Elevated levels of vitamin B12 in chronic stable heart failure: a marker for subclinical liver damage and impaired prognosis

BACKGROUND: Elevated vitamin B12 is a sign for liver damage, but its significance in chronic stable heart failure (HF) is less known. The present study investigated the clinical correlates and prognostic significance of vitamin B12 levels in stable systolic HF. METHODS: A total of 129 consecutive patients with HF and 50 control subjects were enrolled. Data regarding demographics, clinical signs, therapeutic and conventional echocardiographic measurements were recorded for all patients. Right-sided HF was defined as the presence of at least one of the typical symptoms (ankle swelling) or specific signs (jugular venous distention or abdominojugular reflux) of right HF. Cox proportional hazards regression analyses were performed to determine the independent prognostic determinants of mortality. RESULTS: Baseline B12 levels in HF patients (n=129) with and without right sided HF were significantly higher compared to healthy controls (n=50): Median 311 pg/mL and 235 pg/mL vs 198 pg/mL, respectively (P=0.005). Folic acid levels were similar between the study groups. Age, ejection fraction, left atrial size, estimated glomerular filtration rate, and direct and indirect bilirubin levels were significantly correlated to serum B12 level in univariate analysis. In multivariate analysis, independent correlates of B12 were direct bilirubin (R=0.51, P<0.001) and age (R=0.19, P=0.028). Patients with HF were followed-up for a median period of 32 months. Median B12 levels were significantly higher in patients who subsequently died (n=35) compared to survivors, but folic acid was not different between the two groups. ROC analysis showed that B12 values ≥270 pg/mL had 80% sensitivity and 58% specificity for predicting all-cause mortality (area under the curve=0.672, 95% CI=0.562−0.781; P=0.003). However, in Cox regression analysis, only left atrial diameter, level of direct bilirubin, and the presence of abdominojugular reflux were independent predictors of death. CONCLUSION: Increased B12 in stable HF patients is associated with increased direct bilirubin due to right HF, indicating a cardiohepatic syndrome, but neither B12 nor folic acid are independently associated with mortality.