Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality: systematic review and meta-regression analysis.
OBJECTIVE
To investigate the association between treatment induced change 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 cholesterol and drug class in randomised trials of lipid modifying interventions.


METHODS
Systematic review and meta-regression analysis of randomised controlled trials.


METHODS
Medline, Embase, Central, CINAHL, and AMED to October 2006 supplemented by contact with experts in the field.


METHODS
In teams of two, reviewers independently determined eligibility of randomised trials that tested lipid modifying interventions to reduce cardiovascular risk, reported high density lipoprotein cholesterol and mortality or myocardial infarctions separately for treatment groups, and treated and followed participants for at least six months.


METHODS
Using standardised, pre-piloted forms, reviewers independently extracted relevant information from each article. The change in lipid concentrations for each trial and the weighted risk ratios for clinical outcomes were calculated.


RESULTS
The meta-regression analysis included 108 randomised trials involving 299 310 participants at risk of cardiovascular events. All analyses that adjusted for changes in low density lipoprotein cholesterol showed no association between treatment induced change in high density lipoprotein cholesterol and risk ratios for coronary heart disease deaths, coronary heart disease events, or total deaths. With all trials included, change in high density lipoprotein cholesterol explained almost no variability (<1%) in any of the outcomes. The change in the quotient of low density lipoprotein cholesterol and high density lipoprotein cholesterol did not explain more of the variability in any of the outcomes than did the change in low density lipoprotein cholesterol alone. For a 10 mg/dl (0.26 mmol/l) reduction in low density lipoprotein cholesterol, the relative risk reduction was 7.2% (95% confidence interval 3.1% to 11%; P=0.001) for coronary 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 lipoprotein cholesterol and drug class.


CONCLUSIONS
Available data suggest that simply increasing the amount of circulating high density lipoprotein cholesterol does not reduce the risk of coronary heart disease events, coronary heart disease deaths, or total deaths. The results support reduction in low density lipoprotein cholesterol as the primary goal for lipid modifying interventions.
Briel
Matthias
M
Department of Clinical Epidemiology and Biostatistics, McMaster University, 1200 Main Street West, Hamilton, ON, Canada. brielm@uhbs.ch
Ferreira-Gonzalez
Ignacio
I
You
John J
JJ
Karanicolas
Paul J
PJ
Akl
Elie A
EA
Wu
Ping
P
Blechacz
Boris
B
Bassler
Dirk
D
Wei
Xinge
X
Sharman
Asheer
A
Whitt
Irene
I
Alves da Silva
Suzana
S
Khalid
Zahira
Z
Nordmann
Alain J
AJ
Zhou
Qi
Q
Walter
Stephen D
SD
Vale
Noah
N
Bhatnagar
Neera
N
O'Regan
Christopher
C
Mills
Edward J
EJ
Bucher
Heiner C
HC
Montori
Victor M
VM
Guyatt
Gordon H
GH
D002318:Cardiovascular Diseases / Q000097:blood / Q000188:drug therapy / Q000401:mortality*; D008076:Cholesterol, HDL / Q000378:metabolism*; D002986:Clinical Trials as Topic; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D012044:Regression Analysis
D008076:Cholesterol, HDL; D000960:Hypolipidemic Agents