Diabetes and microvascular complications predict outcomes in HFpEF

The Prognostic Significance of Diabetes and Microvascular Complications in Patients With Heart Failure With Preserved Ejection Fraction

Literature - Sandesara PB, O’Neal WT, Kelli HM, et al. - Diabetes Care 2017; published online ahead of print


Almost half of patients with heart failure with preserved ejection fraction (HFpEF) also have diabetes mellitus (DM), which is associated with nearly a twofold increase in morbidity and mortality in these patients [1-3]. Diabetes is, however, not a uniform disorder, and the risk of adverse CV outcomes may vary with disease severity (e.g., presence of microvascular complications).

In this analysis of the TOPCAT study [4], the prognostic significance of DM and its microvascular complications was evaluated in 3,385 patients with symptomatic HF and an EF ≥45%. The microvascular complications included neuropathy, nephropathy, and retinopathy, and the study outcome was the composite of CV mortality, aborted cardiac arrest, or HF hospitalization

Main results

  • During a median follow-up of 3.4 years, a total of 1,524 hospitalizations, 437 hospitalizations for HF, 516 deaths, and 330 CV deaths occurred. 1109 Patients (32%) of the patients included in this analysis had diabetes.
  • An increased risk for hospitalization (HR 1.54, 95% CI 1.25, 1.89; P-trend<0.001), HF hospitalization (HR 1.97, 95%CI 1.38, 2.80; P-trend <0.001), death (HR 1.73,
  • 95%CI 1.22, 2.45; P-trend = 0.0017), and CV death (HR 1.70, 95% CI 1.09, 2.65, P-trend = 0.018) was observed in patients with diabetes and microvascular complications as compared with patients without diabetes. Patients with diabetes without microvascular complications also showed a higher risk of these events but to a lesser extent.
  • When the analysis was limited to DM participants who reported prior hospitalization for HF, a higher risk of re-hospitalization for HF was observed in patients with as compared with those without microvascular complications (HR for DM without microvascular complications: 1.40; 95% CI: 1.01 - 1.96; HR for DM plus microvascular complications: 1.78; 95% CI: 1.18 - 2.70; P-trend = 0.0036).
  • In a secondary analysis (model corrected for multiple CV risk factors and medications) limited to persons with DM, a higher risk of hospitalization (with no complications as references: HR: 1.29 for those with 1 complications, HR: 1.57 for those with ≥2 complications, P-trend <0.001), HF hospitalization (HR: 1.20 [non-significant) and HR: 1.63 respectively, P-trend = 0.0063), and death (HR: 1.24 [non-sign) and HR: 1.49 respectively, P-trend = 0.037) was observed with a higher number of microvascular complications.
  • The risk of CV death did not increase with a higher number of microvascular complications (non-significant HR: 1.31 and 1.27 for 1 and ≥2 microvascular complications, respectively, P-trend = 0.45).


In the TOPCAT study, diabetes and its microvascular complications carried important prognostic information regarding adverse outcomes in HFpEF patients. In addition, the microvascular disease burden predicts HF re-hospitalization in this high-risk group. These findings show that additional preventive strategies to reduce morbidity and mortality in HFpEF patients with DM are needed.


1. Mentz RJ, Kelly JP, von Lueder TG, et al. Noncardiac comorbidities in heart failure with reduced versus preserved ejection fraction. J Am Coll Cardiol 2014;64:2281–2293

2. Brownrigg JR, Hughes CO, Burleigh D, et al. Microvascular disease and risk of cardiovascular events among individuals with type 2 diabetes: a population-level cohort study. Lancet Diabetes Endocrinol 2016;4:588–597

3. Kristensen SL, Mogensen UM, Jhund PS, et al. Clinical and echocardiographic characteristics and cardiovascular outcomes according to diabetes status in patients with heart failure and preserved ejection fraction: a report from the Irbesartan in Heart Failure with Preserved Ejection Fraction Trial (I-Preserve). Circulation 2017;135:724–735

4. Desai AS, Lewis EF, Li R, et al. Rationale and design of the treatment of preserved cardiac function heart failure with an aldosterone antagonist trial: a randomized, controlled study of spironolactone in patients with symptomatic heart failure and preserved ejection fraction. Am Heart J 2011; 162:966–972. e910

Find this article online at Diabetes Care

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