More Data Links Diabetes with Higher Heart Failure Risk

Diabetes with cardiomyopathy (DbCM) among community-dwelling individuals pinpointed a group at high risk for developing heart failure (HF), regardless of how cardiomyopathy was defined, researchers reported.

Among nearly 3,000 people with diabetes, the prevalence of DbCM ranged from 11.7% using the least restrictive criteria to 67% based on the most restrictive criteria, according to Ambarish Pandey, MD, MSCS, of the University of Texas Southwestern Medical Center in Dallas, and co-authors.

In addition, the 5-year incidence of HF for people with DbCM ranged from 8.4% by the least restrictive definitions to 12.8% with the most restrictive, they wrote in the Journal of the American College of Cardiology.

The authors also found that higher fasting glucose, high BMI, older age, and worse kidney function were linked with higher risk of DbCM. And they reported that “DbCM, irrespective of the criteria used to define it, was associated with significantly higher risk of HF compared with individuals with euglycemia as well as those with diabetes without cardiomyopathy.”

While they acknowledged that the results “do not establish causal association between diabetes and cardiomyopathy as patients with diabetes have high burden of other comorbidities such as hypertension and obesity that are associated with abnormal LV [left ventricular] remodeling,” the findings still “highlight the clinical utility of the DbCM phenotype for identifying individuals who are at an increased risk for progression to incident HF,” Pandey’s group advised.

In a 2020 Nature Reviews Cardiology article, Yi Tan, PhD, of the University of Louisville, and co-authors explained that “[d]iabetic cardiomyopathy occurs as a result of the dysregulated glucose and lipid metabolism associated with diabetes mellitus, which leads to increased oxidative stress and the activation of multiple inflammatory pathways that mediate cellular and extracellular injury, pathological cardiac remodeling, and diastolic and systolic dysfunction.”

Diabetes is tied to multiple complications—diabetic retinopathy, nephropathy, neuropathy—but “when we think about [cardiovascular complications], we think about atherosclerosis, MIs [myocardial infarctions], and stroke… I think that heart failure is largely unrecognized [in the clinic],” noted E. Dale Abel, MD, PhD, of the University of Iowa in Iowa City, in a 2018 NIH VideoCast.

Abel cited the long-standing research on diabetic cardiomyopathy, including a 2001 study in Diabetes Care by Gregory A. Nichols, PhD, of Kaiser Permanente Center for Health Research in Portland, Oregon, and co-authors; a 2013 study of a risk score by Roman Pfister, MD, of the University of Cologne, and co-authors; and two 2016 studies (both registry-based) from Justin B. Echouffo-Tcheugui, MD, PhD, MPhil, of Brigham and Women’s Hospital in Boston and co-authors.

A 2019 JACC State-of-the-Art Review noted that diabetes “has a prevalence of approximately 45% in HFpEF [HF with preserved ejection fraction], but characteristics and outcomes of this population are poorly understood,” although again, there is plenty of research on the condition, such as the CHARM, DIG, RELAX, and I-PRESERVE trials.

More recently, research from Germany and the Cleveland Clinic, as well as an international meta-analysis, made a strong case for what the Cleveland Clinic group called a “Marriage of Inconvenience… [t]raditionally, diabetes and heart failure have been treated as 2 distinct disease entities, but recent advances in individual therapies have shown remarkable concomitant improvements in both diabetes and cardiovascular outcomes.”

Pandey’s group looked at the prevalence of DbCM among people with diabetes in a pooled cohort of three community-based epidemiological studies. None of the participants had established cardiovascular disease.

DbCM was defined in three ways:

• Least restrictive: ≥1 echocardiographic abnormality.
• Intermediate restrictive: ≥2 echocardiographic abnormalities.
• Most restrictive: elevated N-terminal pro–B-type natriuretic peptide levels (>125 in normal/overweight or >100 pg/mL in obese) plus ≥2 echocardiographic abnormalities.

Their final cohort from the three studies came to 10,208 participants, of which 2,900 (28.4%) had diabetes. In all three groups based on DbCM-level of restriction, age was 72, around 40% were men, and over a fourth were Black.

The authors reported that, compared with euglycemia, DbCM was significantly tied to a higher risk of incident HF, and that risk climbed based on DbCM definition:

• Most restrictive: hazard ratio 2.55 (95% CI 1.69-3.86).
• Least restrictive: HR 1.99 (95% CI 1.50-2.65).

They also noted that in a sex-stratified analyses, the prevalence of DbCM was higher among women versus men across all definitions of DbCM, while in a race-stratified analyses, prevalence was higher among Black people versus non-Black people.

Pandey’s group also reported that their cohort-specific analysis demonstrated that the prevalence of DbCM was higher in participants with diabetes within the chronic kidney disease in the CRIC study cohort compared with participants with diabetes from the ARIC and CHS cohorts, regardless of the criteria defining DbCM.

Other study limitations included the fact that ARIC and CHS were done in the late ’80s and early ’90s so may not represent a “contemporary cohort,” and that evaluation of “the association of DbCM with risk of HF subtypes because of fewer number of events for each HF subtype, according to the authors.

Still, “[t]hese results highlight the prognostic importance of identifying a universally accepted clinical definition and diagnostic approach to DbCM to identify individuals at high-risk of progression to HF,” noted Vanita R. Aroda, of Brigham and Women’s Hospital in Boston, and co-authors in an editorial comment accompanying the study.

But the study also calls attention to the “challenges of diagnosis and translation,” they noted. “Although clinically relevant, these findings do not demonstrate direct causality between diabetes, DbCM, and HF, particularly given the high prevalence of comorbid hypertension and obesity, which can also contribute to abnormal cardiac remodeling and HF risk.”

Aroda’s group also pointed out that there’s no consensus in place “to precisely define which patients are at risk for HF, who to screen or when to screen for DbCM, the extent of assessments required to diagnose DbCM, or the comprehensive therapeutic pathway once identified.” Guidelines from the American Heart Association/American College of Cardiology/Heart Failure Society of America support biomarker-based screening plus “team-based care” for at-risk HF patients, while the American Diabetes Association does not clarify which patients with diabetes should undergo DbCM or HF screening, they added.

To address that gap, Aroda and co-authors offered a multi-step “Proposed Cascade of Care for Diabetes with Cardiomyopathy,” that starts with screening and diagnosis, then outlines steps for care and support, retaining patients in the care continuum, appropriate prevention therapy, and end with assessing if prevention goals have been achieved.

1. Diabetes with cardiomyopathy (DbCM) identified a high-risk subgroup for the development of heart failure (HF), regardless of whether a lessrestrictive or more restrictive definition of DbCM was used.

2. The findings in community-dwelling adults do not establish a causal link between diabetes and cardiomyopathy, but they do call attention to the clinical utility of the DbCM phenotype for identifying people who are at an increased risk for progression to incident HF.

Shalmali Pal, Contributing Writer, BreakingMED™

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Topic ID: 76,12,730,446,914,12,669,918