FADD (Fas-Associated Protein With Death Domain), Caspase-3, and Caspase-8 and Incidence of Ischemic Stroke

Background and Purpose Apoptosis has been implicated in atherosclerosis and plaque rupture. This population-based study examined the relationship between 3 markers of apoptosis, that is, FADD (Fas-associated protein with death domain), caspase-3, and caspase-8, and incidence of ischemic stroke. Methods-The study population included 4356 participants from the MDCS (Malmo Diet and Cancer Study) cardiovascular cohort, without a history of stroke. Incidence of ischemic stroke was followed by linkages to local and national registers. Cox proportional hazards regression was used to assess the incidence of ischemic stroke in relation to quartiles of FADD, caspase-3, and caspase-8, adjusted for potential confounders. Results-During a mean follow-up period of 19.5 +/- 4.9 years, a total of 321 (7.4%) participants were diagnosed with incident ischemic stroke. Individuals with high levels of FADD and caspase-8 had a significantly increased risk of ischemic stroke, after adjustment for potential confounders. The multivariable-adjusted hazard ratios for Q4 versus Q1-Q3 of FADD and caspase-8 were 1.49 (95% CI, 1.18-1.87; P<0.01) and 1.77 (95% CI, 1.41-2.22; P<0.001), respectively. The hazard ratios per 1-SD increment of FADD and caspase-8 were 1.27 (95% CI, 1.14-1.41) and 1.31 (95% CI, 1.18-1.45), respectively. No association was observed for caspase-3 with ischemic stroke. Conclusions-Elevated levels of FADD and caspase-8, but not caspase-3, are associated with increased incidence of ischemic stroke.