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C-reactive protein is a strong but nonspecific risk factor of fatal stroke in elderly persons
J Gussekloo1, M C Schaap, M Frölich
1Section of Gerontology and Geriatrics, Department of General Internal Medicine, Leiden University Medical Center, The Netherlands. JGussekloo@aig.azl.nl
Insights
Elevated C-reactive protein (CRP) predicts fatal strokes in the elderly. However, CRP appears to be a nonspecific marker of inflammation, not a direct cause of vascular damage.
Area of Science:
- Gerontology
- Cardiovascular Disease
- Neurology
Background:
- Elevated C-reactive protein (CRP) is a known predictor of cardiovascular events in older adults.
- The precise role of CRP—whether a direct vascular threat or a marker of systemic inflammation—remains unclear.
Purpose of the Study:
- To investigate the association between baseline CRP levels and the incidence of fatal strokes in elderly individuals.
- To determine if CRP has direct adverse vascular effects contributing to cerebrovascular disease.
Main Methods:
- The Leiden 85-Plus Study, a population-based prospective cohort, analyzed CRP levels in elderly participants.
- Serum CRP was measured at baseline in 80 individuals who died from stroke, 82 survivors, and 83 non-stroke, non-cardiovascular deaths within 5 years.
- Logistic regression adjusted for multiple risk factors was used to estimate mortality risks.
Main Results:
- Individuals who died from stroke had significantly higher baseline CRP levels (median 5.7 mg/L) compared to controls (median 2.7 mg/L).
- Highest CRP levels were associated with a 10-fold increased risk of death from both stroke and non-cardiovascular causes.
- CRP levels were lower when the time between blood sampling and death increased, suggesting a dynamic inflammatory process.
Conclusions:
- C-reactive protein is a potent, albeit nonspecific, risk factor for fatal stroke in the elderly population.
- The study findings do not support a direct causal role for CRP in the pathogenesis of fatal cerebrovascular disease.
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, P<0.005). 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, P=0.7). 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 (P<0.001). The levels of C-reactive protein were lower when more time had elapsed between blood sampling and time of death during follow-up (P=0.01). 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.