Microthrombi as a Major Cause of Cardiac Injury in COVID-19: A Pathologic Study.

BACKGROUND: Cardiac injury is common in patients who are hospitalized with coronavirus disease 2019 (COVID-19) and portends poorer prognosis. However, the mechanism and the type of myocardial damage associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain uncertain. METHODS: We conducted a systematic pathological analysis of 40 hearts from hospitalized patients dying of COVID-19 in Bergamo, Italy, to determine the pathological mechanisms of cardiac injury. We divided the hearts according to presence or absence of acute myocyte necrosis and then determined the underlying mechanisms of cardiac injury. RESULTS: Of the 40 hearts examined, 14 (35%) had evidence of myocyte necrosis, predominantly of the left ventricle. Compared with subjects without necrosis, subjects with necrosis tended to be female, have chronic kidney disease, and have shorter symptom onset to admission. The incidence of severe coronary artery disease (ie, >75% cross-sectional narrowing) was not significantly different between those with and without necrosis. Three of 14 (21.4%) subjects with myocyte necrosis showed evidence of acute myocardial infarction, defined as ≥1 cm2 area of necrosis, whereas 11 of 14 (78.6%) showed evidence of focal (>20 necrotic myocytes with an area of ≥0.05 mm2 but <1 cm2) myocyte necrosis. Cardiac thrombi were present in 11 of 14 (78.6%) cases with necrosis, with 2 of 14 (14.2%) having epicardial coronary artery thrombi, whereas 9 of 14 (64.3%) had microthrombi in myocardial capillaries, arterioles, and small muscular arteries. We compared cardiac microthrombi from COVID-19-positive autopsy cases to intramyocardial thromboemboli from COVID-19 cases as well as to aspirated thrombi obtained during primary percutaneous coronary intervention from uninfected and COVID-19-infected patients presenting with ST-segment-elevation myocardial infarction. Microthrombi had significantly greater fibrin and terminal complement C5b-9 immunostaining compared with intramyocardial thromboemboli from COVID-19-negative subjects and with aspirated thrombi. There were no significant differences between the constituents of thrombi aspirated from COVID-19-positive and -negative patients with ST-segment-elevation myocardial infarction. CONCLUSIONS: The most common pathological cause of myocyte necrosis was microthrombi. Microthrombi were different in composition from intramyocardial thromboemboli from COVID-19-negative subjects and from coronary thrombi retrieved from COVID-19-positive and -negative patients with ST-segment-elevation myocardial infarction. Tailored antithrombotic strategies may be useful to counteract the cardiac effects of COVID-19 infection.

Trypanosoma cruzi infection induces morphological reorganization of the myocardium parenchyma and stroma, and modifies the mechanical properties of atrial and ventricular cardiomyocytes in rats.

BACKGROUND: This study investigates morphofunctional adaptations of the heart stroma and parenchyma in rats that are chronically infected with Trypanosoma cruzi. METHODS: Four-month-old male Wistar rats were randomized into control (n=14) and infected (n=14) groups. Infected animals were inoculated with T. cruzi Y strain. After 9 weeks, the animals were euthanized, and the right atrium (RA) and left ventricle (LV) were removed for biochemical, stereological, and cardiomyocyte mechanical analyses. RESULTS: Infected animals presented cardiomyocyte atrophy and myocardial fibrosis. For these animals, the total volume, length, surface area, and cross-sectional area of cardiomyocytes were significantly reduced, and the total interstitial and collagen volumes were significantly increased in the RA and LV compared to the controls. The total volume and length of blood vessels were significantly increased in the LV, and the total blood vessel surface area was significantly higher in the RA of infected animals. RA and LV cardiomyocytes from infected animals exhibited a significant reduction in cell shortening (43.02% and 24.98%, respectively), prolongation of the time to the peak of contraction (17.09%) and the time to half relaxation (23.68%) compared to non-infected animals. Lipid hydroperoxides, but not mineral concentrations, were significantly increased in the RA and LV from infected animals, showing an inverse correlation with cell shortening. CONCLUSIONS: T. cruzi infection induces global structural remodeling of the RA and LV in rats. This remodeling coexists with cardiomyocyte contractility dysfunction, which is possibly related to the abnormal organization of the myocardial stroma and increased cellular lipid peroxidation.

