Background: Lipoprotein(a) (Lp(a)) is a causal genetic risk factor for atherosclerotic cardiovascular disease. Likewise, diabetes mellitus is a major risk factor for atherosclerotic cardiovascular disease. However, the interaction between elevated Lp(a) and diabetes mellitus has not been evaluated in detail in patients with CAD.
Aims: We aimed to evaluate the influence of diabetes mellitus on survival in patients with CAD, in the presence or absence of elevated Lp(a).
Methods: The present analysis is based on the longitudinal Essen Coronary Artery Disease (ECAD) Registry, which enrolled consecutive patients undergoing coronary angiography with percutaneous revascularisation therapy at the West German Heart and Vascular Centre between 2004 and 2019. Lp(a) was quantified at hospital admission using a particle-enhanced immunonephelometric method. HbA1c was quantified at hospital admission using standardized enzymatic methods. Baseline clinical characteristics were compared among patients with Lp(a) levels ≥50 mg/dL vs Lp(a) <50mg/dl).
The incidence of death due to any cause was evaluated during follow-up. Cox regression analysis was used to determine the association between HbA1c and all-cause mortality, adjusting for age, sex, LDL-cholesterol, smoking status, systolic blood pressure, and family history of premature cardiovascular disease, stratified by Lp(a) levels. Standard deviation of HbA1c was 1.13%.
Results: Among 3523 patients (mean age 66.4 ± 11.3 years, 79% male), median Lp(a) was 16 (7; 58) mg/dL and 1003 (28.5%) patients had elevated Lp(a)-levels. Median HbA1c was 5.9% (5.5%;6.5%). 911 (25.9%) patients had diabetes mellitus. There was no significant correlation between Lp(a) and HbA1c (correlation coefficient: -0.0167, p = 0.322).Patients with Lp(a) ≥ 50mg/dL were more often female, had less often diabetes mellitus, a higher LDL- and higher HDL- Cholesterol at admission. Other risk factors, including systolic blood pressure, smoking history and positive family history for cardiovascular disease levels, were not significantly different among groups.
During a median follow-up of 3.01 (0.64; 6.35) years 419 patients (11.9%) died. In multivariable Cox regression analysis, higher Hba1c levels were independently associated with a 17.4% (CI: [6.2%; 29.8%], p = 0.002) increase in all-cause mortality per standard deviation of HbA1c. Interestingly, in patients with Lp(a) ≥ 50mg/dl higher Hba1c levels were associated with two-fold increase in all-cause mortality comparing to the subgroup of patients with lp(a) < 50mg/dl (30.9% [7.7%; 59.1%] vs. 15.7% [2.6%; 30.3%] per standard deviation HbA1c).
Conclusion: In patients with coronary artery disease, elevated Lp(a)-levels amply the association between HbA1c and long-term mortality. Our results suggests that the additive risk of Lp(a) in atherosclerotic disease may in parts be explained by an interaction with other cardiovascular risk factors such as glycaemic control.
