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.
Subject(s)
Cardiovascular Diseases/epidemiology , Nutritional Status , Vitamin B 6 Deficiency/complications , Vitamin B 6/blood , Adult , Aged , C-Reactive Protein/analysis , Cardiovascular Diseases/etiology , Cardiovascular Diseases/prevention & control , Female , Glycoproteins/blood , Heart Disease Risk Factors , Humans , Inflammation , Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/etiology , Kidney Failure, Chronic/prevention & control , Male , Middle Aged , Proportional Hazards Models , Prospective Studies , Pyridoxal Phosphate/blood , Sex Factors , Vitamin B 6 Deficiency/bloodABSTRACT
BACKGROUND: We aimed to compare the associations of smoking exposure as assessed by self-reports and urine cotinine with cardiovascular disease (CVD) risk and determine the potential utility of cotinine for CVD risk prediction. METHODS AND RESULTS: Smoking status by self-reports and urine cotinine were assessed at baseline in 4737 participants (mean age, 53 years) of the PREVEND (Prevention of Renal and Vascular End-Stage Disease) prospective study. Participants were classified as never, former, light current (≤10 cigarettes/day), and heavy current smokers (>10 cigarettes/day) according to self-reports and analogous cutoffs for urine cotinine. During a median follow-up of 8.5 years, 296 first CVD events were recorded. Compared with self-reported never smokers, the hazard ratios (95% confidence interval) of CVD for former, light current, and heavy current smokers were 0.86 (0.64-1.17), 1.28 (0.83-1.97), and 1.80 (1.27-2.57) in multivariate analysis. Compared with urine cotinine-assessed never smokers, the corresponding hazard ratios of CVD for urine cotinine-assessed former, light current, and heavy current smokers were 1.70 (1.03-2.81), 1.62 (1.15-2.28), and 1.95 (1.39-2.73) respectively. The C-index change on adding urine cotinine-assessed smoking status to a standard CVD risk prediction model (without self-reported smoking status) was 0.0098 (0.0031-0.0164; P=0.004). The corresponding C-index change for self-reported smoking status was 0.0111 (0.0042-0.0179; P=0.002). CONCLUSIONS: Smoking status as assessed by self-reports and urine cotinine is associated with CVD risk; however, the nature of the association of urine cotinine with CVD is consistent with a dose-response relationship. The ability of urine cotinine to improve CVD risk assessment is similar to that of self-reported smoking status.
