Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality: systematic review and meta-regression analysis

doi:10.1136/bmj.b92

Published 16 February 2009, doi:10.1136/bmj.b92
Cite this as: BMJ 2009;338:b92

Research

Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality: systematic review and meta-regression analysis

Matthias Briel, senior researcher ¹^,2, Ignacio Ferreira-Gonzalez, senior researcher³, John J You, assistant professor¹^,4, Paul J Karanicolas, senior researcher⁵, Elie A Akl, assistant professor⁶, Ping Wu, research associate⁷, Boris Blechacz, instructor in medicine⁸, Dirk Bassler, senior researcher⁹, Xinge Wei, physician¹, Asheer Sharman, physician⁴, Irene Whitt, physician⁸, Suzana Alves da Silva, senior researcher¹⁰, Zahira Khalid, physician⁴, Alain J Nordmann, senior researcher², Qi Zhou, statistician¹, Stephen D Walter, professor¹, Noah Vale, junior researcher¹, Neera Bhatnagar, librarian¹, Christopher O’Regan, research associate¹¹, Edward J Mills, assistant professor¹², Heiner C Bucher, professor², Victor M Montori, associate professor¹³, Gordon H Guyatt, professor¹^,4

¹ Department of Clinical Epidemiology and Biostatistics, McMaster University, 1200 Main Street West, Hamilton, ON, Canada, ² Basel Institute for Clinical Epidemiology, University Hospital Basel, Basel, Switzerland, ³ Department of Cardiology, Vall d’Hebron Hospital, Barcelona, and CIBER de Epidemiologia y Salud Pública (CIBERESP), Spain, ⁴ Department of Medicine, McMaster University, ⁵ Department of Surgery, University of Western Ontario, London, ON, ⁶ Department of Medicine, State University of New York at Buffalo, Buffalo, NY, USA, ⁷ Canadian College of Naturopathic Medicine, Toronto, ON, ⁸ Department of Medicine, Mayo Clinic, Rochester, MN, USA, ⁹ Department of Neonatology, University Children’s Hospital, Tuebingen, Germany, ¹⁰ Department of Research, Teaching and Research Center of Pro-Cardiaco/PROCEP, Rio de Janeiro, Brazil, ¹¹ Pfizer Ltd, Walton on the Hill, Surrey, ¹² British Columbia Centre for Excellence in HIV/AIDS, St Paul’s Hospital, Vancouver, BC, Canada, ¹³ Division of Endocrinology and Knowledge and Encounter Research Unit, Mayo Clinic

Correspondence to: M Briel brielm{at}uhbs.ch

Objective To investigate the association between treatment inducedchange in high density lipoprotein cholesterol and total death,coronary heart disease death, and coronary heart disease events(coronary heart disease death and non-fatal myocardial infarction)adjusted for changes in low density lipoprotein cholesteroland drug class in randomised trials of lipid modifying interventions.

Design Systematic review and meta-regression analysis of randomisedcontrolled trials.

Data sources Medline, Embase, Central, CINAHL, and AMED to October2006 supplemented by contact with experts in the field.

Study selection In teams of two, reviewers independently determinedeligibility of randomised trials that tested lipid modifyinginterventions to reduce cardiovascular risk, reported high densitylipoprotein cholesterol and mortality or myocardial infarctionsseparately for treatment groups, and treated and followed participantsfor at least six months.

Data extraction and synthesis Using standardised, pre-pilotedforms, reviewers independently extracted relevant informationfrom each article. The change in lipid concentrations for eachtrial and the weighted risk ratios for clinical outcomes werecalculated.

Results The meta-regression analysis included 108 randomisedtrials involving 299 310 participants at risk of cardiovascularevents. All analyses that adjusted for changes in low densitylipoprotein cholesterol showed no association between treatmentinduced change in high density lipoprotein cholesterol and riskratios for coronary heart disease deaths, coronary heart diseaseevents, or total deaths. With all trials included, change inhigh density lipoprotein cholesterol explained almost no variability(<1%) in any of the outcomes. The change in the quotientof low density lipoprotein cholesterol and high density lipoproteincholesterol did not explain more of the variability in any ofthe outcomes than did the change in low density lipoproteincholesterol alone. For a 10 mg/dl (0.26 mmol/l) reduction inlow density lipoprotein cholesterol, the relative risk reductionwas 7.2% (95% confidence interval 3.1% to 11%; P=0.001) forcoronary heart disease deaths, 7.1% (4.5% to 9.8%; P<0.001)for coronary heart disease events, and 4.4% (1.6% to 7.2%; P=0.002)for total deaths, when adjusted for change in high density lipoproteincholesterol and drug class.

Conclusions Available data suggest that simply increasing theamount of circulating high density lipoprotein cholesterol doesnot reduce the risk of coronary heart disease events, coronaryheart disease deaths, or total deaths. The results support reductionin low density lipoprotein cholesterol as the primary goal forlipid modifying interventions.

© Briel et al 2009
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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