High-density lipoprotein particle size and concentration and coronary risk.
BACKGROUND
High-density lipoprotein (HDL) cholesterol levels are inversely related to risk for coronary artery disease (CAD). Because HDL particles are heterogeneous in size and composition, they may be differentially associated with other cardiovascular risk factors and with cardiovascular risk.


OBJECTIVE
To study the independent relationships of HDL size and particle concentration to risk for future CAD.


METHODS
Nested case-control study within the EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk cohort; baseline survey between 1993 and 1997, follow-up until November 2003.


METHODS
Norfolk, United Kingdom.


METHODS
Case patients were 822 apparently healthy men and women who developed CAD during follow-up. Control participants were 1401 participants who remained without CAD and were matched to case patients by sex, age, and enrollment time.


METHODS
First CAD event leading to either hospitalization or death.


RESULTS
Nuclear magnetic resonance spectroscopy-measured HDL particle concentration (mean, 33.9 micromol/L [SD, 5] vs. 32.9 micromol/L [SD, 6]; P < 0.001) and HDL size (mean, 8.9 nm [SD, 0.5] vs. 8.8 nm [SD, 0.5]; P < 0.001), as well as gradient gel electrophoresis-measured HDL size (mean, 8.9 nm [SD, 0.4] vs. 8.8 nm [SD, 0.4]; P = 0.005) were lower in case patients than in control participants. High-density lipoprotein size and HDL particle concentration were only weakly correlated (r = 0.08, for those measured with nuclear magnetic resonance spectroscopy; r = 0.10, for those measured with gradient gel electrophoresis). High-density lipoprotein size was strongly associated with risk factors characteristic of the metabolic syndrome, including waist-to-hip ratio, triglyceride level, and apolipoprotein B level, whereas HDL particle concentration was not. Both HDL size and HDL particle concentration were independently associated with CAD risk. The association between HDL size and CAD risk was abolished on adjustment for apolipoprotein B and triglyceride levels (adjusted odds ratio, 1.00 [95% CI, 0.71 to 1.39] for top vs. bottom quartile), whereas HDL particle concentration remained independently associated with CAD risk (adjusted odds ratio, 0.50 [CI, 0.37 to 0.66]).


CONCLUSIONS
Measurements were performed in nonfasting blood samples, and residual confounding cannot be excluded.


CONCLUSIONS
Both HDL size and HDL particle concentration were independently associated with other cardiovascular risk factors and with the risk for CAD. The relationship between HDL size and CAD risk was explained by markers associated with the metabolic syndrome, indicating that part of the relationship between HDL cholesterol and CAD risk is merely a reflection of this metabolic risk.
El Harchaoui
Karim
K
Academic Medical Center, Amsterdam, the Netherlands.
Arsenault
Benoit J
BJ
Franssen
Remco
R
Després
Jean-Pierre
JP
Hovingh
G Kees
GK
Stroes
Erik S G
ES
Otvos
James D
JD
Wareham
Nicholas J
NJ
Kastelein
John J P
JJ
Khaw
Kay-Tee
KT
Boekholdt
S Matthijs
SM
D000368:Aged; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood* / Q000737:chemistry*; D003324:Coronary Artery Disease / Q000097:blood*; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D011446:Prospective Studies; D012307:Risk Factors
D008076:Cholesterol, HDL