[Effect of anticoagulant therapy on the course of COVID-19 in comorbid patients].

INTRODUCTION: Analysis of the pathogenesis of coronavirus infection caused SARS-CoV-2 indicates a significant impact of hemorheological disorders on its course and outcomes. It is known that chronic cardiovascular diseases are associated with the risk of severe course and lethal outcomes both in COVID-19 and other infectious diseases. Therefore, in each case it is necessary to study the interaction and mutual influence of different components of the treatment program prescribed to such patients.The purpose of this work was to evaluate the effect of coagulation activity on the course of a novel coronavirus infection (COVID-19) and to justify the management of comorbid patients having been received novel oral anticoagulants (NOACs) in previously selected doses according to indications in concomitant somatic diseases. MATERIAL AND METHODS: Total 76 cases of confirmed coronavirus infection in patients who had been received initial therapy on an outpatient basis were analyzed. 26 patients who received NOACs (rivaroxaban, apixaban, dabigatran) made up the main group and 50 - the comparison (control) group in which patients had not been administered any drugs that affect blood clotting until the episode of COVID-19. All patients have been prescribed therapy following the Provisional guidelines «Prevention, diagnosis and treatment of coronavirus infection (COVID-19)¼ (https://static-0.minzdrav.gov.ru/system/attachments/attaches/). RESULTS AND DISCUSSION: The number of hospitalizations was significantly fewer in the group of patients who had been received NOACs (19 vs. 66% in the control group). No deaths or cases of severe respiratory and/or renal failure were observed in the main group, while adverse outcomes were noted in 14% of patients who had not been administered these drugs. CONCLUSION: Taking NOACs reduces the probability of severe course and adverse outcomes in the development of coronavirus infection caused by SARS-CoV-2, which indicates a significant contribution of coagulation mechanisms to the pathogenesis in COVID-19. There were no indications for drug replacement and correction of anticoagulant therapy regimens in patients who received adequate therapy with oral anticoagulants for treating a non-severe form of coronavirus infection in ambulatory patient settings.

Sympathetic activation: a potential link between comorbidities and COVID-19.

In coronavirus disease 2019 (COVID-19), higher morbidity and mortality are associated with age, male gender, and comorbidities, such as chronic lung diseases, cardiovascular pathologies, hypertension, kidney diseases, diabetes mellitus, and obesity. All of the above conditions are characterized by increased sympathetic discharge, which may exert significant detrimental effects on COVID-19 patients, through actions on the lungs, heart, blood vessels, kidneys, metabolism, and/or immune system. Furthermore, COVID-19 may also increase sympathetic discharge, through changes in blood gases (chronic intermittent hypoxia, hyperpnea), angiotensin-converting enzyme (ACE)1/ACE2 imbalance, immune/inflammatory factors, or emotional distress. Nevertheless, the potential role of the sympathetic nervous system has not yet been considered in the pathophysiology of COVID-19. In our opinion, sympathetic overactivation could represent a so-far undervalued mechanism for a vicious circle between COVID-19 and comorbidities.

Cardiac injuries in coronavirus disease 2019 (COVID-19).

As the coronavirus disease 2019 (COVID-19) epidemic worsens, this global pandemic is impacting more than 200 countries/regions and more than 4,500,000 confirmed cases worldwide. COVID-19 is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which might attack not only the respiratory system, but also the other important organs, including the heart. It was reported that COVID-19 patients with a past history of cardiovascular diseases would have a higher mortality. Meanwhile, elevated troponin levels were frequently observed in COVID-19 cases. Besides the comprehensive treatments for COVID-19, as a cardiologist, we should also remain vigilant about the cardiac injuries, especially those with severe emergent cardiovascular symptoms.

Predicted coronary heart disease risk in croatian HIV infected patients treated with combination antiretroviral therapy.

