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High-density lipoprotein cholesterol increase and non-cardiovascular mortality: a meta-analysis
  1. Elena Burillo1,
  2. Eva Maria Andres2,
  3. Rocio Mateo-Gallego1,
  4. Sarah Fiddyment1,
  5. Estibaliz Jarauta1,
  6. Ana Cenarro1,
  7. Fernando Civeira1
  1. 1Unidad de Lípidos and Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud (I+CS), Zaragoza, Spain
  2. 2Unidad de Investigación – Epidemiología Clínica, Hospital Universitario 12 de Octubre, CIBER de Epidemiología y Salud Pública, Edificio Materno-Infantil (planta-2) CEIC, Madrid, Spain
  1. Correspondence to Ms Elena Burillo, Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Avda, Isabel La Católica,1-3, Zaragoza 50009, Spain; eburilloi.iacs{at}


Context Many observational prospective studies have confirmed the inverse relationship between high-density lipoprotein (HDL) cholesterol and coronary heart disease. However, the potential benefit of the pharmacological increase in HDL cholesterol has not been clearly demonstrated. Moreover, in some interventions an increase in total mortality has been reported.

Objective The objective of this meta-analysis was to determine the relationship between HDL cholesterol increase and non-cardiovascular mortality in randomised trials.

Data sources Authors searched Medline up to December 2008.

Study selection Four reviewers identified randomised trials in which, through different types of interventions, HDL cholesterol increase in the treatment group was >4% compared to control group, both groups reported separately non-cardiovascular mortality and the duration of the study was, at least, one year.

Data extraction Data of HDL cholesterol concentrations and deaths were collected as they appeared in the original studies. If necessary, reviewers calculated data by using trial information.

Results Meta-regression analysis included 44 articles corresponding to 107 773 participants. Analysis showed an association between HDL cholesterol increase and non-cardiovascular mortality (p=0.023), however, the correlation disappeared when we excluded the ILLUMINATE (Investigation of Lipid Level Management to Understand its Impact in Atherosclerosis Events) trial from the analysis (p=0.972).

Conclusions Meta-regression analysis results suggest that increases in HDL cholesterol up to 40% are not associated with higher non-cardiovascular death. The increase in adverse events observed in some trials where HDL cholesterol was raised in large amounts could be related with the drug mechanisms more than the HDL cholesterol increase itself.

  • HDL
  • systematic review
  • meta-analysis
  • non-cardiovascular mortality
  • lipid trials
  • community cardiology

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  • All authors had access to the data and all authors had a role in writing the manuscript.

  • Funding Grant from the Spanish Ministry of Health FIS PI06/0365, PI07/1221, RETIC C06/01 (RECAVA) supported this work.

  • Competing interests None.

  • Ethics approval Each study included in this meta-analysis was conducted with approval of the corresponding ethics committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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