U-shaped relationship between vitamin D levels and long-term outcome in large cohort of survivors of acute myocardial infarction.

BACKGROUND: Previous studies in the setting of patients with acute myocardial infarction (AMI) have demonstrated that hypovitaminosis D is associated with increased mortality risk during a follow-up whose median did not exceed two years. OBJECTIVE: To evaluate the impact of vitamin D levels on long-term mortality in patients with AMI. RESULTS: In our study 477 patients with AMI were included. During a median follow-up period of 57 (IQR 53-64) months, 93 patients (20%) died. A non-linear U-shaped relationship between 25(OH)D levels and long-term mortality was observed; patients with vitamin D<10ng/mL and >30ng/mL had higher mortality rate than those with intermediate values. After adjustment for differences in baseline features and treatment, it was confirmed that extreme values of vitamin D (<10 or >30ng/mL) are independent predictors of mortality with HR of 3.02 (95% CI 1.78-5.11). Other independent predictors of outcome were age, NYHA class at discharge, treatment with ACE inhibitors and statins. The estimated time-dependent ROC curve of the multivariable model including vitamin D showed an AUC significantly higher than the model without vitamin D: AUC 0.82 (95% CI 0.76-0.87) vs. 0.77 (95% CI 0.71-0.83), p=0.005. Addition of vitamin D to the model that included all significant factors for mortality improved the prognostic accuracy as showed by the metrics of reclassification (NRI 0.34 (95% CI 0.14-0.48), p=0.003 and IDI 0.06 (95% CI 0.01-0.12, p=0.005 p=0.03). CONCLUSIONS: We report a U-shaped relationship between vitamin D levels and long-term outcome of patients surviving AMI.

Factor-V HR2 haplotype and thromboembolic disease.

OBJECTIVES: The objective of this study is to evaluate the prevalence of HR2 polymorphism among patients with pulmonary embolism (PE) and healthy subjects. BACKGROUND: Polymorphism in the factor V gene named HR2 has been described as a possible risk factor for venous thromboembolism (VTE) development. Contradictive results on this association have been reported. METHODS: Eighty-five patients admitted for PE and 72 healthy subjects were included in the study. Thrombophilia screening using genetic tests for factor V Leiden (G1691A/Leiden and HR2 haplotype) and other genetic mutations were investigated. RESULTS: Of 85 patients with PE, 20 (23.53%) carried the HR2 haplotype. Further, a majority of the patients with HR2 haplotype had recurrent venous thrombosis or PE (15 out of 20 patients). The HR2 haplotype was detected in 6 (8.3%) out of 72 healthy subjects. Patients had significantly higher HR2 haplotype frequency than healthy controls (P = 0.001). HR2 carriers had a three-fold increase in risk of developing PE (OR = 3.38, 95% CI = 1.27-8.96, P = 0.011). After adjustment for other tested defects for thrombophilia, HR2 haplotype was associated with increased risk of thromboembolic events (OR = 3.05, 95% CI = 1.11-8.35, P = 0.03). However, after adjustment for sex and age, HR2 polymorphism was no longer associated with the risk of thromboembolic event (OR = 1.22, 95% CI = 0.34-4.38, P = 0.76). CONCLUSIONS: Our study does not support the notion that factor V HR2 haplotype might be a risk factor for thrombosis despite its high prevalence among patients with PE.