Higher ACE2 expression levels in epicardial cells than subcutaneous stromal cells from patients with cardiovascular disease: Diabetes and obesity as possible enhancer.

AIMS: Obesity, diabetes and cardiovascular disease are associated with COVID-19 risk and severity. Because epicardial adipose tissue (EAT) expresses ACE2, we wanted to identify the main factors associated with ACE2 levels and its cleavage enzyme, ADAM17, in epicardial fat. MATERIALS AND METHODS: Epicardial and subcutaneous fat biopsies were obtained from 43 patients who underwent open-heart surgery. From 36 patients, biopsies were used for RNA expression analysis by real-time PCR of ACE1, ACE2 and ADAM17. From 8 patients, stromal vascular cells were submitted to adipogenesis or used for studying the treatment effects on gene expression levels. Soluble ACE2 was determined in supernatants by ELISA. RESULTS: Epicardial fat biopsies expressed higher levels of ACE2 (1.53 [1.49-1.61] vs 1.51 [1.47-1.56] a.u., P < .05) and lower ADAM17 than subcutaneous fat (1.67 [1.65-1.70] vs 1.70 [1.66-1.74] a.u., P < .001). Both genes were increased in epicardial fat from patients with type 2 diabetes mellitus (T2DM) (1.62 [1.50-2.28] vs 1.52 [1.49-1.55] a.u., P = .05 for ACE2 and 1.68 [1.66-1.78] vs 1.66 [1.63-1.69] a.u., P < .05 for ADAM17). Logistic regression analysis determined that T2DM was the main associated factor with epicardial ACE2 levels (P < .01). The highest ACE2 levels were found on patients with diabetes and obesity. ACE1 and ACE2 levels were not upregulated by antidiabetic treatment (metformin, insulin or thiazolidinedione). Its cellular levels, which were higher in epicardial than in subcutaneous stromal cells (1.61 [1.55-1.63] vs 1 [1-1.34]), were not correlated with the soluble ACE2. CONCLUSION: Epicardial fat cells expressed higher levels of ACE2 in comparison with subcutaneous fat cells, which is enhanced by diabetes and obesity presence in patients with cardiovascular disease. Both might be risk factors for SARS-CoV-2 infection.

Exploring The Obesity Paradox In Atrial Fibrillation. AFBAR (Atrial Fibrillation Barbanza Area) Registry Results.

INTRODUCTION AND OBJECTIVES: Previous studies have described an inverse relationship between obesity and adverse events in a variety of conditions. Our aim was to investigate the relationship between obesity and prognosis in patients with atrial fibrillation. METHODS: We studied 746 patients who were prospectively included, between January and April 2008, in the AFBAR (Atrial Fibrillation in BARbanza area) registry. Patients were categorized into 3 body mass index groups using baseline measurements: normal (< 25 kg/m2), overweight (25-30 kg/m2), and obese (≥30 kg/m2). Survival free from the composite endpoint hospitalization for cardiovascular causes or all-cause mortality was compared across the 3 body mass index groups. A multivariable Cox proportional hazard regression was also performed to determine the independent effect of obesity as well as overweight, with respect to normal body mass index as a reference category, regarding the study endpoint. Median follow-up time was 36 (28-36) months. RESULTS: 49.3% were obese and 38.2% had overweight. The composite endpoint rate was 70.9%, 67.5%, and 57.6% for obese, overweight, and normal weight patients, respectively (log rank test; p=0.02). An inverse association of obesity with a favorable prognosis persisted even after multivariable adjustment: hazard ratio 0.668; 95% confidence interval 0.449-0.995; p=0.047. Hazard ratio of overweight, however, was 0.741; 95% confidence interval: 0.500-1.098; p=0.096. CONCLUSIONS: Obesity, defined as a body mass index ≥ 30 kg/m2, is associated with better prognosis in a community-based cohort of patients with atrial fibrillation.