PATIENTS AND METHODS: Fasting plasma PP concentrations were measured in 104 overweight and obese subjects (46 men and 58 women). In the same subjects, total and regional adipose tissue, including total visceral adipose tissue (VAT) and total subcutaneous adipose tissue (TSAT), were measured using whole-body magnetic resonance imaging. Intrahepatocellular lipid content (IHCL) was quantified by proton magnetic resonance spectroscopy.
RESULTS: Fasting plasma PP concentrations positively and significantly correlated with both VAT (r = 0.57, P < .001) and IHCL (r = 0.51, P < .001), but not with TSAT (r = 0.02, P = .88). Fasting PP concentrations independently predicted VAT after controlling for age and sex. Fasting PP concentrations independently predicted IHCL after controlling for age, sex, body mass index (BMI), waist-to-hip ratio, homeostatic model assessment 2-insulin resistance, (HOMA2-IR) and serum concentrations of triglyceride (TG), total cholesterol (TC), and alanine aminotransferase (ALT). Fasting PP concentrations were associated with serum ALT, TG, TC, low- and high-density lipoprotein cholesterol, and blood pressure (P < .05). These associations were mediated by IHCL and/or VAT. Fasting PP and HOMA2-IR were independently significantly associated with hepatic steatosis (P < .01).
CONCLUSIONS: Pancreatic polypeptide is a novel predictor of visceral and liver fat content, and thus a potential biomarker for cardiovascular risk stratification and targeted treatment of patients with ectopic fat deposition.
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.