SERUM CREATININE CONCENTRATION AND RISK OF CARDIOVASCULAR-DISEASE - APOSSIBLE MARKER FOR INCREASED RISK OF STROKE

Background and Purpose Elevated serum creatinine has been associated w ith increased mortality in hypertensive persons, the elderly, and pati ents with myocardial infarction or stroke in whom cardiovascular disea se is the major cause of death. We have examined the relationship betw een serum creatinine concentration and the risk of major ischemic hear t disease and stroke events and all-cause mortality in a general popul ation of middle-aged men. Methods We present a prospective study of mi ddle-aged men (aged 40 to 59 years) drawn from 24 British towns who ha ve been followed up for an average of 14.75 years. Data on serum creat inine 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. Results The median serum creatinine conce ntration was 98 mu mol/L (95% range, 76 to 129 mu mol/L). Stroke risk was significantly increased at levels above 116 mu mol/L (90th percent ile) even after adjustment for a wide range of cardiovascular risk fac tors (relative risk [RR], 1.6; 95% CI, 1.1 to 2.1; greater than or equ al to 116 mu mol/L versus the rest). Risk of a major ischemic heart di sease event was significantly increased at or above 130 mu mol/L (97.5 percentile), but this was attenuated after adjustment (RR, 1.2; 95% C I, 0.8 to 1.7; greater than or equal to 130 mu mol/L versus the rest). There was a weak but significant positive association between diastol ic blood pressure and creatinine concentration. However, elevated crea tinine concentration (greater than or equal to 116 mu mol/L) was assoc iated with a significant increase in stroke in both normotensive and h ypertensive men. All-cause mortality and overall cardiovascular mortal ity were significantly increased only above the 97.5 percentile, and n o significant association was seen with cancer or other noncardiovascu lar mortality. Conclusions A high serum creatinine concentration withi n the normal range is a marker for increased risk of cerebrovascular d isease in both normotensive and hypertensive subjects. These findings support the evidence indicating that subtle impairment of renal functi on is a factor for increased risk of stroke and suggest mechanisms in the pathogenesis of stroke that warrant further investigation.