Association of lipoprotein(a) and diabetes in primary prevention of coronary heart disease: The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND AND AIMS: Lipoprotein(a) [Lp(a)] and diabetes are both independently associated with cardiovascular disease. Studies demonstrate that elevated Lp(a) is associated with increased incidence of cardiovascular disease in those with and without diabetes. However, it is unclear if Lp(a) modifies the association of diabetes and coronary heart disease (CHD) in primary prevention.

METHODS

The present analysis included 6668 participants from the Multi-Ethnic Study of Atherosclerosis, a community-based cohort without clinical cardiovascular disease at baseline. Participants were categorized as follows: group 1: Lp(a) < 50 mg/dL without diabetes, group 2: Lp(a) ≥50 mg/dL without diabetes, group 3: Lp(a) < 50 mg/dL with diabetes, and group 4: Lp(a) ≥50 mg/dL with diabetes. Survival analysis using Kaplan-Meier and multivariable Cox proportional hazard models were performed to assess the relationship between Lp(a), diabetes, and time to incident CHD.

RESULTS

In a fully adjusted model, log[Lp(a)] and diabetes were both independently associated with CHD (HR: 1.10; 95 % CI: 1.01, 1.20) and (HR:1.65; 95 % CI: 1.31, 2.06), respectively. There was a significant multiplicative interaction between logLp(a) and diabetes (p = 0.033). Compared to the reference group (Lp(a) < 50 mg/dL without diabetes), in a fully adjusted model, those with Lp(a) ≥50 mg/dL without diabetes (group 2) had increased risk of CHD (HR: 1.29; 95 % CI: 1.00, 1.65). Similarly, individuals with Lp(a) < 50 mg/dL with diabetes (group 3) also had greater risk of CHD (HR: 1.52; 95 % CI: 1.16, 1.98). The highest risk for CHD were in those with Lp(a) ≥50 mg/dL with diabetes (group 4) (HR: 2.57; 95 % CI: 1.77, 3.72).

CONCLUSION

The results of this analysis suggest that Lp(a) may modify the association between diabetes and CHD or that diabetes may modify the association between Lp(a) and CHD in those without cardiovascular disease at baseline. Further research is needed to clarify underlying mechanisms between Lp(a), diabetes, and CHD.