Associations of Homeostatic Model Assessment for Insulin Resistance Trajectories with Cardiovascular Disease Incidence and Mortality

Background: Whether trends in insulin resistance changes are related to the risk of cardiovascular disease (CVD) incidence and mortality remains unclear. We aimed to examine the association of homeostatic model assessment for insulin resistance (HOMA-IR) trajectories with CVD incidence and mortality. Methods: Data from 6755 adults aged 40 to 69 years in the Korea Epidemiology and Genome Study were analyzed. During the exposure period (2001-2006), participants were classified into the increasing HOMA-IR trajectory group and the stable HOMA-IR trajectory group using a latent class mixture model. During the event accrual period (2007-2018), information about CVD and mortality were collected. Results: During the median 9.83-year event accrual period, there were 379 (5.6%) new-onset CVD, 535 (7.9%) all-cause mortality, 102 (1.5%) CVD mortality, and 47 (0.7%) major adverse cardiovascular event mortality cases. Compared with the stable HOMA-IR trajectory group, the fully adjusted hazard ratios (95% CIs) for the increasing HOMA-IR trajectory group were 1.59 (1.04-2.44) for incident CVD, 1.87 (1.30-2.69) for all-cause mortality, 2.33 (1.11-4.89) for CVD mortality, and 3.67 (1.38-9.76) for major adverse cardiovascular event mortality. Conclusions: An increasing HOMA-IR appears to be independently and positively related to incident CVD, all-cause mortality, CVD mortality, and major adverse cardiovascular event mortality. Early lifestyle interventions for individuals with increasing HOMA-IR trend could be a practical strategy to prevent CVD and CVD mortality.