Is cytomegalovirus infection causative for coronary heart disease?

Zin Naing
2013 Microbiology Australia  
Coronary heart disease (CHD) is the leading cause of death in Australia, representing 16% of all deaths registered in 2009. Atherosclerosis is the major pathological process involved in CHD that usually leads to a clinical condition such as acute myocardial infarction or angina. Epidemiological studies have indicated cigarette smoking, family history, diabetes, hypercholesterolemia and hypertension as independent risk factors for CHD; however, a considerable proportion of patients do not have
more » ... ese classical risk factors. Chronic infections with bacteria and viruses, including cytomegalovirus (CMV), have been proposed to play causative roles in the pathogenesis of CHD. Detection of CMV in atherosclerotic plaques, seroepidemiological data and in vitro and animal experiments suggests evidence for a direct role (viral presence in atherosclerotic plaques, increased LDL uptake and proliferative activity in CMV-infected arterial smooth muscle cells, upregulation of inflammatory cytokines in vascular endothelial cells), as well as an indirect role (viral presence in uninvolved aortic tissue of surgical patients, systemic upregulation of cytokines) for CMV infection in the development of CHD. Several lines of evidence exist that implicate microbial agents, including CMV, in the pathogenesis of CHD. CMV is a highly prevalent herpes virus, with 40-80% of Australians seropositive for the virus, and the prevalence of seropositivity increases with age 1 . Once acquired, CMV can establish a latent infection in the host that persists for a lifetime and may undergo periodic reactivation, especially in immunocompromised individuals 2 . Evidence for CMV as a potential atherogenic agent came from the detection of CMV antigens and virus-specific nucleic acid sequences in cells derived from atherogenic plaques of patients with severe arterial disease 3,4 . This observation was supported by higher prevalence of CMV genome in the coronary arteries of patients with severe atherosclerosis (90%) compared with specimens taken from patients with mild or no atherosclerosis (50%) 5 . Furthermore, CMV DNA was detected in early lesions of atherosclerosis in young trauma victims without symptomatic disease 6 . These observations suggest the human arterial wall might be the site of latency for CMV, and reactivation of the virus could have direct effects on the components of the vascular wall and subsequent development of atherosclerotic lesions. There is supportive evidence for an indirect role of CMV infection in CHD since viral DNA was also detected in uninvolved aortic tissues of patients undergoing surgery for symptomatic atherosclerotic disease as well as in matched controls 7,8 . More recently, Liu and colleagues investigated the coronary plaques of acute CHD patients using CMV-specific immunohistochemical staining and observed a significantly higher number of CMV-positive cells in specimens from patients with severe CHD, compared with patients with stable angina 9 , indicating the contribution of CMV infection to the severity of the disease. However, other studies have reported lack of evidence for CMV involvement in atherosclerotic tissue 10,11 . Kol et al. 12 assessed the expression of CMV MIE gene mRNA as an early marker for viral replication in coronary atherectomy specimens, but reported the absence of active CMV replication within these tissues, suggesting CMV might be localised within the vessel wall without being involved in the pathogenic process of CHD. Seroepidemiological studies also suggest that CMV seropositivity is associated with an increased risk of CHD. Danesh and colleagues reviewed several seroepidemiological studies and reported a positive correlation between CMV antibodies and cardiovascular disease 13 . However, evidence for the contribution of CMV to cardiovascular disease in these studies is weakened by small sample sizes, incomplete adjustment for known confounders, as well as focusing mainly on restenosis and transplant atherosclerosis rather than classic CHD. Recent meta-analysis involving six prospective and 49 retrospective case-control studies found that CMV infection was associated with an increased risk for CHD in both prospective and retrospective studies, as well as in Asian and non-Asian
doi:10.1071/ma13045 fatcat:g77cakuxzfcrhcx4gk4fa4rwem