In the Journals

Role of biomarkers in HFpEF uncertain

Jennifer En-Sian Ho

Biomarkers of renal dysfunction, endothelial dysfunction and inflammation were independently associated with incident HF with reduced ejection fraction, but only natriuretic peptides and urinary albumin-to-creatinine ratio were linked to HF with preserved ejection fraction, according data published in JAMA Cardiology.

According to the study by Rudolf A. de Boer, MD, PhD, from the department of cardiology at the University Medical Center Groningen, University of Groningen, the Netherlands, and colleagues, these findings underscore a need to identify novel biomarkers characterizing HFpEF risk.

“While we have many proven therapies for HFrEF, there are as of yet no effective treatments for HFpEF, and yet about half of patients with HF have HFpEF. Our study was motivated by this major knowledge gap in HF,” Jennifer En-Sian Ho, MD, cardiologist in the heart failure and transplantation section at Massachusetts General Hospital and assistant professor of medicine at Harvard Medical School, told Cardiology Today. “We asked a very simple question: Do circulating biomarker profiles differ among adults who will develop future HFpEF vs. HFrEF? If we think of underlying pathways leading to HFpEF vs. HFrEF as distinct, then this study may lend insights into biochemical differences among HF subtypes.”

To evaluate the link between 12 CV biomarkers with incident HFpEF vs. HFrEF, de Boer and colleagues conducted a data analysis from June 2015 to November 2017, including 22,756 participants from four longitudinal community-based studies: the Cardiovascular Health Study, the Framingham Heart Study, the MESA study and the Prevention of Renal and Vascular End-stage Disease study.

The study examined N-terminal pro-B-type natriuretic peptide or brain natriuretic peptide, high-sensitivity troponin T or I, C-reactive protein, urinary albumin-to-creatinine ratio (UACR), renin-to-aldosterone ratio, D-dimer, fibrinogen, soluble suppressor of tumorigenicity, galectin-3, cystatin C, plasminogen activator inhibitor-1 and interleukin-6 biomarkers.

The primary outcome of the study was development of incident HFpEF and incident HFrEF.

Researchers found that 633 participants developed incident HFpEF and 841 developed HFrEF during a median 12-year follow-up.

Biomarker links

There was a significant association between HFpEF and UACR (HR = 1.33; 95% CI, 1.2-1.48) and natriuretic peptides (HR = 1.27; 95% CI, 1.16-1.4) and suggestive associations between HFpEF and high-sensitivity troponin (HR = 1.11; 95% CI, 1.03-1.19), plasminogen activator inhibitor-1 (HR = 1.22; 95% CI, 1.03-1.45) and fibrinogen (HR = 1.12; 95% CI, 1.03-1.22).

Conversely, the researchers found significant associations between HFrEF and six biomarkers: natriuretic peptides (HR = 1.54; 95% CI, 1.41-1.68), UACR (HR = 1.21; 95% CI, 1.11-1.32), high-sensitivity troponin (HR = 1.37; 95% CI, 1.29-1.46), cystatin C (HR = 1.19; 95% CI, 1.11-1.27), D-dimer (HR = 1.22; 95% CI, 1.11-1.35), and CRP (HR = 1.19; 95% CI, 1.11-1.28).

Natriuretic peptides, high-sensitivity troponin, and CRP all had much stronger associations with HFrEF than HFpEF, according to the researchers.

Underlying mechanisms

According to Ho, limitations of the present study suggest avenues for future research.

“One of the challenges in studying HFpEF is that it is a complex and heterogeneous disease, and so ‘lumping’ together people with diverse pathophysiologies may limit biological insights we can glean,” she said. “It may be that we need to break HFpEF down into distinct subphenotypes in order to tease out underlying mechanisms.” – by Dave Quaile

Disclosures: de Boer reports that he receives grants from AstraZeneca, Bristol-Myers Squibb and Trevena and has served as a consultant for and received research and personal honoraria from Novartis and Roche. Ho reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

 

Jennifer En-Sian Ho

Biomarkers of renal dysfunction, endothelial dysfunction and inflammation were independently associated with incident HF with reduced ejection fraction, but only natriuretic peptides and urinary albumin-to-creatinine ratio were linked to HF with preserved ejection fraction, according data published in JAMA Cardiology.

