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Previous Volume 359:1897-1908 October 30, 2008 Number 18 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Supplementary Material Editorial by Schunkert, H. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear

ABSTRACT

Background Elevated levels of C-reactive protein (CRP) are associated with increased risks of ischemic heart disease and ischemic cerebrovascular disease. We tested whether this is a causal association.

Methods We studied 10,276 persons from a general population cohort, including 1786 in whom ischemic heart disease developed and 741 in whom ischemic cerebrovascular disease developed. We examined another 31,992 persons from a cross-sectional general population study, of whom 2521 had ischemic heart disease and 1483 had ischemic cerebrovascular disease. Finally, we compared 2238 patients with ischemic heart disease with 4474 control subjects and 612 patients with ischemic cerebrovascular disease with 1224 control subjects. We measured levels of high-sensitivity CRP and conducted genotyping for four CRP polymorphisms and two apolipoprotein E polymorphisms.

Results The risk of ischemic heart disease and ischemic cerebrovascular disease was increased by a factor of 1.6 and 1.3, respectively, in persons who had CRP levels above 3 mg per liter, as compared with persons who had CRP levels below 1 mg per liter. Genotype combinations of the four CRP polymorphisms were associated with an increase in CRP levels of up to 64%, resulting in a theoretically predicted increased risk of up to 32% for ischemic heart disease and up to 25% for ischemic cerebrovascular disease. However, these genotype combinations were not associated with an increased risk of ischemic vascular disease. In contrast, apolipoprotein E genotypes were associated with both elevated cholesterol levels and an increased risk of ischemic heart disease.

Conclusions Polymorphisms in the CRP gene are associated with marked increases in CRP levels and thus with a theoretically predicted increase in the risk of ischemic vascular disease. However, these polymorphisms are not in themselves associated with an increased risk of ischemic vascular disease.

Source Information

From the Department of Clinical Biochemistry (J.Z., B.G.N.) and the Copenhagen General Population Study (J.Z., A.T.-H., J.S.J., B.G.N.), Herlev Hospital; the Departments of Clinical Biochemistry (A.T.-H.), Cardiology (P.G.), and Vascular Surgery (H.S.), Rigshospitalet; the Copenhagen City Heart Study, Bispebjerg Hospital (A.T.-H., J.S.J., B.G.N.); and the Department of Cardiology, Gentofte Hospital (J.S.J.) — all at Copenhagen University Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen.

Address reprint requests to Dr. Nordestgaard at the Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark, or at brno{at}heh.regionh.dk.

Full Text of this Article

Related Letters:

Genetically Elevated C-Reactive Protein and Vascular Disease
Harbord R. M., Lawlor D. A., Smith G. D., Bubb M. R., Morita H., Nagai R., Zacho J., Tybjærg-Hansen A., Nordestgaard B. G.
Extract | Full Text | PDF  
N Engl J Med 2009; 360:933-935, Feb 26, 2009. Correspondence

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