Epidemiology
Diabetes and elevated Lp(a) interact multiplicatively, giving patients with both a 2.57-fold coronary heart disease risk, MESA study of 6,668 finds (Atherosclerosis 2025)
Original title: Association of lipoprotein(a) and diabetes in primary prevention of coronary heart disease: The Multi-Ethnic Study of Atherosclerosis (MESA)
This analysis of 6,668 participants without baseline cardiovascular disease from the Multi-Ethnic Study of Atherosclerosis (MESA) tested whether Lp(a) modifies diabetes's association with incident coronary heart disease (CHD), grouping participants by Lp(a) (50 mg/dL threshold) and diabetes status. In a fully adjusted model, log-transformed Lp(a) (HR 1.10, 95% CI 1.01-1.20) and diabetes (HR 1.65, 95% CI 1.31-2.06) were each independently associated with CHD, with a significant multiplicative interaction between them (P = 0.033). Compared with the reference group (Lp(a) below 50 mg/dL, no diabetes), those with elevated Lp(a) alone had higher CHD risk (HR 1.29, 95% CI 1.00-1.65), those with diabetes alone also had higher risk (HR 1.52, 95% CI 1.16-1.98), and those with both elevated Lp(a) and diabetes had the highest risk by far (HR 2.57, 95% CI 1.77-3.72). The authors conclude Lp(a) and diabetes interact to amplify CHD risk beyond their individual effects, warranting further mechanistic research into this combination.
Original abstract
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.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.