Lipoprotein(a): A Residual Cardiovascular Risk Factor in Statin-Treated Stroke Survivors: Insights From the SPARCL Trial.

Autor:	Chemello K; Inserm, UMR1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), Université de La Réunion, Sainte-Pierre, France., Gallo A; Inserm, UMR1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), Université de La Réunion, Sainte-Pierre, France.; Department of Endocrinology and Prevention of Cardiovascular Disease, Institute of Cardio Metabolism and Nutrition (ICAN), Sorbonne Université Pitié-Salpêtrière Hospital, SU-APHP, Paris, France., Guedon AF; APHP, Service de Médecine Interne, Département Hospitalo-Universitaire Inflammation Immunopathologie Biothérapie (DMUi3), Sorbonne Université, Paris, France., Techer R; Inserm, UMR1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), Université de La Réunion, Sainte-Pierre, France., Croyal M; CHU Nantes, CNRS, Inserm, BioCore, US16, SFR Bonamy, Nantes Université, Nantes, France.; CHU Nantes, CNRS, Inserm, Institut du Thorax, Nantes Université, Nantes, France.; CRNH-Ouest Mass Spectrometry Core Facility, Nantes, France., Swietek MJ; Pfizer Inc, Groton, Connecticut, USA., Meilhac O; Inserm, UMR1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), Université de La Réunion, Sainte-Pierre, France.; CHU de La Réunion, Saint-Denis, France., Amarenco P; INSERM 1148, Bichat Stroke Centre, Paris Université, Paris, France., Lambert G; Inserm, UMR1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), Université de La Réunion, Sainte-Pierre, France.
Jazyk:	angličtina
Zdroj:	JACC. Advances [JACC Adv] 2023 Aug 22; Vol. 2 (7), pp. 100557. Date of Electronic Publication: 2023 Aug 22 (Print Publication: 2023).
DOI:	10.1016/j.jacadv.2023.100557
Abstrakt:	Background: In the SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol levels) trial, atorvastatin (80 mg/d) was compared to placebo in patients with recent stroke or transient ischemic attack (TIA) and no known coronary artery disease. Objectives: This study aimed to assess the contribution of lipoprotein(a) [Lp(a)] to subsequent cerebrovascular and cardiovascular events in stroke/TIA survivors. Methods: Lp(a) levels and apolipoprotein(a) [apo(a)] isoform size were determined by liquid-chromatography mass spectrometry in samples collected at baseline from 2,814 SPARCL participants (1,418 randomized to atorvastatin and 1,396 to placebo). Within each treatment arm, patients in the highest quartile (≥84.0 nmol/L) were compared with those in the lowest quartiles of Lp(a) concentrations. Patients in the lowest quartile (≤25.9 Kringle IV domains) of apo(a) isoform sizes were compared with those in the highest quartiles. Multivariable-adjusted HRs were calculated using Cox proportional regression models. Results: There was no significant association between Lp(a) concentrations or apo(a) isoform sizes and the risk of recurrent stroke, the primary outcome of SPARCL, or cerebrovascular events in patients randomized to atorvastatin or placebo. In contrast, in patients randomized to atorvastatin, elevated Lp(a) concentrations and short apo(a) isoforms were positively and independently associated with an increased risk of coronary events (HR: 1.607 [95% CI: 1.007-2.563] and HR: 2.052 [95% CI: 1.303-3.232]). No such association was found in patients randomized to placebo (HR: 1.025 [95% CI: 0.675-1.555] and HR: 1.097 [95% CI: 0.735-1.637]). Conclusions: Lp(a) contributes to the residual coronary artery disease risk of statin-treated stroke/TIA survivors, paving the way for use of therapies targeting Lp(a) in this population with stroke. (Lipitor In The Prevention Of Stroke, For Patients Who Have Had A Previous Stroke [SPARCL]; NCT00147602). Competing Interests: This work was supported by the 10.13039/501100001665Agence Nationale de la Recherche (Paris, France) Project Grant KRINGLE2 ANR-20-CE14-0009 and by La Fondation De France (Paris, France) Project Grant FDF-00096274. These agencies had no role in the design and conduct of the study, in the collection, analysis, and interpretation of the data, and in the preparation, review, or approval of the manuscript. Dr Chemello is supported by a scholarship from the European Regional Development Fund & La Région Réunion (Saint-Denis de La Réunion, France). Dr Gallo is supported by a postdoctoral fellowship SPF 202004011793 from La Fondation Pour La Recherche Médicale (Paris, France; and reports consultancy fees and honoraria from Akcea Therapeutics, Amgen, Mylan, Novartis, Sanofi, Unilever, and MSD. Dr Swietek is an employee of Pfizer. Dr Amarenco has received research grant support from Pfizer, Sanofi, BMS, Merck, AstraZeneca, Boston Scientific, Althera Pharmaceutical, and the French government; consulting fees from Pfizer, BMS, AstraZeneca, Bayer, Jansen, Kowa, Amgen, and Portola; and lecture fees from Amgen, Pfizer and Sanofi. Dr Lambert has received research grant support and consulting fees for serving on the scientific advisory board from Nyrada. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.PERSPECTIVESCOMPETENCY IN MEDICAL KNOWLEDGE: Statins are indicated for patients in secondary prevention of symptomatic cerebrovascular disease to reduce their risk of recurrent stroke or cardiovascular events. Our study demonstrates that even when high-intensity statin treatment is implemented, elevated levels of Lp(a) independently and significantly contribute to the residual CAD risk of these patients. TRANSLATIONAL OUTLOOK: Therapies that lower Lp(a) (currently limited to PCSK9i but in the future to antisense and siRNAs targeting Lp(a) production) should be added on top of statins for patients in secondary prevention of stroke or TIA with elevated Lp(a). (© 2023 The Authors.)
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