Baseline and on-statin treatment lipoprotein(a) levels for prediction of cardiovascular events: individual patient-data meta-analysis of statin outcome trials
Willeit P, Ridker PM, Nestel PJ, Simes J, Tonkin AM, Pedersen TR, Schwartz GG, Olsson AG, Colhoun HM, Kronenberg F, Drechsler C, Wanner C, Mora S, Lesogor A, Tsimikas S
Lancet (London, England) · 439 citas
Cómo se estudió
- Diseño
- Metaanálisis (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Eventos clínicos como enfermedad o muerte
Quién lo pagó
- Financiación
- Financiación independiente
- Organización sin fines de lucro
- Heart and Stroke Foundation of Canada
- Gobierno
- National Institutes of Health
- Gobierno
- National Heart, Lung, and Blood Institute
- Gobierno
- NIH
- Gobierno
- NHLBI NIH HHS
- Subvenciones
- National Heart, Lung, and Blood Institute (R01 HL134811); National Heart, Lung, and Blood Institute (P01HL055798); National Heart, Lung, and Blood Institute (R01HL117861); National Institutes of Health (R01 HL117861); National Institutes of Health (R01-HL134811); National Heart, Lung, and Blood Institute (K24HL136852)
Según 5 financiadores declarados.
Publicación
- Publicado
- 2018-10-01 · Lancet · vol. 392 · número 10155 · págs. 1311–1320
- Editorial
- Elsevier BV
- Citado
- 564 citas · más que el 100% de estudios similares · 13.6× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 41 trabajos
- Acceso
- Acceso abierto (copia en repositorio) · OTHER-OA
- Áreas de investigación
- Lipoproteins and Cardiovascular Health · Diabetes, Cardiovascular Risks, and Lipoproteins · Cholesterol and Lipid Metabolism
- Palabras clave
- lipoprotein(a), statin therapy, cardiovascular risk prediction, cardiovascular events, LDL cholesterol, coronary artery disease, stroke, revascularization, genetic risk factors, individual patient data meta-analysis, cardiovascular disease prevention, cardiovascular risk stratification
- MeSH
- humans, cardiovascular diseases, hypercholesterolemia, lipoprotein(a), hydroxymethylglutaryl-coa reductase inhibitors, risk factors, aged, middle aged, female, male, cholesterol, ldl, cholesterol, hdl, randomized controlled trials as topic, biomarkers
15 autores
- Peter Willeit🇦🇹🇬🇧 · autor de correspondenciaInnsbruck Medical University; Universität Innsbruck; University of Cambridge
- Paul M. Ridker🇺🇸Brigham and Women's Hospital; Harvard University
- Paul John Nestel🇦🇺Baker Heart and Diabetes Institute
- John R. Simes🇦🇺The University of Sydney
- Andrew Maxwell Tonkin🇦🇺Monash University
- Terje Rolf Pedersen🇳🇴Oslo University Hospital; University of Oslo
- Gregory G. Schwartz🇺🇸Denver VA Medical Center; University of Colorado Anschutz; University of Colorado Denver
- ANDERS G. OLSSON🇸🇪Linköping University
- Helen Martina Colhoun🇬🇧Institute of Genetics and Cancer; MRC Human Genetics Unit
- Florian Kronenberg🇦🇹Innsbruck Medical University; Universität Innsbruck
- Christiane Drechsler🇩🇪University of Würzburg; Universitätsklinikum Würzburg
- Christoph Wanner🇩🇪University of Würzburg; Universitätsklinikum Würzburg
- Samia Mora🇺🇸Brigham and Women's Hospital; Harvard University
- Anastasia Lesogor🇨🇭Novartis (Switzerland)
- Sotirios Tsimikas🇺🇸 · autor de correspondenciaUC San Diego Health System; University of California San Diego
Resumen
El texto original del estudio, en el idioma en que se publicó.
Background
Elevated lipoprotein(a) is a genetic risk factor for cardiovascular disease in general population studies. However, its contribution to risk for cardiovascular events in patients with established cardiovascular disease or on statin therapy is uncertain.
Methods
Patient-level data from seven randomised, placebo-controlled, statin outcomes trials were collated and harmonised to calculate hazard ratios (HRs) for cardiovascular events, defined as fatal or non-fatal coronary heart disease, stroke, or revascularisation procedures. HRs for cardiovascular events were estimated within each trial across predefined lipoprotein(a) groups (15 to <30 mg/dL, 30 to <50 mg/dL, and ≥50 mg/dL, vs <15 mg/dL), before pooling estimates using multivariate random-effects meta-analysis.
Findings
Analyses included data for 29 069 patients with repeat lipoprotein(a) measurements (mean age 62 years [SD 8]; 8064 [28%] women; 5751 events during 95 576 person-years at risk). Initiation of statin therapy reduced LDL cholesterol (mean change -39% [95% CI -43 to -35]) without a significant change in lipoprotein(a). Associations of baseline and on-statin treatment lipoprotein(a) with cardiovascular disease risk were approximately linear, with increased risk at lipoprotein(a) values of 30 mg/dL or greater for baseline lipoprotein(a) and 50 mg/dL or greater for on-statin lipoprotein(a). For baseline lipoprotein(a), HRs adjusted for age and sex (vs <15 mg/dL) were 1·04 (95% CI 0·91-1·18) for 15 mg/dL to less than 30 mg/dL, 1·11 (1·00-1·22) for 30 mg/dL to less than 50 mg/dL, and 1·31 (1·08-1·58) for 50 mg/dL or higher; respective HRs for on-statin lipoprotein(a) were 0·94 (0·81-1·10), 1·06 (0·94-1·21), and 1·43 (1·15-1·76). HRs were almost identical after further adjustment for previous cardiovascular disease, diabetes, smoking, systolic blood pressure, LDL cholesterol, and HDL cholesterol. The association of on-statin lipoprotein(a) with cardiovascular disease risk was stronger than for on-placebo lipoprotein(a) (interaction p=0·010) and was more pronounced at younger ages (interaction p=0·008) without effect-modification by any other patient-level or study-level characteristics.
Interpretation
In this individual-patient data meta-analysis of statin-treated patients, elevated baseline and on-statin lipoprotein(a) showed an independent approximately linear relation with cardiovascular disease risk. This study provides a rationale for testing the lipoprotein(a) lowering hypothesis in cardiovascular disease outcomes trials.
Funding
Novartis Pharma AG.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial.
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