Risk of Cardiovascular Events in Patients With Type 2 Diabetes and Metabolic Dyslipidemia Without Prevalent Atherosclerotic Cardiovascular Disease

Abstract

Background: The relationship between achieved low-density lipoprotein cholesterol (LDL-C) levels and risk of incident atherosclerotic cardiovascular disease events among patients with diabetes and metabolic dyslipidemia has not been well described.

Methods: We conducted an observational cohort study of statin-treated adults (ages 21-90 years) with type 2 diabetes without established atherosclerotic cardiovascular disease (as of January 1, 2006) who had metabolic dyslipidemia (elevated triglycerides ≥150 mg/dL and low high-density lipoprotein cholesterol, <50 mg/dL [women] and <40 mg/dL [men]). All subjects were members of Kaiser Permanente Northern California, an integrated health care delivery system. Adjusted multivariable Cox models were specified to estimate hazard ratios (HRs) for incident atherosclerotic cardiovascular disease events by achieved LDL-C levels (<50, 50-<70, 70-<100, and ≥100 mg/dL). Incident atherosclerotic cardiovascular disease events were defined as a composite of nonfatal myocardial infarction, ischemic stroke, or coronary heart disease death through December 31, 2013.

Results: A total of 19,095 individuals met the selection criteria. Mean age was 63.4 years, 53.5% were women, and the mean follow-up was 5.9 years. Unadjusted rates of atherosclerotic cardiovascular disease events were not significantly different across specified LDL-C categories. In models adjusted for demographics and clinical characteristics, the risk was significantly lower with decreasing achieved LDL-C levels (P <0.0001 for trend). Relative to achieved LDL-C ≥100 mg/dL, LDL-C <50 mg/dL had an hazard ratio of 0.66 (95% confidence interval [CI] 0.52-0.82).

Conclusion: In a large, contemporary cohort of statin-treated patients with type 2 diabetes and metabolic dyslipidemia without established atherosclerotic cardiovascular disease, lower achieved LDL-C levels were associated with a monotonically lower risk of incident atherosclerotic cardiovascular disease events. The benefits of achieving very-low LDL-C (<50 mg/dL) in this population requires further evaluation in prospective interventional studies.

Keywords: Atherosclerotic cardiovascular disease; Diabetes; Metabolic dyslipidemia.