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 Pinteraction = 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.

Association of Serum Vitamin B6 with All-Cause and Cause-Specific Mortality in a Prospective Study

“…It was estimated that low circulating concentrations of PLP were common in renal disease patients [ 27 ]. A low PLP concentration and renal disease could both increase the risk for CVD [ 8 , 28 ]. Another study found that renal transplant recipients deficient in vitamin B6 had a worse functional vitamin B6 status than healthy people and renal transplant recipients sufficient in vitamin B6 [ 20 ].…”

“…It is involved in many enzyme activities as a cofactor, including molecule synthesis, interconversion, and degradation [ 5 ]. Researchers have found that suboptimal levels of vitamin B6 were associated with increased risk of chronic diseases such as diabetes [ 6 ], cancer [ 7 ], and cardiovascular disease (CVD) [ 8 ].…”

Association of Plasma Vitamin B6 With Coronary Heart Disease in Patients Undergoing Diagnostic Coronary Angiography: New Insight on Sex Differences

“…Dierkes et al ( 23 ) conducted a nested case-cohort study based on 26,761 participants aged 35–65 years at baseline and found that the association between plasma PLP and CHD was abolished after adjusting for inflammation and smoking. Minovi et al ( 24 ) used data from 6,249 participants and found that the plasma PLP-cardiovascular outcomes association was confounded by traditional risk factors and inflammation. These conflicting results might be attributed to differences in study design, sample size, populations, PLP level, and adjustment of confounders.…”

“…Two previous population-based cohort studies analyzed the association between vitamin B6 and CVD with a particular attention to sex differences and yielded conflicting results. Minov et al ( 24 ) found that the association of plasma PLP with risk of cardiovascular outcomes was stronger in women compared to men. In contrast, a prospective cohort study enrolling 9,142 Korean participants aged 40–69 years found that higher intake of B6 could reduced CVD risk in men, but not in women ( 25 ).…”

“…However, several reports failed to identify an association between plasma PLP and risk of CHD. Dierkes et al (23) conducted a nested casecohort study based on 26,761 participants aged 35-65 years at baseline and found that the association between plasma PLP and CHD was abolished after adjusting for inflammation and smoking. Minovi et al ( 24) used data from 6,249 participants and found that the plasma PLP-cardiovascular outcomes association was confounded by traditional risk factors and inflammation.…”