Trial reportEuropean heart journal2025
Near-universal prevalence of central adiposity in heart failure with preserved ejection fraction: the PARAGON-HF trial.
Trial report in European heart journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT01920711 (A Multicenter, Randomized, Double-blind, Parallel Group, Active-controlled Study to Evaluate the Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients), which is not on this map. Cited by 41 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Multicenter, Randomized, Double-blind, Parallel Group, Active-controlled Study to Evaluate the Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients (NYHA Class II-IV) With Preserved Ejection Fraction (PARAGON-HF)
Who cites it
41 citing papers in PubMed.
- Review
- Adipose Tissue, Natriuretic Peptides, and HFpEF: Clinical Implications of the Obesity Paradox.Biomedicines · 2026Review
- The Pathophysiological Interrelationship Between Metabolic Dysfunction-Associated Steatotic Liver Disease and Cardiovascular Disease.Antioxidants (Basel, Switzerland) · 2026Review
- Review
- Concurrence of the Core Mechanistic Tenets of the American Heart Association Statement on the Cardiovascular-Kidney-Metabolic Syndrome and the Adipokine Hypothesis of Heart Failure With Preserved Ejection Fraction.Diabetes, obesity & metabolism · 2026Article
- Risk factor heterogeneity across cardiovascular disease outcomes in treatment-eligible hypertensive patients.Journal of hypertension · 2026Article
- Heart Failure with Preserved Ejection Fraction as a Multisystem Syndrome: A Mechanistically Anchored Endotype Framework for Precision Therapy.Journal of clinical medicine · 2026Review
- Adiposity Rebound or Fat-Free Mass Anabolism in Children-Challenging a 42-Year-Old BMI Puzzle with Waist-to-Height Ratio: The ASNF-NNF 2025 Inaugural Flemming Quaade Award for Innovation in Childhood Obesity Lecture.The Journal of nutrition · 2026Article
- Cardiac Magnetic Resonance to Define Myocardial Structure in Obesity-Associated Heart Failure.Current cardiology reports · 2026Review
- DXA-measured truncal adiposity in adolescence but not in childhood longitudinally predicts worsening cardiac outcomes.European journal of endocrinology · 2026Article
- Novel Waist-to-Height Ratio Estimated Fat Mass Pediatric Cut-offs Predict Hypertension Better than Body Mass Index in Multiracial United States Youths and Adults: The National Health and Nutrition Examination Survey 2015-2023 Cycle.The Journal of nutrition · 2026Article
- Benefits of sacubitril/valsartan alone and in combination with dapagliflozin in a preclinical female model of cardiometabolic and age-related cardiac dysfunction.Cardiovascular diabetology · 2026Article
- Longitudinal Insights Into Pediatric Hypertension, Cardiac Consequences, and Physical Activity.Current hypertension reports · 2026Review
- Long-term trends in central obesity in England: an age-period-cohort approach.International journal of obesity (2005) · 2026Article
- Standard and Non-standard Cardiovascular Risk Factors in Ischemic Heart Disease and Atherosclerotic Cardiovascular Disease: A Clinical Review.Internal medicine (Tokyo, Japan) · 2026Review
- Pharmacologic treatment of obesity in adults: Standards of care in overweight and obesity.BMJ open diabetes research & care · 2026Review
- Do obesity and visceral adiposity promote heart failure with reduced ejection fraction?European heart journal · 2026Review
- Left ventricular hypertrophy and myocardial fibrosis in heart failure with preserved ejection fraction: mechanisms and treatment.European heart journal · 2026Review
- Joint assessment of white blood cell-to-HDL cholesterol ratio and waist-to-height-hemoglobin A1c for cardiometabolic multimorbidity risk: a prospective cohort study and cross-sectional study.Frontiers in nutrition · 2026Article
- Metabolic dysfunction-associated steatotic liver disease and heart failure with preserved ejection fraction: mechanisms and clinical implications from a heart-liver metabolic axis perspective.Frontiers in pharmacology · 2026Review
Corrections and comments
- Erratum issued
Authors and funding
18 authors.
Funding
Abstract
BACKGROUND AND
aimsAn 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.
methodsThe PARAGON-HF trial randomized 4796 patients with heart failure (HF) 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.
resultsAbout half (49%) of the participants were considered obese by BMI (≥30 kg/m2), but nearly every patient (96%) had central adiposity (WHtR ≥.5). Among patients who were not obese (BMI <30 kg/m2), 860 (37%) had marked central adiposity (WHtR ≥.6). Higher BMI and WHtR were both associated with higher risk of total HF hospitalizations, but as compared with BMI, WHtR was linearly associated with HF 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 HF 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.
conclusionsIn PARAGON-HF, in contrast with BMI, nearly every patient with HFpEF had central adiposity (as assessed by WHtR), and the risks of adverse HF 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. CLINICAL
trial registrationhttps://www.clinicaltrials.gov. Unique identifier: NCT01920711.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.