A large body of evidence exists that implicates a number of microbial agents in the pathogenesis of coronary heart disease (CHD). This, if proven, may have far-reaching implications for the prevention and treatment of CHD and other atherosclerotic disease. The histopathology of atherosclerosis and its natural history suggest infectious causation at many points along the progression of disease, particularly with regard to CHD, and a number of pathogens have been the focus of study. Viral agents implicated include Coxsackie B4 virus, for which tenuous sero-epidemiological associations exist, and the Herpesviridae. The animal herpesvirus causing Marek’s disease in chickens causes atherosclerotic lesions in these animals. Herpes simplex virus I and II have been found in aortic smooth muscle and produce changes in vitro in smooth muscle that are similar to those seen at the beginning of atherosclerosis and which may also explain some of the features of atherosclerotic complications. Cytomegalovirus is implicated more strongly sero-epidemiologically by in-vivo detection in atherosclerotic lesions and by its links with post-cardiac transplant vasculopathy - a syndrome similar to atherosclerosis. Bacteria have also been shown to have links with CHD. Chlamydia pneumoniae and Helicobacter pylori have both been associated sero-epidemiologically with CHD, and these findings have been consolidated by recent work showing their presence in atherosclerotic lesions in adults. Bacterial infections in general lead to many changes in lipid, thrombic and other acute-phase protein metabolism, and some of these changes occur with both C. pneumoniae and H. pylori infections. The ubiquity and similar epidemiological features to CHD of all these microbial pathogens make the resolution of the causative issue impossible by retrospective means. All that can be shown at present are a variety of weak and strong links, the significance of which can only be determined by large and perhaps lifetime prospective studies.
SpodickD. H.,
FlessasA. P.,
JohnsonM. M. Association of acute respiratory symptoms with onset of acute myocardial infarction: prospective investigation of 150 consecutive patients and matched control patients. Am J Cardiol1984; 53:481–482
WoodsJ. D.,
NimmoM. J.,
Mackay-ScollayE. M. Acute transmural myocardial infarction associated with active Coxsackie virus B infection. Am Heart J1975; 89:283–287
YamashiroyaH. M.,
GhoshL.,
YangR.,
RobertsonA. L. Herpes-viridae in the coronary arteries and aorta of young trauma victims. Am J Pathol1988; 130:71–79
GyorkeyF.,
MelnickJ. L.,
GuinnG. A.,
GyorkeyP.,
DeBakeyM. E. Herpesviridae in the endothelial and smooth muscle cells of the proximal aorta of atherosclerosis patients. Exp Mol Pathol1984; 40:328–339
HendricksM. G. R.,
SalimensM. M. M.,
VaubovenC. P. A.,
BruggemanC. A. High prevalence of latently present cytomegalovirus in arterial walls of patients suffering from grade III atherosclerosis. Am J Pathol1990; 136:23–28
DummerS.,
LeeA.,
BreinigM. K.,
KormosR.,
HoM.,
GriffithB. Investigation of cytomegalovirus infection as a risk factor for coronary atherosclerosis in the explanted hearts of patients undergoing heart transplantation. J Med Virol1994; 44:305–309
NormannS. J.,
SalomonD. R.,
LeelachaikulP. Acute vascular rejection of the coronary arteries in human heart transplantation: pathology and correlations with immunosuppression and cytomegalovirus infection. J Heart Lung Transplant1991; 10:674–687
KoskinenP. K.,
NieminenM. S.,
KrogerusL. A. Cytomegalovirus infection and accelerated cardiac allograft vasculopathy in human cardiac allografts. J Heart Lung Transplant1993; 12:724–729
EtinginO. R.,
SilversteinR. L.,
FriedmanH. M.,
HajjarD. P. Viral activation of the coagulation cascade: molecular interactions at the surface of infected endothelial cells. Cell1990; 61:657–662
VisserM. R.,
TracyP. B.,
VercellottiG. M.,
GoodmanJ. L.,
WhiteJ. G.,
JacobsH. S. Enhanced thrombin generation and platelet binding on herpes simplex vims-infected endothelium. Proc Natl Acad Sei USA1988; 85:8227–8230
SaikkuP.,
MattilaK.,
NieminenM. S. Serological evidence of an association of a novel chlamydia, TWAR, with chronic coronary heart disease and acute myocardial infarction. Lancet1988; ii:983–985
SaikkuP.,
LeinonenM.,
TenkanenL. Chronic Chlamydia pneumoniae infection as a risk factor for coronary heart disease in the Helsinki Heart Study. Ann Intern Med1992; 116:273–278
PatelP.,
MendallM. A.,
CarringtonD. Association of Helicobacter pylori and Chlamydia pneumoniae infections with coronary heart disease and cardiovascular risk factors. BMJ1995; 311:711–714
KuoC.-C.,
ShorA.,
CampbellL. A.,
FukushiA.,
PattonD. L.,
GraystonJ. T. Demonstration of Chlamydia pneumoniae in atherosclerotic lesions of coronary arteries. J Infect Dis1993; 167:841–849
WangS.-P.,
GraystonJ. T. Population prevalence of antibody to Chlamydia pneumoniae strain TWAR. In
BowieW. R.,
CaldwellH. D.,
JonesR. P.
(eds) Chlamydial infections Cambridge: Cambridge University Press; 1990402–405
CunninghamA.,
WardM.,
MatthewsR.,
EllisR.Helicobacter pylori and Chlamydia pneumoniae in tissues of myocardial infarction cases. 1st European Congress of Chemotherapy, Glasgow1996 Abstract W149
Lopes-VirellaM. E. Interactions between bacterial lipopolysaccharides and serum lipoproteins and their possible role in coronary heart disease. Eur Heart J1994; 14: Suppl K118–124
ReinesH. D.,
HalushkaP. Y.,
CookJ. A.,
WiseW. C.,
RamboW. Plasma thromboxane concentrations are raised in patients dying with septic shock. Lancet1982; 2:174–175
YamellJ. W. G.,
BakerI. A.,
SweetmanP. M. Fibrinogen, viscosity, and white blood cell count are major risk factors for ischemic heart disease. The Caerphilly and Speedwell collaborative heart disease studies. Circulation1991; 83:836–844
LiuzzoG.,
BiasucciL. M.,
GallimoreJ. R. The prognostic value of C-reactive protein and serum amyloid A protein in severe unstable angina. N Engl J Med1994; 331:417–424
MendallM. A.,
PatelP.,
BallamL.,
StrachanD.,
NorthfieldT. C. C reactive protein and its relation to cardiovascular risk factors: a population based cross sectional study. BMJ1996; 312:1061–1065