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Association of Lipidomic Profiles With Progression of Carotid Artery Atherosclerosis in HIV Infection.

ABSTRACT: Importance:Lipid metabolism disruption and excess risk of cardiovascular disease (CVD) have been observed in HIV-infected individuals, but the associations among HIV infection, plasma lipidome, and CVD risk have not been well understood. Objective:To evaluate plasma lipidomic profiles and their associations with carotid artery atherosclerosis in individuals with HIV and individuals without HIV. Design, Setting, and Participants:Prospective analysis in the Women's Interagency HIV Study and Multicenter AIDS Cohort Study during a 7-year follow-up (from 2004-2006 to 2011-2013) at multicenter HIV cohorts in the United States. The study included 737 participants aged 35 to 55 years (520 with HIV and 217 without HIV) without CVD or carotid artery plaque at baseline. Data were analyzed between April 2017 and July 2019. Exposures:Two hundred eleven plasma lipid species. Main Outcomes and Measures:Poisson regression was used to examine the associations of baseline lipid species with risk of plaque measured by repeated B-mode carotid artery ultrasonography imaging. Results:Of the 737 included participants, 398 (54%) were women, 351 (48%) were African American (non-Hispanic), 156 of 737 (21%) were nonwhite Hispanic, and the mean (SD) age was 45 (6) years. After adjusting for demographic and behavioral factors, we identified 12 lipid species, representing independent signals for 10 lipid classes, associated with risk of plaque. Nine lipid species remained significant after further adjusting for conventional CVD risk factors, although many of them showed moderate to high association with conventional blood lipids (eg, total and low-density lipoprotein cholesterols and triglycerides). Cholesteryl ester (16:1) (risk ratio [RR] per standard deviation, 1.28; 95% CI, 1.08-1.52), ceramide (16:0) (RR, 1.29; 95% CI, 1.02-1.63), lysophosphatidylcholine (20:4) (RR, 1.28; 95% CI, 1.05-1.58), lysophosphatidylethanolamine (16:0) (RR, 1.28; 95% CI, 1.05-1.57), phosphatidylethanolamine (38:6) (RR, 1.33; 95% CI, 1.08-1.64), phosphatidylethanolamine-plasmalogen (36:2) (RR, 1.25; 95% CI, 1.04-1.52), phosphatidylserine-plasmalogen (36:3) (RR, 1.19; 95% CI, 1.00-1.43), and triacylglycerol (54:6) (RR, 1.26; 95% CI, 1.04-1.54) were associated with increased risk of plaque, while phosphatidylcholine (36:4) (RR, 0.65; 95% CI, 0.54-0.77) was associated with decreased risk of plaque. Most of these plaque-increased lipid species showed higher levels in individuals with HIV, particularly among individuals with HIV using antiretroviral therapy compared with individuals without HIV. Network analysis identified 9 lipid modules, and 2 modules composed of triacylglycerols and phosphatidylcholines with long and unsaturated acyl chains, respectively, showed the strongest associations with increased risk of plaque. Conclusions and Relevance:This study identified multiple plasma lipid species associated with carotid artery atherosclerosis, and alterations in these lipid species might be associated with HIV infection and antiretroviral therapy. Our data suggest unfavorable associations of long-chain and unsaturated triacylglycerols and phosphatidylcholines with carotid artery plaque formation.

SUBMITTER: Chai JC

PROVIDER: S-EPMC6813587 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Association of Lipidomic Profiles With Progression of Carotid Artery Atherosclerosis in HIV Infection.

Chai Jin Choul JC Deik Amy A AA Hua Simin S Wang Tao T Hanna David B DB Xue Xiaonan X Haberlen Sabina A SA Shah Sanjiv J SJ Suh Yousin Y Lazar Jason M JM Gustafson Deborah D Hodis Howard N HN Landay Alan L AL Anastos Kathryn K Post Wendy S WS Kaplan Robert C RC Clish Clary B CB Qi Qibin Q

JAMA cardiology 20191201 12

<h4>Importance</h4>Lipid metabolism disruption and excess risk of cardiovascular disease (CVD) have been observed in HIV-infected individuals, but the associations among HIV infection, plasma lipidome, and CVD risk have not been well understood.<h4>Objective</h4>To evaluate plasma lipidomic profiles and their associations with carotid artery atherosclerosis in individuals with HIV and individuals without HIV.<h4>Design, setting, and participants</h4>Prospective analysis in the Women's Interagenc ...[more]

