Possible 'Treatment' May Cut HFpEF Risk from Subclinical Myocardial Injury in Blacks

June 14, 2021

African Americans with biomarker evidence of heart damage may cut their risk for at least some forms of heart failure (HF) with greater participation in at least moderate-intensity exercise, suggests a new analysis from a venerable cohort study.

It's known that the risk of future HF in community-based populations climbs with chronic levels of cardiac troponin by high-sensitivity assay (hs-cTn), a relationship that may be driven by poor control of conditions like obesity, hypertension, and diabetes.  

That process in African Americans applies to HF with either preserved or reduced ejection fraction (HFpEF and HFrEF, respectively), suggests the study, which may also have identified regular exercise as a preventive "therapy" with a big limitation: it seems to work on risk for HFpEF exclusively.

The analysis, based on 4000 African Americans in the long-running Jackson Heart Study, highlights the contrasting pathophysiologies of HFpEF and HFrEF, but is also novel for suggesting that "physical activity can modify the excess risk of HFpEF associated with chronic myocardial injury in this population," Ambarish Pandey, MD, MSCS, UT Southwestern Medical Center, Dallas, told theheart.org | Medscape Cardiology. "This effect modification was not seen for HFrEF."

The findings were published June 9 in JACC: Heart Failure with lead author Kershaw V. Patel, MD, Houston Methodist DeBakey Heart and Vascular Center, Houston, Texas, and Pandey as senior author.

About one fourth of the predominantly female cohort had subclinical myocardial injury, defined by hs-cTnI sex-specific cut points. Risk of developing HFpEF and, independently, HFrEF over the next 12 years went up sharply with rising levels of the biomarker.

Troponin elevations predicted HFrEF independently of physical activity, but there was a significant interaction for HFpEF risk between hs-cTnI and physical activity. Rising levels of physical activity progressively weakened the link between HFpEF risk and subclinical myocardial injury. The risk went down 7% for every 1-unit log increase in metabolic equivalent of task (METs).

Physical activity, the report concludes, "modified the association between subclinical myocardial injury and risk of HFpEF such that active individuals with subclinical myocardial injury had comparable risk to those who had no subclinical myocardial injury."

That finding is "consistent with prior works showing a unique contribution of physical inactivity to HFpEF development," Pandey said. "Considering the high burden of HFpEF and myocardial injury in Blacks, physical activity could be a tool to attenuate their excess risk of heart failure."

Also important for improving HFpEF risk, he added, "is reducing the burden of cardiometabolic disorders by effectively managing comorbidities like diabetes, chronic kidney disease, and hypertension."

The prospective Jackson Heart Study has been following a cohort of African Americans living in the greater Jackson, Mississippi region who underwent baseline examinations between 2000 and 2004. The current analysis included participants initially without HF but with available data on hs-cTnI and physical activity, the report notes.

Of the 3959 participants, 48.2% were "inactive," that is, they reported performing no moderate to vigorous physical activity. About 25% of the entire cohort had subclinical myocardial injury, defined as hs-cTnI at least 4 ng/L for women, who made up 63% of the cohort, and 6 ng/L for men. But the proportion with subclinical myocardial injury reached 29% for those who were inactive and only 21.3% for the remainder (P < .001).

The adjusted hazard ratio (HR) for an HF event, per 1-unit log increase in hs-cTnI, over the 12-year follow-up was:

  • 1.47 (95% CI, 1.25 - 1.72, P < .001) for HFpEF

  • 1.57 (95% CI, 1.35 - 1.83, P < .001) for HFrEF

The adjusted HR for an HF event, per 1-unit log increase in physical activity as measured by MET minutes per week, was:

  • 0.93 (95% CI, 0.88 - 0.99, P = .01) for HFpEF

  • 0.96 (95% CI 0.91 - 1.02, P = .17) for HFrEF

Also in adjusted analyses, HFpEF risk tied to subclinical myocardial injury varied by physical activity levels "such that higher risk of HFpEF was observed among participants with subclinical myocardial injury who were inactive," the report notes. But for HFrEF, the risk "was consistently higher among individuals with subclinical myocardial injury at baseline regardless of their physical activity status."

The observed interaction for HFpEF risk between subclinical myocardial injury and physical activity is important, an accompanying editorial notes, because such injury "may be one of the strongest predictors of HF risk in African American adults."

That's partly the result of higher rates of obesity, physical inactivity, hypertension, left-ventricular hypertrophy, and diabetes in African Americans, contend the authors, led by Carl J. Lavie, MD, University of Queensland School of Medicine, New Orleans, Louisiana.

"The promotion of physical activity, exercise, and improved fitness would not only likely lead to a reduction in obesity and its severity, but would also improve prognosis and reduce the prevalence of HF, especially HFpEF," they write.

That could currently have a special impact among African Americans, in that those with low fitness and activity levels and obesity "have had more severe complications in COVID-19, which is worsened by comorbidities, including HF."

Interventions aimed at reducing obesity, sedentary behavior, and HF, "especially HFpEF, are desperately needed in modern society. And this is more strongly highlighted in the African American population," write Lavie and colleagues.

Funding for natriuretic peptide assays was provided by Abbott Diagnostics. Pandey discloses serving on an advisory board for Roche Diagnostics and receiving nonfinancial support from Pfizer and Merck, and receiving research support from Applied Therapeutics; Patel has disclosed no relevant financial relationships; potential conflicts for the other authors are in the report. Lavie discloses speaking and consulting for AstraZeneca, DSM Nutritional Products, and the trade group Global Organization for EPA and DHA Omega-3; disclosures for the other editorialists are in the original article.

JACC: Heart Failure. Published online June 9, 2021. Abstract, Editorial

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