According to the study by Rudolf A. de Boer, MD, PhD, from the department of cardiology at the University Medical Center Groningen, University of Groningen, the Netherlands, and colleagues, these findings underscore a need to identify novel biomarkers characterizing HFpEF risk.

“While we have many proven therapies for HFrEF, there are as of yet no effective treatments for HFpEF, and yet about half of patients with HF have HFpEF. Our study was motivated by this major knowledge gap in HF,” Jennifer En-Sian Ho, MD, cardiologist in the heart failure and transplantation section at Massachusetts General Hospital and assistant professor of medicine at Harvard Medical School, told Cardiology Today. “We asked a very simple question: Do circulating biomarker profiles differ among adults who will develop future HFpEF vs. HFrEF? If we think of underlying pathways leading to HFpEF vs. HFrEF as distinct, then this study may lend insights into biochemical differences among HF subtypes.”

To evaluate the link between 12 CV biomarkers with incident HFpEF vs. HFrEF, de Boer and colleagues conducted a data analysis from June 2015 to November 2017, including 22,756 participants from four longitudinal community-based studies: the Cardiovascular Health Study, the Framingham Heart Study, the MESA study and the Prevention of Renal and Vascular End-stage Disease study.

The study examined N-terminal pro-B-type natriuretic peptide or brain natriuretic peptide, high-sensitivity troponin T or I, C-reactive protein, urinary albumin-to-creatinine ratio (UACR), renin-to-aldosterone ratio, D-dimer, fibrinogen, soluble suppressor of tumorigenicity, galectin-3, cystatin C, plasminogen activator inhibitor-1 and interleukin-6 biomarkers.

The primary outcome of the study was development of incident HFpEF and incident HFrEF.

Researchers found that 633 participants developed incident HFpEF and 841 developed HFrEF during a median 12-year follow-up.

Biomarker links

There was a significant association between HFpEF and UACR (HR = 1.33; 95% CI, 1.2-1.48) and natriuretic peptides (HR = 1.27; 95% CI, 1.16-1.4) and suggestive associations between HFpEF and high-sensitivity troponin (HR = 1.11; 95% CI, 1.03-1.19), plasminogen activator inhibitor-1 (HR = 1.22; 95% CI, 1.03-1.45) and fibrinogen (HR = 1.12; 95% CI, 1.03-1.22).

Conversely, the researchers found significant associations between HFrEF and six biomarkers: natriuretic peptides (HR = 1.54; 95% CI, 1.41-1.68), UACR (HR = 1.21; 95% CI, 1.11-1.32), high-sensitivity troponin (HR = 1.37; 95% CI, 1.29-1.46), cystatin C (HR = 1.19; 95% CI, 1.11-1.27), D-dimer (HR = 1.22; 95% CI, 1.11-1.35), and CRP (HR = 1.19; 95% CI, 1.11-1.28).

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Natriuretic peptides, high-sensitivity troponin, and CRP all had much stronger associations with HFrEF than HFpEF, according to the researchers.

Underlying mechanisms

According to Ho, limitations of the present study suggest avenues for future research.

“One of the challenges in studying HFpEF is that it is a complex and heterogeneous disease, and so ‘lumping’ together people with diverse pathophysiologies may limit biological insights we can glean,” she said. “It may be that we need to break HFpEF down into distinct subphenotypes in order to tease out underlying mechanisms.” – by Dave Quaile

Disclosures: de Boer reports that he receives grants from AstraZeneca, Bristol-Myers Squibb and Trevena and has served as a consultant for and received research and personal honoraria from Novartis and Roche. Ho reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.