Andreas Knudsen

increased prevalence of coronary artery disease risk markers in patients with chronic hepatitis c - a cross-sectional study

Objective Chronic hepatitis C is a global health problem and has been associated with coronary artery disease. Our aim was to examine the prevalence of coronary artery disease risk markers including endothelial biomarkers in patients with chronic hepatitis C and matched comparisons without manifest cardiovascular disease or diabetes in a cross-sectional design. Methods Sixty patients with chronic hepatitis C (mean age 51 years) were recruited from the Department of Infectious Diseases at Copenhagen University Hospital, and compared with 60 age-matched non-hepatitis C virus-infected individuals from a general population survey. We examined traditional coronary artery disease risk factors, metabolic syndrome, carotid intima media thickness, and a range of endothelial biomarkers. Results Patients with chronic hepatitis C had more hypertension (40% versus 25%, prevalence ratio [PR] 1.6; 95% confidence interval [CI] 0.9–2.7) and smoked more (53% versus 38%, PR 1.4; 95% CI 0.9–2.1). The two groups had similar body mass index (mean 25.0 versus 25.7 kg/m2), whereas those with chronic hepatitis C had less dyslipidemia (including significantly lower low-density lipoprotein and cholesterol/high-density lipoprotein ratio), higher glycosylated hemoglobin level (mean 6.2 versus 5.7, difference of means 0.5; 95% CI 0.3–0.8), and a higher prevalence of metabolic syndrome (28% versus 18%, PR 1.6; 95% CI 0.8–3.0). Increased carotid intima media thickness above the standard 75th percentile was seen more frequently in chronic hepatitis C (9% versus 3%, PR 1.7; 95% CI 0.4–6.7), though difference of means was only 0.04 mm (95% CI 0.00–0.10). Patients with chronic hepatitis C had increased hsCRP (high-sensitivity C-reactive protein), sICAM-1 (soluble intercellular adhesion molecule-1), sVCAM-1 (soluble vascular cell adhesion molecule-1), and soluble E-selectin, but lower levels of tPAI-1 (tissue-type plasminogen activator inhibitor-1), MMP9 (matrix metallopeptidase 9), and MPO (myeloperoxidase) than their comparisons. Conclusion Our findings indicate that patients with chronic hepatitis C have increased prevalence of several coronary artery disease risk markers. These results may be important when evaluating the appropriateness of screening for coronary artery disease and its risk factors in chronic hepatitis C.

Microbiota-Dependent Marker TMAO Is Elevated in Silent Ischemia but Is Not Associated With First-Time Myocardial Infarction in HIV Infection.

Objectives:HIV infection is associated with increased risk of coronary heart disease beyond that explained by traditional risk factors, and altered gut microbiota has been proposed as a potential trigger. Trimethylamine-N-oxide (TMAO) is a proatherogenic substance formed in the liver from trimethylamine, exclusively generated by gut microbiota from dietary phosphatidylcholine. We aimed to investigate whether TMAO is associated with subclinical and clinical coronary heart disease in HIV infection. Methods:Two previously described cohorts were examined as follows: (1) cross-sectional cohort of HIV-infected persons and uninfected controls with known atherosclerotic plaque burden as assessed by myocardial perfusion scintigraphy, coronary artery calcium score, and intima-media thickness and (2) nested case–control study of HIV-infected persons with first-time myocardial infarction (MI) compared with HIV-infected persons without MI, assessed at 4 time points from before initiation of antiretroviral therapy (ART) to last sample before the cases MI (median: 51, range: 0–239 days). Results:There was no difference in plasma TMAO when comparing HIV-infected persons and uninfected controls. TMAO was elevated in HIV-infected persons with myocardial perfusion defects but was not associated with coronary artery calcium score, intima media thickness, or Framingham risk score. In the nested case control study, plasma TMAO was not associated with first-time MI. However, TMAO increased after ART introduction and was associated with the use of protease inhibitors in both cohorts. Conclusions:TMAO was elevated in HIV-infected persons with myocardial perfusion defects, but was not associated with first-time MI. Our data question TMAO as a useful biomarker of cardiovascular risk in HIV infection, at least in ART-treated individuals.

