Relation of coagulation factor XI with incident coronary heart disease and stroke

Abstract

OBJECTIVES The role of coagulation factor XI (FXI) in the etiology of arterial thrombotic events remains uncertain. We examined the association of FXI with incident coronary heart disease (CHD), ischemic stroke (IS), and hemorrhagic stroke (HS). METHODS Data were from 3394 adults (mean age: 74.5 years) enrolled in the Cardiovascular Health Study who had FXI antigen from plasma samples drawn in 1992–1993 and were followed for cardiovascular events until June 30, 2013. RESULTS Approximately 63% of participants were women and 17% were black. FXI levels were higher in blacks and women, showed positive associations with HDL and total cholesterol, body mass index and diabetes, and negative associations with age and alcohol intake. During median follow-up of 13 years, we identified 1232 incident CHD, 473 IS, and 84 HS events. In multivariable Cox models adjusted for traditional CVD risk factors, the hazard ratio per 1 standard deviation (32.2 mg/dl) increment of FXI was 1.02 (95% CI: 0.96–1.08) for CHD; 0.94 (0.85–1.04) for IS and 0.85 (0.65–1.10) for HS. CONCLUSIONS In this prospective cohort of elderly adults, there was no statistically significant association of higher FXI levels with incident CHD and stroke.

Liver-heart cross-talk mediated by coagulation factor XI protects against heart failure

“…Inactivating mutations of F11 are relatively common among Ashkenazi Jews (33). A number of studies investigated the relationship between FXI and incident coronary heart disease, stroke, and ischemic cardiomyopathy (34,35). FXI was reported to improve or protect against the inflammatory responses and cytokine responses to infections independently of its intrinsic coagulation activity (36)(37)(38)(39)(40).…”

Associations of coagulation factor X and XI with incident acute coronary syndrome and stroke: A nested case‐control study

“…Other prospective studies were inconsistent with ours, showing that FXI was not associated with stroke or ischemic stroke in Whites and African Americans. 11 , 15 , 33 However, these prospective studies were all focused on Europeans and Americans, to our knowledge, we first performed the prospective study and found high FXI levels were associated with higher risk of incident stroke and ischemic stroke among Chinese. Thus, the population difference might be a possible explanation for the inconsistency.…”

Coagulation factor with potential for the treatment of heart failure

“… 4 A number of studies revealed the relationship between FXI and stroke, coronary heart disease, and ischemic cardiomyopathy. 5 In addition, the observation that mice with FXI overexpression exhibit other systemic metabolic benefits, including less body fat gain and improved lipid homeostasis, suggests potential effects of FXI beyond the heart. Whether other organs respond to FXI and whether these additional effects are mediated by the BMP7‐SMAD1/5 pathway need further investigation.…”

“…FXI has been found to protect against sepsis in part by enhancing the phagocytic capacity of neutrophils, a mechanism that is independent of activation via FXIIa 4 . A number of studies revealed the relationship between FXI and stroke, coronary heart disease, and ischemic cardiomyopathy 5 . In addition, the observation that mice with FXI overexpression exhibit other systemic metabolic benefits, including less body fat gain and improved lipid homeostasis, suggests potential effects of FXI beyond the heart.…”

“…4 A number of studies revealed the relationship between FXI and stroke, coronary heart disease, and ischemic cardiomyopathy. 5 In addition, the observation that mice with FXI overexpression exhibit Clin. Transl.…”