Blood soluble Fas levels and mortality from cardiovascular disease in middle-aged Japanese: The JACC study

Background and aims Limited evidence has been available on the relationship between apoptosis and cardiovascular disease in population-based samples. We examined whether blood soluble Fas (sFas) are associated with mortality from cardiovascular diseases. Methods In a nested case-control study under a large prospective cohort, the Japan Collaborative Cohort (JACC) Study, where a total of 39,242 subjects, 40–79 years of age, provided serum samples and were followed up for 9 years, we measured sFas levels among cases and controls, matched for sex, age, area of residence and year of serum storage. Conditional logistic regression models were used to calculate odds ratio (95% CI) of mortality from stroke and stroke types, according to quartiles and 1-SD increment of sFas levels. Results During the follow-up (1988–1997), we identified 233 (121 in men and 112 in women) deaths from total stroke, comprising 49 (18 and 31) subarachnoid hemorrhages, 55 (27 and 28) intraparenchymal hemorrhages, 71 (44 and 27) ischemic strokes, and 97 (53 and 44) coronary heart diseases. After adjustment for cardiovascular risk factors, the multivariable odds ratio (95% CI) of subarachnoid hemorrhage associated with a 1-SD increment of sFas (1.3 ng/ml in both men and women) was 4.04 (1.07–15.3; p = 0.04). No association was found between blood sFas levels and risk of intraparenchymal hemorrhage, ischemic stroke or coronary heart disease. Conclusions Higher blood sFas levels were associated with higher mortality from subarachnoid hemorrhage, suggesting a potential role of apoptosis factors in the development or prognosis of subarachnoid hemorrhage.