T-cell Activation and E-selectin Are Associated With Coronary Plaque in HIV-infected Young Adults.
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ABSTRACT:
SUBMITTER: Mattingly AS
PROVIDER: S-EPMC5154863 | biostudies-literature | 2017 Jan
REPOSITORIES: biostudies-literature
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T-cell Activation and E-selectin Are Associated With Coronary Plaque in HIV-infected Young Adults.
Mattingly Aviva S AS Unsal Aylin B AB Purdy Julia B JB Gharib Ahmed M AM Rupert Adam A Kovacs Joseph A JA McAreavey Dorothea D Hazra Rohan R Abd-Elmoniem Khaled Z KZ Hadigan Colleen C
The Pediatric infectious disease journal 20170101 1
We evaluated immune activation and coronary artery plaque in young adults with human immunodeficiency virus acquired in early life (n = 31). Coronary plaque was positively associated with lipids, immune activation marker %CD8+CD38+DR+ and E-selectin, a marker of endothelial inflammation. Immune activation and endothelial inflammation may drive coronary plaque formation during the early stages of atherosclerosis in the context of chronic human immunodeficiency virus. ...[more]
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Project description:BackgroundLittle is known about coronary plaque in human immunodeficiency virus (HIV)-infected women.MethodsSixty HIV-infected and 30 non-HIV-infected women without symptoms or history of cardiovascular disease were recruited to assess coronary plaque with coronary computed tomographic angiography and immune activation. Data from 102 HIV-infected men and 41 non-HIV-infected male controls were compared.ResultsHIV-infected women demonstrated significantly higher percentages of segments with noncalcified plaque (mean ± SD, 74% ± 28% vs 23% ± 39% compared to female control subjects; median [interquartile range], 75% [63%-100%] vs 0% [0%-56%]; P = .007) and more segments with noncalcified plaque (mean ± SD, 0.92 ± 1.48 vs 0.40 ± 1.44; median [interquartile range], 0 [0-2] vs 0 [0-0]; P = .04). Immune activation parameters, including soluble CD163 (sCD163; P = .006), CXCL10 (P = .002), and percentages of CD14(+)CD16(+) monocytes (P = .008), were higher in HIV-infected women than in female control subjects, but no differences were seen in general inflammatory markers. Among HIV-infected women with noncalcified coronary plaque, sCD163 levels were significantly higher than in HIV-infected women without noncalcified plaque (P = .04). In multivariate modeling for sCD163 levels among male and female subjects, significant effects of HIV (P < .0001), age (P = .002), and sex (P = .0002) were seen.ConclusionsYoung, asymptomatic, HIV-infected women, demonstrate increased noncalcified coronary plaque and increased immune activation, particularly monocyte activation. Independent effects of sex, HIV status, and aging on immune activation may contribute to cardiovascular disease in this population.Clinical trials registrationNCT00455793.
| S-EPMC3814845 | biostudies-literature
Project description:BackgroundIndividuals with long-term human immunodeficiency virus (HIV) infection are at risk for premature vasculopathy and cardiovascular disease (CVD). We evaluated coronary vessel wall thickening, coronary plaque, and epicardial fat in patients infected with HIV early in life compared with healthy controls.MethodsThis is a prospective cross-sectional study of 35 young adults who acquired HIV in early life and 11 healthy controls, free of CVD. Time resolved phase-sensitive dual inversion recovery black-blood vessel wall magnetic resonance imaging (TRAPD) was used to measure proximal right coronary artery (RCA) wall thickness, and multidetector computed tomography (CT) angiography was used to quantify coronary plaque and epicardial fat.ResultsRCA vessel wall thickness was significantly increased in HIV-infected patients compared with sex- and race-matched controls (1.32 ± 0.21 mm vs 1.09 ± 0.14 mm, P = .002). No subject had discrete plaque on CT sufficient to cause luminal narrowing, and plaque was not related to RCA wall thickness. In multivariate regression analyses, smoking pack-years (P = .004) and HIV infection (P = .007) were independently associated with thicker RCA vessel walls. Epicardial fat did not differ between groups. Among the HIV-infected group, duration of antiretroviral therapy (ART) (P = .02), duration of stavudine exposure (P < .01), low-density lipoprotein cholesterol (P = .04), and smoking pack-years (P < .01) were positively correlated with RCA wall thickness.ConclusionsThis investigation provides evidence of subclinical coronary vascular disease among individuals infected with HIV in early life. Increased duration of ART, hyperlipidemia, and smoking contributed to proximal RCA thickening, independent of atherosclerotic plaque quantified by CT. These modifiable risk factors appear to influence early atherogenesis as measured by coronary wall thickness and may be important targets for CVD risk reduction.