We assessed the coronary heart disease (CHD) risk in 130 HIV-infected patients with no major past cardiovascular event treated with combination antiretroviral therapy (CART) between May 2004 and June 2005. We also investigated the association of HIV disease parameters (CD4 + T-cell counts, HIV viral load, AIDS diagnosis, antiretroviral medications and lipodystrophy), demographics, anthropometrics, clinical features, smoking status, dyslipidemia, adherence to the Mediterranean diet, and the metabolic syndrome (MS) to the Framingham risk score. The median 10-year CHD risk was 6.4% (IQR 3.3-13.0) for males and 1.8% (IQR 1.0-6.7) for females. The CHD risk was > or = 10% in 31.1% (32 of 103) males and in 14.8% (4 of 27) females. MS was present in 27 (20.8%) individuals. Participants who met the definition of the MS had a 2.63 times greater chance of having a CHD risk 210% (95% CI, 1.09-6.39; p = 0.032). On multivariable analysis, we found that a CHD risk > or = 10% was associated with: a lowest ever CD4+ T-cell counts of less than 50 per microliter and a past history of AIDS (OR, 6.26; 95% CI, 1.61-24.36; p = 0.008); alcohol consumption 210 g/day (OR, 3.87; 95% CI, 1.56-14.22; p = 0.041); and age 243 years (OR, 1.30; 95% CI, 1.17-1.45; p < 0.001). Interventions to reduce the modifiable cardiovascular risk are needed in Croatian patients treated with CART

High prevalence of intramural coronary infection in patients with drug-resistant cardiac syndrome X: comparison with chronic stable angina and normal controls.

BACKGROUND: Coronary microvascular dysfunction has been reported along with myocardial viral infection. Whether intramural coronary vessels infection plays a role in patients with cardiac syndrome X (CSX) is unknown. METHODS: Thirteen consecutive patients (four men, nine women, mean age 51±10.5 years) with drug-resistant CSX underwent left ventricular endomyocardial biopsy. Myocardial tissue was examined for histology, immunohistochemistry and for the presence of cardiotropic viruses by PCR analysis. In the presence of a viral infection on the whole tissue, laser microdissection was performed to analyse the viral genome selectively in intramural vessels and cardiomyocytes. Controls were surgical cardiac biopsies from patients with chronic stable angina and from patients with mitral stenosis and normal cardiac function (normal controls). RESULTS: Histology showed hypertrophy and degeneration of cardiomyocytes with interstitial and replacement fibrosis in all CSX, while focal lymphocytic myocarditis was additionally recognised in three patients. No vasculitis was observed. Viral genomes were detected in nine of 13 CSX (Epstein-Barr virus in four, adenovirus in three, human herpes virus (HHV) 6 in one, Epstein-Barr adenovirus co-infection in one). Laser microdissection showed that Epstein-Barr and adenovirus localised both in cardiomyocytes and intramural vessels, while HHV-6 infection was confined to the vessel wall. CONCLUSIONS: Viral genomes can be detected in intramural vessels of up to 69% of drug-resistant CSX. Coronary small vessels infection represents an alternative pathophysiological mechanism of this syndrome and can explain the poor response to anti-ischaemic drugs.

Viral endomyocardial infection is an independent predictor and potentially treatable risk factor for graft loss and coronary vasculopathy in pediatric cardiac transplant recipients.

