Hyperhomocysteinemia and low B vitamin levels are independently associated with venous thromboembolism: results from the EDITH study: a hospital‐based case–control study

Abstract

Summary. Background: Moderate hyperhomocysteinemia and B vitamins deficiency are thought to be risk factors for venous thromboembolism (VTE). The causality and independence of those associations are still questioned. Methods: We measured fasting serum total homocysteine, folates, and vitamin B12 levels as well as 5,10‐methylenetetrahydrofolate reductase (MTHFR) C677T genotypes in 467 patients hospitalized with a first well‐documented deep vein thrombosis and/or pulmonary embolism not related to a major acquired risk factor and 467 controls matched for gender and age. Results: Mild hyperhomocysteinemia, low serum folates, and vitamin B12 were associated with VTE independently of each other. In multivariate analysis, odds ratios (OR) (95% CI) for VTE associated with mild hyperhomocysteinemia (>15 μmol L−1), low serum folates (≤ 4.9 nmol L−1), and vitamin B12 (≤ 253 pmol L−1) were 1.48 (1.05–2.08), 3.14 (1.35–7.32) and 1.42 (1.03–1.98), respectively. An MTHFRC677T genotype was not significantly associated with VTE; OR (95% CI): 1.13 (0.70–1.81) Conclusions: The current data provides further knowledge in the complex relationship between hyperhomocysteinemia, low vitamin levels, and VTE.

Low vitamin B6 levels and the risk of recurrent venous thromboembolism

“…This level favorably compares with the results of our previous case-control study which found an association between PLP <21.7 nmol/L and an increased risk of first venous thrombosis. 8 Compared with patients with PLP ≥68.1 nmol/L, recurrence risk was almost twice as high among patients with PLP ≤23.3 nmol/L, and increase was independent of potential confounders including hyperhomocysteinemia (RR 1.72, 95% CI 1.00-3.00). Levels of vitamin B12 and folate were not measured and, therefore, the …”

“…However, in our previous study, levels of folate, vitamin B12 and B6 were measured, and a homocysteine-independent association with the risk of first DVT was only found for low vitamin B6. 8 Cumulative probability of recurrent VTE after four years was 22.3% (95% CI, 13.5%-31.1%) among patients with PLP ≤23.3 nmol/L and 14.4% (95% CI 11.5%-17.4%) among patients with higher levels (p=0.02, Figure 1). After adjustment for confounders including tHcy, RR of recurrence was 1.78 (95% CI 1.01-3.14) among patients with PLP ≤23.3 nmol/L compared with patients with higher levels.…”

“…7 In a case-control study, mild hyperhomocysteinemia, low folate and low vitamin B12 levels were independently associated with an increased risk of VTE. 8 In a case-control study, we found no significant increase in risk of first VTE in patients with low vitamin B12 or folate levels. 9 However, levels of pyridoxal-5´-phosphate (PLP), the coenzyme form of vitamin B6, < 21.7 nmol/L gave a two-fold higher thrombotic risk.…”

Antiplatelet drugs and risk of venous thromboembolism: results from the EDITH case-control study

“…5 Briefly, all patients ≥18 years hospitalized with a well-documented symptomatic VTE, were eligible for enrolment. For this report, we retained only outpatients, i.e.…”

A Case of Massive Pulmonary Embolism Due to Diabetic Ketoacidosis and Hyperhomocysteinemia

“…In the study conducted by Oger et al (10), vitamin B12 deficiency was stated to be a risk factor for venous thromboembolism. In our patient, the increased level of homocysteine appeared to be associated with B12 deficiency.…”