Molecular study of human herpesvirus 6 and 8 involvement in coronary atherosclerosis and coronary instability.

Several lines of evidence suggest the involvement of infectious agents in the pathogenesis of atherosclerosis. Furthermore, a correlation between infection-driven inflammatory burden and acute manifestation of coronary artery disease has been hypothesized. The aim of this work was to assess whether human herpesvirus (HHV)-6 and HHV-8, two DNA viruses with a distinct tropism for endothelium and lymphocytes, may be associated with coronary instability. An age- and gender-matched cross-sectional study was undertaken in 70 patients with testing of plasma HHV-6 and HHV-8 DNA load in different cardiovascular clinical settings: 29 patients with acute myocardial infarction, 21 patients with stable coronary artery disease, and 20 patients without coronary and carotid artery atherosclerosis subjected to cardiac valve replacement. In all patients, HHV-6 and HHV-8 plasma DNA was tested by using highly sensitive, calibrated quantitative real-time PCR assays which employ a synthetic DNA calibrator to adjust for DNA extraction and amplification efficiency. HHV-8 viremia was undetectable in all three groups. HHV-6 viremia was detected in a substantial fraction of the samples examined (18.6%) without significant differences among the three groups (ST segment elevation myocardial infarction: 17.2%; stable coronary artery disease: 14.3%; patients without coronary and carotid artery atherosclerosis: 25%). Furthermore, no significant differences in plasma HHV-6 load were observed amongst the three groups of patients. These findings indicate that coronary instability is not associated specifically with active HHV-6 or HHV-8 infection. However, an unusually high rate of active HHV-6 infection was documented among patients without atherosclerosis admitted to hospital with cardiac disease.

Cytomegalovirus localization in atherosclerotic plaques is associated with acute coronary syndromes: report of 105 patients.

It has been shown that cytomegalovirus (CMV) is present in coronary atherosclerotic plaques, but the clinical relevance of this presence remains to be elucidated. In this study we sought to examine CMV infection in atherosclerosis patients defined by different methods and to identify the clinical significance of CMV replication in the atherosclerotic plaques. The study included 105 consecutive patients who were admitted to our department and underwent coronary artery bypass grafting (CABG) surgical interventions. Coronary atherosclerotic specimens as well as 53 specimens from the mamillary artery of these same patients were analyzed. Enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) methods were used for evaluations. The CMV PCR test result was positive for 28 (26.7%) of patients with coronary artery atherosclerosis. After adjusting for other risk factors, coronary artery disease patients with a history of acute coronary syndrome were more likely to be positive for CMV PCR test (P=0.027; odds ratio: 4.2; 95% CI: 1.18-15.0). They were also more likely to have a positive family history for cardiovascular diseases (CVD). This study confirms previous evidence about the replication of CMV virus in the atherosclerotic plaques of coronary arteries and brings clinical significance to this observation by showing a higher prevalence of acute coronary syndromes in those patients with CMV-infected plaques. Our study also suggests a familial vulnerability to CMV replication in the coronary artery walls.

Demonstration of Chlamydophila pneumoniae, Mycoplasma pneumoniae, Cytomegalovirus, and Epstein-Barr virus in atherosclerotic coronary arteries, nonrheumatic calcific aortic and rheumatic stenotic mitral valves by polymerase chain reaction.