OBJECTIVES: This study sought to evaluate the outcome and prevalence of viral endomyocardial infection after cardiac transplantation. BACKGROUND: Viral myocardial infection causes heart failure, but its role after cardiac transplantation is unclear. We hypothesized that viral infection of the cardiac allograft reduces graft survival. METHODS: Between June 1999 and November 2004, 94 pediatric cardiac transplant patients were screened for the presence of viral genome in serial endomyocardial biopsies (EMBs) using polymerase chain reaction (PCR) assays. Graft loss, advanced transplant coronary artery disease (TCAD), and acute rejection (AR) were compared in the PCR-positive (n = 37) and PCR-negative (n = 57) groups, using time-dependent Kaplan-Meier and Cox regression analyses. From November 2002 to November 2004, intravenous immunoglobulin therapy (IVIG) was administered to patients with PCR-positive EMBs. The outcomes of the IVIG-treated, PCR-positive patients (n = 20) were compared with IVIG-untreated, PCR-positive patients (n = 17). RESULTS: Viral genomes were detected in EMBs from 37 (39%) patients; parvovirus B19, adenovirus, and Epstein-Barr virus (EBV) were the most common. The PCR-positive group (n = 37, 25% graft loss at 2.4 years) had decreased graft survival (p < 0.001) compared with the PCR-negative group (n = 57, 25% graft loss at 8.7 years) and developed advanced TCAD prematurely (p = 0.001). The number of AR episodes was similar in both groups. On multivariate analysis, presence of viral genome was an independent risk factor for graft loss (relative risk: 4.2, p = 0.015). The time to advanced TCAD after becoming PCR-positive was longer in the IVIG-treated patients (p = 0.03) with a trend toward improved graft survival (p = 0.06). CONCLUSIONS: Viral endomyocardial infection is an independent predictor of graft loss in pediatric cardiac transplant recipients. This effect appears to be mediated through premature development of advanced TCAD. IVIG therapy in this subgroup may improve survival and merits further investigation.

[Relation between local CMV infection and inflammatory cytokine expressionon in pts sheduled for CABG]. / Obecnosc wirusa cytomegalii w obrebie sciany aorty a miejscowa aktywacja zapalna u pacjentów z przewlekla choroba wiencowa poddawanych zabiegowi pomostowania aortalno-wiencowego.

INTRODUCTION: Cytomegalovirus (CMV) infection has been suggested to play a role in the development of cardiovascular diseases. It has not yet been established yet whether the possible adverse vascular effect is associated with chronic inflammation process caused by CMV. The aim of our study was to evaluate a possible role of CMV infection in local inflammatory activation in pts with coronary artery disease (CAD). MATERIAL AND METHODS: We enrolled 55 patients (mean age 62 years, 42 males, 13 females) with angiographically proven CAD scheduled for CABG surgery. Vessel specimens retrieved from ascending aorta (as a part of routine proximal venous graft development procedure) and peripheral blood mononuclear cells (PBMC) were evaluated for the transcriptional activity of IL-6 and TNF-alpha (the key cytokines involved in atherosclerosis) and for CMV DNA presence. Polymerase chain reaction reaction was performed in order to detect DNA of CMV as well as IL-6 and TNF-alpha transcriptional activity. RESULTS: CMV was present in 67.3% of aortic and in 60% of blood specimens accordingly; median level in aorta tissues: 114.63 +/- 116.54, PBMC: 107.89 +/- 132.39; non statistically significant (NS). An inflammatory response expressed as IL-6 and TNF-alpha transcriptional activity equaled in aorta 159.93 +/- 120.15, 299.55 +/- 154.89 and in PBMC: 190.85 +/- 122.08, 249.64 +/- 32.4; (NS). CMV DNA in PBMC was associated with CMV DNA in aortal tissue p = 0.0049. The analysis revealed positive correlation between IL-6 transcriptional activity and CMV DNA titer in aortic samples R = 0.35, p = 0.036. There were no statistically significant correlations between TNF-alpha transcriptional levels and CMV DNA concentration. Statistical analysis was made by use of Statistica 8.0; StatSoft program. We used arithmetical mean value, standard deviation, Spearmann correlation, X2 and U Mann-Whitney test. CONCLUSIONS: A local inflammatory response expressed against CMV could be a marker of longstanding inflammatory response that eventually would cause advanced clinical atherosclerosis. Our findings support the infectious theory and an association between CMV infection and atherosclerosis.

Accelerated telomere shortening in leukocyte subpopulations of patients with coronary heart disease: role of cytomegalovirus seropositivity.

