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 µmol/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.