OBJECTIVE: The aim of this study was to investigate whether bacterial and viral infectious agents can be demonstrated in atherosclerotic lesions of patients with coronary artery disease (CAD) as well as in stenotic aortic and mitral valves from patients undergoing heart valve replacement. METHODS: In this cross-sectional study, the presence of Chlamydophila pneumoniae, Mycoplasma pneumoniae, Cytomegalovirus (CMV), and Epstein-Barr virus (EBV) was investigated by polymerase chain reaction in atherosclerotic and non-atherosclerotic vascular samples taken from patients undergoing coronary artery bypass surgery due to CAD, and from patients undergoing aortic (AVR) and/or mitral valve replacement (MVR) secondary to valvular stenosis. For statistical analyses ANOVA, Chi-square test or Fisher's exact test were used. RESULTS: The presence of C. pneumoniae, M. pneumoniae, and CMV in atherosclerotic versus non-atherosclerotic samples was as follows: 30% vs. 16.7% (p=0.222), 6.7% vs. 3.3% (p=0.554), and 10% vs. 0% (p=0.076), respectively. In valve group, same pathogens were present in AVR and MVR patients as follows: 24.2% vs. 21.4% (p=0.773), 9.1% vs. 7.1% (p=0.758), and 21.2% vs. 11.9% (p=0.275). EBV DNA was not detected in any of vascular specimens, but in one (3%) patient with AVR (p=0.256). CONCLUSION: Our results suggest that C. pneumoniae, M. pneumoniae, and CMV are present with similar frequency both in atherosclerotic and non-atherosclerotic vessels. We conclude that although non-atherosclerotic, vascular samples of CAD patients are invaded by infectious agents as like as atherosclerotic vessels. We further conclude that C. pneumoniae, M. pneumoniae, and CMV are present in stenotic aortic and mitral valves and atherosclerotic tissues with similar frequency indicating that atherosclerosis and valvular stenosis might share a common etiology related to infection.

Detection of human herpesvirus 6 DNA but not human herpesvirus 7 or 8 DNA in atherosclerotic and nonatherosclerotic vascular tissues.

INTRODUCTION: Various viral infections are thought to play a role in the development of atherosclerosis. A number of studies suggest that certain viruses from the Herpesviridae family in particular may lead to atherosclerosis. METHODS: We investigated the presence of human herpesvirus 6 (HHV-6), human herpesvirus 7 (HHV-7), and human herpesvirus 8 (HHV-8) DNA in carotid, iliac, and coronary artery specimens obtained from a group of adult autopsy cases by means of polymerase chain reaction (PCR) analysis and nested PCR techniques. A 28-subject study group with at least type IV atherosclerosis and a 25-subject control group with no visible atherosclerosis were enrolled. RESULTS: HHV-6 DNA was found in the carotid artery specimen of 1 subject with atherosclerosis, in an iliac artery specimen of another subject, and in the iliac artery specimen of one of the control subjects. HHV-7 or HHV-8 DNA was not found in either the atherosclerosis or control cases. CONCLUSIONS: This study is the first to demonstrate the presence of HHV-6 in atherosclerotic vascular tissues. HHV-7 and HHV-8 were not found in atherosclerotic tissues; however, further research on broader study groups and with different protocols is needed to determine whether these viruses play a role in the formation of atherosclerosis.

Impact of intimal pathogen burden in acute coronary syndromes--correlation with inflammation, thrombosis, and autoimmunity.

BACKGROUND: Increasing evidence supports a link between serological evidence of pathogen burden (PB) and the risk for future cardiovascular events. Our study evaluates the intimal presence of 4 pathogens in atheroma, clinically associated with acute coronary syndromes (ACS) and stable angina (SA), and the effect on the expression of intimal C-reactive protein (CRP), tissue factor (TF) and human heat-shock protein 60 (hHSP60). METHODS: Coronary atherectomy specimens retrieved from 60 primary lesions of patients with ACS (n=35) or SA (n=25) were assessed immunohistochemically for the presence of Chlamydia pneumoniae (Cpn), Helicobacter pylori (HP), Cytomegalovirus (CMV) and Epstein­Barr Virus (EBV) and for the expression of CRP, TF, and hHSP60. RESULTS: Analysis revealed eight lesions without, 22 lesions with one, 19 lesions with two, seven lesions with three, and four lesions with four pathogens. Cpn was present in 73%, HP in 31%, CMV in 16%, and EBV in 40%. Mean value of PB in ACS-lesions was significantly increased. Expressions of CRP, TF, and hHSP60 were significantly higher in ACS lesions. The number of infectious pathogens correlated significant with the expressions of CRP, TF, and hHSP60. CONCLUSIONS: Our data demonstrate the impact of PB in plaque instability and suggest local proinflammatory, prothrombotic, and proimmunogenic effects.

Use of in vivo phage display to engineer novel adenoviruses for targeted delivery to the cardiac vasculature.