BACKGROUND: Shortening of mean telomere length (TL) in white blood cells is correlated with the development of coronary heart disease (CHD) and with increased mortality due to infectious disease. The goal of the present study was to investigate whether telomere shortening in CHD is restricted to specific peripheral blood lymphocyte and/or myeloid cell subpopulations. Results were correlated to TL in CD34+ hematopoietic peripheral blood stem cells and progenitor cells obtained from the same individual patients. METHODS AND RESULTS: TL was measured by multicolor flow cytometry-fluorescent in situ hybridization in 12 leukocyte subpopulations after immunomagnetic bead sorting. We investigated TL in 14 young (mean age 25 years) and 13 older (mean age 65 years) healthy male volunteers and in 25 age-matched patients with CHD (mean age 65 years). We show that TL in granulocytes and monocytes mirrors TL of CD34+ peripheral blood stem cells and progenitor cells extremely well (r=0.95, P<0.0001) in patients and in healthy adults. TL was approximately 0.5 kilobases (kb) shorter in leukocytes from patients with CHD than in their age-matched control subjects. This difference was identical for CD34+ peripheral blood stem cells and progenitor cells, monocytes, granulocytes, B lymphocytes, and CD4+ T cells, including their memory and naïve subpopulations. Surprisingly, only in cytotoxic CD8+ T lymphocytes, we found a substantially increased TL deficit of 1.0 kb in CHD patients as opposed to control subjects. Further analysis revealed that TL shortening was particularly pronounced in CD8+CD28(-) T cells obtained from cytomegalovirus-seropositive CHD patients, whereas such a difference was not observed in healthy cytomegalovirus-positive as opposed to cytomegalovirus-negative control subjects. Finally, TL shortening of CD8+CD45(RA+) T cells was correlated with the decrease in left ventricular function in CHD patients (r=0.629, P=0.001). CONCLUSIONS: Telomere shortening in patients with CHD could potentially be attributed to either inherited TL shortening or acquired accelerated telomere shortening restricted to the hematopoietic system, which affects the baseline TL of all peripheral blood cell populations, including peripheral blood stem cells and progenitor cells. In addition, cytomegalovirus-seropositive patients but not healthy control subjects exhibited further shortening of their cytotoxic T lymphocytes. Surprisingly, TL shortening of CD8+ T lymphocytes in CHD patients demonstrated a very strong correlation with cardiac dysfunction, which suggests a mechanistic link between CHD and immunosenescence.

Association of hepatitis C virus seropositivity with inflammatory markers and heart failure in persons with coronary heart disease: data from the Heart and Soul study.

BACKGROUND: How hepatitis C virus (HCV) affects coronary heart disease (CHD) risk factors and outcomes is largely unknown. METHODS AND RESULTS: Among a cohort of patients with stable CHD, we examined the association between HCV seropositivity and levels of inflammatory markers (C-reactive protein [CRP], fibrinogen, interleukin-6, and tumor necrosis factor [TNF]-alpha) and risk for the following outcomes: death, cardiovascular (CV) events, and heart failure events. A total of 84 (8.6%) participants were found to be seropositive for HCV. HCV-seropositive patients were found to have significantly lower adjusted mean levels of CRP (2.6 vs. 4.4; P < .01) and fibrinogen (340 vs. 398; P < .01), but higher levels of TNF-alpha (7.1 vs. 4.8; P < .01). Age-adjusted rates for HCV seropositive vs. seronegative were as follows: death 93 vs. 42/1,000p-y (P < .01), CV events 62 vs. 40 (P=.13), and heart failure 76 vs. 29 (P < .01). After adjustment for demographic and clinical factors, HCV remained significantly associated with an increased risk for heart failure events (HR=2.13; 95% CI: 1.19-3.80). CONCLUSIONS: In this cohort with CHD, HCV seropositive participants had higher rates of death, CV events, and heart failure hospitalizations during follow-up. After adjustment for CV risk factors, HCV seropositivity remained independently associated with risk for heart failure events.

