Association Between Elevated Total Homocysteine and Heart Failure Risk in the Multi-Ethnic Study of Atherosclerosis Cohort

BACKGROUND: Limited studies show an association between elevated total homocysteine (tHcy) and heart failure (HF) risk, but no studies have assessed whether this association differs by HF subtype. This study examines the relationship between tHcy, HF overall, and HF subtype (HF with preserved ejection fraction [HFpEF] and HF with reduced ejection fraction) in the Multi-Ethnic Study of Atherosclerosis cohort. METHODS: Multi-Ethnic Study of Atherosclerosis participants with baseline tHcy and HF data were included (N=6765). Cox proportional hazards regression was used to calculate hazard ratios and 95% CI for tHcy and risk of HF. Models were stratified by impaired fasting glucose/type 2 diabetes status, and the combined impact of elevated tHcy and impaired fasting glucose/ type 2 diabetes on HF incidence was examined. RESULTS: Elevated tHcy (>12 μmol/L) was statistically significantly associated with HF overall and HFpEF, and conferred a higher risk for HF overall among individuals with dysglycemia impaired fasting glucose/type 2 diabetes compared with those with normoglycemia. Additionally, there was a statistically significant increased risk of HF overall and HF with reduced ejection fraction and a trend towards increased risk of HFpEF in individuals with both elevated tHcy and dysglycemia. tHcy appears to be a more significant contributor to HFpEF risk than dysglycemia, whereas dysglycemia seems to be more important in driving HF with reduced ejection fraction risk. CONCLUSIONS: Our study confirms an association between hyperhomocysteinemia and HF risk in a large, multi-ethnic cohort. This is the first study to demonstrate that the impact of tHcy differs by HF subtype and appears to contribute more to HFpEF risk than HF with reduced ejection fraction risk.