We performed in vivo phage display in the stroke prone spontaneously hypertensive rat, a cardiovascular disease model, and the normotensive Wistar Kyoto rat to identify cardiac targeting peptides, and then assessed each in the context of viral gene delivery. We identified both common and strain-selective peptides, potentially indicating ubiquitous markers and those found selectively in dysfunctional microvasculature of the heart. We show the utility of the peptide, DDTRHWG, for targeted gene delivery in human cells and rats in vivo when cloned into the fiber protein of subgroup D adenovirus 19p. This study therefore identifies cardiac targeting peptides by in vivo phage display and the potential of a candidate peptide for vector targeting strategies.

Analysis of foot-and-mouth disease virus integrin receptor expression in tissues from naïve and infected cattle.

Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-hoofed animals principally affecting cattle, pigs and sheep. FMD virus (FMDV) uses the alpha(V)beta(1), alpha(V)beta(3), alpha(V)beta(6), and alpha(V)beta(8) integrins as receptors in vitro via a highly conserved arginine-glycine-aspartic acid amino acid sequence motif located within the betaG-betaH loop of VP1. Immunofluorescence and confocal microscopy were used to study the expression of two major FMDV receptors, alpha(V)beta(3) and alpha(V)beta(6), within epithelial tissues from FMDV-infected and uninfected cattle in order to understand the role of these receptors in tissue tropism. Integrin alpha(V)beta(6) was expressed by epithelial cells in tissues that are important sites for FMDV replication (i.e. tongue and coronary band). Integrin alpha(V)beta(3) was detected in epithelium of all tissues examined except tongue. In addition, alpha(V)beta(3) expression was associated with blood vessels in all tissues examined. In infected tissues, alpha(V)beta(6) integrin was distributed on the surface of those epithelial cells also expressing FMDV antigen. Although integrin alpha(V)beta(3) has been shown to be a receptor for FMDV, no expression of alpha(V)beta(3) was associated with FMDV-positive keratinocytes in the tongue. In contrast, podal epithelial cells containing FMDV antigen also expressed alpha(V)beta(3) integrin. Thus, at the cellular level the expression of these two integrins correlates with susceptibility to infection and may contribute substantially to viral tropism in FMD pathogenesis.

Detection of cytomegalovirus in atherosclerotic plaques and nonatherosclerotic arteries.

Several studies have reported an association between infectious agents and atherosclerosis. Cytomegalovirus (CMV) is the most commonly implicated viral pathogen. However, the role of CMV in atherosclerosis remains obscure. The present study evaluated the presence of CMV DNA in atherosclerotic plaques and normal vessel walls. A total of 40 arterial specimens from coronary plaques and 27 samples from normal vessels were obtained from 26 patients who underwent aortocoronary bypass surgery. The specimens were analyzed by polymerase chain reaction for the presence of the CMV immediate early genomic region. CMV DNA was detected in 9 out of 26 patients (34.6%). Viral DNA was detected in both nonatherosclerotic tissues and atherosclerotic plaques. No statistically significant differences were observed between normal and diseased vessels. Our findings, in accordance with previous studies, do not support a direct causative role of CMV in the development of atherosclerotic plaques.

[Distribution of cytomegalovirus DNA in vascular tissues and the relationship between virus and atherosclersogenesis].

OBJECTIVE: To explore the distribution of cytomegalovirus (CMV) in vascular tissues and the relationship between virus and atherosclerogenesis after CMV infecting mice. METHODS: (1) C57 BL/6J Murine model of CMV infection was established by intraperitoneal injection of CMV lethiferous amount. (2) After 12 weeks of CMV infection, the sera, carotids, aorta, hearts and postcaval veins from the mice were collected under euthanasia. The tissues would be used to DNA extraction, PCR and pathological examination. (3) Interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1) in serum were measured with ILELISA. RESULTS: (1) The typical pathologic feature in 2 aorta samples of 6 mice infected by CMV was found and the mice uninfected by CMV did not show any pathologic change. (2) CMV DNA appeared in 6 aorta, 6 postcaval veins, 4 carotids and 4 heart tissues including endocardium, cardiac muscle and coronary artery from the CMV infected mice. CMV DNA was not found in the vascular and heart tissues from 6 mice uninfected by CMV. (3) The ELISA test showed the significant difference (Mann-Witney test of Nonparametric Test, P < 0.05) in serum IL-6 (Median among 25% and 75% percentile: 113.7 pg/ml vs. 49.77 pg/ml) and MCP-1 (Median among 25% and 75% percentile: 128.7 pg/ml vs. 45.36 pg/ml) between CMV infected mice and uninfected mice. CONCLUSION: Cardiovascular cells are CMV latent reservoir in host body and CMV infection and the cytokines induced by CMV infection probably relate to atherosclerogenesis.

