TY - JOUR
T1 - Near-universal prevalence of central adiposity in heart failure with preserved ejection fraction
T2 - the PARAGON-HF trial
AU - Peikert, Alexander
AU - Vaduganathan, Muthiah
AU - Claggett, Brian L
AU - Kulac, Ian J
AU - Litwin, Sheldon
AU - Zile, Michael
AU - Desai, Akshay S
AU - Jhund, Pardeep S
AU - Butt, Jawad H
AU - Lam, Carolyn S P
AU - Martinez, Felipe
AU - Van Veldhuisen, Dirk J
AU - Zannad, Faiez
AU - Rouleau, Jean
AU - Lefkowitz, Martin
AU - McMurray, John J V
AU - Solomon, Scott D
AU - Packer, Milton
N1 - © The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology.
PY - 2025/7/1
Y1 - 2025/7/1
N2 - BACKGROUND AND AIMS: An expansion of fat mass is an integral feature of patients with heart failure and preserved ejection fraction (HFpEF). While body mass index (BMI) is the most common anthropometric measure, a measure of central adiposity-the waist-to-height ratio (WHtR)-focuses on body fat content and distribution; is not distorted by bone or muscle mass, sex, or ethnicity; and may be particularly relevant in HFpEF.METHODS: The PARAGON-HF trial randomized 4796 patients with heart failure and ejection fraction ≥45% to valsartan or sacubitril/valsartan. The current work characterizes the association of BMI and WHtR with clinical features, outcomes, and the response to neprilysin inhibition.RESULTS: About half (49%) of the participants were considered obese by BMI (≥30 kg/m2), but nearly every patient (96%) had central adiposity (WHtR ≥0.5). Among patients who were not obese (BMI <30 kg/m2), 860 (37%) had marked central adiposity (WHtR ≥0.6). Higher BMI and WHtR were both associated with higher risk of total heart failure hospitalizations, but as compared with BMI, WHtR was linearly associated with heart failure outcomes and identified a higher proportion of patients who had a particularly elevated risk (i.e., 30% or greater). An obesity-survival paradox (i.e., improved outcomes in those with greater adiposity) was apparent with BMI in unadjusted analyses, but it was not observed with WHtR. Although neprilysin inhibition appeared to have greater effects on heart failure outcomes in patients with higher BMI and WHtR, analyses of interaction with obesity metrics did not show significant heterogeneity across the range of values for adiposity.CONCLUSIONS: In PARAGON-HF, in contrast with BMI, nearly every patient with HFpEF had central adiposity (as assessed by WHtR), and the risks of adverse heart failure events were more robustly related to WHtR. These data challenge the current reliance on BMI as an appropriate metric of adiposity, and they suggest that-rather than obesity-related HFpEF being regarded as a select HFpEF subgroup-central adiposity is a ubiquitous feature of HFpEF.
AB - BACKGROUND AND AIMS: An expansion of fat mass is an integral feature of patients with heart failure and preserved ejection fraction (HFpEF). While body mass index (BMI) is the most common anthropometric measure, a measure of central adiposity-the waist-to-height ratio (WHtR)-focuses on body fat content and distribution; is not distorted by bone or muscle mass, sex, or ethnicity; and may be particularly relevant in HFpEF.METHODS: The PARAGON-HF trial randomized 4796 patients with heart failure and ejection fraction ≥45% to valsartan or sacubitril/valsartan. The current work characterizes the association of BMI and WHtR with clinical features, outcomes, and the response to neprilysin inhibition.RESULTS: About half (49%) of the participants were considered obese by BMI (≥30 kg/m2), but nearly every patient (96%) had central adiposity (WHtR ≥0.5). Among patients who were not obese (BMI <30 kg/m2), 860 (37%) had marked central adiposity (WHtR ≥0.6). Higher BMI and WHtR were both associated with higher risk of total heart failure hospitalizations, but as compared with BMI, WHtR was linearly associated with heart failure outcomes and identified a higher proportion of patients who had a particularly elevated risk (i.e., 30% or greater). An obesity-survival paradox (i.e., improved outcomes in those with greater adiposity) was apparent with BMI in unadjusted analyses, but it was not observed with WHtR. Although neprilysin inhibition appeared to have greater effects on heart failure outcomes in patients with higher BMI and WHtR, analyses of interaction with obesity metrics did not show significant heterogeneity across the range of values for adiposity.CONCLUSIONS: In PARAGON-HF, in contrast with BMI, nearly every patient with HFpEF had central adiposity (as assessed by WHtR), and the risks of adverse heart failure events were more robustly related to WHtR. These data challenge the current reliance on BMI as an appropriate metric of adiposity, and they suggest that-rather than obesity-related HFpEF being regarded as a select HFpEF subgroup-central adiposity is a ubiquitous feature of HFpEF.
KW - Body Mass Index
KW - Obesity, Abdominal/epidemiology
KW - Humans
KW - Middle Aged
KW - Male
KW - Stroke Volume/physiology
KW - Biphenyl Compounds
KW - Tetrazoles/therapeutic use
KW - Neprilysin/antagonists & inhibitors
KW - Waist-Height Ratio
KW - Adiposity/physiology
KW - Heart Failure/physiopathology
KW - Aminobutyrates/therapeutic use
KW - Female
KW - Hospitalization/statistics & numerical data
KW - Aged
KW - Valsartan/therapeutic use
KW - Angiotensin Receptor Antagonists/therapeutic use
KW - Drug Combinations
U2 - 10.1093/eurheartj/ehaf057
DO - 10.1093/eurheartj/ehaf057
M3 - Article
C2 - 39873282
SN - 0195-668X
VL - 46
SP - 2372
EP - 2390
JO - European heart journal
JF - European heart journal
IS - 25
ER -