Nonlinear associations of serum cobalamin with risk of all-cause and cardiovascular mortality in hypertensive adults

Our study aims to evaluate the associations between the serum cobalamin (vitamin B12) and related biomarkers with mortality in hypertensive adults. Data on serum cobalamin from the National Health and Nutrition Examination Survey (NHANES) 1999–2006 and 2011–2014 were included. Mortality status was linked to National Death Index mortality data through 31 December, 2019. Cox regression and restricted cubic spline (RCS) analyses were used to determine the hazard ratios (HRs) and 95% CIs for mortality risk. A total of 9934 hypertensive adults were included in the analysis (mean age, 58.1 ± 17.5 years; 4899 [49.3%] men). At 11.0 years of mean follow-up, 935 cardiovascular deaths and 3096 all-cause deaths were identified. Compared to the third quartiles, the first and fourth quartiles of serum cobalamin were associated with risk of cardiovascular mortality, with multivariable-adjusted HRs of 1.26 (1.05–1.53) and 1.40 (1.17–1.68). Similar results were observed in the relationship between serum cobalamin and all-cause mortality. These results were supported by the RCS analysis. The inflection points for the nonlinear associations of serum cobalamin with cardiovascular and all-cause mortality were 649.9 pg/mL and 577.2 pg/mL, respectively. In addition, compared with the second quartile of circulating methylmalonic acid (MMA, a cobalamin-deficiency marker), this association with the fourth quartile was evident for an increased rate of cardiovascular and all-cause mortality, with 111% (HR = 2.11, 1.71–2.61) and 73% (HR = 1.73, 1.55–1.93) increase. Findings suggest that both lower and higher serum cobalamin concentrations were associated with a higher risk of cardiovascular and all-cause mortality in hypertensive adults.