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While cardiovascular biomarkers may point to a higher risk of developing heart failure, predicting whether ejection fraction will be preserved is a tougher challenge, a study suggested.

From four longitudinal datasets following patients for a median of 12 years, two biomarkers turned out to be strongly tied to heart failure with preserved ejection fraction (HFpEF) after adjusting for clinical risk factors:

• Urinary albumin to creatinine ratio (UACR; HR 1.33, 95% CI 1.20-1.48)
• Natriuretic peptides (HR 1.27, 95% CI 1.16-1.40)

The problem is that these were also predictors of heart failure with reduced ejection fraction (HFrEF), Jennifer Ho, MD, of Boston's Massachusetts General Hospital, and colleagues reported online in .

For HFrEF, natriuretic peptides were linked to 54% higher odds (HR 1.54, 95% CI 1.41-1.68), while UACR was associated with a 21% elevated risk (HR 1.21, 95% CI 1.11-1.32).

High-sensitivity troponin was yet another biomarker shared by HFpEF (HR 1.11, 95% CI 1.03-1.19) and HFrEF (HR 1.37, 95% CI 1.29-1.46).

"These findings highlight the need for future studies focused on identifying novel biomarkers of the risk of HFpEF," according to Ho's group. "In general, biomarkers modestly improved risk estimation, and discrimination metrics overall were lower for HFpEF models, highlighting current limitations in our understanding of factors underlying the development of HFpEF."

The study encompassed four longitudinal community-based cohorts (n=22,756): the Cardiovascular Health Study, the Framingham Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Prevention of Renal and Vascular End-stage Disease study. Twelve cardiovascular biomarkers were assessed in a study population that counted more than 2,000 incident heart failure events.

Shared biomarkers aside, HFpEF did have its own predictors in plasminogen activator inhibitor (HR 1.22, 95% CI 1.03-1.45), and fibrinogen (HR 1.12, 95% CI 1.03-1.220) -- though these didn't appear so robust compared to the unique HFrEF biomarkers:

• Cystatin C (HR 1.19, 95% CI 1.11-1.27)
• D-dimer (HR 1.22, 95% CI 1.11-1.35)
• C-reactive protein (HR 1.19, 95% CI 1.11-1.28)

It should be mentioned, however, that not all 12 biomarkers were assessed in each of the four cohorts, according to Ho and colleagues. What's more, 30% of cases were left unclassified because patients did not get left ventricular function assessed at the time of heart failure presentation.

"Whereas HFpEF and HFrEF have a shared clinical presentation and common clinical risk factors, these findings suggest that some antecedent factors preceding HFpEF and HFrEF may be distinct," the authors maintained. "For example, myocyte necrosis (high-sensitivity troponin) appears to play a larger role in the development of HFrEF, whereas low-grade albuminuria, a marker of endothelial dysfunction, seems to precede both HFpEF and HFrEF."

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