Cytokine expression during syphilis infection in HIV-1-infected individuals.

Background: Little is known about cytokine responses to syphilis infection in HIV–1-infected individuals. Methods: We retrospectively identified patients with HIV-1 and Treponema pallidum coinfection. Plasma samples from before, during, and after coinfection were analyzed for interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, interferon (IFN)-&ggr;, and tumor necrosis factor (TNF)-&agr;. Results: Thirty-six patients were included. IL-10 levels increased significantly in patients with primary or secondary stage syphilis from a median of 12.8 pg/mL [interquartile range (IQR), 11.0–27.8] before infection to 46.7 pg/mL (IQR, 28.4–78.9) at the time of diagnosis (P = 0.027) and decreased to 13.0 pg/mL (IQR, 6.2–19.4) after treatment of syphilis (P <0.001). TNF-&agr; levels showed no significant change from before to during syphilis in patients with primary or secondary stage syphilis (median 3.9 pg/mL (IQR, 3.3–9.6) and 9.0 pg/mL (IQR, 5.4–12.6), respectively (P = 0.31); however, treatment of syphilis was associated with a significant decrease in TNF-&agr; to a median of 4.2 pg/mL (IQR, 2.7–6.8) (P <0.001). No significant changes in cytokine levels were observed in coinfected with latent stage syphilis. IL-10 and TNF-&agr; levels correlated positively with plasma HIV RNA values at the time of diagnosis (r = 0.38, P = 0.023, and r = 0.64, P <0.001, respectively) and correlated inversely with CD4 T cell counts (−0.35, P = 0.036 and r = −0.34, P = 0.042, respectively). Conclusion: HIV-1 and early stage syphilis coinfection were associated with an increase in IL-10. IL-10 and TNF-&agr; both decreased after treatment of syphilis. TNF-&agr; and IL-10 correlated with low CD4 T cell counts and high plasma HIV RNA values.

Plasma plasminogen activator inhibitor-1 predicts myocardial infarction in HIV-1-infected individuals.

Objectives:Biomarkers of endothelial dysfunction, inflammation and coagulation are associated with atherosclerosis and cardiovascular disease, but their association and possible predictive value remain controversial among HIV-1-infected individuals. We sought to investigate the association of seven biomarkers with first-time myocardial infarction (MI) in an HIV-1-infected population. Design:A matched case–control study of 54 cases and 54 controls. Methods:We compared 54 HIV-1-infected patients with verified first-time MI and 54 HIV-1-infected controls matched for age, duration of antiretroviral therapy, sex, smoking and no known cardiovascular disease. Levels of high-sensitivity C-reactive protein, soluble endothelial selectin, soluble vascular cell adhesion molecule, soluble intercellular adhesion molecule, matrix metalloprotease 9, myeloperoxidase, and plasminogen activator inhibitor 1 (PAI-1) were measured using a Luminex assay in plasma samples from routine visits both 12 and 2 months prior to the case patients MI. Results:The two groups had similar HIV characteristics and traditional cardiovascular risk factors. In univariate analysis, PAI-1 levels were associated with MI, whereas none of the other markers showed any association.In multivariate analyses adjusting for the D:A:D risk score, HIV viral load and high-sensitivity C-reactive protein, PAI-1 levels in the highest quartile were associated with a six to seven-fold increased risk of MI in both samples. Conclusion:High levels of PAI-1 were associated with risk of first-time MI in HIV-1-infected individuals independently of cardiovascular risk factors, HIV parameters and antiretroviral therapy. Therefore PAI-1 may be used for risk stratification and prediction of CHD, but further studies are needed.

