Are Morphological or Functional Changes in the Carotid Artery Wall Associated With Chlamydia pneumoniae, Helicobacter pylori, Cytomegalovirus, or Herpes Simplex Virus Infection?

Background and Purpose Chronic infection with Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus (CMV), and herpes simplex virus (HSV) has been implicated in the pathogenesis of atherosclerosis. The carotid intima-media thickness (IMT) can be taken to indicate early atherosclerosis, the presence of a carotid stenosis is a marker of a manifest carotid atherosclerosis, and an increase in arterial stiffness is used as marker of structural and functional changes in an atherosclerotic vessel wall. Methods In 504 patients (75% men; mean age 62.9 [SD 10] years), we measured the IMT and the elastic pressure modulus (EP; n=445) of the common carotid artery and the prevalence of a internal or external carotid artery stenosis. Blood samples were taken, and antibodies against C pneumoniae, H pylori, CMV, and HSV types 1 and 2 were evaluated. Statistical evaluation was performed with regression procedures and multivariate logistic regression analyses. Results Seropositivity for C pneumoniae was an independent predictor for a combined end point of highest category of IMT and carotid artery stenosis (OR 1.8, 95% CI 1.1 to 3.1; adjusted) for IgG titers. Independently, CMV increased the risk for the combined end point (OR 1.7, 95% CI 1.1 to 2.8; adjusted) for IgG titers and for IgA titers (OR 2.3, 95% CI 1.1 to 4.9; adjusted). We found a significant correlation between IgG antibodies against CMV and EP; HSV type 2 IgG titers were associated with IMT and carotid stenosis, but the latter results were no longer significant after adjustment. There was no association with H pylori or HSV type 1. Conclusions We found a significant association of IgG antibodies against C pneumoniae and CMV with early and advanced carotid atherosclerosis. CMV was also correlated to functional changes of the carotid artery, but this could not be confirmed after adjustment.

[1]  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.

[2]  M. Daemen,et al.  Cytomegalovirus nucleic acid distribution within the human vascular tree. , 1991, The American journal of pathology.

[3]  R. Baggott DISEASE , 1947, Social Policy & Administration.

[4]  G. Vercellotti,et al.  Herpes simplex virus and atherosclerosis. , 1993, European heart journal.

[5]  J M Reid,et al.  Quantitation of Carotid Stenosis with Continuous‐Wave (C‐W) Doppler Ultrasound , 1979, Stroke.

[6]  P. Ridker,et al.  C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. , 2000, The New England journal of medicine.

[7]  G. Lip,et al.  Chlamydia pneumoniae antibody titers are significantly associated with acute stroke and transient cerebral ischemia: the West Birmingham Stroke Project. , 1998, Stroke.

[8]  D. Strachan,et al.  Prospective relations between Helicobacter pylori infection, coronary heart disease and stroke in middle-aged men , 1997, Heart.

[9]  A. Gasbarrini,et al.  Association of virulent Helicobacter pylori strains with ischemic heart disease. , 1998, Circulation.

[10]  H. Miller,et al.  High anti-cytomegalovirus (CMV) IgG antibody titer is associated with coronary artery disease and may predict post-coronary balloon angioplasty restenosis. , 1998, The American journal of cardiology.

[11]  Gerardo Heiss,et al.  Carotid Artery Intimal‐Medial Thickness Distribution in General Populations As Evaluated by B‐Mode Ultrasound , 1993, Stroke.

[12]  D. Strachan,et al.  Relation of Helicobacter pylori infection and coronary heart disease. , 1994, British heart journal.

[13]  H. Steinmetz,et al.  Chlamydia pneumoniae infection and early asymptomatic carotid atherosclerosis. , 1999, Circulation.

[14]  S. Sasayama,et al.  Stiffness of systemic arteries in patients with myocardial infarction. A noninvasive method to predict severity of coronary atherosclerosis. , 1989, Circulation.

[15]  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.

[16]  M. Nieminen,et al.  SEROLOGICAL EVIDENCE OF AN ASSOCIATION OF A NOVEL CHLAMYDIA, TWAR, WITH CHRONIC CORONARY HEART DISEASE AND ACUTE MYOCARDIAL INFARCTION , 1988, The Lancet.

[17]  S. Epstein,et al.  The immediate early gene products of human cytomegalovirus increase vascular smooth muscle cell migration, proliferation, and expression of PDGF beta-receptor. , 1999, Biochemical and biophysical research communications.

[18]  A. Coulson,et al.  Chlamydia pneumoniae (TWAR) in atherosclerosis of the carotid artery. , 1995, Circulation.

