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Associate Professor; Residency Director, Department of Family Medicine, University of California, Irvine
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Associate Professor; Residency Director, Department of Family Medicine, University of California, Irvine
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CME Released: 7/19/2005
Valid for credit through: 7/19/2006
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July 19, 2005 — For women, non–high-density lipoprotein cholesterol (HDL-C) and the ratio of total cholesterol to HDL-C are as good as, if not better than, using apolipoprotein fractions to predict risk of future cardiovascular events, according to the results of a large, prospective cohort study published in the July 20 issue of The Journal of the American Medical Association. Furthermore, high-sensitivity C-reactive protein (CRP) may offer added prognostic information.
"Current guidelines for cardiovascular risk detection are controversial with regard to the clinical utility of different lipid measures, non–HDL-C, lipid ratios, apolipoproteins, and CRP," write Paul M. Ridker, MD, from Harvard Medical School in Boston, Massachusetts, and colleagues.
Between November 1992 and July 1995, 15,632 initially healthy U.S. women age 45 years or older (interquartile range, 48 - 59 years) were enrolled and monitored for 10 years for the occurrence of cardiovascular events. Primary endpoints were hazard ratios (HRs) and 95% confidence intervals (CIs) for first-ever major cardiovascular events (n = 464), according to baseline levels of each potential marker of cardiovascular risk, after adjustment for age, smoking status, blood pressure, diabetes, and body mass index.
In the extreme quintiles, HRs for future cardiovascular events were 1.62 (95% CI, 1.17 - 2.25) for low-density lipoprotein cholesterol (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).
For the lipid ratios, the HRs 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 total cholesterol to HDL-C (P < .001 for trend across all quintiles).
Correlation coefficients between high-sensitivity CRP and lipid parameters ranged from -0.33 to 0.15. Clinical cut points for CRP of less than 1, 1 to 3, and higher than 3 mg/L offered prognostic information on risk across increasing levels of each lipid measure and lipid ratio.
"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," the authors write. "After adjustment for age, blood pressure, smoking, diabetes, and obesity, high-sensitivity CRP added prognostic information beyond that conveyed by all lipid measures."
Study limitations include evaluation of plasma levels only once, creating susceptibility to intra-individual variation; inclusion of middle-aged women in whom adverse effects on several blood variables can occur during and after menopause; incomplete assessment of triglyceride levels in these women; and overall low usage of statin therapy.
"With regard to high-sensitivity CRP, recent data suggest potential utility for this inflammatory biomarker as an adjunctive method to monitor statin efficacy, not as a replacement for LDL-C," the authors conclude. "The possible role of combined apolipoprotein and high-sensitivity CRP evaluation to monitor patients taking statins needs to be evaluated."
The Donald W. Reynolds Foundation (Las Vegas, Nevada), the Leducq Foundation (Paris, France), and the Doris Duke Charitable Foundation (New York, New York) supported the research for this article. The National Heart, Lung, and Blood Institute and the National Cancer Institute supported the Women's Health Study. Dr. Ridker is listed as a coinventor on patents held by the Brigham and Women's Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease (CVD).
JAMA. 2005;294:326-333
