Homocysteine, Frailty, and All-Cause Mortality in Older Men: The Health in Men Study

Background. Frailty and hyperhomocysteinemia are common in the older population. The researchers' objectives were to determine whether elevated homocysteine (tHcy) is associated with frailty and mortality. Methods. The researchers conducted a prospective cohort study. tHcy was measured by immunoassay in 4,248 community-dwelling men aged 70-88 years. Frailty was assessed with the Fatigue, Resistance, Ambulation, Illness and Loss of weight (FRAIL) scale. Mortality was determined from the death registry. Results. At baseline, 1,117 men (26.3%) had high tHcy (>= 15 mu mol/L) and 685 (16.2%) were frail (ie, having three or more deficits in the FRAIL scale). There were 749 deaths during a follow-up duration of 5.1 +/- 1.3 years. In cross-sectional analysis, high tHcy was associated with increased prevalent frailty (odds ratio 1.49, 95% CI 1.22-1.81) after adjusting for confounding factors. After a period of 5.3 +/- 0.8 years, the longitudinal relationship between high tHcy and frailty was weakened in multivariate analysis (hazards ratio 1.25, 95% CI 0.95-1.65). When assessing the relationship between tHcy and incident frailty, the odds of being frail at follow-up for men with high tHcy and having zero deficit at baseline (ie, FRAIL scale = 0) were 1.59 (95% CI 0.88-2.89) in adjusted analysis. High tHcy also predicted all-cause mortality (hazards ratio 1.25, 95% CI 1.06-1.48) after adjusting for frailty and other covariates. Conclusions. Hyperhomocysteinemia is associated with the prevalence of frailty. It is also predictive of all-cause mortality, independent of frailty. The results suggest that the association between tHcy and mortality is largely not mediated through the occurrence of frailty.