Abstract
Chronic inflammatory stimuli such as cytomegalovirus (CMV) infection and various genetic polymorphisms determining the inflammatory response are assumed to be important risk factors in atherosclerosis. We investigated whether patients with stable coronary artery disease (CAD) and homozygous for allele 2 of the interleukin 1 receptor antagonist (IL-1RA) gene and seropositive for CMV represent a group particular susceptible for recurrent cardiovascular events. In a series of 300 consecutive patients with angiographically defined CAD a prospective follow-up was conducted (mean age 57.9 years, median follow-up time 38.2 months). No statistically significant relationship was found between CMV serostatus and IL-1RN*2 (alone or in combination) and risk for future cardiovascular events (CVE). The hazard ratio (HR) for a CVE given positive CMV-serology and IL-1RN*2 was 1.07 (95% confidence interval (CI) 0.32-3.72) in the fully adjusted model compared to seronegative CMV patients not carrying the IL-1RN*2 allele. In this prospective cohort study involving 300 patients with angiographically defined CAD at baseline, homozygosity for allele 2 of the IL-1 RA and seropositivity to CMV alone and in combination were not associated with an increased risk for cardiovascular events during follow-up; in addition, combination of the CMV-seropositivity and IL-1RN*2 allele were not associated with a proinflammatory response. Our study suggests that seropositivity to CMV and IL-1RA*2 genotype alone or in combination might not be a strong risk factor for recurrent cardiovascular events in patients with manifest CAD, and is not associated with levels of established inflammatory markers.
MeSH Terms
Adult
Aged
Cardiovascular Diseases/blood,etiology,genetics
Coronary Artery Disease/blood,genetics
Cytomegalovirus Infections/blood
Female
Follow-Up Studies
Homozygote
Humans
Interleukin 1 Receptor Antagonist Protein
Male
Middle Aged
Multivariate Analysis
Polymorphism, Genetic
Prospective Studies
Risk Factors
Serologic Tests
Sialoglycoproteins/genetics
Chemicals
IL1RN protein, human
Interleukin 1 Receptor Antagonist Protein
Sialoglycoproteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Rothenbacher Dietrich
Department of Epidemiology, The German Centre for Research on Ageing, University of Heidelberg, Germany.
[email protected]
Brenner Hermann
Mertens Thomas
Hoffmann Michael M
Hoffmeister Albrecht
Koenig Wolfgang
References (16)
16 references, click to expand
-
Relationship between infectious burden, systemic inflammatory response, and risk of stable coronary artery disease: role of confounding and reference group.
Atherosclerosis. 2003 Oct;170(2):339-45
PMID: 14612216
-
Potential infectious etiologies of atherosclerosis: a multifactorial perspective.
Emerg Infect Dis. 2001 Sep-Oct;7(5):780-8
PMID: 11747688
-
Chronic infections and coronary heart disease: is there a link?
Lancet. 1997 Aug 9;350(9075):430-6
PMID: 9259669
-
Prospective study of herpes simplex virus, cytomegalovirus, and the risk of future myocardial infarction and stroke.
Circulation. 1998 Dec 22-29;98(25):2796-9
PMID: 9860778
-
Atherosclerosis--an inflammatory disease.
N Engl J Med. 1999 Jan 14;340(2):115-26
PMID: 9887164
-
Cytomegalovirus infection and coronary heart disease: results of a german case-control study.
J Infect Dis. 1999 Mar;179(3):690-2
PMID: 9952378
-
Interleukin-1 receptor antagonist gene polymorphism and coronary artery disease.
Circulation. 1999 Feb 23;99(7):861-6
PMID: 10027806
-
Infection and atherosclerosis: emerging mechanistic paradigms.
Circulation. 1999 Jul 27;100(4):e20-8
PMID: 10421626
-
The pathogenicity of cytomegalovirus.
FEMS Microbiol Rev. 1999 Jul;23(4):457-82
PMID: 10422262
-
Coronary heart disease, Helicobacter pylori, dental disease, Chlamydia pneumoniae, and cytomegalovirus: meta-analyses of prospective studies.
Am Heart J. 1999 Nov;138(5 Pt 2):S434-7
PMID: 10539843
-
Cytomegalovirus in the pathogenesis of atherosclerosis: the role of inflammation as reflected by elevated C-reactive protein levels.
J Am Coll Cardiol. 1999 Nov 15;34(6):1738-43
PMID: 10577564
-
Cytomegalovirus seropositivity and C-reactive protein have independent and combined predictive value for mortality in patients with angiographically demonstrated coronary artery disease.
Circulation. 2000 Oct 17;102(16):1917-23
PMID: 11034939
-
Protective role against restenosis from an interleukin-1 receptor antagonist gene polymorphism in patients treated with coronary stenting.
J Am Coll Cardiol. 2000 Dec;36(7):2168-73
PMID: 11127457
-
Cytomegalovirus infection with interleukin-6 response predicts cardiac mortality in patients with coronary artery disease.
Circulation. 2001 Jun 19;103(24):2915-21
PMID: 11413080
-
Influence of interleukin-1 receptor antagonist gene polymorphism on disease.
Clin Infect Dis. 2002 Jan 15;34(2):204-9
PMID: 11740709
-
Association between prior cytomegalovirus infection and the risk of restenosis after coronary atherectomy.
N Engl J Med. 1996 Aug 29;335(9):624-30
PMID: 8687516