A coronary heart disease risk model for predicting the effect of potent antiretroviral therapy in HIV-1 infected men.

BACKGROUND: Many HIV-infected patients on highly active antiretroviral therapy (HAART) experience metabolic complications including dyslipidaemia and insulin resistance, which may increase their coronary heart disease (CHD) risk. We developed a prognostic model for CHD tailored to the changes in risk factors observed in patients starting HAART. METHODS: Data from five cohort studies (British Regional Heart Study, Caerphilly and Speedwell Studies, Framingham Offspring Study, Whitehall II) on 13,100 men aged 40-70 and 114,443 years of follow up were used. CHD was defined as myocardial infarction or death from CHD. Model fit was assessed using the Akaike Information Criterion; generalizability across cohorts was examined using internal-external cross-validation. RESULTS: A parametric model based on the Gompertz distribution generalized best. Variables included in the model were systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, triglyceride, glucose, diabetes mellitus, body mass index and smoking status. Compared with patients not on HAART, the estimated CHD hazard ratio (HR) for patients on HAART was 1.46 (95% CI 1.15-1.86) for moderate and 2.48 (95% CI 1.76-3.51) for severe metabolic complications. CONCLUSIONS: The change in the risk of CHD in HIV-infected men starting HAART can be estimated based on typical changes in risk factors, assuming that HRs estimated using data from non-infected men are applicable to HIV-infected men. Based on this model the risk of CHD is likely to increase, but increases may often be modest, and could be offset by lifestyle changes.

Virulent strains of Helicobacter pylori and vascular diseases: a meta-analysis.

BACKGROUND: Cytotoxin-associated gene A (CagA)-positive strains of Helicobacter pylori are an etiological factor for peptic ulcer and gastric cancer. Studies on the role of these virulent strains in vascular diseases yield conflicting results. METHODS: We searched the MEDLINE database for relevant studies. Meta-analysis was performed using the random effects method. RESULTS: We found 10 retrospective case-control studies (with 1527 case patients and 1661 control subjects) and 3 prospective cohort studies (with 701 case patients and 1439 control subjects) on CagA status and ischemic heart disease and 4 retrospective case-control studies (with 513 case patients and 590 control subjects) on CagA status and cerebral ischemia. In the case-control studies, an association of ischemic heart disease with CagA-positive strains (OR 1.87, 95% CI 1.46-2.40) but no significant association with CagA-negative strains (OR 1.15, 95% CI 0.83-1.60) has been found; in the 3 prospective studies, association with ischemic heart disease was weaker but still significant (OR 1.26, 95% CI 1.05-1.51). In the 4 case-control studies, CagA-positive strains were significantly associated with cerebral ischemia (OR 2.43, 95% CI 1.89-3.13), again with no association for CagA-negative strains. CONCLUSIONS: We found a small but significant association between vascular diseases and virulent CagA-positive strains of H. pylori. The lack of association with CagA-negative strains further supports the hypothesis of an independent relationship between virulent strains of H. pylori and vascular diseases. The magnitude of the association with cerebral ischemia needs to be confirmed by prospective studies.

HIV infection, highly active antiretroviral therapy and the cardiovascular system.

Cardiovascular complications in the course of human immunodeficiency virus (HIV) infection are multifactorial and may be caused by the virus itself or by the related opportunistic infections and neoplasms. Highly active antiretroviral therapy (HAART) has prolonged many patients' lives, but many cardiac sequelae of HIV are not affected by HAART and continue to develop even with treatment. In addition, HAART itself causes in a high proportion of patients a metabolic syndrome, characterized by lipodystrophy/lipoatrophy, dyslipidemia and insulin resistance that may be associated with an increase in peripheral artery and coronary artery diseases. Careful cardiovascular evaluation in the course of HIV disease can identify cardiac complications early enough to treat. All HIV-infected patients candidate to antiretroviral therapy and patients already under treatment should undergo an assessment that includes the evaluation of the cardiovascular risk with the available guidelines.

