The relative strength of C-reactive protein and lipid levels as determinants of ischemic stroke compared with coronary heart disease in women

Abstract

Objectives: We sought to determine the relative strength of high-sensitivity C-reactive protein (hs-CRP) and lipid levels as markers for future ischemic stroke compared with coronary heart disease (CHD) in women.

Background: Although hs-CRP and lipid levels are established risk determinants for vascular disease, the relative strength of these biomarkers for ischemic stroke compared with CHD is uncertain.

Methods: Among 15,632 initially healthy women who were followed for a 10-year period, we compared hs-CRP, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoproteins A-I and B100, and lipid ratios as determinants of ischemic stroke compared with CHD.

Results: After adjustment for age, smoking status, blood pressure, diabetes, and obesity, the hazard ratios (HRs) and 95% confidence intervals (CIs) for the third versus the first tertile for future ischemic stroke compared with CHD were, respectively, 1.91 (95% CI 1.13 to 3.21) and 2.26 (95% CI 1.64 to 3.12) for TC, 1.29 (95% CI 0.83 to 2.02) and 2.09 (95% CI 1.53 to 2.85) for LDL-C, 0.57 (95% CI 0.36 to 0.92) and 0.38 (95% CI 0.27 to 0.52) for HDL-C, 1.72 (95% CI 1.03 to 2.86) and 2.93 (95% CI 2.04 to 4.21) for non-HDL-C, and 2.76 (95% CI 1.51 to 5.05) and 1.66 (95% CI 1.17 to 2.34) for hs-CRP. Of the lipid ratios, that of TC to HDL-C had the largest HR for both future ischemic stroke and CHD (HR 1.95 [95% CI 1.16 to 3.26] and 4.20 [95% CI 2.79 to 6.32], respectively).

Conclusions: In this large prospective cohort of initially healthy women, lipid levels are significant risk determinants for ischemic stroke, but with a magnitude of effect smaller than that observed for CHD. High-sensitivity CRP associates more closely with ischemic stroke than with CHD. Concomitant evaluation of lipid levels and hs-CRP may improve risk assessment for stroke as well as CHD. (The Women's Health Study; http://www.clinicaltrials.gov/ct/show/NCT00000479/; NCT00000479).

Conflict of interest statement

Conflicts of Interest: Dr. Ridker is listed as a co-inventor on patents held by the Brigham and Women’s Hospital that pertain to the use of inflammatory biomarkers in cardiovascular disease.

Figures

Figure 1

Adjusted hazard ratios and 95% confidence intervals for future ischemic stroke (○) and coronary heart disease (●) among those in extreme tertiles of each lipid variable and high-sensitivity CRP. Hazard ratios are adjusted for age (years), blood pressure (Framingham categories), diabetes, current smoking status, body mass index, and randomized treatment assignment. For ease of comparison, we have used the highest tertile as the referent for high-density lipoprotein cholesterol and apolipoprotein A-I. Abbreviations: Apo A-I, apolipoprotein A-I; Apo B100, apolipoprotein B100; CI, confidence interval; HR, hazard ratio; Hs-CRP, high-sensitivity C-reactive protein; LDL-C, LDL cholesterol; Non-HDL-C, non-HDL cholesterol; Total Chol, total cholesterol.

Figure 2

Adjusted hazard ratios and 95% confidence intervals for future ischemic stroke (○) and coronary heart disease (●) among those in extreme tertiles of each lipid ratio. Hazard ratios are adjusted for age (years), blood pressure (Framingham categories), diabetes, current smoking status, body mass index, and randomized treatment assignment. Abbreviations: Apo A-I, apolipoprotein A-I; Apo B100, apolipoprotein B100; CI, confidence interval; HR, hazard ratio; LDL-C, LDL cholesterol; Non-HDL-C, non-HDL cholesterol; Total Chol, total cholesterol.