| S-EPMC4274345 | biostudies-literature
Project description:Among HIV-infected patients, high rates of myocardial infarction (MI) and sudden cardiac death have been observed. Exploring potential underlying mechanisms, we used multidetector spiral coronary computed tomography angiography (coronary CTA) to compare atherosclerotic plaque morphology in HIV-infected patients and non-HIV-infected controls.Coronary atherosclerotic plaques visualized by CTA in HIV-infected (101) and non-HIV-infected (41) men without clinically apparent heart disease matched on cardiovascular risk factors were analyzed for three vulnerability features: low attenuation, positive remodeling, and spotty calcification.Ninety-five percent of HIV-infected patients were receiving ART (median duration 7.9 years) and had well controlled disease (median CD4 cell count, 473?cells/?l; median HIV RNA <50?copies/ml). Age and traditional cardiovascular risk factors were similar in HIV-infected patients and controls. Among the HIV-infected (versus control) group, there was a higher prevalence of patients with at least one: low attenuation plaque (22.8 versus 7.3%, P?=?0.02), positively remodeled plaque (49.5 versus 31.7%, P?=?0.05) and high-risk 3-feature plaque (7.9 versus 0%, P?=?0.02). Moreover, patients in the HIV-infected (versus control) group demonstrated a higher number of low attenuation plaques (P?=?0.01) and positively remodeled plaques (P?=?0.03) per patient.Our data demonstrate an increased prevalence of vulnerable plaque features among relatively young HIV-infected patients. Differences in coronary atherosclerotic plaque morphology - namely, increased vulnerable plaque among HIV-infected patients - are here for the first time reported and may contribute to increased rates of MI and sudden cardiac death in this population.
| S-EPMC3740057 | biostudies-literature
Project description:Anaemia has been linked with mortality in HIV infection. The mechanism of anaemia in the era of contemporary antiretroviral therapy is not understood. The aim of this study was to describe the association between anaemia and markers of immune activation and inflammation in a cohort of HIV-infected adults on stable antiretroviral therapy.We performed a cross-sectional study of HIV-infected adults on antiretroviral therapy with HIV-1 RNA<1,000 copies/ml. Soluble and cellular markers of inflammation and immune activation were measured. Relationships between haemoglobin levels, anaemia (haemoglobin <13 g/dl for men and <12 g/dl for women) and mild anaemia (haemoglobin <14 g/dl for men and <13 g/dl for women) and these markers were explored using multivariable linear regression.Among the 147 participants, median age was 46 years, 78% were men, 68% were African American and 29% were Caucasian. Median body mass index (BMI) was 26.7 kg/m(2), nadir and current CD4(+) T-cell counts were 179 and 613 cells/mm(3), respectively, and 78% had HIV-1 RNA<50 copies/ml (range 20-600 copies/ml). Median (IQR) haemoglobin was 14.3 (13.1-15.1) g/dl; 14% were anaemic and 33% had at least mild anaemia. In multivariable analyses, mild anaemia was independently associated with female sex, older age, shorter duration of antiretroviral therapy, lower white blood cell count, higher platelet count, higher sCD14 and a greater number of CD14(dim)CD16(+) cells or 'patrolling' monocytes, which remained significant after further adjusting for race and BMI.Having haemoglobin <14 g/dl for men and <13 g/dl for women was independently associated with monocyte activation (sCD14 and CD14(dim)CD16(+) cells) in HIV-infected adults on stable antiretroviral therapy.
| S-EPMC4531107 | biostudies-literature
Project description:BACKGROUND:Mechanisms predisposing HIV-infected patients to increased cardiovascular disease (CVD) risk remain unclear. OBJECTIVE:To determine the interrelationship between arterial inflammation and high-risk coronary plaque morphology in HIV-infected patients with subclinical coronary atherosclerosis. METHODS:Forty-one HIV-infected patients on stable antiretroviral therapy without known CVD but with atherosclerotic plaque on coronary CT angiography were evaluated with F-FDG-PET. Patients were stratified into 2 groups based on relative degree of arterial inflammation [aortic target-to-background ratio (TBR)]. High-risk coronary atherosclerotic plaque morphology features were compared between groups. RESULTS:HIV-infected patients with higher and lower TBRs were similar with respect to traditional CVD risk parameters. Among HIV-infected patients with higher TBR, an increased percentage of patients demonstrated at least 1 low-attenuation coronary atherosclerotic plaque (40% vs. 10%, P = 0.02) and at least 1 coronary atherosclerotic plaque with both low attenuation and positive remodeling (35% vs. 10%, P = 0.04). Moreover, in the higher TBR group, both the number of low-attenuation plaques per patient (P = 0.02) and the number of vulnerability features in the most vulnerable plaque (P = 0.02) were increased. TBR grouping remained significantly related to the number of low-attenuation plaques/subject (? = 0.35, P = 0.004), controlling for age, gender, low-density lipoprotein, duration of HIV, and CD4. CONCLUSIONS:These data demonstrate a relationship between arterial inflammation on F-FDG-PET and high-risk coronary atherosclerotic plaque features among HIV-infected patients with subclinical coronary atherosclerosis. Further studies are needed to determine whether arterial inflammation and related high-risk coronary morphology increase the risk of clinical CVD events in the HIV population.