PMID: 31642867

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Project description:ObjectiveTo evaluate plasma acylcarnitine profiles and their relationships with progression of carotid artery atherosclerosis among individuals with and without HIV infection.DesignProspective cohort studies of 499 HIV-positive and 206 HIV-negative individuals from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study.MethodsTwenty-four acylcarnitine species were measured in plasma samples of participants at baseline. Carotid artery plaque was assessed using repeated B-mode carotid artery ultrasound imaging in 2004-2013. We examined the associations of individual and aggregate short-chain (C2-C7), medium-chain (C8-C14) and long-chain acylcarnitines (C16-C26) with incident carotid artery plaque over 7 years.ResultsAmong 24 acylcarnitine species, C8-carnitines and C20 : 4-carnitines showed significantly lower levels comparing HIV-positive to HIV-negative individuals (false discovery rate adjusted P < 0.05); and C20-carnitines and C26-carnitines showed significantly higher levels in HIV positive using antiretroviral therapy than those without antiretroviral therapy (false discovery rate adjusted P < 0.05). In the univariate analyses, higher aggregated short-chain and long-chain acylcarnitine scores were associated with increased risk of carotid artery plaque [risk ratios (RRs) = 1.22 (95% confidence interval 1.02-1.45) and 1.20 (1.02-1.41) per SD increment, respectively]. The association for the short-chain acylcarnitine score remained significant [RR = 1.23 (1.05-1.44)] after multivariate adjustment (including traditional cardiovascular disease risk factors). This association was more evident in HIV-positive individuals without persistent viral suppression [RR = 1.37 (1.11-1.69)] compared with those with persistent viral suppression during follow-up [RR = 1.03 (0.76-1.40)] or HIV-negative individuals [RR = 1.02 (0.69-1.52)].ConclusionIn two HIV cohorts, plasma levels of most acylcarnitines were not significantly different between HIV-positive and HIV-negative individuals. However, higher levels of aggregated short-chain acylcarnitines were associated with progression of carotid artery atherosclerosis.

Project description:BackgroundCeramides have been implicated in the pathophysiology of HIV infection and cardiovascular disease. However, no study, to our knowledge, has evaluated circulating ceramide levels in association with subclinical cardiovascular disease risk among HIV-infected individuals.MethodsPlasma levels of 4 ceramide species (C16:0, C22:0, C24:0, and C24:1) were measured among 398 women (73% HIV+) and 339 men (68% HIV+) without carotid artery plaques at baseline from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study. We examined associations between baseline plasma ceramides and risk of carotid artery plaque formation, assessed by repeated B-mode carotid artery ultrasound imaging over a median 7-year follow-up.ResultsPlasma levels of C16:0, C22:0, and C24:1 ceramides were significantly higher in HIV-infected individuals compared with those without HIV infection (all P<0.001), and further analysis indicated that elevated ceramide levels were associated with antiretroviral therapy use, particularly protease inhibitor use, in HIV-infected individuals (all P<0.001). All 4 ceramides were highly correlated with each other ( r=0.70-0.94; all P<0.001) and significantly correlated with total-cholesterol ( r=0.42-0.58; all P<0.001) and low-density lipoprotein cholesterol ( r=0.24-0.42; all P<0.001) levels. Of note, C16:0 and C24:1 ceramides, rather than C22:0 and C24:0 ceramides, were more closely correlated with specific monocyte activation and inflammation markers (eg, r=0.30 between C16:0 ceramide and soluble CD14; P<0.001) and surface markers of CD4+ T-cell activation. A total of 112 participants developed carotid artery plaques over 7 years, and higher levels of C16:0 and C24:1 ceramides were significantly associated with increased risk of carotid artery plaques (relative risk [95% CI]=1.55 [1.29, 1.86] and 1.51 [1.26, 1.82] per standard deviation increment, respectively; both P<0.001), after adjusting for demographic and behavioral factors. After further adjustment for cardiovascular disease risk factors and immune activation markers, these associations were attenuated but remained significant. The results were consistent between men and women and between HIV-infected and HIV-uninfected participants.ConclusionsIn 2 HIV cohorts, elevated plasma levels of C16:0 and C24:1 ceramides, correlating with immune activation and inflammation, were associated with antiretroviral therapy use and progression of carotid artery atherosclerosis.