The effect of Epstein-Barr virus infection on medium-term survival after orthotopic heart transplantation.

UNLABELLED: Our aim was to assess the medium-time results after orthotopic heart transplantation (OHT) depending on the serostatus of heart transplant recipients at the time of transplantation. MATERIALS AND METHODS: We enrolled 120 patients in this retrospective study including 107 males and an overall mean age of 49.1 +/- 8.6 years ischemic heart disease (IHD) was the diagnosis before OHT in 46%. The mean follow-up was 48 months. The first diagnostic coronary angiography was routinely preformed at 1 year after OHT, and then every second year. We evaluated every incidence of a change in the coronary arteries, the presence of significant stenosis (requiring percutaneous coronary intervention), acute myocardial infarction, death, or retransplantation. Using indirect immunofluorescence assays we detected Epstein-Barr virus (EBV) antigenemia by identification of antibodies against early antigens of EBV (EA) of IgM and IgG classes as well as IgG antibodies against nuclear antigen of EBV (EBNA). Since April 2001 all three types of antibodies were routinely investigated on admission to the hospital for OHT. RESULTS: At the time of transplantation, IgM-EA antibodies were detected in 17 (14%) patients, IgG-EA in 35 (29%), and IgG-EBNA in 113 (94%). Survival rate, incidence of cardiac allograft vasculopathy and death, as a function of the serostatus of the heart recipient at the time of transplantation were estimated by Kaplan-Meier curves; the results were compared by log-rank tests. The findings among IgM EA, IgG EA, and IgG EBNA-positive and -negative groups were statistically comparable. CONCLUSION: Infection with EBV before OHT did not worsen the prognosis over the first 4 years after transplantation.

A diet high in saturated fat and cholesterol accelerates simian immunodeficiency virus disease progression.

Several lines of evidence suggest that dietary fat and cholesterol may play a role in the pathogenesis of human immunodeficiency virus (HIV) infection and disease progression. We examined the effect that an atherogenic diet (AD) high in saturated fatty acids and cholesterol has on disease progression and systemic inflammation in the simian immunodeficiency virus (SIV)-infected macaque model of acquired immunodeficiency syndrome. Macaques fed an AD had significantly more rapid disease progression, resulting in an increased risk of SIV-related death compared with that in control macaques (hazard ratio, 5.4 [95% confidence interval, 1.7-17.0]; P<.001). Peak viral load was higher in the AD group compared with control values, but further statistically significant differences were not detected at viral set point. The baseline plasma interleukin-18 level after 6 months of the AD was predictive of disease progression. Our findings may have important implications for HIV-infected individuals, because they suggest that dietary changes and manipulation of lipid metabolism could offer potential benefits by slowing disease progression.

Detection of cytomegalovirus and Helicobacter pylori DNA in arterial walls with grade III atherosclerosis by PCR.

It has been suggested that some microorganisms may play a role in the etiology or progression of atherosclerotic plaques. The purpose of this study was to assess for the presence of Helicobacter pylori and cytomegalovirus (CMV) DNA using polymerase chain reaction (PCR) technique in vascular-wall specimens obtained during autopsy. Four to 5 mm long samples from 3 different vascular wall specimens (coronary, carotid and abdominal aortas) of 30 patients (23 male, 7 female) were taken for pathologic and microbiologic investigations during autopsy. H. pylori DNA was found in 48.2% atherosclerotic and 19.6% non-atherosclerotic vascular wall specimens, whereas CMV DNA was found in 37.9% atherosclerotic and 32.7% non-atherosclerotic vascular wall specimens. In terms of CMV DNA detection, no statistically significant differences between the atherosclerotic and non-atherosclerotic groups were present (P > 0.05). However, there was a statistically significant difference between the atherosclerosis and non-atherosclerotic groups in terms of H. pylori DNA in coronary and abdominal aorta arteries (p = 0.016 and p = 0.0029 respectively) but not in carotid arteries (p = 1.00). In conclusion, the correlation between H. pylori and atherosclerosis could be suggested. These finding warrant further investigation regarding the role of H. pylori in atherosclerosis.

