Myhre PL, et al. - In this secondary analysis of the TOPCAT study, researchers investigated the potential impact of age, race/ethnicity, obesity, renal function, and atrial fibrillation (AF) on levels of natriuretic peptides (NPs) in heart failure with preserved ejection fraction (HFpEF), and determined if the prognostic significance of NPs varies in these clinically important subgroups. In HFpEF, NPs were identified to have an important role as biomarkers of prognosis, even in subgroups who tend to have lower NP levels. Based on the findings, certain demographic and clinical subgroups may be underrepresented on account of a single, absolute NP threshold for inclusion in contemporary HFpEF trials.

Methods

• This study included 6 subgroups—age, black race, body mass index (BMI), waist circumference, estimated glomerular filtration rate, and history of AF—representing 1,057 adult patients (60%) in the Americas region of TOPCAT with symptomatic heart failure (HF) and a left ventricular ejection fraction of ≥ 45% with available NPs at baseline.
• NPs were log-transformed, standardized, and assessed in the six subgroups.
• At mean 2.4-year follow-up, the investigators assessed time to composite cardiovascular death, hospitalization for HF, or aborted cardiac arrest.

Results

• Among the 1,057 participants, history of AF was obtained in 472 (45%) and 183 (17.3%) were black.
• These participants had a mean age of 72 years, mean BMI of 33.4 kg/m², and a mean estimated glomerular filtration rate (eGFR) of 64.6 mL/min/1.73 m².
• Median B-type NP (n=698) concentrations were 257 ng/L and median N-terminal pro-B-type NP concentrations (n=359) were 959 ng/L.
• NP concentrations varied by up to 0.5 SD within the subgroups and were higher in older patients with non-black race, as well as those who had a lower BMI measure, lower waist circumference, lower eGFR, and a history of AF.
• Findings revealed an independent association of elevated NP levels (per 1-SD increase) with an increased risk of the primary outcome; this observation was consistent across all investigated subgroups.
• On the basis of elevated NP levels as the qualifying criterion (as opposed to a history of HF hospitalization), 791 (45%) were enrolled in TOPCAT Americas (n=1,767).
• For black race, younger than 70 years of age, and a BMI of ≥ 30 kg/m² , this proportion was 31%, 34%, and 39%, respectively.