Serum creatinine concentration and risk of cardiovascular disease: a possible marker for increased risk of stroke.

Elevated serum creatinine has been associated with increased mortality in hypertensive persons, the elderly, and patients with myocardial infarction or stroke in whom cardiovascular disease is the major cause of death. We have examined the relationship between serum creatinine concentration and the risk of major ischemic heart disease and stroke events and all-cause mortality in a general population of middle-aged men. We present a prospective study of middle-aged men (aged 40 to 59 years) drawn from 24 British towns who have been followed up for an average of 14.75 years. Data on serum creatinine were available for 7690 men in whom there were 287 major stroke events, 967 major ischemic heart disease events, and 1259 deaths from all causes during follow-up. The median serum creatinine concentration was 98 micromol/L (95% range, 76 to 129 micromol/L). Stroke risk was significantly increased at levels above 116 micromol/L (90th percentile) even after adjustment for a wide range of cardiovascular risk factors (relative risk [RR], 1.6; 95% CI, 1.1 to 2.1; > 116 micromol/L versus the rest). Risk of a major ischemic heart disease event was significantly increased at or above 130 micromol/L (97.5 percentile), but this was attenuated after adjustment (RR, 1.2; 95% CI, 0.8 to 1.7; > or = 130 micromol/L versus the rest). There was a weak but significant positive association between diastolic blood pressure and creatinine concentration. However, elevated creatinine concentration (> or = 116 micromol/L) was associated with a significant increase in stroke in both normotensive and hypertensive men. All-cause mortality and overall cardiovascular mortality were significantly increased only above the 97.5 percentile, and no significant association was seen with cancer or other noncardiovascular mortality. A high serum creatinine concentration within the normal range is a marker for increased risk of cerebrovascular disease in both normotensive and hypertensive subjects. These findings support the evidence indicating that subtle impairment of renal function is a factor for increased risk of stroke and suggest mechanisms in the pathogenesis of stroke that warrant further investigation.