Diabetes Tied to Faster Progression to Overt Heart Failure – Medscape

Diabetes, especially when uncontrolled, is strongly associated with progression to overt heart failure in patients with preclinical signs of heart failure, a new study shows.

"Until now, studies of diabetes and heart failure have mainly been done in patients with overt heart failure. The novelty of this study is that we looked at the influence of diabetes in the early stages of heart failure before patients develop symptoms," lead author Justin Echouffo-Tcheugui, MD, Johns Hopkins University, Baltimore, Maryland, told theheart.org | Medscape Cardiology.

"Our results suggest that the rigorous control of diabetes could be a very effective way of slowing the progression to overt heart failure in these patients," he added. "Our simplest message is that if we take better care of diabetes, we will reduce the number of people developing overt heart failure.

"This is a unique opportunity to reduce the population of patients with overt heart failure, and an additional reason to treat diabetes aggressively," he added.

The study was published online June 6 in the Journal of the American College of Cardiology.

The authors point out that a new universal definition of heart failure includes two preclinical stages (A and B) and two clinical stages (C and D), and that there is growing focus in heart failure guidelines on halting progression from the preclinical to clinical stages.

They explain that stage A of theheart failure risk continuum is defined as the presence of at least one of the following clinical heart failure risk factors in the absence of structural heart disease or symptoms of heart failure: prevalent atherosclerotic cardiovascular disease (coronary artery disease, stroke, or peripheral artery disease), hypertension, diabetes mellitus, obesity, metabolic syndrome, or chronic kidney disease.

Stage B of the heart failure risk continuum is defined as the presence of structural heart disease on echocardiography or elevated cardiac biomarkers N-terminal pro-B-type natriuretic peptide (NT-proBNP) and/or high sensitivity cardiac troponin T, but without signs or symptoms of heart failure.

For the current study, researchers conducted a prospective cohort analysis of data from the Atherosclerosis Risk In Communities (ARIC) study to characterize the influence of diabetes on the progression from preclinical stages of heart failure to overt heart failure.

The study included 4774 adults (mean age 75 years, 58% women, 20% Black) with preclinical heart failure, 1551 in stage A and 3223 in stage B, and 30% of the study population had diabetes.

Within each heart failure stage, associations were assessed between diabetes and glycemic control with progression to heart failure. The primary outcome was a new diagnosis of definite or probable acute decompensated heart failure or the development of chronic stable heart failure.

During a median follow-up of 7.5 years there were 470 heart failure events.

Results showed that diabetes was associated with progression to heart failure (with a younger age of heart failure onset and a shorter time to event) and increased heart failure risk across stages A and B. There were significantly higher absolute and relative risks related to diabetes among individuals in stage B, as compared with persons with diabetes in stage A.

Patients with diabetes and stage B heart failure had at least four times the absolute risk of developing overt heart failure than those in stage A without diabetes.

Uncontrolled diabetes (A1c > 7%) was associated with a higher risk of incident heart failure for individuals in both stage A and B.

Compared with individuals without diabetes and in preclinical stage A, those in preclinical stage B with uncontrolled diabetes had a 7.6-fold higher risk of incident heart failure. Those in stage B with controlled diabetes had a 4.6-fold increased risk of incident heart failure and those in stage A with uncontrolled diabetes had a 1.5-fold increased risk.

The observed associations of diabetes and diabetes control with heart failure progression were independent of other cardiovascular risk factors and the intervening development of incident coronary heart disease.

"Our results suggest that targeting diabetes early in the heart failure process is critical. There are likely substantial benefits for heart failure prevention by aggressively treating diabetes as early as possible in the heart failure disease process," the authors write.

They say the study further informs the understanding of the natural history of diabetes-related cardiac dysfunction and reinforces that prevention of diabetes should be a clinical and public health priority.

Echouffo-Tcheugui added that these results also raise issues about the choice of diabetes medication.

"We already know that SGLT2 inhibitors and GLP-1 agonists reduce heart failure hospitalizations in patients with established heart failure, but we don't know if they change the natural history of heart failure. There may be potential for use of these medications earlier on to reduce the development of heart failure," he said.

In an accompanying editorial, Subodh Verma, MD, University of Toronto, Ontario, Canada, Ambarish Pandey, MD, University of Texas Southwestern Medical Center, Dallas, and Deepak Bhatt, MD, Brigham and Women's Hospital, Boston, Massachusetts, say the current study "reinforces the contribution of diabetes, and specifically, long-standing or poorly controlled diabetes, as key risk factors toward hastening the transition from preclinical to overt heart failure."

They note that because the step up is steepest in those who are in stage B heart failure, any evidence of structural heart disease or an increase in biomarkers should alert clinicians to an impending heart failure risk.

Such an approach may also aid in identifying patients who may derive the greatest absolute risk reduction from SGLT2 inhibitors, which have been shown in various trials to prevent incident heart failure in diabetes, the editorialists add.

The ARIC study was funded by the National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), and the Department of Health & Human Services. Echouffo-Tcheugui was supported by an NIH/NHLBI grant. Verma has reported receiving research grants and/or speaker honoraria from Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, EOCI Pharmacomm, HLS Therapeutics, Janssen, Novartis, Novo Nordisk, Pfizer, PhaseBio, Sanofi, Sun Pharmaceuticals, and the Toronto Knowledge Translation Working Group. Pandey has reported receiving grant funding outside the present study from Applied Therapeutics, Gilead Sciences, and a National Institute of Aging GEMSSTAR grant; honoraria outside of the present study as an advisor/consultant for Tricog Health,Lilly, Rivus, and Roche Diagnostics; and has received nonfinancial support from Pfizer and Merck. Bhatt has reported being an advisory board member for Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, Janssen, Level Ex, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, and Stasys; being on the board of directors for Boston VA Research Institute, DRS.LINQ (stock options), the Society of Cardiovascular Patient Care, and Tobesoft; and being the inaugural chair of the American Heart Association Quality Oversight Committee. Further disclosures for Bhatt are included with the editorial.

J Am Coll Cardiol. Published online June 6, 2022.Abstract, Editorial

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Diabetes Tied to Faster Progression to Overt Heart Failure - Medscape