Project description:BackgroundAlterations in gut microbiota have been implicated in HIV infection and cardiovascular disease. However, how gut microbial alterations relate to host inflammation and metabolite profiles, and their relationships with atherosclerosis, have not been well-studied, especially in the context of HIV infection. Here, we examined associations of gut microbial species and functional components measured by shotgun metagenomics with carotid artery plaque assessed by B-mode carotid artery ultrasound in 320 women with or at high risk of HIV (65% HIV +) from the Women's Interagency HIV Study. We further integrated plaque-associated microbial features with serum proteomics (74 inflammatory markers measured by the proximity extension assay) and plasma metabolomics (378 metabolites measured by liquid chromatography tandem mass spectrometry) in relation to carotid artery plaque in up to 433 women.ResultsFusobacterium nucleatum, a potentially pathogenic bacteria, was positively associated with carotid artery plaque, while five microbial species (Roseburia hominis, Roseburia inulinivorans, Johnsonella ignava, Odoribacter splanchnicus, Clostridium saccharolyticum) were inversely associated with plaque. Results were consistent between women with and without HIV. Fusobacterium nucleatum was positively associated with several serum proteomic inflammatory markers (e.g., CXCL9), and the other plaque-related species were inversely associated with proteomic inflammatory markers (e.g., CX3CL1). These microbial-associated proteomic inflammatory markers were also positively associated with plaque. Associations between bacterial species (especially Fusobacterium nucleatum) and plaque were attenuated after further adjustment for proteomic inflammatory markers. Plaque-associated species were correlated with several plasma metabolites, including the microbial metabolite imidazole-propionate (ImP), which was positively associated with plaque and several pro-inflammatory markers. Further analysis identified additional bacterial species and bacterial hutH gene (encoding enzyme histidine ammonia-lyase in ImP production) associated with plasma ImP levels. A gut microbiota score based on these ImP-associated species was positively associated with plaque and several pro-inflammatory markers.ConclusionAmong women living with or at risk of HIV, we identified several gut bacterial species and a microbial metabolite ImP associated with carotid artery atherosclerosis, which might be related to host immune activation and inflammation. Video Abstract.

Project description:BackgroundSoluble Tumor Necrosis Factor Weak Inducer of Apoptosis (sTWEAK) has been proposed as a novel biomarker of cardiovascular disease risk. This study compares levels of sTWEAK, sCD163 and the sCD163/sTWEAK ratio in HIV-infected and uninfected patients and their associations with cardiovascular and inflammatory factors.MethodsThe data for our analysis come from 274 HIV-infected adults and 59 controls. HIV participants were on stable antiretroviral therapy (ART). Wilcoxon-Mann-Whitney tests were used for comparing markers between HIV-infected participants with HIV viral load <50 copies/mL (aviremic group), HIV-infected participants with detectable viremia (HIV-1 RNA ≥50 copies/mL; viremic group) and HIV negative participants. Multivariable quantile regression analyses were used to assess associations of sTWEAK and sCD163 with other markers of inflammation and carotid intima-media thickness (cIMT).ResultsOverall, 74% of participants were male; 59% were African-Americans; median age was 40 years and CD4 595 cells/mm3. Overall, HIV-infected participants had reduced sTWEAK and increased sCD163 levels compared to HIV-uninfected participants (p = 0.0001 for both markers). In addition, these biomarkers were significantly different between HIV-infected viremic and aviremic patients (p ≤ 0.01 for both markers). In multivariable models, sTWEAK and sCD163 in aviremic patients were significantly correlated with common carotid artery IMT (p ≤ 0.05). In HIV-infected aviremic participants, sTWEAK and sCD163 were both associated with IL-6, CD14 + CD16 + monocytes (p ≤ 0.02); additionally, sCD163 was associated with D-dimer- (β = -69.5, 0.05), VCAM (β = 72.4, p = 0.05), TNF RI (β = 91.1, p < 0.01), and TNF RII (β = 87.8, p < 0.01).ConclusionsHIV-infected participants showed increased systemic inflammatory and monocyte activation markers. Soluble CD163 and sTWEAK levels were associated with carotid intima-media thickness.

Dataset Information

Association of Lipidomic Profiles With Progression of Carotid Artery Atherosclerosis in HIV Infection.

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Association of Lipidomic Profiles With Progression of Carotid Artery Atherosclerosis in HIV Infection.

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