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) intra-parenchymal 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.(C) 2017 Published by Elsevier Ireland Ltd.