Financiado en parte por Novartis, Astellas Pharma, Medtronic
Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: a Mendelian randomization analysis
Ference BA, Yoo W, Alesh I, Mahajan N, Mirowska KK, Mewada A, Kahn J, Afonso L, Williams KA, Flack JM
Journal of the American College of Cardiology · 688 citas
Etiquetas de revisión
Financiado por la industriaDatos neutrales que nuestra revisión registró sobre cómo se hizo este estudio. Describen el método, nunca si nos gusta el resultado.
Cómo se estudió
- Diseño
- Metaanálisis (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Eventos clínicos como enfermedad o muerte
Quién lo pagó
- Financiación
- Financiado por la industria
- Empresa
- Novartis
- Universidad u hospital
- University of Oxford
- Empresa
- Astellas Pharma
- Gobierno
- National Institutes of Health
- Empresa
- Medtronic
- Gobierno
- NIH
Según 6 financiadores declarados.
Publicación
- Publicado
- 2012-10-17 · J Am Coll Cardiol · vol. 60 · número 25 · págs. 2631–2639
- Editorial
- Elsevier BV
- Citado
- 899 citas · más que el 100% de estudios similares · 44.2× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 44 trabajos
- Acceso
- Lectura gratuita
- Áreas de investigación
- Lipoproteins and Cardiovascular Health · Genetic Associations and Epidemiology · Paraoxonase enzyme and polymorphisms
- Palabras clave
- LDL cholesterol, coronary heart disease risk, genetic polymorphism, Mendelian randomization, statin therapy, LDL cholesterol lowering, cardiovascular risk reduction
- MeSH
- humans, genetic predisposition to disease, genetic markers, incidence, risk assessment, risk factors, follow-up studies, polymorphism, genetic, time factors, cholesterol, ldl, coronary artery disease, mendelian randomization analysis, global health
10 autores
- Brian A. Ference🇺🇸🇬🇧 · autor de correspondenciaWayne State University; University of Oxford
- Wonsuk Yoo🇺🇸University of Tennessee Health Science Center
- Issa G. Alesh🇺🇸Wayne State University
- Nitin Mahajan🇺🇸Wayne State University
- Karolina K. Mirowska🇺🇸Wayne State University
- Abhishek Mewada🇺🇸Wayne State University
- Joel Kahn🇺🇸Detroit Medical Center
- Luis Afonso🇺🇸Wayne State University
- Kim Allan Williams Sr.🇺🇸Wayne State University
- John M. Flack🇺🇸Wayne State University
Resumen
El texto original del estudio, en el idioma en que se publicó.
Objectives
The purpose of this study was to estimate the effect of long-term exposure to lower plasma low-density lipoprotein cholesterol (LDL-C) on the risk of coronary heart disease (CHD).
Background
LDL-C is causally related to the risk of CHD. However, the association between long-term exposure to lower LDL-C beginning early in life and the risk of CHD has not been reliably quantified.
Methods
We conducted a series of meta-analyses to estimate the effect of long-term exposure to lower LDL-C on the risk of CHD mediated by 9 polymorphisms in 6 different genes. We then combined these Mendelian randomization studies in a meta-analysis to obtain a more precise estimate of the effect of long-term exposure to lower LDL-C and compared it with the clinical benefit associated with the same magnitude of LDL-C reduction during treatment with a statin.
Results
All 9 polymorphisms were associated with a highly consistent reduction in the risk of CHD per unit lower LDL-C, with no evidence of heterogeneity of effect (I(2) = 0.0%). In a meta-analysis combining nonoverlapping data from 312,321 participants, naturally random allocation to long-term exposure to lower LDL-C was associated with a 54.5% (95% confidence interval: 48.8% to 59.5%) reduction in the risk of CHD for each mmol/l (38.7 mg/dl) lower LDL-C. This represents a 3-fold greater reduction in the risk of CHD per unit lower LDL-C than that observed during treatment with a statin started later in life (p = 8.43 × 10(-19)).
Conclusions
Prolonged exposure to lower LDL-C beginning early in life is associated with a substantially greater reduction in the risk of CHD than the current practice of lowering LDL-C beginning later in life.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial.
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