| S-EPMC4023912 | biostudies-literature
Project description:BackgroundPro-inflammatory monocytes/macrophages may contribute to increased atherosclerosis in human immunodeficiency virus (HIV)-infected patients. We investigate--to our knowledge, for the first time--sCD163 and other markers of monocyte activation in relationship to atherosclerotic plaque in HIV-infected patients.MethodsOne hundred two HIV-infected and 41 HIV-seronegative men with equivalent cardiovascular risk factors and without history of coronary artery disease were prospectively recruited and underwent computed tomography coronary angiography.ResultssCD163 levels and presence of plaque were significantly higher among antiretroviral-treated subjects with undetectable HIV RNA levels, compared with seronegative controls (1172 ± 646 vs. 883 ± 561 ng/mL [P = .02] for sCD163 and 61% vs. 39% [P = .03] for presence of plaque). After adjusting for age, race, lipids, blood pressure, glucose, smoking, sCD14, and HIV infection, sCD163 remained independently associated with noncalcified plaque (P = .008). Among HIV-infected patients, sCD163 was associated with coronary segments with noncalcified plaque (r = 0.21; P = .04), but not with calcium score. In contrast, markers of generalized inflammation, including C-reactive protein level, and D-dimer were not associated with sCD163 or plaque among HIV-infected patients.ConclusionssCD163, a monocyte/macrophage activation marker, is increased in association with noncalcified coronary plaque in men with chronic HIV infection and low or undetectable viremia. These data suggest a potentially important role of chronic monocyte/macrophage activation in the development of noncalcified vulnerable plaque.Clinical trial registrationNCT00455793.
| S-EPMC3203384 | biostudies-literature
Project description:BackgroundCardiovascular disease (CVD) rates are increased in HIV. The degree to which myocyte injury, strain, and fibrosis occur prior to clinical disease and relate to coronary plaque in HIV is unknown.ObjectiveTo investigate newer cardiac biomarkers of subclinical myocyte injury [high-sensitivity troponin T (hs-cTnT)], strain (amino terminal proB-type natriutretic peptide), fibrosis (soluble ST2, Galectin-3), and vascular inflammation (oxidized LDL, lipoprotein-associated phospholipase A2) in HIV-infected individuals and non-HIV controls and relate these to coronary plaque by cardiac computed tomography angiography.DesignObservational.MethodsMarkers were investigated in 155 HIV-infected and 70 non-HIV-infected participants without known CVD and with low traditional CVD risk and related to cardiac computed tomography angiography data.ResultsAge, sex, and race did not differ between the groups. Hs-cTnT [3.1 (3.0, 6.4) vs. 3.0 (3.0, 4.0) ng/l, P = 0.03], Galectin-3 [13.5 (10.6, 18.1) vs. 11.6 (9.9, 14.5) ng/ml, P = 0.002], and soluble ST2 [31.5 (24.5, 41.5) vs. 28.3 (20.2, 33.5) ng/ml, P = 0.01] were significantly higher in HIV-infected participants vs.ControlsDetectable hs-cTnT (seen in 50% of HIV participants) related to the overall presence of plaque [odds ratio (OR) 2.3, P = 0.01] and particularly to coronary calcium (OR for Agatston calcium score > 0, 3.3, P = 0.0008 and OR for calcified plaque 7.4, P = 0.01) in HIV, but not in non-HIV.ConclusionSubclinical myocyte injury is observed among young, asymptomatic HIV-infected individuals with low traditional cardiac risk factors. In the setting of HIV infection, the presence of detectable cardiac troponin is strongly associated with coronary plaque, particularly calcified plaque among an asymptomatic group. Future studies are needed to assess if early subclinical injury marked by hs-cTnT predicts plaque progression and cardiac events in HIV.
