Associations between non-insulin-based insulin resistance surrogates and pulmonary hypertension due to left heart failure: a multicenter cohort study

Abstract

Abstract Background Insulin resistance (IR) has been reported to have a close relationship with the development and adverse outcomes of various cardiovascular disorders, while its association with pulmonary hypertension due to left heart failure (PH-HF) remains to be elucidated. This study aimed to evaluate the association between non-insulin-based IR surrogates and the presence and outcomes of PH-HF. Methods A retrospective analysis of a prospective cohort of patients with left heart failure undergoing right heart catheterization was performed. The primary endpoint was all-cause mortality or transplantation. PH-HF was hemodynamically defined as a mean pulmonary arterial pressure > 20 mmHg and a pulmonary arterial wedge pressure > 15 mmHg. IR was assessed by four non-insulin-based indices, including the metabolic score for IR (METS-IR), triglyceride to high-density lipoprotein cholesterol (TG/HDL) ratio, triglyceride and glucose (TyG) index, and triglyceride-glucose-body mass index (TyG-BMI). The correlation between IR surrogates and the presence of pulmonary hypertension was determined by restricted cubic spline analysis and logistic regression analysis. Nested logistic regression models and residual analyses were applied to address the contribution of BMI to METS‑IR and TyG‑BMI. Cox proportional hazards models and the Fine–Gray subdistribution hazard models were used to identify the association between variables and the prognosis of patients with PH-HF. Results A total of 229 patients with left heart failure were enrolled, and 142 patients were classified as PH-HF. During a median follow-up of 25.2 months, 87 patients met the primary endpoint. Restricted cubic splines demonstrated a linear association between IR surrogates and the presence of PH-HF. METS-IR and TyG-BMI showed consistently significant associations with PH-HF both in univariate logistic regression analyses [odds ratio (OR): 1.79, 95% confidence interval (CI): 1.30–2.45, p < 0.001, and OR:1.43, 95% CI: 1.08–1.91, p = 0.014, respectively] and in multivariate logistic models (OR: 2.43, 95% CI: 1.37–4.34, p = 0.003, and OR: 2.39, 95% CI: 1.36–4.23, p = 0.003, respectively), whereas nested logistic regression and residual analyses revealed that METS-IR and TyG-BMI yielded no incremental value beyond BMI. Cox regression analyses indicated that higher levels of METS-IR (hazard ratio: 0.63, 95% confidence interval: 0.46–0.85, p = 0.002) and TyG-BMI (hazard ratio: 0.60, 95% confidence interval: 0.43–0.82, p = 0.002) were significantly related to better transplant-free survival of patients with PH-HF. In competing risk models for death or transplantation, only TyG-BMI remained significantly associated with transplantation (sHR: 0.68, 95%CI: 0.47–0.99, p = 0.042). Conclusions IR surrogates were associated with PH-HF, yet these associations appear mainly attributable to BMI rather than independent effects of IR. Elevated IR surrogate levels were linked to improved transplant-free survival among patients with PH-HF, although this prognostic relationship was not consistently observed in competing-risk analyses for death or transplantation. Trial registration NCT02164526 (ClinicalTrials.gov).