C-Reactive Protein Is a Strong but Nonspecific Risk Factor of Fatal Stroke in Elderly Persons

Abstract

Abstract-An elevated level of C-reactive protein is a strong predictor of cardiovascular events in elderly persons. Whether C-reactive protein has direct adverse vascular effects or is a marker of aspecific systemic inflammation remains to be determined. The aim of this study was to investigate the relation between C-reactive protein and the occurrence of fatal strokes in elderly persons. In the Leiden 85-Plus Study, a population-based prospective follow-up study, we studied the levels of C-reactive protein in 80 participants who died from stroke within the first 5 years of follow-up. Levels of C-reactive protein were determined in serum samples at baseline. Levels of C-reactive protein were also determined in 82 control subjects who survived for the first 5 years of follow-up and in 83 participants who died from noncardiovascular causes. Mortality risks were estimated with logistic regression and adjusted for differences in age, sex, smoking, medication, total cholesterol, history of diabetes or hypertension, and previous cardiovascular events. Levels of C-reactive protein at baseline were 2-fold higher in subjects who died from stroke than in control subjects (median 5.7 versus 2.7 mg/L, PϽ0.005). The levels of C-reactive protein in subjects who died from stroke or from noncardiovascular causes were similar (median 5.7 versus 4.9 mg/L, Pϭ0.7). The risk of death from stroke as well as from noncardiovascular causes increased linearly up to 10-fold in subjects with the highest levels of C-reactive protein at baseline (PϽ0.001). The levels of C-reactive protein were lower when more time had elapsed between blood sampling and time of death during follow-up (P‫.)10.0؍‬ C-reactive protein is a strong but nonspecific risk factor of fatal stroke in old persons. The data do not support the idea that C-reactive protein has direct vascular effects that underlie fatal cerebrovascular disease.

C-Reactive Protein, Carotid Intima-Media Thickness, and Incidence of Ischemic Stroke in the Elderly

“…To the best of our knowledge, this is the first prospective study to explore the joint associations of CRP and carotid IMT in incidence of ischemic stroke, although a case-control study published by CHS investigators demonstrated the interrelation of subclinical atherosclerosis and CRP in relation to coronary artery disease. 17 We confirmed prior observations that higher CRP is associated with future stroke [1][2][3][4] and extended prior findings to examine the independent roles of CRP and carotid atherosclerosis in relation to ischemic stroke. An independent association of CRP from carotid IMT in the risk of stroke suggests a hypothesis of an additional pathophysiological role for CRP to that of measurable atherosclerosis in relation to stroke.…”

“…[1][2][3][4] Higher CRP is also associated with higher IMT, 5,6 although this has not been confirmed in all studies. 7,8 It is not clear whether CRP and carotid IMT each play an independent role in the pathogenesis of stroke.…”

Inflammatory Biomarkers, Statins, and the Risk 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 Study 6 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 CRP as an adjunct in the global prediction of cardiovascular risk.…”

Immuno-inflammatory and thrombotic/fibrinolytic variables associated with acute ischemic stroke diagnosis

“…Accumulating evidence suggests that inflammation plays an important role in the development of cardiovascular and cerebrovascular disease [1,2]. Over the past few years has been stressed the role of inflammation in the pathophysiology of acute brain ischemia and how most inflammatory events are mediated by cytokines, small glycoproteins expressed by many cell types in response to acute cerebral ischemia [3,4].…”