Koen W Streng1, Adriaan A Voors1, Hans L Hillege1, Stefan D Anker2, John G Cleland3, Kenneth Dickstein4,5, Gerasimos Filippatos6, Marco Metra7, Leong L Ng8, Piotr Ponikowski9, Nilesh J Samani8, Dirk J van Veldhuisen1, Aeilko H Zwinderman10, Faiez Zannad11, Kevin Damman1, Peter van der Meer1, Chim C Lang12. 1. University of Groningen, Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands. 2. Division of Cardiology and Metabolism, Department of Cardiology (CVK); and Berlin-Brandenburg Center for Regenerative Therapies (BCRT); German Centre for Cardiovascular Research (DZHK) partner site Berlin, Charité Universitätsmedizin Berlin, Berlin, Germany. 3. National Heart and Lung Institute, Imperial College London; and Robertson Centre for Biostatistics and Clinical Trials, University of Glasgow, Glasgow, UK. 4. University of Bergen, Bergen, Norway. 5. Stavanger University Hospital, Stavanger, Norway. 6. National and Kapodistrian University of Athens, School of Medicine, Department of Cardiology, Heart Failure Unit, Athens University Hospital Attikon, Athens, Greece. 7. Institute of Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy. 8. Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, and NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK. 9. Department of Heart Diseases, Wroclaw Medical University, and Cardiology Department, Military Hospital, Wroclaw, Poland. 10. Department of Epidemiology, Biostatistics and Bioinformatics, Academic Medical Centre, Amsterdam, The Netherlands. 11. Inserm CIC 1433, Université de Lorraine, CHU de Nancy, Nancy, France. 12. School of Medicine Centre for Cardiovascular and Lung Biology, Division of Medical Sciences, University of Dundee, Ninewells Hospital & Medical School, Dundee, UK.
Abstract
AIMS: A higher body mass index (BMI) is associated with better survival in heart failure (HF) patients, also known as the obesity paradox. However, BMI does not account for body composition. We therefore analysed the association between abdominal fat, measured via waist-to-hip ratio (WHR), BMI and all-cause mortality in patients with HF. METHODS AND RESULTS: For this analysis, 1738 patients from the Scottish BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) validation study were included. Patients without waist and hip measurements were excluded. WHR was defined as waist circumference/hip circumference, divided into tertiles and split for sex. A linear regression of principal components from an extensive panel of biomarkers was performed to provide insight in the pathophysiology behind a higher WHR. In total, 1479 patients were included, of which 33% were female and mean age was 75 ±11 years. A higher WHR was independently associated with a higher BMI, a higher prevalence of diabetes and higher New York Heart Association functional class. There was a significant interaction between sex and WHR on its association with mortality (P <0.001). In women, a higher WHR was associated with a higher mortality risk [hazard ratio (HR) 2.23, 95% confidence interval (CI) 1.37-3.63; P =0.001], whereas no significant association was found in men (HR 0.87, 95% CI 0.63-1.20; P = 0.409). We found a strong association between a higher WHR and elevated markers of inflammation and MAPK cascade in women, while these associations were less profound in men. CONCLUSIONS: A higher WHR was associated with a higher risk of death in female but not in male HF patients. These findings challenge the obesity paradox, and suggest that fat deposition is pathophysiologically harmful and may be a target for therapy in female patients with HF.
AIMS: A higher body mass index (BMI) is associated with better survival in heart failure (HF) patients, also known as the obesity paradox. However, BMI does not account for body composition. We therefore analysed the association between abdominal fat, measured via waist-to-hip ratio (WHR), BMI and all-cause mortality in patients with HF. METHODS AND RESULTS: For this analysis, 1738 patients from the Scottish BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) validation study were included. Patients without waist and hip measurements were excluded. WHR was defined as waist circumference/hip circumference, divided into tertiles and split for sex. A linear regression of principal components from an extensive panel of biomarkers was performed to provide insight in the pathophysiology behind a higher WHR. In total, 1479 patients were included, of which 33% were female and mean age was 75 ±11 years. A higher WHR was independently associated with a higher BMI, a higher prevalence of diabetes and higher New York Heart Association functional class. There was a significant interaction between sex and WHR on its association with mortality (P <0.001). In women, a higher WHR was associated with a higher mortality risk [hazard ratio (HR) 2.23, 95% confidence interval (CI) 1.37-3.63; P =0.001], whereas no significant association was found in men (HR 0.87, 95% CI 0.63-1.20; P = 0.409). We found a strong association between a higher WHR and elevated markers of inflammation and MAPK cascade in women, while these associations were less profound in men. CONCLUSIONS: A higher WHR was associated with a higher risk of death in female but not in male HFpatients. These findings challenge the obesity paradox, and suggest that fat deposition is pathophysiologically harmful and may be a target for therapy in female patients with HF.
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