Cumulative Insulin Resistance Metabolic Score and Heart Failure Risk: A Prospective Study

• This large-scale cohort study demonstrates that cumulative METS-IR exposure is a significant independent risk factor for incident heart failure (HF). • Longer durations of high METS-IR exposure (2, 4, and 6 years) were associated with progressively increased risks of HF, corresponding to a 23%, 49%, and 57% rise in risk, respectively. • High-risk populations meriting targeted preventive strategies were identified (males and older adults aged ≥60 years). • The addition of cumulative METS-IR to a conventional risk model provided significant incremental predictive value for HF risk, outperforming models using only single-timepoint METS-IR. • A cutoff value for time-averaged cumulative METS-IR (36.2) was established, supporting its potential use in clinical practice for long-term metabolic health monitoring and early HF risk stratification. This large-scale cohort study demonstrates that cumulative METS-IR exposure is a significant independent risk factor for incident heart failure (HF). Longer durations of high METS-IR exposure (2, 4, and 6 years) were associated with progressively increased risks of HF, corresponding to a 23%, 49%, and 57% rise in risk, respectively. High-risk populations meriting targeted preventive strategies were identified (males and older adults aged ≥60 years). The addition of cumulative METS-IR to a conventional risk model provided significant incremental predictive value for HF risk, outperforming models using only single-timepoint METS-IR. A cutoff value for time-averaged cumulative METS-IR (36.2) was established, supporting its potential use in clinical practice for long-term metabolic health monitoring and early HF risk stratification. The Metabolic Score for Insulin Resistance (METS-IR) is recognized as an indicator associated with the risk of Heart Failure (HF). However, evidence regarding its long-term impact is limited. This study aimed to evaluate the association between cumulative METS-IR (cumMETS-IR) and the risk of incident HF. We performed a prospective cohort analysis involving 51,155 participants from the Kailuan Study who underwent three health examinations (2006-2010) and were followed for incident HF until December 31, 2022. CumMETS-IR was calculated and analyzed using Cox proportional hazards models. Over a median follow-up of 12 years, higher cumMETS-IR was strongly and progressively associated with an increased risk of HF. Participants in the highest quartile had a 59% higher risk than those in the lowest. The incidence density of HF per 1,000 person-years increased progressively across quartiles: Q1: 0.90 (0.76–1.07), Q2: 1.61 (1.41–1.83), Q3: 2.38 (2.14–2.64), and Q4: 3.60 (3.30–3.93). Maintaining high exposure for 2, 4, and 6 years increased risk by 23%, 49%, and 57%, respectively. Notably, these associations were significantly stronger in males and in adults aged ≥60 years. Adding cumMETS-IR to a conventional risk model also improved the prediction of HF. Higher levels of cumMETS-IR are associated with an increased risk of HF, particularly pronounced in males and older adults. Long-term monitoring of METS-IR may facilitate the early identification of high-risk individuals.