The relationship between insulin resistance and incidence and progression of coronary artery calcification: the Multi-Ethnic Study of Atherosclerosis (MESA)

OBJECTIVE

We sought to determine whether insulin resistance predicts the incidence and progression of coronary artery calcification (CAC).

RESEARCH DESIGN AND METHODS

We studied 5,464 participants not on hypoglycemic therapy from the Multi-Ethnic Study of Atherosclerosis (MESA). Each had baseline homeostasis model assessment of insulin resistance (HOMA-IR) and baseline and follow-up CAC scores. Incident CAC was defined as newly detectable CAC; progression was defined as advancing CAC volume score at follow-up.

RESULTS

Median HOMA-IR was 1.2 (0.8–2.0). Across all ethnicities, there was a graded increase in CAC incidence and progression with increasing HOMA-IR. When compared with those in the 1st quartile, participants in the 2nd–4th quartiles had 1.2, 1.5, and 1.8 times greater risk of developing CAC. Median annualized CAC score progression was 8, 14, and 17 higher, respectively. However, HOMA-IR was not predictive after adjustment for metabolic syndrome components.

CONCLUSIONS

HOMA-IR predicts CAC incidence and progression, but not independently of metabolic syndrome.Sensitivity to insulin-mediated glucose uptake varies at least sixfold in the general healthy population, with variability attributable to genetic and behavioral factors (1–4). In the clinical setting, insulin resistance is commonly inferred via its adverse consequences, which include dysglycemia, hypertension, low HDL cholesterol (HDL-C), high triglycerides, and subclinical inflammation (collectively, the metabolic syndrome) (5).Insulin resistance and the metabolic syndrome have both been shown to be strongly associated with measures of subclinical atherosclerosis, including coronary artery calcification (CAC) (6,7). Consistent with these observations, prospective studies have demonstrated that insulin resistance and metabolic syndrome are independent predictors of cardiovascular events (8,9). However, the degree to which insulin resistance and metabolic syndrome are mutually independent predictors remains debated, with prior results mixed (7,10). We sought to determine whether insulin resistance prospectively predicts the onset and progression of CAC, independent of metabolic syndrome.