Hyperhomocysteinemia and Risk of First Venous Thrombosis: The Influence of (Unmeasured) Confounding Factors

Abstract

Meta-analyses have reported a 2–3 fold increased risk of venous thrombosis (VT) in individuals with hyperhomocysteinemia, however, confounding factors were generally not considered. In contrast, randomized trials of homocysteine-lowering therapy and VT risk were negative. We investigated if hyperhomocysteinemia is associated with VT in the MEGA case-control study (1999–2004) from the Netherlands (1,689 cases and 1,726 controls), taking into account measured and unmeasured confounders. We compared patients with population controls to estimate odds ratios (OR) by unconditional logistic regression and adjusted for various potential confounders. We matched patients to their partners to additionally adjust for unmeasured confounders (e.g., lifestyle factors) using conditional logistic regression. We found that elevated homocysteine concentrations were not associated with an increased risk for VT when comparing patients to population controls, neither as a continuous variable (OR = 1.00, 95% CI:0.99, 1.01), or in terms of 0.7 mg/L increase (OR = 0.99, 95% CI: 0.93, 1.05), or within different homocysteine categories. We obtained similar results when patients were compared with their partners. Stratification by sex, deep vein thrombosis, pulmonary embolism, provoked and unprovoked VT also provided no evidence of an association. In conclusion, after extensive adjustments for confounding, hyperhomocysteinemia was not associated with an increased risk of venous thrombosis in this study.