| S-EPMC5007151 | biostudies-literature
Project description:ObjectiveTo characterize the genetic and clinical correlates of soluble P-selectin, and the relationship of P-selectin to atherosclerotic risk, in young European-American (EA) and African-American (AA) adults.Methods and resultsWe assessed the interrelationships between 25 common SELP polymorphisms, soluble P-selectin, and atherosclerotic risk in 1222 EA and 1072 AA from the longitudinal population-based CARDIA study. Male sex, smoking, blood pressure, and metabolic status were strong cross-sectional correlates of soluble P-selectin among CARDIA subjects aged 33 to 45 years, explaining 13% of the variance. Among EAs, higher soluble P-selectin predicted carotid intima-media thickness (IMT) measured 5 years later, even after accounting for traditional risk factors. Common SELP nucleotide sequence variants explained 11% and 5% of the interindividual variation in soluble P-selectin levels in EAs and AAs, respectively. Four distinct variants contributed to P-selectin phenotype in EAs, including a polymorphism of the 5' SELP haplotype block associated with carotid IMT. Half of the phenotypic variation attributable to SELP in EAs could be explained by the Thr715Pro polymorphism, whereas Val599Leu was more strongly associated with soluble P-selectin among AAs.ConclusionsCommon SELP polymorphisms were associated with soluble P-selectin and carotid IMT in young adults, but the patterns of association differed between EAs and AAs. These results support the role of P-selectin in the preclinical stages of atherosclerosis.
| S-EPMC5643197 | biostudies-literature
Project description:Some intestinal microbiota-generated metabolites of phosphatidylcholine are recognized to be proatherogenic. As the HIV population is vulnerable to cardiovascular disease and can develop intestinal dysbiosis associated with systemic inflammation, we investigated the novel relationship between microbiota-derived metabolites of phosphatidylcholine and coronary atherosclerosis in HIV.One hundred and fifty-five HIV-infected and 67 non-HIV-infected individuals without known history of cardiovascular disease were previously recruited to assess coronary plaque by computed tomography angiography. In the current study, we evaluate whether serum choline, trimethylamine (TMA), or trimethylamine-N-oxide (TMAO) levels are associated with plaque features.Young, asymptomatic HIV-infected patients (age 47?±?7 years) demonstrated significantly higher prevalence of plaque (53 vs. 35%, P?=?0.01) and number of total plaque segments (1.8?±?2.5 vs. 1.2?±?2.2, P?=?0.03) when compared with well matched noninfected individuals with similar comorbidities. TMA was significantly associated with calcium score (r?=?0.22, P?=?0.006), number of total (r?=?0.20, P?=?0.02) and calcified (r?=?0.18, P?=?0.03) plaque segments, and calcium plaque volume (r?=?0.19, P?=?0.02) and mass (r?=?0.22, P?=?0.009) in the HIV cohort only. In multivariate modeling among HIV-infected patients, TMA remained significantly associated with calcium score (P?=?0.008), number of total (P?=?0.005) and calcified (P?=?0.02) plaque segments, and calcium plaque volume (P?=?0.01) and mass (P?=?0.007), independent of Framingham risk score. In contrast, there was no association of TMAO to coronary plaque features in either cohort.A link between TMA and atherosclerosis has not previously been established. The current study suggests that TMA may be a nontraditional risk factor related to the number of plaque segments and severity of calcified plaque burden in HIV.
| S-EPMC4410017 | biostudies-literature
Project description:To investigate differences in subclinical coronary atherosclerotic plaque and markers of immune activation among HIV-infected and non-HIV-infected women categorized by degree of ovarian reserve and menopause status.Cross-sectional evaluation.Seventy-four women (49 HIV-infected, 25 non-HIV-infected) without known cardiovascular disease (CVD) were classified as premenopausal, premenopausal with reduced ovarian reserve, or postmenopausal based on menstrual history and anti-Müllerian hormone (AMH) levels. Participants underwent contrast-enhanced coronary computed tomography angiography and immune phenotyping. Comparisons in coronary atherosclerotic plaque burden and immune markers were made between the HIV-infected and non-HIV-infected women overall and within the HIV-infected and non-HIV-infected women by reproductive classification group.Among the overall group of HIV-infected women, the women with reduced ovarian reserve (undetectable AMH) had a higher prevalence of coronary atherosclerotic plaque (52 versus 6%, P?=?0.0007) and noncalcified plaque (48 versus 6%, P?=?0.002), as well as higher levels of log sCD163 (P?=?0.0004) and log MCP-1 (P?=?0.006), compared with the premenopausal women with measurable AMH. Furthermore, reduced ovarian reserve in the HIV-infected group related to noncalcified plaque, controlling for traditional CVD risk factors (P?=?0.04) and sCD163 (P?=?0.03).HIV-infected women with reduced ovarian reserve have increased subclinical coronary atherosclerotic plaque compared with premenopausal women in whom AMH is measurable. This relationship holds when controlling for CVD risk factors (including age) and immune activation. Our findings demonstrate that reduced ovarian reserve may contribute to CVD burden in HIV-infected women and support a comprehensive assessment of CVD risk prior to completion of menopause in this population.
| S-EPMC4713275 | biostudies-literature