Plasma concentrations of folate and vitamin B12 and risk of fatal and non-fatal cardiovascular disease: a nested case-control study nested in a population-based cohort

Purpose: Despite plausible biological mechanisms, epidemiological evidence on the link between folate and vitamin B12 and cardiovascular risk remains inconsistent. We investigate the relationship between plasma concentration of folate and vitamin B12 and the risk of fatal and non-fatal cardiovascular disease (CVD). Methods: The data come from the Health, Alcohol and Psychosocial factors In Eastern Europe (HAPIEE) prospective cohorts based in Krakow (Poland), Kaunas (Lithuania) and 6 Czech towns that followed up random population samples of men and women aged 45-69 since baseline in 2002-06. After median follow up of 6.5 years, all 495 incident cases of CVD (including 198 deaths) and 4,884 controls sampled from disease free subjects were included in a nested casecontrol study. Plasma concentrations of folate and vitamin B12 were analysed in a central laboratory. Odds ratios (OR) of fatal and non-fatal CVD by cohort-specific quartiles of plasma concentrations were estimated by logistic regression models controlling for potential confounders (age, sex, cohort, smoking, education and material deprivation). Since results were consistent across study centres, results of pooled analyses are presented. Results: After adjustment for covariates, folate concentrations were inversely associated with mortality from all causes (OR for highest vs. lowest quartile 0.78, 95% CI 0.65-0.93 (p-value for trend by quartile 0.009). For CVD, the association was similar for non-fatal (OR for highest vs. lowest quartile 0.69, 95% CI 0.53- 0.90, p for trend 0.005) and fatal CVD (OR 0.72, 95%CI 0.55-0.94, p-for trend 0.022). For the combined fatal and non-fatal CVD, the ORs quartiles 2, 3 4 vs. quartile 1 were 0.79 (0.65-0.95), 0.76 (0.62-0.92) and 0.70 (0.57-0.86), respectively, p for trend <0.001. Adjustment for further covariates did not change the results. We found no association of vitamin B12 with total mortality or with fatal or non-...