Background: Whether cardiovascular health (CVH) modifies the associations between insulin resistance (IR) and prognosis remains unclear. This study aims to evaluate the varying relationships between IR, future cardiovascular disease (CVD), and all-cause mortality across different CVH statuses. Methods: This was a nationwide cohort study using data from the China Health and Nutrition Survey. The CVH was assessed using the Life's Essential 8 (LE8) metrics, and IR was determined by the homeostasis model assessment of insulin resistance (HOMA-IR) index and the triglyceride-glucose (TyG) index. The study outcomes included incident CVD and all-cause mortality. Results: 47.0% of the included participants (n = 8635) were men, and the mean age (SD) was 49.7 (15.8) years, with 37.5%, 51.6%, and 10.9% having poor, intermediate, and ideal CVH. During a 6-year follow-up, 482 (5.6%) participants had incident CVD, and 435 individuals died (incidence rate: 7.9 (95% CI: 7.2, 8.7) 1000 person-years). HOMA-IR and the TyG index were positively associated with increased risks of CVD and mortality among participants with intermediate or poor CVH, while no significant associations were found between IR indexes with CVD and death in those with ideal CVH (P for interaction < .05). 13.0% and 16.8% of the associations between CVH and CVD were mediated by HOMA-IR and the TyG index. Similar significant indirect effects of HOMA-IR and the TyG index on the relationship between CVH and all-cause mortality were observed. Conclusions: CVH significantly modified the associations between two IR surrogates and long-term CVD and all-cause mortality. Increased risk probabilities of future CVD and mortality were observed among individuals with intermediate or poor CVH. IR mediated a substantial proportion of the associations between CVH and CVD and all-cause mortality, emphasizing the importance of maintaining healthy behaviors and factors to reduce the burden of CVD and mitigate the detrimental impact of IR. Key message What is already known on this subject The global prevalence of insulin resistance (IR) and diabetes mellitus (DM) is extremely high and their associated disease burden is heavy. Ideal cardiovascular health (CVH) is significant associated with a lower risk of IR and better prognosis. What this study adds Only 10.9% of the participants maintained ideal CVH in this large Chinese cohort, while more than one-third had poor CVH. CVH significantly modified the associations between two IR surrogates and long-term CVD and all-cause mortality. Increased risk probabilities of future CVD and mortality were observed among individuals with intermediate or poor CVH. IR mediated a substantial proportion of the associations between CVH and CVD and all-cause mortality. How this study might affect research, practice, or policy Our study indicated that a large number of Chinese citizens still have suboptimal CVH, emphasizing the urgent need for efforts to mitigate the heavy burden of CVDs at the population level. Maintaining optimal CVH could help slow down IR and reduce the risks of future CVD and premature death, as well as mitigate the negative effects of IR on prognosis.
