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Insulin Resistance Correlates With Disease Severity In CTEPH: Study
Insulin resistance or IR — a reduced response of body tissues to insulin, a hormone that regulates blood sugar levels — was found to correlate with disease severity in people with chronic thromboembolic pulmonary hypertension (CTEPH), according to a new study from researchers in China.
Further, the team determined that an indicator of insulin resistance, called METS-IR, may help predict clinical worsening — ranging from the need for PH-related hospitalization or a lung transplant to all-cause death — in CTEPH patients.
"METS-IR is an independent predictor of clinical worsening in patients with CTEPH," the researchers wrote. "It offers a convenient marker for assessing disease severity and long-term outcomes in clinical risk assessment."
In people, IR results in high blood sugar and contributes to diabetes. The metabolic score for IR, or METS-IR, assesses insulin resistance based on blood sugar levels, fatty molecules including triglycerides and HDL cholesterol, and body mass index, known as BMI, which is a measure of body fat based on a ratio of weight to height.
According to the researchers, "this is the first study to compare the relationships of surrogate markers for [insulin resistance] with disease severity and adverse outcomes in patients with CTEPH." The team noted that their work "provides novel clinical evidence for the risk stratification of patients with CTEPH."
The study, "Association of insulin resistance surrogates with disease severity and adverse outcomes in chronic thromboembolic pulmonary hypertension: a multicenter cohort study," was published in the journal Cardiovascular Diabetology.
Worse disease severity found in patients with greater insulin resistanceCTEPH is a type of pulmonary hypertension (PH), or high pressure in the pulmonary arteries — the blood vessels that carry blood through the lungs — caused by the formation of blood clots. Such clots obstruct blood flow in the pulmonary arteries, ultimately leading to a shortage of oxygen to tissues and right heart failure. Studies have shown that diabetes and insulin resistance are associated with PH.
However, "the ability of [insulin resistance indices] to predict disease severity and long-term adverse outcomes in patients with CTEPH has not yet been reported," the researchers wrote.
To learn more, the team conducted a retrospective study involving 516 CTEPH patients diagnosed or treated at three specialized hospitals in China between January 2013 and December 2022. The patients had a median age of 57, and nearly all were of Han ethnicity (96.9%). Slightly more than half (51.9%)were men.
During a median follow-up of nearly 25 months, or about two years, 110 patients — 21.3% in total — experienced clinical worsening. This comprised all-cause death, lung transplant, unplanned PH-related hospitalization, and re-hospitalization due to heart failure.
These patients also had more severe disease according to the World Health Organization functional class, or WHO-FC, than those without clinical worsening. Lower exercise capacity, as seen in a test of six-minute walking distance, and higher levels of NT-proBNP, a marker of heart damage, were also seen in individuals with clinical worsening versus those without.
Data also showed that the patients with clinical worsening had lower levels of cholesterol (4.00 vs. 4.39 mmol/L), changes in heart structure and function, higher pulmonary arterial pressure, and lower oxygen levels in the blood. In addition, they had diabetes more often (41.8% vs. 23.4%), and had more pulmonary vascular resistance, which is resistance to blood flow in pulmonary blood vessels.
Most patients (96.7%) were treated with anticoagulants, medications that prevent the formation of blood clots, and about 74% were given PH-targeted therapies during their initial hospitalization.
With METS-IR, each increase linked to 27% greater risk of clinical worseningRegarding insulin resistance, the METS-IR index was significantly higher in people with clinical worsening (39 vs. 36.5). Also, METS-IR correlated with measures of disease severity, including WHO-FC, NT-proBNP, pulmonary arterial pressure, and pulmonary vascular resistance, and exercise capacity.
Patients were classified as low risk, intermediate-low, intermediate-high, or high risk using the COMPERA 2.0 risk score, which assesses the risk of death within one year. The results showed that patients with intermediate-high to high risk had significantly higher METS-IR than those with low to intermediate-low risk (37.7 vs. 36.2).
After adjusting for factors such as patient age, sex, ethnicity, diabetes mellitus, markers of disease severity, PH-specific treatments, pulmonary vascular resistance, and blood oxygen levels, METS-IR was an independent predictor of clinical worsening, the researchers found.
Specifically, with every standard deviation increase in METS-IR, the risk of clinical worsening jumped by 27%. Standard deviation is a measure of dispersed data in relation to the mean.
Surrogates for [insulin resistance], particularly METS-IR, may serve as indicators for assessing disease severity and prognosis in patients with CTEPH.
Further analysis demonstrated that adding METS-IR to COMPERA 2.0 significantly improved its ability to predict adverse outcomes, the team noted.
"Therefore, surrogates for [insulin resistance], particularly METS-IR, may serve as indicators for assessing disease severity and prognosis in patients with CTEPH," the researchers wrote.
The team noted several study limitations, including its retrospective nature and a lack of "dynamic data" collection.
"Future research should aim to incorporate direct insulin measurements and additional potential confounders to enhance the robustness of findings," the researchers wrote.
Insulin Resistance As A Prognostic Marker In CTEPH
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
Chronic Thromboembolic Pulmonary Hypertension
Content
Once CTEPH develops, the most effective cure is a surgical procedure known as pulmonary endarterectomy that reestablishes normal blood flow to the lungs.
This surgery can reverse pulmonary hypertension and reverse damage to the heart and other organs. With surgery, patients can expect excellent long-term survival approaching 90% at five years. Without surgery, patients have substantially reduced long-term survival and quality of life.
Are there non-surgical options for CTEPH?
Medications may be an option for patients with CTEPH to prevent further clot buildup and to relax the wall of the blood vessels.
In addition, patients may be candidates for a minimally invasive procedure called pulmonary balloon angioplasty.
How do you know if you have CTEPH?
CTEPH is a vastly underdiagnosed disease. But some of the symptoms include:
Any patient with a history of blood clot formations should consider seeing a specialist if they are having trouble performing daily activities due to less energy or shortness of breath.
Survivors of acute pulmonary embolism can develop long-term pulmonary hypertension. So any patient with a history of acute pulmonary embolism should undergo an annual echocardiogram to check the function of the heart.
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