Glycemic Markers and Heart Failure Subtypes: The Multi-Ethnic Study of Atherosclerosis (MESA)


      • Glycemic dysregulation and its markers are precursors of heart failure (HF) .
      • Diabetes, fasting glucose, and hemoglobin A1c were similarly associated with high risks of both HF subtypes.
      • Greater insulin resistance and hyperinsulinemia were not significantly associated with either HF subtype.



      Although diabetes increases heart failure (HF) risk, it is unclear how various dysglycemia markers (hemoglobin A1C [HbA1C], fasting plasma glucose [FPG], homeostasis model assessment of insulin resistance, and fasting insulin) are associated with HF subtypes (HF with preserved ejection fraction [HFpEF] and HF with reduced ejection fraction [HFrEF]). We assessed the relation of markers of dysglycemia and risks of HFpEF and HFrEF.

      Methods and Results

      We included 6688 adults without prevalent cardiovascular disease who attended the first MESA visit (2000–2002) and were followed for incident hospitalized HF (HFpEF or HFrEF). Association of glycemic markers and status (normoglycemia, prediabetes, diabetes) with HFpEF and HFrEF were evaluated using adjusted Cox models. Over a median follow-up of 14.9 years, there were 356 HF events (145 HFpEF, 173 HFrEF, and 38 indeterminate HF events). Diabetes status conferred higher risks of HFpEF (hazard ratio [HR] 1.85, 95% confidence interval [CI] 1.57–2.68) and HFrEF (HR 2.02, 95% CI 1.38–2.97) compared with normoglycemia. Higher levels of FPG (126 mg/dL) and HbA1C (≥6.5%) were associated with similarly higher risks of HFpEF (HR for FPG 1.96, 95% CI 1.21–3.17; HR for HbA1C 2.00, 95% CI 1.20–3.31) and HFrEF (HR for FPG 1.84, 95% CI 1.18–2.88; HR for HbA1C 1.99, 95% CI 1.28–3.09) compared with reference values. Prediabetic range HbA1C (5.7%–6.4%) or FPG (100%–125 mg/dL), homeostasis model assessment of insulin resistance, and fasting insulin were not significantly associated with HFpEF or HFrEF.


      Among community-dwelling individuals, HbA1C and FPG in the diabetes range were each associated with higher risks of HFpEF and HFrEF, with similar magnitudes of their associations.

      Lay Abstract

      Heart failure (HF) has 2 major subtypes (the heart's inability to pump or to fill up). Diabetes is known to increase HF risk, but its effects and that of markers of high glucose levels (fasting blood glucose and hemoglobin A1C) on the occurrence of HF subtypes remains unknown. Among 6688 adults without known cardiovascular disease followed for nearly 15 years, diabetes conferred significantly higher risks of both HF types, compared with those with normal blood glucose levels. Higher levels of fasting blood glucose and hemoglobin A1C were similarly associated with higher risks of both types of HF.

      Key Words

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