Association of Lipoprotein(a) With Risk of Recurrent Ischemic Events Following Acute Coronary Syndrome: Analysis of
Gregory G Schwartz1, Christie M Ballantyne2, Philip J Barter3
1Cardiology Section, Veterans Affairs Medical Center and University of Colorado School of Medicine, Denver.
Insights
Lipoprotein(a) [Lp(a)] levels after acute coronary syndrome (ACS) were not associated with recurrent cardiovascular events in patients receiving statin therapy. This suggests that Lp(a)-targeted treatments may not reduce risk post-ACS.
Area of Science:
- Cardiology
- Biochemistry
- Clinical Trials
Background:
- Lipoprotein(a) [Lp(a)] is linked to cardiovascular disease.
- Its role as an independent risk factor for recurrent events after acute coronary syndrome (ACS) remains uncertain.
- Understanding this association is crucial for secondary prevention strategies.
Purpose of the Study:
- To investigate the association between Lp(a) concentration post-ACS and the risk of subsequent ischemic cardiovascular events.
- To evaluate Lp(a) as a predictor of recurrent cardiovascular outcomes in the context of modern secondary prevention.
Main Methods:
- Nested case-cohort analysis within the dal-Outcomes randomized clinical trial.
- Included 969 patients with cardiovascular outcomes and 3170 event-free controls after ACS.
- Lp(a) concentration measured by immunoturbidimetric assay; analyzed using case-cohort regression.
Main Results:
- No significant association was found between baseline Lp(a) levels and the risk of cardiovascular events (HR per doubling: 1.01; P=.66).
- This lack of association persisted after adjusting for multiple baseline variables and study treatment.
- The distribution of Lp(a) levels did not differ between case patients and control patients.
Conclusions:
- In patients with recent ACS treated with statins, Lp(a) concentration is not associated with adverse cardiovascular outcomes.
- These findings question the benefit of therapies specifically targeting Lp(a) reduction for lowering ischemic event risk post-ACS.
- Further research is needed to clarify the role of Lp(a) in specific patient subgroups or treatment settings.
Importance:
It is uncertain whether lipoprotein(a) [Lp(a)], which is associated with incident cardiovascular disease, is an independent risk factor for recurrent cardiovascular events after acute coronary syndrome (ACS).
Objective:
To determine the association of Lp(a) concentration measured after ACS with the subsequent risk of ischemic cardiovascular events.
Design, Setting, And Participants:
This nested case-cohort analysis was performed as an ad hoc analysis of the dal-Outcomes randomized clinical trial. This trial compared dalcetrapib, the cholesteryl ester transfer protein inhibitor, with placebo in patients with recent ACS and was performed between April 2008 and September 2012 at 935 sites in 27 countries. There were 969 case patients who experienced a primary cardiovascular outcome, and there were 3170 control patients who were event free at the time of a case event and had the same type of index ACS (unstable angina or myocardial infarction) as that of the respective case patients. Concentration of Lp(a) was measured by immunoturbidimetric assay. Data analysis for this present study was conducted from June 8, 2016, to April 21, 2017.
Interventions:
Patients were randomly assigned to receive treatment with dalcetrapib, 600 mg daily, or matching placebo, beginning 4 to 12 weeks after ACS.
Main Outcomes And Measures:
Death due to coronary heart disease, a major nonfatal coronary event (myocardial infarction, hospitalization for unstable angina, or resuscitated cardiac arrest), or fatal or nonfatal ischemic stroke.
Results:
The mean (SD) age was 63 (10) years for the 969 case patients and 60 (9) years for the 3170 control patients, and both cohorts were composed of predominantly male (770 case patients [79%] and 2558 control patients [81%]; P = .40) and white patients (858 case patients [89%] and 2825 control patients [89%]; P = .62). At baseline, the median (interquartile range) Lp(a) level was 12.3 (4.7-50.9) mg/dL. There was broad application of evidence-based secondary prevention strategies after ACS, including use of statins in 4030 patients (97%). The cumulative distribution of baseline Lp(a) levels did not differ between cases and controls at P = .16. Case-cohort regression analysis showed no association of baseline Lp(a) level with risk of cardiovascular events. For a doubling of Lp(a) concentration, the hazard ratio (case to control) was 1.01 (95% CI, 0.96-1.06; P = .66) after adjustment for 16 baseline variables, including assigned study treatment.
Conclusions And Relevance:
For patients with recent ACS who are treated with statins, Lp(a) concentration was not associated with adverse cardiovascular outcomes. These findings call into question whether treatment specifically targeted to reduce Lp(a) levels would thereby lower the risk for ischemic cardiovascular events after ACS.
Trial Registration:
clinicaltrials.gov Identifier: NCT00658515.
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