Soluble CD163 does not predict first-time myocardial infarction in patients infected with human immunodeficiency virus: a nested case–control study

BackgroundSoluble CD163 (sCD163) has been associated with arterial inflammation and non-calcified plaques in human immunodeficiency virus (HIV)-infected individuals and has therefore been suggested as a predictive biomarker of myocardial infarction (MI).MethodsWe conducted a nested case–control study of 55 cases with first-time MI and 182 controls matched for age, duration of antiretroviral therapy (ART), gender, smoking, and no known cardiovascular disease. All patients had four available plasma samples, 1: Before initiation of antiretroviral therapy (ART), 2: Three months after ART, 3: One year before the case’s MI, and 4: The last sample available before the case’s MI. We used conditional logistic regression to estimate the association of sCD163 with first-time MI.ResultsThe two groups had similar HIV-parameters and cardiovascular risk factors were equally distributed. There was no significant association between sCD163 and MI neither in samples obtained one year before (OR 1.05, CI 95% 0.85 – 1.29, p = 0.66) nor two months before (OR 1.20, CI 95% 0.98-1.47 p = 0.08).ConclusionsCD163 did not prove to be a useful biomarker for prediction of first-time MI in a HIV-infected population.

HIV infection and arterial inflammation assessed by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET): A prospective cross-sectional study

BackgroundHIV-infected patients are at increased risk of myocardial infarction and arterial inflammation has been suggested as a pathophysiological explanation. We compared the uptake of 18F-fluorodeoxyglucose (FDG) by PET in four arterial regions, and factors associated with FDG uptake in well-treated HIV-infected patients without cardiovascular disease (CVD) and healthy controls.Methods and ResultsWe prospectively scanned 26 HIV-infected patients on stable antiretroviral therapy and 25 healthy volunteers with FDG PET/CT, measuring standardized uptake values (SUV) in the carotid arteries, the ascending, descending, and abdominal aorta. We performed correlation analyses between FDG uptake and intima-media thickness (IMT), and soluble biomarkers of inflammation. We found no difference in arterial FDG uptake between the HIV-infected patients and healthy controls quantified either as mean SUVmax or target-to background ratio in the carotid region, the ascending aorta, the descending aorta, or the abdominal aorta. Correlations between SUV, IMT, and soluble biomarkers were scarce in both groups.ConclusionIn a group of optimally treated HIV-infected patients with full viral suppression, low Framingham risk score and no known CVD, we found no evidence of increased arterial inflammation as assessed by FDG PET/CT compared to healthy volunteers.

Soluble urokinase plasminogen activator receptor (suPAR) is a novel, independent predictive marker of myocardial infarction in HIV-1-infected patients: a nested case-control study

Patients infected with HIV are at increased risk of myocardial infarction (MI). Increased plasma levels of the inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) have been associated with increased risk of cardiovascular diseases (CVD), including MI in the general population. We tested suPAR as a predictive biomarker of MI in HIV‐1‐infected individuals.

Angiographic Features and Cardiovascular Risk Factors in Human Immunodeficiency Virus-Infected Patients With First-Time Acute Coronary Syndrome

A matched cohort study was conducted comparing patients with first-time acute coronary syndromes infected with human immunodeficiency virus (HIV) to non-HIV-infected patients with and without diabetes matched for smoking, gender, and type of acute coronary syndrome who underwent first-time coronary angiography. A total of 48 HIV-infected patients were identified from a national database. Coronary angiography showed that the HIV-infected patients had significantly fewer lesions with classification B2/C than the 2 control groups (p <0.001) but the same extent of multivessel disease. The HIV-infected patients were a decade younger than the non-HIV-infected controls and had significantly higher concentrations of total cholesterol (6.3 vs 4.8 and 4.5 mmol/L, p <0.0001), low-density lipoprotein (4.0 vs 2.9 and 2.5 mmol/L, p <0.001), and triglycerides (2.8 vs 1.0 and 1.4 mmol/L, p <0.01) compared to the nondiabetic and diabetic non-HIV-infected groups, respectively. In conclusion, HIV-infected patients with first-time acute coronary syndromes have fewer complex lesions than non-HIV-infected patients. This finding supports the idea that the pathogenesis of atherosclerotic disease in HIV patients is different from that in the general population.

