Cardiovascular-renal-metabolic syndrome and mortality in non-obstructive coronary artery disease: prognostic impact of diabetes in women
D P S Martins, R A Mansur, M E Bergamo, F B La Puente, L A M Cesar, A P MansurAbstract
Introduction
In non-obstructive coronary artery disease (NOCA), the absence of significant epicardial stenosis shifts the prognostic focus to structural, functional, and systemic mechanisms. In this context, interactions among left ventricular remodeling, renal dysfunction, and metabolic disorders reflect activation of common pathways, including chronic inflammation, oxidative stress, endothelial dysfunction, and neuroendocrine activation, that together comprise the cardiovascular-renal-metabolic syndrome (CRMS). Understanding these interactions, particularly by sex, is fundamental for risk stratification and clinical management.
Purpose
To determine the main predictors of mortality in patients with NOCA, with emphasis on sex differences.
Methods
Observational study of 716 patients with NOCA confirmed by coronary angiography, stratified by sex and clinical stage (survivors and non-survivors). Clinical variables, comorbidities, laboratory tests, echocardiographic parameters, and renal function were examined. Multivariate Cox regression models were constructed for the total population and for each sex.
Results
Death was associated with advanced age and the most severe markers of CRMS, including lower left ventricular ejection fraction (LVEF), higher left ventricular mass index (LVMI), and worse renal function. Kaplan-Meier curves showed that diabetes significantly affects mortality only in females (p=0.022) (Figure). In the overall multivariate analysis, myocardial infarction (HR 1.010; 95% CI: 1.007–1.013), creatinine clearance <60 mL/min (HR 2.272; 95% CI: 1.852–2.786), age (HR 1.021; 95% CI: 1.011–1.031), and diabetes mellitus (HR 1.414; 95% CI: 1.160–1.724) were independent predictors of death. Among men, creatinine clearance <60 mL/min (HR 2.380; 95% CI: 1.750–3.145), LVEF (HR 0.978; 95% CI: 0.968–0.989), and LVMI (HR 1.008; 95% CI: 1.003–1.012) were associated with mortality. In women, LVMI (HR 1.012; 95% CI: 1.008–1.016), creatinine clearance <60 mL/min (HR 2.328; 95% CI: 1.746–3.104), and diabetes mellitus (HR 1.455; 95% CI: 1.096–1.932) were the main independent determinants.
Conclusion
In patients with NOCA, diabetes mellitus acts as a critical and sex-specific determinant of mortality, being an independent predictor of death exclusively in women. In these patients, diabetes is the central axis of the CRMS, increasing systemic vulnerability and the risk of death. These results reinforce the need for preventive strategies and personalized therapy specifically for the management of diabetes in the female population with NOCA.Figure