Abstract Body (Do not enter title and authors here): Background: Coronary artery disease (CAD) remains a leading cause of death in the United States. Cholesterol-lowering medications such as statins are key to reducing mortality and morbidity, though studies have demonstrated an increased risk of new-onset diabetes mellitus (DM) following statin initiation. Patients who develop DM following statin therapy may represent a particularly high-risk subgroup.
Research Question: What risk factors influence CAD incidence in patients who develop DM following statin therapy compared to those who do not?
Methods: We reviewed data on over 73,000 patients initiated on statin monotherapy within our health system. We compared the risk of incident CAD between patients who developed DM after statin initiation and those who did not. Proportional hazards models were adjusted for age, sex, race, ethnicity, and baseline high-density and low-density lipoprotein (HDL and LDL) levels.
Results: The average age of the cohort was 61 ± 12 years; 50.0% were women, 3.4% African American, and 6.7% Hispanic. Of 24,282 patients who did not have prevalent or incident DM, 2,858 (11.8%) developed incident CAD. Of 1,520 subjects who developed incident DM, 158 (10.4%) developed incident CAD. Time to incident DM did not significantly differ between those who developed incident CAD and those who did not (672.4 ± 900.6 versus 740.9 ± 896.4 days, P=0.13). In both groups, increased age and male sex were significant predictors of incident CAD (P<0.05). Among patients without incident DM, baseline LDL was protective (HR 0.78 per 50 mg/dL increase, 95% CI 0.75–0.82, P<0.001) and low baseline HDL (< 40 mg/dL) increased risk of incident CAD (HR 1.18, 95% CI 1.08–1.29, P<0.001). In contrast, in patients who developed incident DM after statin prescription, the baseline LDL was not a significant predictor of incident CAD (HR 1.05 per 50 mg/dL, 95% CI 0.85–1.28, P=0.649), although baseline low HDL remained significant (HR 1.57, 95% CI 1.12–2.18, P=0.008).
Conclusions: In this observational analysis of patients started on statin therapy, low baseline HDL was associated with increased CAD risk in those with incident DM. However, the lack of LDL association in this population suggests distinct biological mechanisms compared to those without incident DM. Prospective studies are needed to identify modifiable risk factors in those who develop DM following statin therapy.