Inflammatory biomarkers, statins, and the risk of stroke: cracking a clinical conundrum.

Abstract

A central paradox of the cholesterol hypothesis is that long-term treatment with statins reduces the risk of stroke, yet LDL cholesterol is not a strong risk factor for stroke. In almost all major prospective epidemiological studies, relationships between any measure of cholesterol and the risk of incident stroke are minimal. Nonetheless, as clearly demonstrated in large-scale randomized trials,1–3⇓⇓ therapy with HMG-CoA reductase inhibitors reduces stroke risk by as much as 25%, a reduction similar to that for myocardial infarction and cardiovascular death. See p 2632 Early recognition of this apparent paradox played a major role in spurring research into nonlipid effects of statin therapy and the search for inflammatory biomarkers that might be strong determinants of stroke. In this regard, data for C-reactive protein (CRP) have been particularly informative. Not only has CRP been shown in several studies to predict incident stroke independent of LDL cholesterol,4–8⇓⇓⇓⇓ but statins have been shown to reduce CRP in an LDL-independent fashion.9–11⇓⇓ Moreover, differences between cholesterol and CRP in terms of predictive value provide considerable insight into the paradox facing the epidemiology of stroke. In the Physicians’ Health Study of healthy middle-aged men and in the Women’s Health Study of healthy postmenopausal women, total cholesterol and CRP both predict incident myocardial infarction, yet only CRP predicts incident stroke.4,5⇓ Almost identical data regarding CRP and thromboembolic stroke have now been presented in cross-sectional data from the National Health And Nutrition Examination Survey (NHANES)7 as well as in two prospective cohorts, the Leiden 85-Plus Study6 and the Framingham Heart Study.8 In Framingham, for example, baseline CRP proved to be a strong linear predictor of incident stroke even after adjustment for other atherothrombotic risk factors, data that confirm the utility of …