Delaying onset of diabetes and targeting patients with longer diabetes with cardioprotective therapies may lower risk of HF

A longer duration of diabetes is associated with greater risk of heart failure (HF), independent of age, coronary heart disease, and other coexisting risk factors, according to a recent analysis of data from the Atherosclerosis Risk in Communities (ARIC) study, published in JACC: Heart Failure.

Researchers stressed the importance of these results for both clinical practice and public health: Delaying onset of diabetes and targeting cardioprotective therapies at patients with longer diabetes may lower the risk of HF.

To assess any possible associations between the duration of diabetes and incident HF, Justin B. Echouffo-Tcheugui, MD, PHD, of Johns Hopkins University School of Medicine, Baltimore, and colleagues conducted this analysis of the ARIC study.

“Type 2 diabetes and heart failure (HF) are important and common concurrent conditions. Community-based studies have shown that diabetes is a potent risk factor for HF, raising the risk by 2- to 4-fold. However, there is a paucity of data on the link between diabetes duration and incident HF,” they wrote.

“Although diabetes is also strongly associated with the development of atherosclerotic cardiovascular disease, the multitude of data suggesting independent effects of diabetes on the myocardium indicate that any association between diabetes duration and incident HF will be independent of intervening ischemic events. Knowledge of the independent effect of diabetes duration on the incidence of HF can also help guide a more effective identification of high-risk diabetic patients who may benefit from more aggressive initiation of cardioprotective preventative therapies, especially in the context of emerging novel therapies such as sodium-glucose cotransporter-2 (SGLT2) inhibitors,” added Echouffo-Tcheugui and fellow researchers.

For their analysis, they included 9,734 subjects (mean age: 63 years; 58% women; 22% Black) from Visit 4 (1996-1998) of the ARIC study, with incident HF defined as the first hospitalization or death related to HF occurring after Visit 4.

In all, 19% of patients had a diagnosis of diabetes by Visit 4. Those with the longest diabetes duration were older, more likely to be Black, had lower diastolic blood pressures and lower estimated glomerular filtration rates (eGFR), weremore likely to develop coronary heart disease during follow-up, and had worse cardiometabolic profiles compared with patients without diabetes.

Over a median follow-up of 22.5 years, 1,968 HF events occurred, comprised of 617 HF with preserved ejection fraction (HFpEF), 495 HF with reduced ejection fraction (HFrEF), and 876 unclassified HF events.

In patients with longer diabetes duration, the risk of HF increased compared to those without diabetes. The highest risk was seen in patients with a diabetes duration of 15 years or more (HR: 2.82; 95% CI: 2.24-3.63), with an HF incidence rate that was 4-fold higher in those with a diabetes duration of greater than or equal to 15 years compared to those without diabetes.

Each 5-year increase in the duration of diabetes was associated with a 17% relative increase in the risk of HF, and results were similar across all HF subtypes. The increases in HF risk across categories of longer diabetes duration were progressive:

  • 0 to ˂5 years: HR: 1.29; 95% CI: 1.10-1.51.
  • 5 years to ˂10 years: HR: 1.97; 95% CI: 1.68-2.30.
  • 10 years to ˂15 years: HR: 2.10; 955 CI: 1.57-2.80.
  • ≥15 years: HR: 2.82; 95% CI: 2.22-3.63.

Researchers also found that prediabetes was associated with an increased risk of HF (HR: 1.22; 95% CI: 1.08-1.37). In addition, the following factors were associated with stronger associations between diabetes duration and HF (all P interactions ˂0.05):

  • Age >65 years.
  • HbA1c ≥7%.
  • Body mass index ≥30 kg/m2.
  • Female sex.
  • Black.

In conclusion, stressed Echouffo-Tcheugui and colleagues, these findings offer myriad implications for the management of patients with diabetes, for both patients and clinicians.

“First, our observations suggest the potential prognostic relevance of diabetes duration in assessing HF. Although some diabetes-specific risk algorithms like the UKPDS (United Kingdom Prospective Diabetes Study) risk prediction tools have included the duration of diabetes in the prediction of atherosclerotic cardiovascular disease (coronary heart disease and stroke), this metric has not yet been taken into account in HF prediction algorithms. Additionally, the integration of the duration of diabetes in HF risk estimation among people with diabetes could help refine the selection of high-risk individuals who may derive the greatest absolute benefits from aggressive cardioprotective preventative therapies, especially novel therapies such as SGLT2 inhibitors,” they stressed.

“Our observations also suggest that delaying the onset of diabetes with the consequential shortening in diabetes duration, using strategies similar to those implemented in the U.S. Diabetes Prevention Program, may also prevent the onset of HF,” they concluded.

Study limitations include the inconsistent use of HbA1c measures in diagnosing diabetes at all study visits, the underestimation of the duration of diabetes in patients diagnosed after Visit 1, the use of self-reported diabetes diagnosis date, survival bias, and the exclusion of outpatient HF cases.

  1. The duration of diabetes is strongly associated with the risk of heart failure, according to an analysis of data from the ARIC study.

  2. Results suggested that delaying onset of diabetes and targeting cardioprotective therapies at patients with longer duration of diabetes may lower risk of HF.

Liz Meszaros, Deputy Managing Editor, BreakingMED™

The ARIC study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), and Department of Health and Human Services.

Echouffo-Tcheugui was supported by a grant from the NIH.

Cat ID: 914

Topic ID: 74,914,730,914,12,187,192,669,918,925