Herpes simplex virus as a determinant risk factor for coronary artery atherosclerosis and myocardial infarction.

BACKGROUND: Viruses have been detected in atherosclerotic and non-atherosclerotic vascular tissues and may be involved in the mechanisms of atherogenesis. In the present study, we investigated the role of herpes simplex virus (HSV) in the early and late stages of coronary artery atherosclerosis. METHODS AND RESULTS: HSV prevalence was investigated in coronary artery samples from 42 autopsy cases, in which death was related to myocardial infarction (MI), and 28 young age autopsy cases without heart disease, who had died from fatal injuries (young victim group), using nested polymerase chain reaction (nPCR) and the highly sensitive in situ hybridization with tyramide signal amplification (ISH-TSA). HSV was detected by nPCR in 18 out of 42 (43%) myocardial infarction cases and in 7 out of 28 (25%) young victim group cases, respectively. Using ISH-TSA, HSV DNA was detected in the coronary arteries of the MI group in 16 out of 42 (38%) of the cases; the hybridization signal was localized in the nuclei of endothelial cells, the nuclei of smooth muscle cells, the macrophages around the atheroma, and in the lymphocytes infiltrating the vascular wall. In the young victim group, HSV DNA was detected by ISH-TSA in 7 out of 28 (25%) autopsy cases; the signal was localized in the endothelial and the intimal spindle cells of the coronary arteries. CONCLUSION: The findings of this study suggest that HSV seems to play a significant role in the initiation and progression of coronary atherosclerosis, and may open new perspectives in preventing the development of vascular damage via an appropriate antiviral treatment.

Vascular transfer of adenovirus is augmented by nitric oxide in the rat heart.

Reversible opening of the endothelial barrier remains a major obstacle when hearts are transfected via the coronary system. Our aim was to establish an experimental system permitting the continuous analysis of vascular transfer of virus in the intact heart. Isolated saline-perfused rat hearts were inverted and covered with a latex cap to collect interstitial transudate (IT) on the pericardial surface. Adenovirus (10(9) pfu/ml) was stably labeled with rhodamine fluorescent dye. Analysis of IT and coronary perfusate revealed that under baseline conditions, adenovirus in the IT reached 75% of its vascular concentration within 3 min. The nitric oxide-donors S-nitroso-N-acetyl penicillamine (SNAP) and bradykinin (BK) were the most effective substances to increase total IT volume and adenoviral interstitial concentration. Perfusion with 9% serum markedly reduced IT volume flow and delayed the SNAP/BK effect. Our findings demonstrate that SNAP and BK effectively increased coronary transfer of adenovirus suggesting that the inverted isolated heart is a suitable model to optimize vascular transfer of virus under standardized conditions.

Ebola virus glycoprotein-mediated anoikis of primary human cardiac microvascular endothelial cells.

Ebola virus glycoprotein (EGP) has been implicated for the induction of cytotoxicity and injury in vascular cells. On the other hand, EGP has also been suggested to induce massive cell rounding and detachment from the plastic surface by downregulating cell adhesion molecules without causing cytotoxicity. In this study, we have examined the cytotoxic role of EGP in primary endothelial cells by transduction with a replication-deficient recombinant adenovirus expressing EGP (Ad-EGP). Primary human cardiac microvascular endothelial cells (HCMECs) transduced with Ad-EGP displayed loss of cell adhesion from the plastic surface followed by cell death. Transfer of conditioned medium from EGP-transduced HCMEC into naive cells did not induce loss of adhesion or cell death, suggesting that EGP needs to be expressed intracellularly to exert its cytotoxic effect. Subsequent studies suggested that HCMEC death occurred through apoptosis. Results from this study shed light on the EGP-induced anoikis in primary human cardiac endothelial cells, which may have significant pathological consequences.

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.