors of future cardiovascular events in women.

Design, Setting, and Participants  Prospective cohort study of 15 632 initially healthy US women aged 45 years or older (interquartile range, 48-59 years) who were enrolled between November 1992 and July 1995. All participants were followed up over a 10-year period for the occurrence of future cardiovascular events.

Main Outcome Measure  Hazard ratios (HRs) and 95% confidence intervals (CIs) for first-ever major cardiovascular events (N = 464) according to baseline levels of each biomarker.

Results  After adjustment for age, smoking status, blood pressure, diabetes, and body mass index, the HRs for future cardiovascular events for those in the extreme quintiles were 1.62 (95% CI, 1.17-2.25) for LDL-C, 1.75 (95% CI, 1.30-2.38) for apolipoprotein A-I, 2.08 (95% CI, 1.45-2.97) for total cholesterol, 2.32 (95% CI, 1.64-3.33) for HDL-C, 2.50 (95% CI, 1.68-3.72) for apolipoprotein B₁₀₀, 2.51 (95% CI, 1.69-3.72) for non–HDL-C, and 2.98 (95% CI, 1.90-4.67) for high-sensitivity CRP (P<.001 for trend across all quintiles). The HRs for the lipid ratios were 3.01 (95% CI, 2.01-4.50) for apolipoprotein B₁₀₀ to apolipoprotein A-I, 3.18 (95% CI, 2.12-4.75) for LDL-C to HDL-C, 3.56 (95% CI, 2.31-5.47) for apolipoprotein B₁₀₀ to HDL-C, and 3.81 (95% CI, 2.47-5.86) for the total cholesterol to HDL-C (P<.001 for trend across all quintiles). The correlation coefficients between high-sensitivity CRP and the lipid parameters ranged from –0.33 to 0.15, and the clinical cut points for CRP of less than 1, 1 to 3, and higher than 3 mg/L provided prognostic information on risk across increasing levels of each lipid measure and lipid ratio.

Conclusions  Non–HDL-C and the ratio of total cholesterol to HDL-C were as good as or better than apolipoprotein fractions in the prediction of future cardiovascular events. After adjustment for age, blood pressure, smoking, diabetes, and obesity, high-sensitivity CRP added prognostic information beyond that conveyed by all lipid measures.

Author Affiliations: Donald W. Reynolds Center for Cardiovascular Research (Drs Ridker, Cook, and Buring); the Leducq Center for Molecular and Genetic Epidemiology (Drs Ridker and Cook); the Center for Cardiovascular Disease Prevention and the Divisions of Preventive Medicine (Drs Ridker, Cook, and Buring) and Cardiology (Dr Ridker), Brigham and Women’s Hospital, and the Department of Laboratory Medicine, Children’s Hospital (Dr Rifai and Mr Bradwin), Harvard Medical School, Boston, Mass; and the Department of Epidemiology, Harvard School of Public Health, Boston, Mass (Drs Ridker, Cook, and Buring).

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