Effect of body mass index on mortality for diabetic patients with aortic stenosis

Abstract Background Several studies suggest an "obesity paradox," associating obesity with better cardiovascular outcomes compared to normal or underweight individuals (1-3). Purpose This study explores the impact of body mass index (BMI) on mortality in patients with diabetic mellitus (DM) and aortic stenosis (AS). Methods This is a retrospective cohort study conducted at a tertiary centre. Between 2014 and 2019, patients with DM who underwent echocardiography were screened (4). Patients were enrolled if AS was diagnosed, according to established guidelines (5). Two echocardiography specialists independently reviewed the echocardiography in the cohort. The index date of the DM-AS cohort was the first AS diagnosis by echocardiography, and detailed data collection methods are described in previous studies (6,7). Patients were categorized as underweight, normal weight, or obese based on BMI (<18.5, 18.5 to 27, and >27 kg/m2, respectively). Outcomes included all-cause mortality, cardiovascular, and non-cardiovascular death, which were adjudicated by a central committee. The occurrence times of the outcomes of interest were determined using diagnosis codes from electronic health records, and medical records were reviewed until the last clinical visit or death. Results Among 74,835 DM patients, 734 had AS. Normal weight comprised 65.5% (n=481), underweight 4.1% (N=30), and 30.4% were obese. With a median follow-up time of 34 months, 285 patients (38.8%) experienced outcomes of death, comprising 93 patients (32.7%) with cardiovascular death and 192 patients (67.3%) with non- cardiovascular death. Underweight patients had significantly higher all-cause mortality (HR 1.96, 95% CI 1.22 – 3.14, p = 0.005), while obese patients had significantly lower mortality (HR 0.79, 95% CI 0.68 - 0.91, p=0.001) compared to the normal group. Regarding etiologies, underweight patients had a higher risk of non- cardiovascular death (HR 2.47, 95% CI 1.44-4.25, p = 0.001), while obese patients had a lower risk of cardiovascular death (HR 0.66, 95% CI 0.50-0.86, p=0.003). Subgroup analysis showed a consistent trend without significant interaction. To elucidate the interaction of BMI as a continuous variable with outcomes, restricted cubic spline analysis was applied. Cardiovascular death showed a negative association with BMI across available BMI levels, and non-cardiovascular death exhibited a U curve, with the lowest hazard ratio occurring when BMI was between 25 to 30. Conclusion Our study underscored the significance of both cardiovascular and non-cardiovascular deaths as crucial contributors to overall mortality in DM patients with AS. Being underweight is associated with increased non- cardiovascular death, while obesity is linked to less cardiovascular death. Proposed mechanisms include reduced frailty, enhanced tolerance to guideline-directed medical therapies (GDMTs), and heightened disease awareness in the obese group (8,9).Kaplan–Meier analysis for outcomesAssociation between BMI and outcomes