High homocysteine linked with frailty and earlier mortality in men

An article published online in The Journals of Gerontology Series A: Biological Sciences and Medical Sciences reveals an association between higher levels of homocysteine and a greater risk of frailty and early death in older men. Homocysteine is a damaging amino acid synthesized in the body from the essential amino acid methionine. High levels of homocysteine have been associated with an increase in cardiovascular events and other conditions. The current study included 4,248 participants in the Health in Men Study, which began enrolling older men living in Australia between 1996 and 1999. One thousand one hundred-seventeen participants had high plasma total homocysteine (tHcy) levels of 15 micromoles per liter or more measured in samples obtained from 2001 to 2004. Six hundred eighty-five subjects were categorized as frail during this time period, as assessed by the Fatigue, Resistance, Ambulation, Illness and Loss of weight (FRAIL) scale. Frailty was reassessed among the participants during 2008-2009. Over an average follow-up period of 5.1 years, 749 deaths occurred. Among subjects who had high homocysteine levels, the adjusted risk of frailty as assessed during 2001-2004 was 49 percent greater than those whose homocysteine was less than 15 micromoles per liter. Having a high level of homocysteine also predicted frailty during the second assessment during 2008-2009, although the adjusted risk was only half of that observed at baseline. High homocysteine was also associated with a 25% increased adjusted risk of dying over follow-up as compared to those with lower homocysteine levels. "The researchers' finding that elevated tHcy predicted all-cause mortality complements and extends those of prior epidemiological studies and suggests that lowering tHcy levels may potentially reduce mortality risk, regardless of the frailty status," Yuen Y. E. Wong and coauthors write. "To address the possibility of reverse causality due to preexisting ill health that might have led to elevated tHcy levels, the researchers repeated the analyses after excluding those men who died within 6 months from baseline. The association with all-cause mortality persisted, suggesting that tHcy might be a risk factor rather than a biomarker of this adverse outcome." "Hyperhomocysteinemia is associated with the prevalence of frailty" they conclude. "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."