Vitamin B6, Inflammation, and Cardiovascular Outcome in a Population-Based Cohort: The Prevention of Renal and Vascular End-Stage Disease (PREVEND) Study

Abstract

Background: a large number of studies have linked vitamin B6 to inflammation and cardiovascular disease in the general population. However, it remains uncertain whether vitamin B6 is associated with cardiovascular outcome independent of inflammation.

Methods: we measured plasma pyridoxal 5'-phosphate (PLP), as an indicator of vitamin B6 status, at baseline in a population-based prospective cohort of 6249 participants of the Prevention of Renal and Vascular End-stage Disease (PREVEND) study who were free of cardiovascular disease. As indicators of low-grade systemic inflammation, we measured high-sensitivity C-reactive protein and GlycA; Results: median plasma PLP was 37.2 (interquartile range, 25.1-57.0) nmol/L. During median follow-up for 8.3 (interquartile range, 7.8-8.9) years, 409 non-fatal and fatal cardiovascular events (composite outcome) occurred. In the overall cohort, log transformed plasma PLP was associated with the composite outcome, independent of adjustment for age, sex, smoking, alcohol consumption, body mass index (BMI), estimated glomerular filtration rate (eGFR), total cholesterol:high-density lipoprotein (HDL)-cholesterol ratio, and blood pressure (adjusted hazard ratio per increment of log plasma PLP, 0.66; 95% confidence interval (CI), 0.47-0.93). However, adjustment for high-sensitivity C-reactive protein and GlycA increased the hazard ratio by 9% and 12% respectively, to non-significant hazard ratios of 0.72 (95% confidence interval, 0.51-1.01) and 0.74 (95% confidence interval, 0.53-1.05). The association of plasma PLP with cardiovascular risk was modified by gender (adjusted P_interaction = 0.04). When stratified according to gender, in women the prospective association with cardiovascular outcome was independent of age, smoking, alcohol consumption, high-sensitivity C-reactive protein, and GlycA (adjusted hazard ratio, 0.50, 95% confidence interval, 0.27-0.94), while it was not in men (adjusted hazard, 0.99, 95% confidence interval, 0.65-1.51).

Conclusions: in this population-based cohort, plasma PLP was associated with cardiovascular outcome, but this association was confounded by traditional risk factors and parameters of inflammation. Notably, the association of low plasma PLP with high risk of adverse cardiovascular outcome was modified by gender, with a stronger and independent association in women.

Keywords: GlycA; cardiovascular; inflammation; pyridoxal 5’-phosphate; vitamin B6.

Figure 1

Unadjusted and fully adjusted continuous associations between plasma pyridoxal 5’-phosphate and cardiovascular outcome. Unadjusted associations for the composite cardiovascular outcome (figure A, P_nonlinearity < 0.001), cardiovascular disease (figure B, P_nonlinearity = 0.002), and cardiovascular mortality (figure C, P_nonlinearity = 0.10) were collectively adjusted for age, sex, smoking, alcohol consumption, BMI, eGFR, albumin excretion, total cholesterol:HDL-cholesterol ratio, systolic and diastolic blood pressure, hs-CRP, and GlycA (figures D–F, respectively). Abbreviations: hs-CRP, high-sensitivity C-reactive protein; BMI, body mass index; HDL, high-density lipoprotein; eGFR, estimated glomerular filtration rate; PLP, pyridoxal 5’-phosphate.

Figure 2

Stratified analyses for potential effect modification of the association between plasma pyridoxal 5’-phosphate and composite cardiovascular outcome. Hazard ratios indicate relative change in risk of composite cardiovascular outcome per increment of log transformed plasma PLP. * Adjusted for age, sex, smoking, and alcohol consumption. For strata according to one of these variables, adjustments were made for the remaining three covariates. ^† Additionally adjusted for hs-CRP and GlycA. Abbreviations: hs-CRP, high-sensitivity C-reactive protein; PLP, pyridoxal 5’-phosphate; BMI, body mass index; SBP, systolic blood pressure; HDL, high-density lipoprotein; eGFR, estimated glomerular filtration rate; CI, confidence interval.