Cytomegalovirus and Heart Disease

Student guest post by Dayna Groskreutz

Heart disease is the leading cause of death in adults in the United States. Acute coronary syndrome (ACS) is a term which includes both heart attacks and unstable angina. ACS occurs, in part, due to atherosclerosis, or plaque accumulation leading to narrowing of the artery. Some known risk factors for atherosclerosis and ACS include smoking, family history, high blood pressure, and high cholesterol. Recently, the role of inflammation in the development of atherosclerosis and ACS has been an area of intense study. Proposed causes of inflammation include bacteria and viruses, including Cytomegalovirus (CMV).

CMV is a common virus, with most people being infected by age 40. For healthy individuals, infection symptoms are minor, but CMV poses a particular threat to immunosuppressed patients and to pregnant woman and their unborn babies. CMV has been associated with heart transplant rejection, but there are conflicting data as to whether CMV is an important pathogen in the development of atherosclerosis and ACS. Thus far, associations have been demonstrated but no clear causative role has been determined.

Basic research studies demonstrated that CMV infection puts individuals at risk for clot formation (1). CMV became a pathogen of interest to cardiologists in 1996 when Zhou et al. reported that a previous CMV infection increased the rate of recurrent clots after clot/plaque removal during a heart catheterization (2). A subsequent study by Neumann and colleagues investigated the effect of previous CMV infection on the risk of complications for 30 days following stent placement. A positive CMV IgG antibody titer (indicating a previous infection with CMV) was found in 62% of the 551 patients included in the study, and 10 of them experienced death (2), infarction (4), or urgent re-intervention (4). No patients with a negative CMV IgG titer had any of these events, even when the data was corrected for potential confounders. A follow-up study by Smieja et al. found a lower prevalence of 17.3% of circulating CMV DNA in the blood (indicating active infection) using polymerase chain reaction (PCR) technique (4). Further, the study demonstrated that the processes of angiography and angioplasty do not increase circulating CMV.

The idea that an infection plays a role in atherosclerosis is intriguing, but Liu and colleagues attempted to determine the role of CMV in the acute coronary syndrome (heart attacks and unstable angina) (5). Coronary plaque specimens from 38 patients who underwent a heart catheterization were divided into an ACS group (21) and a non-ACS group (17). Using special stains to detect CMV, the ACS group was found to have a higher number of CMV-infected cells. The authors concluded that CMV in the coronary plaque is involved with the development of blockages in the heart arteries.

Another study investigated the same association of CMV and ACS but with distinct advantages: they used the more sensitive technique of RT-PCR to detect CMV rather than the less sensitive staining method, and they included a control group (6). In this study, Gredmark et al. studied the prevalence of active CMV infection in 40 patients with ACS, 50 patients with stable angina and coronary artery disease previously proven by catheterization, and 50 healthy controls. White blood cells were obtained from the blood, and RT-PCR was performed to detect CMV. The prevalence of acute CMV infection was significantly higher in ACS patients (15%) and in patients with stable angina (10%) than in healthy controls (2%). Whether CMV is a cause of the ACS and atherosclerosis or whether their ACS and atherosclerosis put these patients at risk for CMV reactivation is uncertain.

Another study compared actual biopsy specimens for the presence of CMV infection (7). 33 patients undergoing heart bypass surgery and 10 control patients underwent biopsy of the aorta and internal mammary artery. Contrary to previous studies, CMV was not detected by real time PCR in either the internal mammary artery or aortic biopsies of both groups.

A later study examined aortic biopsy specimens from 40 patients with three-vessel coronary artery disease undergoing bypass surgery, and 20 control patients undergoing aortic valve replacement (8). CMV was detected by polymerase chain reaction and was found in 55% of the bypass group and 50% of the control group. The authors concluded that the similar frequency of CMV in both groups did not support a role of CMV in atherosclerosis. A potential confounding variable is that many patients requiring a valve replacement also have atherosclerosis, and this confounder may have blunted the differences between the coronary and control groups.

Finally, a study done last fall by Xanaki and colleagues again attempted to quantify CMV DNA in specimens from coronary plaques vs. normal vessels of 26 patients undergoing bypass surgery (9). CMV DNA was detected in 34.6% of patients (9 of 26), but there was no difference between the amount of viral DNA detected in the normal and the diseased vessels. The authors concluded there was no causative role of CMV in the development of atherosclerotic plaques.

There are conflicting data as to whether CMV is an important pathogen in the development of atherosclerosis and the acute coronary syndrome. Several questions remain. Does CMV cause heart disease, or does heart disease put patients at risk for reactivation of CMV? Are the local effects of the virus in the plaque important, or is the systemic response of the body to the infection playing a role? Thus far, associations have been demonstrated but no clear causative role has been determined. Further well-designed studies are needed to clarify the role of this ubiquitous virus in this common disease.

References

1. Vercellotti, G. M. (1998) Blood Coagul Fibrinolysis 9 Suppl 2, S3-6
2. Zhou, Y. F., Leon, M. B., Waclawiw, M. A., Popma, J. J., Yu, Z. X., Finkel, T., and Epstein, S. E. (1996) N Engl J Med 335, 624-630
3. Neumann, F. J., Kastrati, A., Miethke, T., Pogatsa-Murray, G., Seyfarth, M., and Schomig, A. (2000) Circulation 101, 11-13
4. Smieja, M., Chong, S., Natarajan, M., Petrich, A., Rainen, L., and Mahony, J. B. (2001) J Clin Microbiol 39, 596-600
5. Liu, R., Moroi, M., Yamamoto, M., Kubota, T., Ono, T., Funatsu, A., Komatsu, H., Tsuji, T., Hara, H., Nakamura, M., Hirai, H., and Yamaguchi, T. (2006) Int Heart J 47, 511-519
6. Gredmark, S., Jonasson, L., Van Gosliga, D., Ernerudh, J., and Soderberg-Naucler, C. (2007) Scand Cardiovasc J 41, 230-234
7. Iriz, E., Cirak, M. Y., Engin, E. D., Zor, M. H., Erer, D., Imren, Y., Turet, S., and Halit, V. (2007) Acta Cardiol 62, 593-598
8. Reszka, E., Jegier, B., Wasowicz, W., Lelonek, M., Banach, M., and Jaszewski, R. (2008) Cardiovasc Pathol 17, 297-302
9. Xenaki, E., Hassoulas, J., Apostolakis, S., Sourvinos, G., and Spandidos, D. A. (2009) Angiology 60, 504-508

Comments

  1. #1 Russell
    February 23, 2010

    I imagine any disease that might lead to blood transfusion increases the risk of CMV infection, since CMV negative blood typically is reserved for infants and immunosuppressed patients.

  2. #2 Hjärthälsa
    February 24, 2010

    Interesting. I would love to read more on inflammation and what role antioxidants may play in reducing it, and therefore also atherosclerosis.

  3. #3 Sarah
    April 18, 2010

    Today, more new type disease come up. So, we need more care for our health. Anyway,this article more information can we get and we should know about that.

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    June 25, 2010

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