Photo Credit: Rasi Bhadramani
The following is a summary of “Association of insulin resistance surrogates with disease severity and adverse outcomes in chronic thromboembolic pulmonary hypertension: a multicenter cohort study,” published in the February 2025 issue of the Cardiovascular Diabetology by Gao et al.
Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive and life-threatening condition characterized by persistent pulmonary arterial obstruction, leading to right heart failure and increased mortality. While previous studies have demonstrated a strong association between diabetes, insulin resistance (IR), and pulmonary hypertension, the specific role of IR in patients with CTEPH remains largely unexplored. This multicenter, retrospective cohort study aimed to evaluate the relationship between four IR indices and disease severity, hemodynamic parameters, and adverse clinical outcomes in patients with CTEPH. A total of 516 patients diagnosed with CTEPH between January 2013 and December 2022 were included in the analysis. IR was quantified using the metabolic score for IR (METS-IR), triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride and glucose (TyG) index, and triglyceride-glucose-body mass (TyG-BMI) index.
The primary study endpoint was clinical worsening, including all-cause mortality and disease progression. Statistical analyses, including multivariable Cox regression, restricted cubic splines, and ROC analyses, were employed to assess the predictive value of IR surrogates. Results indicated that METS-IR (36.2 ± 6.7 vs. 37.7 ± 8.7, p = 0.038) and TyG-BMI (204.0 ± 36.2 vs. 212.6 ± 46.5, p = 0.022) were significantly elevated in patients classified as high- to intermediate-high risk compared to those at low- to intermediate-low risk. Additionally, METS-IR demonstrated significant correlations with established markers of disease severity, including World Health Organization functional class, 6-minute walk distance, and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Over a mean follow-up period of 2.5 years, 110 patients experienced clinical worsening or death. Importantly, METS-IR emerged as an independent predictor of clinical worsening (hazard ratio: 1.27; 95% confidence interval: 1.06–1.53 per 1.0-standard deviation increment, p = 0.009) after full adjustment for covariates.
Furthermore, integrating METS-IR into the COMPERA 2.0 risk score significantly enhanced its predictive accuracy, reclassification, and discrimination ability. These findings underscore the potential utility of METS-IR as a novel, non-invasive marker for risk stratification in CTEPH, providing valuable insights into disease severity and long-term prognosis. Given its ease of measurement and strong prognostic value, METS-IR may serve as a clinically relevant tool for refining CTEPH risk assessment and guiding therapeutic decision-making. Future research should further explore the mechanistic links between IR and pulmonary vascular remodeling, as well as the potential benefits of targeted metabolic interventions in improving CTEPH outcomes.
Source: cardiab.biomedcentral.com/articles/10.1186/s12933-025-02630-x