Pathogenesis of HIV-associated heart disease.

As longevity increases in HIV-infected individuals after the introduction of highly active antiretroviral therapy regimens, long-term effects such as cardiovascular disease and, more specifically, symptomatic heart failure are emerging as leading health issues. In the present review article, we discuss HIV-associated cardiovascular disease, focusing on etiopathogenetic mechanisms that may play a role in diagnosis, management, and therapy of HIV-associated heart failure in the highly active antiretroviral therapy era.

Coronary heart disease in HIV-infected patients in the highly active antiretroviral treatment era.

OBJECTIVES: To assess the incidence and the clinical features of coronary heart disease in HIV-infected patients. To assess atherosclerosis risk factors in this population. METHODS: A review of our experience consisting of 16 patients with acute myocardial infarction (AMI) was the basis of our retrospective analysis of two cohorts in France. Incidence was compared with the national database on the incidence of AMI in the general population. RESULTS: Incidence appears to be between 5 and 5.5 per 1000 person-years among HIV-infected patients. This accounts for at least a threefold increase in incidence (1.52 per 1000 person-years reported in the Monica database registry in France). Age of onset of AMI in HIV-infected patients (younger than 50 years in most cases) is a point of major concern and is an indirect way to confirm the increased incidence. AMI was typically of sudden onset without prior history of angina pectoris. Treatment and prognosis of AMI in this population has no specificity. Patients with coronary heart disease present several risk factors such as tobacco smoking, hypertension, diabetes mellitus and low high-density lipoprotein level. The links between AMI and protease inhibitor exposure is still a matter of debate, and longer duration of follow-up is needed in order to reach any conclusion. CONCLUSIONS: Coronary heart disease is of a higher than expected incidence in HIV-infected patients. The limitation of risk factors (mainly tobacco smoking) is a new challenge. An adaptation of the Framingham score is necessary to state the individual risk. Prospective, controlled studies are necessary to assess new strategies such as the role of statins and switching therapeutic regimens.

Cardiovascular risk factors, monitoring, and therapy for HIV-infected patients.

Cardiovascular complications are important contributors to morbidity and mortality in HIV-infected patients. These complications can usually be detected at subclinical levels with monitoring, which can help guide targeted interventions. This article reviews available data on types and frequency of cardiovascular manifestations in HIV-infected patients and proposes monitoring strategies aimed at early subclinical detection. In particular, we recommend routine echocardiography for HIV-infected patients, even those with no evidence of cardiovascular disease. We also review preventive and therapeutic cardiovascular interventions. For procedures that have not been studied in HIV-infected patients, we extrapolate from evidence-based guidelines for the general population.

Association of viral genome with graft loss in children after cardiac transplantation.

BACKGROUND: The survival of recipients of cardiac allografts is limited by rejection, lymphoproliferative disease, and coronary vasculopathy. The purpose of this study in children who had received heart transplants was to evaluate the cardiac allografts for myocardial viral infections and to determine whether the presence of viral genome in the myocardium correlates with rejection, coronary vasculopathy, or graft loss. METHODS: We enrolled heart-transplant recipients 1 day to 18 years old who were undergoing evaluation for possible rejection and coronary vasculopathy. Endomyocardial-biopsy specimens were evaluated for evidence of rejection with the use of standard criteria and were analyzed for the presence of virus by the polymerase chain reaction (PCR). RESULTS: PCR analyses were performed on 553 consecutive biopsy samples from 149 transplant recipients. Viral genome was amplified from 48 samples (8.7 percent) from 34 patients (23 percent); adenovirus was found in 30 samples, enterovirus in 9 samples, parvovirus in 5 samples, cytomegalovirus in 2 samples, herpes simplex virus in 1 sample, and Epstein-Barr virus in 1 sample. In 29 of the 34 patients with positive results on PCR (85 percent), an adverse cardiac event occurred within three months after the positive biopsy, and 9 of the 34 patients had graft loss due to coronary vasculopathy, chronic graft failure, or acute rejection. In 39 of the 115 patients with negative results on PCR (34 percent), an adverse cardiac event occurred within three months of the negative PCR finding; graft loss did not occur in any of the patients in this group. The odds of graft loss were 6.5 times as great among those with positive results on PCR (P=0.006). The detection of adenovirus was associated with considerably reduced graft survival (P=0.002). CONCLUSIONS: Identification of viral genome, particularly adenovirus, in the myocardium of pediatric transplant recipients is predictive of adverse clinical events, including coronary vasculopathy and graft loss.

