METHODS AND ANALYSIS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols statement was used as a template for this protocol. A systematic search of Medline, Embase and Global Health from database inception to present will be conducted to identify prospective studies reporting on the associations between major measures of body composition (body mass index, waist circumference, waist-hip ratio, total body fat, visceral adiposity tissue and lean mass) and risk of heart failure. Article screening and selection will be performed by two reviewers independently, and disagreements will be adjudicated by consensus or by a third reviewer. Data from eligible articles will be extracted, and article quality will be assessed using the Newcastle-Ottawa Scale. Relative risks (and 95% CIs) will be pooled in a fixed effect meta-analysis, if there is no prohibitive heterogeneity of studies as assessed using the Cochrane Q statistic and I2 statistic. Subgroup analyses will be by age, sex, ethnicity and heart failure subtypes. Publication bias in the meta-analysis will be assessed using Egger's test and funnel plots.
ETHICS AND DISSEMINATION: This work is secondary analyses on published data and ethical approval is not required. We plan to publish results in an open-access peer-reviewed journal, present it at international and national conferences, and share the findings on social media.
PROSPERO REGISTRATION NUMBER: CRD42020224584.
METHODS AND RESULTS: We prospectively studied 3886 Asian patients (60 ± 13 years, 21% women) with HF (ejection fraction ≤40%) from 11 regions in the Asian Sudden Cardiac Death in Heart Failure study. Anaemia was defined as haemoglobin <13 g/dL (men) and <12 g/dL (women). Ethnic groups included Chinese (33.0%), Indian (26.2%), Malay (15.1%), Japanese/Korean (20.2%), and others (5.6%). Overall, anaemia was present in 41%, with a wide range across ethnicities (33-54%). Indian ethnicity, older age, diabetes, and chronic kidney disease were independently associated with higher odds of anaemia (all P
METHODS AND RESULTS: We compared clinical characteristics and treatment approaches between patients with or without a history of COPD, before and after 1:2 propensity matching (for age, sex, geographical region, income level, and ethnic group) in 5232 prospectively recruited patients with HF and reduced ejection fraction (HFrEF, <40%) from 11 Asian regions (Northeast Asia: South Korea, Japan, Taiwan, Hong Kong, and China; South Asia: India; Southeast Asia: Thailand, Malaysia, Philippines, Indonesia, and Singapore). Among the 5232 patients with HFrEF, a history of COPD was present in 8.3% (n = 434), with significant variation in geography (11.0% in Northeast Asia vs. 4.7% in South Asia), regional income level (9.7% in high income vs. 5.8% in low income), and ethnicity (17.0% in Filipinos vs. 5.2% in Indians) (all P
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.