[19]  P. Ridker,et al.  Plasma concentration of C-reactive protein and risk of developing peripheral vascular disease. , 1998, Circulation.

[20]  P. Ridker,et al.  Prospective study of herpes simplex virus, cytomegalovirus, and the risk of future myocardial infarction and stroke. , 1998, Circulation.

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

[22]  M. Debakey,et al.  CYTOMEGALOVIRUS ANTIGEN WITHIN HUMAN ARTERIAL SMOOTH MUSCLE CELLS , 1983, The Lancet.

[23]  SebastianJander,et al.  Inflammation in High-Grade Carotid Stenosis , 1998 .

[24]  I. Fong,et al.  Chlamydia pneumoniae, cytomegalovirus, and herpes simplex virus in atherosclerosis of the carotid artery. , 1997, Circulation.

[25]  Jianhui Zhu,et al.  Infection and atherosclerosis: emerging mechanistic paradigms. , 1999, Circulation.

[26]  G. Byrne,et al.  Induction of macrophage foam cell formation by Chlamydia pneumoniae. , 1998, The Journal of infectious diseases.

[27]  Chen Yuefeng Relation of Helicobacter Pylori Infection and Coronary Heart Disease , 1999 .

[28]  M. Leon,et al.  Association between prior cytomegalovirus infection and the risk of restenosis after coronary atherectomy. , 1996, The New England journal of medicine.

[29]  H. Steinmetz,et al.  Inflammation in high-grade carotid stenosis: a possible role for macrophages and T cells in plaque destabilization. , 1998, Stroke.

[30]  peterlibby,et al.  Roles of Infectious Agents in Atherosclerosis and Restenosis1 , 1997 .

[31]  D. Strachan,et al.  Relation of Chlamydia pneumoniae serology to mortality and incidence of ischaemic heart disease over 13 years in the caerphilly prospective heart disease study. , 1999, BMJ.

[32]  A. Quyyumi,et al.  Cytomegalovirus in the pathogenesis of atherosclerosis: the role of inflammation as reflected by elevated C-reactive protein levels. , 1999, Journal of the American College of Cardiology.

[33]  D. Strachan,et al.  Cytomegalovirus seropositivity and incident ischaemic heart disease in the Caerphilly prospective heart disease study , 1999, Heart.

[34]  C. Minick,et al.  Brief Definitive Report , 2003 .

[35]  J. Danesh,et al.  Chronic infection with Helicobacter pylori, Chlamydia pneumoniae, or cytomegalovirus: population based study of coronary heart disease , 1999, Heart.

[36]  M. Leinonen Pathogenetic mechanisms and epidemiology of Chlamydia pneumoniae. , 1993, European heart journal.

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

[38]  Veikko Salomaa,et al.  Non-insulin-dependent diabetes mellitus and fasting glucose and insulin concentrations are associated with arterial stiffness indexes. The ARIC Study. Atherosclerosis Risk in Communities Study. , 1995, Circulation.

[39]  P. Libby,et al.  Roles of infectious agents in atherosclerosis and restenosis: an assessment of the evidence and need for future research. , 1997, Circulation.

[40]  K. Bailey,et al.  HIGH LEVELS OF CYTOMEGALOVIRUS ANTIBODY IN PATIENTS REQUIRING VASCULAR SURGERY FOR ATHEROSCLEROSIS , 1987, The Lancet.

[41]  D. Graham,et al.  Helicobacter pylori seropositivity and coronary heart disease incidence. Atherosclerosis Risk In Communities (ARIC) Study Investigators. , 1998, Circulation.

[42]  D. Grobbee,et al.  Carotid artery intima‐media thickness as an indicator of generalized atherosclerosis , 1994, Journal of internal medicine.

[43]  E. Gurfinkel [Infection and atherosclerosis]. , 2001, Revista espanola de cardiologia.

[44]  B. Horne,et al.  Evaluation of C-reactive protein, an inflammatory marker, and infectious serology as risk factors for coronary artery disease and myocardial infarction. , 1998, Journal of the American College of Cardiology.

[45]  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.

[46]  Nilsson,et al.  Helicobacter pylori seropositivity is not associated with inflammatory parameters, lipid concentrations and degree of coronary artery disease , 1998, Journal of internal medicine.

[47]  C. Manegold,et al.  Prior cytomegalovirus infection and the risk of restenosis after percutaneous transluminal coronary balloon angioplasty. , 1999, Circulation.

[48]  A. Robertson,et al.  Herpesviridae in the coronary arteries and aorta of young trauma victims. , 1988, The American journal of pathology.

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