Can Cardiovascular Health and Its Modifiable Healthy Lifestyle Offset the Increased Risk of All-cause and Cardiovascular Deaths Associated with Insulin Resistance?

Background: Insulin resistance(IR) is associated with an increased risk of all-cause and cardiovascular death, and modifiable healthy lifestyles play an active role in the improvement of IR and the reduction of all-cause and cardiovascular death. Whether cardiovascular health (CVH) and modifiable healthy lifestyles within it can attenuate or even offset the heightened perils of both all-cause and cardiovascular deaths associated with insulin resistance remains unclear.

Methods: The study encompassed 14,172 healthy participants from the 2005-2018 NHANES programme. Insulin resistance was evaluated using the TyG index, TyG-WC, and TyG-WHtR, while CVH was assessed employing the LE8 score, in addition to the LE4 index redefined according to four health behaviours. Weighted multifactor Cox regression models were used to assess the association of IR and CVH with all-cause and cardiovascular mortality, and dose-response relationships were assessed using restricted cubic spline. Furthermore, subjects were grouped according to IR and CVH scores, and generalised linear models were used to estimate the weighted mortality and risk of death for each group and to calculate the absolute risk difference. Finally, the predicted probability of all-cause and cardiovascular mortality risk as a function of IR was computed, and the complex relationship between the three was visualised using two-dimensional grouped scatter plots and three-dimensional surface plots.

Results: Among the 14,172 healthy participants included in the study, 1534 deaths occurred over a mean follow-up period of 7.6 years (382 of these deaths were due to cardiovascular causes). The weighted Cox regression analysis indicated that elevated TyG-WC and TyG-WHtR correlated with a greater likelihood of mortality from all causes and cardiovascular events, whereas cardiovascular health was inversely associated with these risks. Additional stratification revealed a notable reduction in the likelihood of mortality from all causes and cardiovascular events as cardiovascular health improved, irrespective of the presence of insulin resistance. Additionally, participants with high insulin resistance but moderate or high cardiovascular health did not have significantly increased risks compared with those with low insulin resistance. Stratified scatter plots and 3D surface plots revealed that cardiovascular health and modifiable healthy lifestyles significantly reduced the risk of insulin resistance-related death, with greater reductions observed at higher insulin resistance levels.

Conclusions: In this cohort study, improving cardiovascular health and modifiable health behaviors significantly reduced the risk of insulin resistance-related all-cause and cardiovascular deaths. Maintaining cardiovascular health at moderate or high levels (LE8 ≥ 50) could offset the increased risks caused by insulin resistance.