Chlamydia pneumoniae but not cytomegalovirus antibodies are associated with future risk of stroke and cardiovascular disease: a prospective study in middle-aged to elderly men with treated hypertension.

BACKGROUND AND PURPOSE Several cross-sectional and prospective studies have indicated that high titers of antibodies to Chlamydia pneumoniae and cytomegalovirus (CMV) are associated with coronary heart disease. The aim of the present study was to examine whether elevated titers of antibodies to these pathogens are predictive of not only coronary but also cerebrovascular disease. METHODS Serum titers of antibodies to C pneumoniae (IgM, IgG, IgA, IgG immune complex) and CMV (IgG) were determined at baseline (n=130) and after 3.5 years (n=111) in a total sample of 152 men. All individuals had treated hypertension and at least 1 additional risk factor for cardiovascular disease (hypercholesterolemia, smoking, or diabetes mellitus) and constituted 93% of a randomly selected subgroup (n=164) of patients participating in a multiple risk factor intervention study. RESULTS Elevations of any or both of the IgA or IgG titers to C pneumoniae at entry or after 3.5 years were found in 84 cases (55%). Of those with high titers at entry, 97% remained high at the 3.5 year reexamination. After 6.5 years of follow-up, high titers to C pneumoniae at entry were associated with an increased risk for future stroke (relative risk [RR], 8.58; P=0.043; 95% CI, 1.07 to 68.82) and for any cardiovascular event (RR, 2.69; P=0.042; 95% CI, 1.04 to 6.97). A high serum titer of antibodies to CMV was found in 125 cases (85%), and this was not associated with an increased risk of future cardiovascular events. CONCLUSIONS Seropositivity for C pneumoniae, but not for CMV, was associated with an increased risk for future cardiovascular disease and, in particular, stroke.

[1]  H. Hallander,et al.  The prevalence of chronic Chlamydia pneumoniae infection as detected by polymerase chain reaction in pharyngeal samples from patients with ischaemic heart disease. , 1998, European heart journal.

[2]  A. Siegbahn,et al.  Increased fibrinogen levels are associated with persistent Chlamydia pneumoniae infection in unstable coronary artery disease. , 1998, European heart journal.

[3]  G. Lip,et al.  Chlamydia pneumoniae antibodies in severe essential hypertension. , 1998, Hypertension.

[4]  B. Fagerberg,et al.  Mortality rates in treated hypertensive men with additional risk factors are high but can be reduced: a randomized intervention study. , 1998, American journal of hypertension.

[5]  G. Vetrovec,et al.  Prior infection with cytomegalovirus is not a major risk factor for angiographically demonstrated coronary artery atherosclerosis. , 1998, The Journal of infectious diseases.

[6]  M. Leinonen,et al.  Chlamydia pneumoniae infection induces inflammatory changes in the aortas of rabbits , 1997, Infection and immunity.

[7]  J. Danesh,et al.  Chronic infections and coronary heart disease: is there a link? , 1997, The Lancet.

[8]  E. Gurfinkel,et al.  Randomised trial of roxithromycin in non-Q-wave coronary syndromes: ROXIS pilot study , 1997, The Lancet.

[9]  A. Camm,et al.  Elevated Chlamydia pneumoniae Antibodies, Cardiovascular Events, and Azithromycin in Male Survivors of Myocardial Infarction , 1997 .

[10]  M. Leinonen,et al.  Chlamydia pneumoniae antibodies and serum lipids in Finnish men: cross sectional study , 1997, BMJ.

[11]  I. Fong,et al.  Rabbit model for Chlamydia pneumoniae infection , 1997, Journal of clinical microbiology.

[12]  J. Gnarpe,et al.  Demonstration of Chlamydia pneumoniae in patients with chronic pharyngitis. , 1997, Scandinavian journal of infectious diseases.

[13]  P. Saikku,et al.  Association of chlamydial infection with cerebrovascular disease. , 1996, Stroke.

[14]  P. Sorlie,et al.  Cohort study of cytomegalovirus infection as a risk factor for carotid intimal-medial thickening, a measure of subclinical atherosclerosis. , 1996, Circulation.