Marker of Endothelial Dysfunction Asymmetric Dimethylarginine Is Elevated in HIV Infection but Not Associated With Subclinical Atherosclerosis.

Background:Cardiovascular disease contributes to excess morbidity and mortality in HIV infection, and endothelial dysfunction may contribute to this pattern. We aimed to determine the endothelial function in treated and untreated HIV-infected individuals and investigate potential associations with viral replication, immune activation, coagulation, platelet function, and subclinical atherosclerosis. Methods:Asymmetric dimethylarginine (ADMA, marker of endothelial dysfunction) and soluble CD14 (sCD14, marker of monocyte activation) were measured in plasma from two previously established cross-sectional cohorts: cohort A including 50 untreated and 50 antiretroviral therapy (ART)–treated HIV-infected individuals with previously assessed coagulation and platelet function and cohort B including 105 HIV-infected individuals on ART and 105 uninfected controls with previously assessed coronary artery calcium score, myocardial perfusion defects, and carotid intima–media thickness. Results:Concentrations of ADMA were higher in HIV-infected individuals compared with uninfected controls, and higher ADMA was found in ART-treated compared with untreated HIV-infected individuals. ADMA was associated with viral load, sCD14, D-dimer, and low CD4+ T-cell count in untreated HIV infection. Only viral load remained significant in multivariate analyses. In ART-treated HIV-infected individuals, ADMA was not associated with coronary artery calcium score, myocardial perfusion defects, or intima–media thickness. Conclusions:Evidence of endothelial dysfunction was found in HIV infection and in untreated compared with treated HIV infection. In untreated HIV infection, the main driver of endothelial dysfunction was viral replication. Importantly, in treated HIV infection, ADMA was not associated with subclinical atherosclerosis. Thus, our data question the potential of ADMA as a useful biomarker of early atherosclerosis in treated HIV infection.

Normal Myocardial Flow Reserve in HIV-Infected Patients on Stable Antiretroviral Therapy: A Cross-Sectional Study Using Rubidium-82 PET/CT.

AbstractStudies have found HIV-infected patients to be at increased risk of myocardial infarction, which may be caused by coronary microvascular dysfunction. For the first time among HIV-infected patients, we assessed the myocardial flow reserve (MFR) by Rubidium-82 (82Rb) positron emission tomography (PET), which can quantify the coronary microvascular function. MFR has proved highly predictive of future coronary artery disease and cardiovascular events in the general population.In a prospective cross-sectional study, HIV-infected patients all receiving antiretroviral therapy (ART) with full viral suppression and HIV-uninfected controls were scanned using 82Rb PET/computed tomography at rest and adenosine-induced stress, thereby obtaining the MFR (stress flow/rest flow), stratified into low ⩽1.5, borderline >1.5 to 2.0, or normal >2.0.Fifty-six HIV-infected patients and 25 controls were included. The HIV-infected patients had a mean age of 53 years (range 37–68 years) with 23% active smokers. The controls had a mean age of 52 years (range 36–68 years) and 26% active smokers. In the HIV-infected group 73% had a normal MFR, 17% borderline, and 10% low values of MFR. Among controls these values were 71%, 19%, and 10%, respectively (P = 0.99). However, the HIV-infected group had lower values of stress myocardial blood flow (MBF) (2.63 ± 0.09 mL/g/min vs 2.99 ± 0.14 mL/g/min; P = 0.03). We found no evidence of decreased MFR as assessed by 82Rb PET among HIV-infected patients on stable ART with full viral suppression compared with HIV-uninfected controls. We did notice a decreased MBF during stress.