Jin Choul Chai1, Amy A Deik2, Simin Hua1, Tao Wang1, David B Hanna1, Xiaonan Xue1, Sabina A Haberlen3, Sanjiv J Shah4, Yousin Suh5, Jason M Lazar6, Deborah Gustafson6, Howard N Hodis7, Alan L Landay8, Kathryn Anastos1,9, Wendy S Post3,10, Robert C Kaplan1,11, Clary B Clish2, Qibin Qi1,12. 1. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York. 2. Broad Institute of MIT and Harvard, Cambridge, Massachusetts. 3. Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland. 4. Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois. 5. Department of Genetics, Albert Einstein College of Medicine, Bronx, New York. 6. Department of Neurology, State University of New York-Downstate Medical Center, Brooklyn, New York. 7. Atherosclerosis Research Unit, Keck School of Medicine, University of Southern California, Los Angeles. 8. Department of Immunology and Microbiology, Rush University Medical Center, Chicago, Illinois. 9. Department of Medicine, Albert Einstein College of Medicine, Bronx, New York. 10. Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland. 11. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. 12. Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
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.
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.
Authors: Christin Stegemann; Ignat Drozdov; Joseph Shalhoub; Julia Humphries; Christophe Ladroue; Athanasios Didangelos; Mark Baumert; Mark Allen; Alun H Davies; Claudia Monaco; Alberto Smith; Qingbo Xu; Manuel Mayr Journal: Circ Cardiovasc Genet Date: 2011-04-21
Authors: Dong D Wang; Estefanía Toledo; Adela Hruby; Bernard A Rosner; Walter C Willett; Qi Sun; Cristina Razquin; Yan Zheng; Miguel Ruiz-Canela; Marta Guasch-Ferré; Dolores Corella; Enrique Gómez-Gracia; Miquel Fiol; Ramón Estruch; Emilio Ros; José Lapetra; Montserrat Fito; Fernando Aros; Luis Serra-Majem; Chih-Hao Lee; Clary B Clish; Liming Liang; Jordi Salas-Salvadó; Miguel A Martínez-González; Frank B Hu Journal: Circulation Date: 2017-03-09 Impact factor: 29.690
Authors: Zhilei Shan; Clary B Clish; Simin Hua; Justin M Scott; David B Hanna; Robert D Burk; Sabina A Haberlen; Sanjiv J Shah; Joseph B Margolick; Cynthia L Sears; Wendy S Post; Alan L Landay; Jason M Lazar; Howard N Hodis; Kathryn Anastos; Robert C Kaplan; Qibin Qi Journal: J Infect Dis Date: 2018-09-22 Impact factor: 5.226
Authors: P-J Touboul; M G Hennerici; S Meairs; H Adams; P Amarenco; N Bornstein; L Csiba; M Desvarieux; S Ebrahim; R Hernandez Hernandez; M Jaff; S Kownator; T Naqvi; P Prati; T Rundek; M Sitzer; U Schminke; J-C Tardif; A Taylor; E Vicaut; K S Woo Journal: Cerebrovasc Dis Date: 2012-11-01 Impact factor: 2.762
Authors: David B Hanna; Mengye Guo; Petra Bůžková; Tracie L Miller; Wendy S Post; James H Stein; Judith S Currier; Richard A Kronmal; Matthew S Freiberg; Siiri N Bennett; Cecilia M Shikuma; Kathryn Anastos; Yanjie Li; Russell P Tracy; Howard N Hodis; Joseph A Delaney; Robert C Kaplan Journal: Clin Infect Dis Date: 2016-04-26 Impact factor: 9.079
Authors: Aki S Havulinna; Marko Sysi-Aho; Mika Hilvo; Dimple Kauhanen; Reini Hurme; Kim Ekroos; Veikko Salomaa; Reijo Laaksonen Journal: Arterioscler Thromb Vasc Biol Date: 2016-10-20 Impact factor: 8.311
Authors: Simin Hua; Justin M Scott; David B Hanna; Sabina A Haberlen; Sanjiv J Shah; Howard N Hodis; Alan L Landay; Jason M Lazar; Jorge R Kizer; Bing Yu; Wendy S Post; Kathryn Anastos; Robert C Kaplan; Clary B Clish; Qibin Qi Journal: AIDS Date: 2019-05-01 Impact factor: 4.632
Authors: Ninad S Chaudhary; Tobias Kind; Amanda L Willig; Michael S Saag; Sadeep Shrestha; Nicholas Funderburg; Howard W Wiener; E Turner Overton; Marguerite R Irvin Journal: Medicine (Baltimore) Date: 2021-07-30 Impact factor: 1.817
Authors: Zheng Wang; Mykhaylo Usyk; Christopher C Sollecito; Yunping Qiu; Jessica Williams-Nguyen; Simin Hua; Ana Gradissimo; Tao Wang; Xiaonan Xue; Irwin J Kurland; Klaus Ley; Alan L Landay; Kathryn Anastos; Rob Knight; Robert C Kaplan; Robert D Burk; Qibin Qi Journal: Clin Infect Dis Date: 2020-12-03 Impact factor: 20.999
Authors: Eric Zhang; Jin Choul Chai; Amy A Deik; Simin Hua; Anjali Sharma; Michael F Schneider; Deborah Gustafson; David B Hanna; Jordan E Lake; Leah H Rubin; Wendy S Post; Kathryn Anastos; Todd Brown; Clary B Clish; Robert C Kaplan; Qibin Qi Journal: J Clin Endocrinol Metab Date: 2021-03-25 Impact factor: 6.134