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February 19, 2025Cardiovascular Diabetology12 citationsOpen Access

Association of insulin resistance surrogates with disease severity and adverse outcomes in chronic thromboembolic pulmonary hypertension: a multicenter cohort study

LGLuyang GaoChinese Academy of Medical Sciences & Peking Union Medical CollegeSZSicheng ZhangChinese Academy of Medical Sciences & Peking Union Medical CollegeSLSicong LiChinese Academy of Medical Sciences & Peking Union Medical College

Key Result

A 1.0-standard deviation increase in the metabolic score for insulin resistance (METS-IR) independently predicted a 27% higher risk of clinical worsening (HR 1.27) in patients with chronic thromboembolic pulmonary hypertension.

Study Design

Type

Cohort (n=516)

Multicenter

Yes

Structured PICO

Do insulin resistance surrogates predict clinical worsening in patients with chronic thromboembolic pulmonary hypertension?

P
Population
516 patients diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH), median age 57.0 years, 48.1% female, 96.9% Han Chinese, treated at three level-3 hospitals in China.
I
Intervention
Higher levels of insulin resistance surrogates (METS-IR, TyG index, TyG-BMI index, TG/HDL-C ratio)
C
Comparator
Lower levels of insulin resistance surrogates
O
Outcome
Clinical worsening (first occurrence of all-cause death, lung transplantation, unplanned PH-related hospitalization, or re-hospitalization due to heart failure)composite

The metabolic score for insulin resistance (METS-IR) is an independent predictor of clinical worsening in patients with chronic thromboembolic pulmonary hypertension and improves the predictive ability of the COMPERA 2.0 risk score.

Main Result

Effect estimate: HR 1.27 (95% CI 1.06-1.53)

p-value: p=0.009

Limitations

  • Retrospective design inherently limits the ability to establish causal relationships.
  • Did not collect dynamic data on blood glucose, lipid levels, or BMI.
  • Residual confounding due to evolving management strategies over the prolonged study period cannot be ruled out.
  • Utilized non-insulin-based IR indices rather than direct insulin measurements.

Abstract

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a severely progressive disease that leads to right heart failure and death. Previous studies have shown that diabetes and insulin resistance (IR) are closely related to pulmonary hypertension, but the role of IR in patients with CTEPH remains unexplored. In this study, we investigated the relationship between four insulin resistance indices and disease severity, hemodynamic parameters, and adverse outcomes in patients with CTEPH. METHODS: We conducted a multicenter, retrospective cohort study involving 516 patients diagnosed with CTEPH between January 2013 and December 2022. 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 were used to quantify IR levels in patients with CTEPH. The primary endpoint events were clinical worsening. Multivariable Cox regression, restricted cubic splines, and receiver operating characteristic analyses were used to evaluate the predictive value of surrogates for IR. RESULTS: Compared with in low to intermediate-low risk patients, the METS-IR (36.2 ± 6.7 vs. 37.7 ± 8.7, p = 0.038) and TyG-BMI index (204.0 ± 36.2 vs. 212.6 ± 46.5, p = 0.022) were significantly increased in high to intermediate-high risk patients. METS-IR correlated with markers of disease severity, such as World Health Organization functional class, 6-minute walk distance, and N-terminal pro-brain natriuretic peptide levels. During a mean of 2.5 years' follow-up, 110 participants experienced all-cause death or worsening condition. METS-IR independently predicted clinical worsening (hazard ratio: 1.27; 95% confidence interval 1.06-1.53 per 1.0-standard deviation increment, p = 0.009) after fully adjusting for covariates. Adding METS-IR to the COMPERA 2.0 risk score significantly improved its predictive ability, reclassification and discrimination ability. CONCLUSIONS: METS-IR is an independent predictor of clinical worsening in patients with CTEPH. It offers a convenient marker for assessing disease severity and long-term outcomes in clinical risk assessment.

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Cite This Study

Gao et al. (2025) conducted a cohort in Chronic thromboembolic pulmonary hypertension (CTEPH) (n=516). Metabolic score for insulin resistance (METS-IR) was evaluated on Clinical worsening (all-cause death, lung transplantation, unplanned PH-related hospitalization, or re-hospitalization due to heart failure) (HR 1.27, 95% CI 1.06-1.53, p=0.009). A 1.0-standard deviation increase in the metabolic score for insulin resistance (METS-IR) independently predicted a 27% higher risk of clinical worsening (HR 1.27) in patients with chronic thromboembolic pulmonary hypertension.

synapsesocial.com/papers/6a171cda0f965e9c137c00f7https://doi.org/10.1186/s12933-025-02630-x
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