Achieving Biomarker-based Treatment Target Goals Implies Good Prognosis For Obese Heart Patients

In a recent study published in the Journal of the American Heart Association by University of Alabama at Birmingham researchers, findings indicate that among patients with heart failure, obesity is associated with a higher risk of heart failure hospitalization or death due to cardiac causes. However, achieving biomarker-based treatment goals in heart failure improves the prognosis for patients irrespective of their obesity status.

Heart failure is one of the leading causes of death in the United States and contributes to nearly 14% of all deaths in the U.S. Highly efficacious medications are now available for management of this disease.

Vibhu Parcha, MD, a clinical research fellow in UAB's Division of Cardiovascular Disease and the first author of this study, says obese individuals frequently have multiple comorbidities, which impacts how the heart functions; but paradoxically they were traditionally thought to have better prognosis in the setting of heart failure.

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"Obese individuals also have low circulating levels of beneficial heart hormones called natriuretic peptides that help control blood pressure and handling of salt," Parcha said. "These hormones are increased in the setting of heart failure and are hence used as biomarkers for how badly the heart is doing. Previously it has been demonstrated that heart failure patients who regularly take their medications and have their NT-proBNP levels (a natriuretic peptide used as a heart failure biomarker) less than 1,000 pg/mL do better in terms of being admitted to hospital for worsening of heart failure or dying due to cardiac causes.

Parcha and his investigative team analyzed heart failure patients enrolled in the NHLBI-sponsored Guiding Evidence-Based Therapy Using Biomarker-Intensified Treatment in Heart Failure, or GUIDE-IT, trial.

"The assessment of heart failure patients in the setting of a randomized clinical trial allows us to look closely at how obesity impacts heart failure outcomes and whether good medical therapy can help improve outcomes for these patients," Parcha said.

Researchers found that, unlike the previously reported obesity paradox of heart failure, increasing body mass index was associated with a higher risk of heart failure hospitalizations for worsening heart failure or death from cardiac causes.

They found that obese patients have nearly 60% lower levels of the natriuretic peptide-based biomarker NTproBNP, but still have worse outcomes. The important finding of the study was that, irrespective of obesity, if heart failure patients are adherent with their treatments and achieve an NTproBNP level of <1,000 pg/mL, they have nearly 50-70% lower risk of being hospitalized for heart failure or dying from cardiac reasons.

"Heart failure is a serious medical condition, and all heart failure patients require close medical attention and care," said senior author Pankaj Arora, MD, a physician-scientist in the UAB's Division of Cardiovascular Disease. "The diseased heart in conditions like heart failure produces higher levels of the natriuretic peptide hormones to restore normal functioning."

Arora added that the secretion of the hormone increases in an attempt to bring back normal function.

"Obese individuals have very low levels of these beneficial hormones even during heart failure, and the low hormone levels are unable to compensate for the worsening heart failure," Arora said. "They also have numerous comorbidities that predispose them to bad outcomes when they develop heart failure, as we noted in our study. The prior understanding of the obesity paradox—a better prognosis for obese people with heart failure—was based primarily on epidemiological studies. Obese patients may report heart failure symptoms early and hence are identified early in the disease course. Resultantly, the prior studies may have indicated a protective effect of obesity in heart failure."

Arora said researchers now have a huge arsenal of extremely effective medications that help physicians manage this disease.

"Our study suggests that, irrespective of the obesity status of the heart failure patients, if we bring the NTproBNP biomarker levels to less than 1,000 pg/mL using these efficacious medications, we can cause a massive reduction in the risk of poor outcomes," Arora said. "It is important for us to convey to heart failure patients that their disease is manageable if they take their heart failure medications regularly and seek medical care to ensure that their medications are being changed appropriately based on their health condition."

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