Inflammation, depressive symptomtology, and coronary artery disease.

OBJECTIVE: Many patients feel exhausted or depressed before the onset of an acute coronary event, but little is known about the origin of these feelings. We tested the hypothesis that the depressive symptomatology is associated with a reactivation of latent viruses and inflammation of a coronary vessel. METHODS: A blood sample was drawn and a biopsy sample was obtained from the coronary lesion of 15 exhausted and 15 nonexhausted patients treated with directional coronary angioplasty because of severe angina. Blood samples were analyzed to measure antibody titers against Chlamydia pneumoniae, cytomegalovirus, and the cytokines interleukin (IL)-1beta, IL-6, and tumor necrosis factor (TNF)-alpha. The biopsy sample was analyzed for the presence of IL-1beta and TNF-alpha. RESULTS: Exhausted/depressed patients had higher antibody titers against cytomegalovirus, higher levels of C. pneumoniae immunoglobulin G, and higher levels of IL-1beta and TNF-alpha. No associations between the mental state of a patient and cytokine mRNA in the biopsy sample were found. CONCLUSIONS: The findings indicate that the mental state of angioplasty patients is positively associated with serological markers of inflammation. It remains to be seen whether the inflammation causes feelings of exhaustion, whether exhaustion and depression set the stage for inflammation, or whether existing feelings of exhaustion are amplified by the inflammation.

A prospective study of cytomegalovirus, herpes simplex virus 1, and coronary heart disease: the atherosclerosis risk in communities (ARIC) study.

BACKGROUND: Conflicting evidence exists implicating infectious disease in the pathological processes leading to coronary heart disease (CHD). The objective of this article is to describe the relationship of previous infection with cytomegalovirus (CMV) and herpes simplex virus 1 to incident CHD in a population-based cohort study. METHODS: Using a nested case-cohort design from the Atherosclerosis Risk in Communities Study, antibody levels to CMV and herpes simplex virus 1 were determined in serum samples that had been frozen at the baseline examination in participants free of CHD. Determinations were made in those who developed incident CHD (n=221) during follow-up of up to 5 years from baseline and in a stratified random sample of all participants (n=515). RESULTS: The population with the highest antibody levels of CMV (approximately the upper 20%) showed an increased relative risk (RR) of CHD of 1.76 (95% confidence interval, 1.00-3.11), adjusting for age, sex, and race. After adjustment for additional covariates of hypertension, diabetes, years of education, cigarette smoking, low-density lipoprotein and high-density lipoprotein cholesterol levels, and fibrinogen level, the RR increased slightly. Based on a priori hypotheses, the RR of CHD at the highest antibody levels in individuals with diabetes was particularly large but with wide confidence intervals (RR, 9.2; 95% confidence interval, 1.8-47.0), and the interaction between high levels of antibody to CMV and diabetes was statistically significant (P=.05). There was no association of CHD with the highest herpes simplex virus 1 antibody levels (adjusted RR, 0.77; 95% confidence interval, 0.36-1.62). CONCLUSIONS: High levels of CMV antibodies are significantly associated with incident CHD. Infection with CMV, particularly in more susceptible disease states such as diabetes, may be an important risk factor for CHD.