Relationship between Lipoprotein(a) and subsequent cardiovascular events in patients with different locations of established cardiovascular disease
J Ebbers, E B Haug, M N Gynnild, T P Van de Hoef, M Teraa, E J van Dijk, Asvold Bo, A T R Bayyoudtamimi, Y S A M Khalil, T H Reitsma, S H J Hageman, F L J Visseren, J A N DorresteijnAbstract
Background
Lipoprotein(a) [Lp(a)] has been widely recognized as an independent causal risk factor for first cardiovascular events. However, the evidence in the setting of secondary prevention remains inconsistent, particularly across patients with different types of baseline atherosclerotic cardiovascular disease (ASCVD).
Purpose
To investigate the causal effects of Lp(a) on the risk of cardiovascular events in patients with different locations of baseline ASCVD.
Methods
Patients with established CVD from the UCC-SMART cohort, an ongoing prospective cohort, were included. Established CVD was defined as having symptomatic coronary artery disease (CAD), cerebrovascular disease (CeVD) or peripheral artery disease or abdominal aortic aneurysm (PAD/AAA). At inclusion, patients underwent a standardized screening protocol, including questionnaires, physical examination, and laboratory measurements. Patients were then followed for occurrence of events. The outcomes of interest included a composite endpoint of myocardial infarction, stroke (ischemic and hemorraghic), cardiovascular death, and coronary or other vascular interventions, as well as each of these components analysed individually. Cox proportional hazards models were used to quantify the effect of Lp(a) on these outcomes, adjusting for a priori specified confounders. Analyses were performed with strata of <500mg/L, 500-1000mg/L and >1000mg/L. Continuous associations were evaluated using restricted cubic spline analysis.
Results
Among 4559 patients with a median follow-up of 6.3 years, 1799 composite endpoint events (39.5%) occurred. Patients with Lp(a) levels above 1000mg/L had the highest risk of the composite endpoint (HR 1.49, 95% CI 1.27 to 1.74). Of the individual outcomes, the association was strongest for myocardial infarction (HR 1.43, 95% CI 1.01 to 2.01) and coronary or other vascular interventions (HR 1.65, 95% CI 1.37 to 1.98) (Figure 1). However, no relationship was observed between Lp(a) level and stroke or cardiovascular death. The associations were generally similar across locations of baseline ASCVD (Figure 2a-c).
Conclusion
Higher levels of Lp(a) consistently increased the risk of subsequent cardiovascular outcomes, specifically myocardial infarction and coronary or other vascular interventions, across all locations of established ASCVD. Following from this, Lp(a) may help identify patients with established ASCVD who remain at increased residual risk of atherosclerotic events, and who may benefit from intensified risk management or emerging Lp(a) lowering therapies.