Plasma C-Reactive Protein, Systolic Hypertension and Risk of Ischemic Stroke and TIA: The Framingham Study
Background: The role of plasma C-reactive protein (CRP) as marker of cerebrovascular risk is currently under investigation. We evaluated relative risk of developing first ischemic stroke and TIA among the patients with elevated systolic blood pressure (SBP) and/or elevated plasma CRP levels versus those patients with unelevated SBP and unelevated CRP. Methods: We studied 591 men and 868 women of the original Framingham Study cohort who were free of stroke and TIA at the time of their 1980–1982 clinic exam. Sex-specific Cox proportional hazards regressions were used to quantify the risk of 14-year incidence of ischemic stroke/TIA associated with elevated SBP and CRP. Unadjusted models and models adjusted for age, smoking, total & HDL cholesterol, and diabetes were used. SBP and CRP were included in the Cox models as sex-specific quartiles. Risk ratios of first ischemic stroke/TIA for individuals with elevated (in the upper quartile) SBP (SBP+) and CRP (CRP+) were determined using the SBP-/CRP- individuals as a reference group. Similarly, simultaneous evaluation of the risk of first ischemic stroke/TIA was done for SBP+/CRP- and SBP-/CRP+ using the individuals in SBP-/CRP- as a reference group. Results: Relative to SBP-/CRP- men (incidence of first ischemic stroke/TIA of 36/328, or 11.0%), SBP+/CRP+ men (where incidence was 8/32, or 25.0%) had unadjusted risk ratio of 3.56 (p=0.001). This ratio was nearly twice that for SBP+/CRP- men (incidence=20/115, or 17.4%; RR=1.89, p=0.023). Relative to SBP-/CRP- women (incidence= 45/485, or 9.3%), the unadjusted risk ratio increased from 2.03 in SBP+/CRP- women (incidence=27/166, or 16.3%; p=0.001) to 3.44 in SBP+/CRP+ women (incidence=15/58, or 25.9%; p<0.001). Adjustment for age did not significantly alter this relationship. Following multivariate adjustment, risk of developing first ischemic stroke/TIA remained significantly elevated in SBP+/CRP+ men (RR=2.7; p=0.018) and women (RR=2.06; p=0.027). Conclusion: Having both CRP levels and systolic BP above the 75th percentile for each of these parameters significantly increased risk of developing first ischemic stroke/TIA in both sexes.