Higher apolipoprotein A1 levels associated with lower risk of ischemic CV outcomes in atrial fibrillation
Dyslipidemia and Risk of Cardiovascular Events in Patients With Atrial Fibrillation Treated With Oral Anticoagulation Therapy: Insights From the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) Trial
Literature - Pol T, Held C, Westerbergh J, et al. - J Am Heart Assoc. 2018;7:e007444Background
Dyslipidemia is a major risk factor for adverse CV events like myocardial infarction (MI), but it’s role as a risk factor in patients with atrial fibrillation (AF) is not known [1,2]. In this sub-study of the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial, the association between the baseline concentrations of apolipoprotein A1 (ApoA1), the main protein component of high-density lipoprotein, and apolipoprotein B (ApoB), the main protein component of low-density lipoprotein, and clinical outcomes was evaluated in patients with AF treated with oral anticoagulation.
ARISTOTLE was a multicenter, double-blind, double-dummy, randomized, clinical trial which enrolled 18,201 patients with AF and at least 1 additional risk factor for stroke or systemic embolism, who were randomized to receive either warfarin or apixaban for stroke prevention in a 1:1 fashion [3,4]. The apolipoprotein biomarker sub-study cohort comprised of the first included 14,884 patients, and the median length of follow-up was 1.9 years.
The primary outcome of this biomarker analysis was a composite of ischemic stroke, systemic embolic event (SEE), MI, and CV death. Other evaluated outcomes were the individual components of the composite ischemic outcome, all-cause mortality and major bleeding, according to the International Society on Thrombosis and Haemostasis criteria [5].
Main results
- In the fully adjusted analyses, higher ApoA1 levels were independently associated with a lower risk in the composite ischemic outcome (HR: 0.81; 95%CI: 0.73–0.90; P<0.0001 per interquartile change).
- ApoB was not statistically significantly associated with the risk of the composite ischemic outcome (HR: 1.01; 95%CI: 0.92–1.12; P=0.8240).
- In the fully adjusted analyses, higher ApoA1 levels were independently associated with a lower risk of stroke or SEE (HR: 0.84; 95%CI: 0.72–0.98; P=0.0248 per interquartile change).
- In the fully adjusted analyses, higher ApoB was independently associated with an increased risk of MI (HR: 1.33; 95%CI: 1.06–1.68; P=0.0144 per interquartile change).
- Higher levels of ApoA1 were statistically significantly associated with lower risk of all-cause and CV mortality, even after adjustment for CV biomarkers (HR: 0.77; 95%CI: 0.70–0.85; P<0.0001 for all-cause mortality, and HR: 0.78; 95%CI: 0.68–0.89; P=0.0002 for CV death, both per interquartile change).
- In fully adjusted models, lower ApoB levels were associated with a higher risk of all-cause mortality (HR: 0.84; 95%CI: 0.76–0.92; P=0.0002 per interquartile change).
- None of the apolipoproteins was significantly associated with major bleeding in fully adjusted models.
- There was no interaction between study treatment (apixaban or warfarin) and apolipoprotein levels for the composite ischemic outcome.
Conclusion
In patients with AF treated with oral anticoagulation, higher levels of ApoA1 were independently associated with a lower risk of ischemic CV outcomes, including stroke/SEE and mortality. Higher ApoB levels were associated with higher rates of MI, and an unanticipated higher risk of all-cause mortality in those with lower ApoB levels. These findings suggest that treating dyslipidemia may be important for the improvement of CV outcomes in patients with AF.
References
1. Gordon T, Castelli WP, Hjortland MC, et al. High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med. 1977;62:707–714.
2. Ference BA, Ginsberg HN, Graham I, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2017;38:2459–2472.
3. Granger CB, Alexander JH, McMurray JJ, et al. ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981–992.
4. Hijazi Z, Siegbahn A, Andersson U, et al; ARISTOTLE Investigators. High-sensitivity troponin I for risk assessment in patients with atrial fibrillation: insights from the Apixaban for Reduction in Stroke and other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. Circulation. 2014;129:625–634.
5. Lopes RD, Alexander JH, Al-Khatib SM, et al; ARISTOTLE Investigators. Apixaban for reduction in stroke and other ThromboemboLic events in atrial fibrillation (ARISTOTLE) trial: design and rationale. Am Heart J. 2010;159:331–339.
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