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In Reply: The overall objective of our study was to examine whether a lifelong lowering of HDL cholesterol levels, without corresponding higher levels of plasma triglycerides or atherogenic remnant lipoproteins,¹ was associated with increased risk of IHD. To test this hypothesis, we used heterozygotes for mutations in ABCA1 associated with low cellular cholesterol efflux, as well as with substantial, lifelong lowering of HDL levels, and showed no increase in risk. These results question the hypothesis of reverse cholesterol transport, an active research field. We agree with Dr Brunham and colleagues that genetic variants in ABCA1 may have effects on atherosclerosis independent of effects on HDL levels.^2-4 However, there are some inaccuracies in their letter.

First, it is correct that the unadjusted reduction in HDL levels in ABCA1 heterozygotes compared with noncarriers was 28% (Table 2); however, the age- and sex-adjusted mean percentile for HDL levels in heterozygotes in the CCHS . . . [Full Text of this Article]

Anne Tybjærg-Hansen, MD, DMSc
at-h@rh.regionh.dk
Department of Clinical Biochemistry
Rigshospitalet

Børge G. Nordestgaard, MD, DMSc
Department of Clinical Biochemistry
Herlev Hospital

Ruth Frikke-Schmidt, MD, PhD
Department of Clinical Biochemistry
Rigshospitalet
University of Copenhagen
Copenhagen, Denmark

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RELATED ARTICLE

Association of Loss-of-Function Mutations in the ABCA1 Gene With High-Density Lipoprotein Cholesterol Levels and Risk of Ischemic Heart Disease
Ruth Frikke-Schmidt, Børge G. Nordestgaard, Maria C. A. Stene, Amar A. Sethi, Alan T. Remaley, Peter Schnohr, Peer Grande, and Anne Tybjærg-Hansen
JAMA. 2008;299(21):2524-2532.
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RELATED LETTER

ABCA1 Gene Mutations, HDL Cholesterol Levels, and Risk of Ischemic Heart Disease
Liam R. Brunham, John J. P. Kastelein, and Michael R. Hayden
JAMA. 2008;300(17):1997-1998.
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All you need to read in the other general journals
BMJ 2008;337:a2463-a2463.
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