[15]  M. Laakso,et al.  Association of Chlamydia pneumoniae and acute coronary heart disease events in non-insulin dependent diabetic and non-diabetic subjects in Finland. , 1996, European heart journal.

[16]  BjörnFagerberg,et al.  Multiple Risk Intervention in High-Risk Hypertensive Patients , 1996 .

[17]  B. Fagerberg,et al.  Multiple risk intervention in high-risk hypertensive patients. A 3-year ultrasound study of intima-media thickness and plaques in the carotid artery. Risk Intervention Study (RIS) Group. , 1996, Arteriosclerosis, thrombosis, and vascular biology.

[18]  J. Gnarpe,et al.  Persistent Chlamydia pneumoniae infection in a Swedish family. , 1996, Scandinavian journal of infectious diseases.

[19]  D. Strachan,et al.  Association of Helicobacter pylori and Chlamydia pneumoniae infections with coronary heart disease and cardiovascular risk factors , 1995, BMJ.

[20]  E. Feskens,et al.  Infection with chlamydia pneumoniae as a risk factor for coronary heart disease (the Zupthen elderly study) , 1995 .

[21]  J. Gnarpe,et al.  Chlamydia pneumoniae and chronic pharyngitis. , 1995, Scandinavian journal of infectious diseases.

[22]  J. Tuomilehto,et al.  Importance of smoking for Chlamydia pneumoniae seropositivity. , 1994, International journal of epidemiology.

[23]  B. Fagerberg,et al.  Ultrasound evaluation of atherosclerotic manifestations in the carotid artery in high-risk hypertensive patients. Risk Intervention Study (RIS) Group. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[24]  T. Tuomi,et al.  Interference of immunoglobulin G (IgG) antibodies in IgA antibody determinations of Chlamydia pneumoniae by microimmunofluorescence test , 1994, Journal of clinical microbiology.

[25]  A. Folsom,et al.  Past infection by Chlamydia pneumoniae strain TWAR and asymptomatic carotid atherosclerosis. Atherosclerosis Risk in Communities (ARIC) Study Investigators. , 1993, The American journal of medicine.

[26]  M. Nieminen,et al.  Chlamydia Pneumoniae‐Specific Circulating Immune Complexes in Patients With Chronic Coronary Heart Disease , 1993, Circulation.

[27]  J. Gnarpe,et al.  Increasing prevalence of specific antibodies to Chlamydia pneumoniae in Sweden , 1993, The Lancet.

[28]  C. Bruggeman.  Cytomegalovirus and latency: an overview , 1993, Virchows Archiv. B, Cell pathology including molecular pathology.

[29]  Grayston Jt.  Infections caused by Chlamydia pneumoniae strain TWAR. , 1992 .

[30]  D. Hahn,et al.  Smoking is a potential confounder of the Chlamydia pneumoniae-coronary artery disease association. , 1992, Arteriosclerosis and thrombosis : a journal of vascular biology.

[31]  M. Leinonen,et al.  Chronic Chlamydia pneumoniae Infection as a Risk Factor for Coronary Heart Disease in the Helsinki Heart Study , 1992, Annals of Internal Medicine.

[32]  J. Grayston.  Infections caused by Chlamydia pneumoniae strain TWAR. , 1992, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[33]  Norman E. Breslow,et al.  Statistical Methods in Cancer Research, Vol. II: The Design and Analysis of Cohort Studies. , 1990 .

[34]  N. Breslow,et al.  Statistical methods in cancer research. Volume II--The design and analysis of cohort studies. , 1987, IARC scientific publications.

[35]  P. Libby,et al.  Endotoxin and tumor necrosis factor induce interleukin-1 gene expression in adult human vascular endothelial cells. , 1986, The American journal of pathology.

[36]  G. Striker,et al.  Effects of lipopolysaccharide on human endothelial cells in culture. , 1983, Thrombosis research.

[37]  L. Kline,et al.  Activation of the classical and properdin pathways of complement by bacterial lipopolysaccharides (LPS). , 1977, Journal of immunology.