Diabetes Independently Linked to Increased Heart Failure

Batya Swift Yasgur MA, LSW

January 09, 2020

Diabetes mellitus (DM) may be an independent risk factor for the development of heart failure (HF), a new population-based study suggests.

Investigators followed 116 adults with diabetes and 232 matched control subjects over 10-year period and found that one-fifth of those with DM developed HF, independent of other causes, such as diastolic dysfunction, compared with only about 10% of those without DM.

"The current study shows that diabetic patients have a significantly increased risk of developing heart failure, compared with nondiabetic patients," lead author Michael Klajda, MD, an internal medicine resident at the Mayo Clinic, Rochester, Minnesota, told theheart.org | Medscape Cardiology.

"Additionally, the study expands on the current fund of knowledge by demonstrating that even without structural heart disease (diastolic dysfunction), diabetic patients are still at risk for developing heart failure," he said.

The findings "support the concept" of diabetic cardiomyopathy (DCM), the authors conclude in their report. "Future research should be focused on whether aggressive management of risk factors such as BMI and glucose and cholesterol levels will decrease the development of HF in patients with DM."

The study was published online January 2 in Mayo Clinic Proceedings.

Unclear Association

Previous work has shown that patients with DM are at increased risk for HF, representing roughly 33% of HF admissions to hospitals in the United States; moreover, 22% of older patients with DM have a diagnosis of HF, the authors write.

"Diabetes is a very common medical condition in the United States and has a well-documented association with cardiovascular disease; however, its association with heart failure has been difficult to define," Klajda observed.

"This is mostly due to the fact that diabetic patients often have other causes of heart failure, like high blood pressure and/or coronary heart disease," he continued.

The current study therefore set out to "determine the long-term impact of DM on the development of HF, both with preserved ejection fraction (EF) and reduced EF, and mortality in a community population, controlling for hypertension (HTN), coronary artery disease (CAD), and diastolic function," the authors state.

To investigate the question, the researchers used data from the Rochester Epidemiology Project (REP), consisting of adults 45 years and older based in Olmsted County, Minnesota.

The final sample consisted of 116 participants with DM, who were matched in a 1:2 ratio for age, HTN, sex, CAD, and diastolic dysfunction with 232 patients without DM.

At baseline, participants underwent physical examination, an array of blood tests, measurement of body mass index (BMI), and echocardiography.

During follow-up, participants were periodically monitored for mortality, as well as subsequent diagnoses of HF, myocardial infarction (MI), or stroke.

Downstream Remodeling

At baseline, participants with DM had higher BMI than those without DM, as well as higher percentages of atrial fibrillation (AF), HF, and metabolic syndrome. In addition, they had higher baseline triglyceride levels, medium insulin levels, and serum glucose levels.

Of patients with DM, 21% (24 of 116) were defined as insulin-dependent diabetics and maintained on treatment with insulin alone, rather than with the newer antidiabetic drugs, such as sodium-glucose cotransporter-2 (SGLT-2) inhibitors or the dipeptidyl pepidase-4 (DPB-4) inhibitors.

The E/e´ ratio (that is, the ratio of E, passive transmitral of LV inflow velocity to tissue Doppler imaging velocity of the medial mitral annulus during passive filling, e´) was higher at baseline in those with DM than in those without DM (9.7 vs 8.5; < .001); however, the EF, left atrial size, and diastolic dysfunction did not statistically differ between the two groups.

Follow-up was conducted over a 10.8-year period (interquartile range [IQR], 7.8 - 11.7), during which the overall development of HF among patients with DM was higher for participants with than without DM (hazard ratio [HR], 2.1; 95% CI, 1.2 - 3.6; P = .01).

At 1 year from the initial data collection, 45 participants with DM had developed HF; at 5 years, 14% had developed HF.

At 10 years, 21% of those with DM had developed HF, as had 12% of their counterparts without DM.

There were no statistical differences between the two groups in cardiac death, MI, stroke, and all-cause mortality.

The researchers compared subgroups of participants without diastolic dysfunction with their matched control subgroups and found that, compared with patients without DM, those with DM — even without diastolic dysfunction at baseline — had an increased risk for HF (HR, 2.5; 95% CI, 1.0 - 6.3; P = .04) over the 10-year follow-up period.

At 10 years, 13% of these participants with DM had developed HF, compared with only 7% of those without DM, although the incidence of death, cardiac death, MI, and stroke events were similar.

In the "subgroup of the cohort with normal LV filling pressure, DM was still associated with increased risk for the development of HF," the authors state.

"Although still an area of ongoing research, the current thought process is that much of the pathophysiology in diabetic HF stems from the negative impact of diabetes itself and the subsequent downstream remodeling that occurs at a cellular level in the cardiac muscle tissue," Klajda noted.

Sea Change

Commenting on the study for theheart.org | Medscape Cardiology, Jorge Plutzky, MD, director of preventive cardiology, Brigham and Women's Hospital, Boston, said a major finding of the study is that "when they did a snapshot of people through Mayo, they found that those with diabetes had more evidence of heart failure and diabetic cardiomyopathy and a higher frequency of going on to heart failure, even when they didn't have it at baseline."

It is a "long-standing paradox, a conundrum, that diabetes increases cardiovascular risk, but when we treated it, we didn't make cardiovascular risk get better," continued Plutzky, who is chair of the American Heart Association's Diabetes Committee and was not involved with the study.

"Despite many attempts over a couple of decades, the big sea change over the past years is that two classes of medications have shown improvement in decreasing cardiovascular risk, including heart attack and heart failure," he stated.

"Recent trials with SGLT-2 inhibitors have been striking and dramatic, showing a decrease in cardiovascular events and admissions to the hospital with heart failure among people who have known diabetes and heart failure, as well as people who didn't carry that history of heart failure — which lines up with this study."

Plutzky noted that the glucagon-like peptide-1 (GLP-1) agonists, which are associated with decreases in weight, may have an "indirect impact" in reducing shortness of breath and HF, but the "data around HF have been less dramatic and less obvious than in the SGLT-1 inhibitors."

He added that an important take-home message of the study is that "if you are a doctor caring for patients with diabetes, you need to think about whether they have heart failure."

Patients with DM and shortness of breath "may be candidates for one of these [newer] drugs," he suggested.

Klajda added: "Our hope would be that by understanding the close connection between these two disease processes, healthcare providers can be better prepared to counsel and monitor diabetic patients for signs and symptoms of heart failure."

This study was made possible by the Rochester Epidemiology Project. The design and conduct of the study, and the collection, management, analysis, and interpretation of the data were supported by grants from the National Institutes of Health. Klajda reports no relevant financial relationships. The other authors' disclosures are listed on the original paper. Plutzky reports serving as a consultant to Boehringer Ingelheim, Eli Lilly/Janssen, Sanofi, and Novo Nordisk, and receiving grant support from Boehringer Ingelheim.

Mayo Clin Proc. 2020;95:124-133. Full text

 

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