Impact of age on obesity paradox in patients with heart failure with reduced ejection fraction: assessment by brain 18F-FDG PET/CT imaging

Introduction: Although over weight and obesity are associated with incident cardiovascular diseases, including heart failure (HF), it paradoxically leads to a more favorable prognosis in patients with chronic HF, a phenomenon commonly defined as "obesity paradox". Aging negatively affects body metabolism and cardiac function, but its precise impact on obesity paradox remains elusive. Brain-heart axis plays a crucial role in the development of HF. This study aimed to assess the effect of age on the obesity paradox by brain metabolic imaging.

Methods: A total of 179 (mean age 57.3 ± 9.8 years old, 86.6% male, median body mass index (BMI) 25.8 ± 3.6 kg/m², and median left ventricular ejection fraction 19.9 ± 6.3%) patients with HF with reduced ejection fraction (HFrEF) who underwent gated single-photon emission computed tomography myocardial perfusion imaging and brain ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) were followed up for a median of 23.2 months. A total of 25 patients (13.9%) were died. Brain PET/CT images were processed using SPM12. The standardized uptake value (SUV) in the whole brain (SUV_whole-brain) and the SUV ratios (SUVR) in 90 brain regions were determined. Patients were classified into three groups based on BMI: obesity group (BMI ≥ 28 kg/m²), over weight group (28 > BMI ≥ 24 kg/m²), and normal weight group (BMI < 24 kg/m²). Additionally, patients were divided into younger group and elder group by the age of 60 years old. Survival curves were obtained by the Kaplan-Meier method and compared by the log-rank test. The mean values of continuous variables were compared between groups by one-way ANOVA or Student’s t-test. Bonferroni correction was applied in multiple comparisons. Categoric data was performed by x² test. Correlations were assessed by application of the Pearson product-moment test. Multiple stepwise linear regression was applied to analyze the factors associated with SUVR in both the right anterior cingulate and left insula.

Results: 1) There was no significant difference in comorbidities and treatment methods (medical therapy and revascularization) among normal weight, over weight, and obesity groups (all p > 0.05). The proportion of elderly adults (age > 60 years) in the normal or over weight groups was higher than that of obesity group (p = 0.034). 2) Survival in the normal group was significantly lower than that in the obesity group (p = 0.016). 3) No statistical difference of brain metabolism in the whole brain and 90 regions was found among the three groups (all p > 0.05). BMI was weakly correlated with the SUVR in the right anterior cingulate (r = 0.161, p = 0.031) and the left insula (r = 0.162, p = 0.031). 4) Multiple stepwise linear regression showed that both age and gender were independent factors for SUVR in the right anterior cingulate and left insula(all p < 0.001), while BMI was not. Multivariate Cox regression analysis showed that age was independently associated with all-cause mortality (hazard ratio = 1.058; p = 0.044), but BMI was not (hazard ratio = 0.896; p = 0.135). 5) Age was negatively correlated with SUVR in the autonomic-related regions (including left insula, right anterior cingulate, and bilateral caudate nucleus) (r: -0.203 ~ -0.316, all p < 0.05), while it was weakly positively correlated with SUVR in the left pallidum (r = 0.147, p = 0.049). In comparison with the younger group, hypometabolism in autonomic-related regions (including left insula, right anterior cingulate, bilateral caudate nucleus, right thalamus) was observed in the elder group (all p < 0.05).

Conclusions: In patients with HFrEF, the protective effects of obesity appeared to be affected by the aging-associated brain metabolism alterations in autonomic-related brain regions.

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