Cohort Study of Cytomegalovirus Infection as a Risk Factor for Carotid Intimal-Medial Thickening, a Measure of Subclinical Atherosclerosis

Nieto, F. Javier; Adam, Ervín; Sorlie, Paul D.; Farzadegan, Homayoon; Melnick, Joseph L.; Comstock, George W.; Szklo, Moysés

doi:10.1161/01.cir.94.5.922

Cited by 257 publications

(151 citation statements)

References 31 publications

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“…Higher levels of CMV antibody have been correlated to the risk of angiographically diagnosed coronary artery disease . Recently, a population-based cohort study showed a correlation between the level of CMV antibodies and the degree of carotid intimal-medial thickening, an indication of subclinical atherosclerosis (Nieto et al, 1996). These findings are consistent with the putative causal role of CMV infection in atherosclerotic disease.…”

supporting

confidence: 65%

Experimental Infection with Bovine Herpesvirus-4 Enhances Atherosclerotic Process in Rabbits

Lin

Jiang

Eng

et al. 2000

Laboratory Investigation

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SUMMARY:An association of herpesvirus and atherosclerosis has been suggested by seroepidemiologic studies and detection of the virus in arterial tissues. To facilitate the studies of the pathogenic role of herpesvirus in atherosclerosis, we established a rabbit model of atherosclerosis with bovine herpesvirus type-4 (BHV-4). Forty New Zealand White rabbits were randomly divided into six groups. Groups 1, 2, and 3 were inoculated iv with BHV-4 and control Groups 4, 5, and 6 with normal saline. Groups 1 and 4 were fed a regular diet throughout the experiment; Groups 2 and 5 were fed a diet supplemented with 2% cholesterol for 3 weeks starting at 3 weeks postinoculation; and Groups 3 and 6 with a diet supplemented with 2% cholesterol for 6 weeks starting at 3 days postinoculation. Extensive atherosclerotic lesions in Groups 2, 3, and 6, and small lesions in two rabbits in Group 1 were observed, but no obvious lesions were observed in Groups 4 and 5. BHV-4 DNA was demonstrated by polymerase chain reaction and liquid hybridization in aortic sections, various tissue samples, and peripheral blood mononuclear cells of all infected rabbits. Our studies demonstrated that BHV-4 can accelerate the atherosclerotic process in rabbits, and that experimental infection of rabbits with BHV-4 can be a useful atherosclerosis model. (Lab Invest 2000, 80:3-11).

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supporting

confidence: 65%

Experimental Infection with Bovine Herpesvirus-4 Enhances Atherosclerotic Process in Rabbits

Lin

Jiang

Eng

et al. 2000

Laboratory Investigation

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“…In autopsies of aortic tissues that were identified histologically as atherosclerotic, DNA of HHV‐1, HHV‐4, and CMV were present more frequently than in nonatherosclerotic tissues 34, 35. In other studies, however, no differences were found between healthy persons and patients with early signs of atherosclerosis regarding the presence of anti–HHV‐1, anti–HHV‐2, and anti‐CMV antibodies36 and HHV‐1, HHV‐4, and HHV‐5 DNA in blood monocytes of patients with CAD 13. These contradictions may stem from the fact that neither serology nor DNA in cells give information about whether HHVs continue to replicate at the time of analysis.…”

Section: Discussionmentioning

confidence: 83%

Cytomegalovirus‐Productive Infection Is Associated With Acute Coronary Syndrome

Nikitskaya

Lebedeva

Ivanova

et al. 2016

JAHA

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BackgroundAlthough an association between human herpesvirus (HHV) infection and atherosclerosis has been suggested, the data supporting such an association are controversial and, in most cases, are based on serological evidence or on the presence of cell‐associated HHV DNA, which do not report about actual viral replication. We quantified the DNA of all 8 types of HHVs in plasma, in which their presence is evidence of viral replication.Methods and ResultsUsing quantitative real‐time polymerase chain reaction, we evaluated the presence of HHV DNA in blood samples obtained at the time of hospitalization from 71 patients with acute coronary syndrome, 26 patients with stable coronary artery disease, and 53 healthy volunteers and in atherosclerotic plaques of 22 patients with peripheral artery disease who underwent endarterectomy. HHV‐5 (cytomegalovirus [CMV]) was the only HHV with a level that was higher in acute coronary syndrome patients than in the control group and that correlated with the level of high‐sensitivity C‐reactive protein. The numbers of effector memory T cells positively correlated with the numbers of CMV genome copies in carotid arteries plaques, whereas the numbers of central memory T cells negatively correlated with CMV copy numbers.ConclusionsOf all HHV levels, only CMV was higher in patients with stable coronary artery disease and acute coronary syndrome than in the healthy group, and its load correlated with the level of high‐sensitivity C‐reactive protein. The level of CMV in atherosclerotic plaques correlated with the state of immunoactivation of lymphocytes in plaques, suggesting that the reactivation of CMV may contribute to the immune activation associated with the progression of atherosclerosis.

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“…Prior infection with CMV has been suggested as a strong independent risk factor for restenosis after coronary atherectomy, 15 and there is a graded relation between the odds of intimal-medial thickening and levels of CMV antibodies that remained significant after adjustment for the main cardiovascular risk factors. 16,17 Other viruses have been "accused" as well, for example, the hepatitis A (HAV) virus. 18 An association of herpesvirus and atherosclerosis has been suggested by seroepidemiologic studies and detection of the virus in arterial tissues.…”

Section: The Infectious Theorymentioning

confidence: 99%

Viral load of the human immunodeficiency virus could be an independent risk factor for endothelial dysfunction

et al. 2005

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SummaryBackground: Recent reports of myocardial infarction in young persons infected with human immunodeficiency virus (HIV) who are receiving protease inhibitor therapy have raised concerns about premature coronary artery disease in this population. However, endothelial dysfunction, hypercoagulability, hypertriglyceridemia, and abnormal coronary artery pathology have been observed in association with HIV infection prior to the availability of protease inhibitor therapy.Hypothesis: The study was undertaken to determine the association between endothelial function, viral load, CD4+ count, and other well-established risk factors for atherosclerosis.Methods: This prospective, case-controlled study compared viral (HIV) load and the CD4+ T-lymphocyte count and endothelial function in 24 HIV-positive carriers. Brachial artery diameter, HIV viral load, and CD4 count were measured.Results: We found that viral load correlated inversely with endothelial function; the higher the viral load, the worse the endothelial dysfunction (p < 0.005).Conclusion: High viral load appears to be associated with endothelial dysfunction in patients with HIV. This preliminary observation supports the infectious theory that viruses may play an important role in the pathogenesis of atherosclerosis.

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Cohort Study of Cytomegalovirus Infection as a Risk Factor for Carotid Intimal-Medial Thickening, a Measure of Subclinical Atherosclerosis

Abstract: The results from this first population-based cohort study of CMV infection and carotid IMT are compatible with the hypothesis of a causal role of CMV in atherosclerosis.

Cited by 257 publications

References 31 publications

Experimental Infection with Bovine Herpesvirus-4 Enhances Atherosclerotic Process in Rabbits

Experimental Infection with Bovine Herpesvirus-4 Enhances Atherosclerotic Process in Rabbits

Cytomegalovirus‐Productive Infection Is Associated With Acute Coronary Syndrome

Viral load of the human immunodeficiency virus could be an independent risk factor for endothelial dysfunction

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