Sex-Specific Impact of Different Obesity/Metabolic Phenotypes on Long-Term Cardiovascular Outcomes in Acute Coronary Syndrome Patients

Abstract

Obesity, a major risk factor for acute coronary syndrome (ACS), is a multifaceted disease with different metabolic phenotypes and sex-specific features. Here, we evaluated the long-term cardiovascular risk by different obesity/metabolic phenotypes and by sex in ACS patients. The occurrence of the composite outcome of death, nonfatal reinfarction with or without PCI and/or stroke was evaluated in 674 patients (504 men; 170 women), consecutively hospitalized for ACS and followed-up for 7 years, who were stratified in metabolically healthy (MHNW) and unhealthy normal weight (MUNW), and in metabolically healthy (MHO) and unhealthy obese (MUO) groups. At baseline, 54.6% of patients were included in the MHNW group, 26.4% in the MUNW, 5.9% in the MHO and 13.1% in the MUO, with no sex-differences in the distribution of phenotypes. The overall rate of major outcome (100 person-years) in the reference group (MHNW) was higher in men than in women (RR: 1.19 vs. 0.6). The Kaplan–Meier curves for cumulative survival free from cardiovascular events according to obesity/metabolic status diverged significantly according to sex (log rank test, p = 0.006), this effect being more prominent in men (log 11.20; p = 0.011), than in women (log 7.98; p = 0.047). Compared to MHNW, the risk increased in obese men (RR: 2.2; 95% 1.11–1.54 in MUO group), whereas in women the risk was confined to metabolically unhealthy subjects (RR: 3.2; 95% CI 1.23–9.98, MUNW group). Our data show a sex-specific impact of obesity phenotypes on long-term cardiovascular risk in patients hospitalized for ACS.

Relationship between obesity severity, metabolic status and cardiovascular disease in obese adults

“…Similar to our results, other studies from The Health Improvement Network (THIN) cohort and Programme de Médicalisation des Systèmes d'Information (PMSI) database demonstrated that metabolic severity was associated with increased CVD risk in a dose‐dependent manner 9,10 . Furthermore, previous studies only stratified participants into four groups according to BMI measures (obese/nonobese) and metabolic status (healthy/unhealthy) for analyses, failing to take obesity severity into account 10–12 . Unlike their studies, we focussed on the obese population with different obesity severity and observed a significant interaction between obesity severity and metabolic status on an additive scale regarding their CVD risk.…”

“…24 Imbalzano et al found the CVD risk in MHO participants was nonsignificantly higher than in metabolically healthy adults with normal weight but significantly lower than in MUO participants. 11 Hinnouho et al found that the CVD risk in MHO participants was higher than in metabolically healthy adults with normal weight but was similar to the MUO participants. 7,25 Zhou et al found those with MHO had a higher CVD risk than metabolically healthy adults with normal weight, whereas the MHO participants had a significantly lower CVD risk than in MUO.…”

“…Besides, the debate over CVD risk related to MHO continues 24 . Imbalzano et al found the CVD risk in MHO participants was nonsignificantly higher than in metabolically healthy adults with normal weight but significantly lower than in MUO participants 11 . Hinnouho et al found that the CVD risk in MHO participants was higher than in metabolically healthy adults with normal weight but was similar to the MUO participants 7,25 .…”

“…Based on various metabolic features including blood pressure, glucose tolerance and lipid profile, obesity can be categorized as metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) 5 . Previous studies investigated the metabolic status in relation to the risk of CVD with inconsistent conclusions reported, requiring more evidence for clarification 6–12 . Moreover, most prior studies have explored the relationship in the mixed populations that included adults with normal weight, overweight and obesity 11,12 .…”

“…5 Previous studies investigated the metabolic status in relation to the risk of CVD with inconsistent conclusions reported, requiring more evidence for clarification. [6][7][8][9][10][11][12] Moreover, most prior studies have explored the relationship in the mixed populations that included adults with normal weight, overweight and obesity. 11,12 Given both the heterogeneity between adults with or without obesity and the increasing prevalence of obesity worldwide, evaluating the relationship between metabolic status and CVD risk in participants with obesity could provide evidence for enhanced risk stratification and effective CVD prevention in this specific population, from the perspective of public health.…”