Association of obesity with heart failure outcomes in 11 Asian regions: A cohort study

Abstract

Background: Asians are predisposed to a lean heart failure (HF) phenotype. Data on the 'obesity paradox', reported in Western populations, are scarce in Asia and have only utilised the traditional classification of body mass index (BMI). We aimed to investigate the association between obesity (defined by BMI and abdominal measures) and HF outcomes in Asia.

Methods and findings: Utilising the Asian Sudden Cardiac Death in Heart Failure (ASIAN-HF) registry (11 Asian regions including Taiwan, Hong Kong, China, India, Malaysia, Thailand, Singapore, Indonesia, Philippines, Japan, and Korea; 46 centres with enrolment between 1 October 2012 and 6 October 2016), we prospectively examined 5,964 patients with symptomatic HF (mean age 61.3 ± 13.3 years, 26% women, mean BMI 25.3 ± 5.3 kg/m2, 16% with HF with preserved ejection fraction [HFpEF; ejection fraction ≥ 50%]), among whom 2,051 also had waist-to-height ratio (WHtR) measurements (mean age 60.8 ± 12.9 years, 24% women, mean BMI 25.0 ± 5.2 kg/m2, 7% HFpEF). Patients were categorised by BMI quartiles or WHtR quartiles or 4 combined groups of BMI (low, <24.5 kg/m2 [lean], or high, ≥24.5 kg/m2 [obese]) and WHtR (low, <0.55 [thin], or high, ≥0.55 [fat]). Cox proportional hazards models were used to examine a 1-year composite outcome (HF hospitalisation or mortality). Across BMI quartiles, higher BMI was associated with lower risk of the composite outcome (ptrend < 0.001). Contrastingly, higher WHtR was associated with higher risk of the composite outcome. Individuals in the lean-fat group, with low BMI and high WHtR (13.9%), were more likely to be women (35.4%) and to be from low-income countries (47.7%) (predominantly in South/Southeast Asia), and had higher prevalence of diabetes (46%), worse quality of life scores (63.3 ± 24.2), and a higher rate of the composite outcome (51/232; 22%), compared to the other groups (p < 0.05 for all). Following multivariable adjustment, the lean-fat group had higher adjusted risk of the composite outcome (hazard ratio 1.93, 95% CI 1.17-3.18, p = 0.01), compared to the obese-thin group, with high BMI and low WHtR. Results were consistent across both HF subtypes (HFpEF and HF with reduced ejection fraction [HFrEF]; pinteraction = 0.355). Selection bias and residual confounding are potential limitations of such multinational observational registries.

Conclusions: In this cohort of Asian patients with HF, the 'obesity paradox' is observed only when defined using BMI, with WHtR showing the opposite association with the composite outcome. Lean-fat patients, with high WHtR and low BMI, have the worst outcomes. A direct correlation between high WHtR and the composite outcome is apparent in both HFpEF and HFrEF.

Trial registration: Asian Sudden Cardiac Death in HF (ASIAN-HF) Registry ClinicalTrials.gov Identifier: NCT01633398.

Fig 1. Central illustration of 4 combined groups of BMI (high, ≥24.5 kg/m² [obese], or low, <24.5 kg/m² [lean]) and waist-to-height ratio (high, ≥0.55 [fat], or low, <0.55 [thin]).

QoL refers to the Kansas City Cardiomyopathy Questionnaire total symptom score. Key differences in characteristics between BMI/WHtR groups in bold. abv, above; BMI, body mass index; HFpEF, heart failure with preserved ejection fraction; NYHA, New York Heart Association; QoL, quality of life; WHtR, waist-to-height ratio.

Fig 2. Prevalence of HFpEF and HFrEF stratified by body mass index and waist-to-height ratio.

HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction.

Fig 3. Association of BMI and waist-to-height ratio with the composite outcome using cubic spline regression models and Cox proportional hazards models.

Cubic spline regression models (A and C); Cox proportional hazards models (B and D). HR, hazard ratio.

Fig 4. Kaplan–Meier survival curves of the composite outcome for combined BMI/WHtR groups.

BMI, body mass index; WHtR, waist-to-height ratio.