Background: Pro-inflammatory Interleukin-1 (IL-1) genotypes have been previously shown to affect the risk of angiographic coronary artery disease (CAD) and cardiovascular events mediated by lipoprotein(a) [Lp(a)] in non-diabetic patients.
Purpose: We investigated whether type 2 diabetes mellitus (DM) may alter the effect of this genotype on the relation of Lp(a) with CAD presence and cardiovascular events.
Methods: We enrolled 1,084 patients (mean age 65 years, 70% males, 44% DM) undergoing diagnostic coronary angiography. Plasma Lp(a) levels were measured. The composite genotype IL-1(+) was defined by 3 single-nucleotide polymorphisms in the IL-1 gene cluster. Angiographic CAD was diagnosed as a >50% stenosis in a coronary artery. Cardiovascular death, non-fatal myocardial infarction and stroke (n=77) were assessed after a median follow-up of 43 months (range 24–68).
Results: Angiographic CAD was more prevalent in DM vs non-DM patients (OR 1.73, p<0.001) while there was no significant difference in the occurrence of events at follow-up in DM vs non-DM (HR 1.10, p=0.645). In the non-DM group, the highest Lp(a) quartile was associated with a higher risk for CAD compared with the lowest quartile in IL-1(+) (OR 1.87, p=0.032); this effect was further accentuated in younger (≤60 years) patients (OR 2.90, p=0.036). In multivariate analysis, Lp(a) levels remained an independent predictor of CAD in younger IL-1(+) patients (OR 1.35, p=0.016) after adjustment of for various confounders. Non-DM IL-1(+) patients with high Lp(a) had worse event-free survival compared with other groups (HR 3.47, p<0.001). After adjustment for risk factors, higher Lp(a) (HR 1.29 per doubling, p<0.001) and IL-1(+) (HR 2.03, p=0.038) were independent predictors of adverse prognosis in non-DM patients. In contrast, no association of IL-1(+) status and Lp(a) was found with CAD presence or cardiovascular events in DM patients.
Conclusions: In non-DM patients, IL-1 genotype influences the Lp(a)-mediated risk for CAD presence mainly in younger patients referred for angiography. Both Lp(a) levels and IL-1 genotype status independently and cumulatively predict cardiovascular events in non-DM patients. The lack of an IL-1/Lp(a) association in patients with DM needs to be further evaluated in future studies.