Homocysteine, frailty, and all-cause mortality in older men: the health in men study

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Background. Frailty and hyperhomocysteinemia are common in the older population. The researchers’ objectiveswere 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 Lossof 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 atbaseline (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.
Original languageEnglish
Pages (from-to)590-598
JournalJournals Of Gerontology Series A-Biological Sciences And Medical Sciences
Issue number5
Early online date15 Oct 2012
Publication statusPublished - 5 May 2013


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