Suman Srinivasa1, Kathleen V Fitch, Janet Lo, Hanane Kadar, Rachel Knight, Kimberly Wong, Suhny Abbara, Dominique Gauguier, Jacqueline Capeau, Franck Boccara, Steven K Grinspoon. 1. aProgram in Nutritional Metabolism, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA bINSERM UMRS1138, Cordeliers Research Centre, Paris cInstitute of Cardiometabolism and Nutrition, University Pierre & Marie Curie, Hospital Pitié Salpetrière, Paris, France dUniversity of Rochester School of Medicine, Rochester, New York, New York eCardiothoracic Imaging Division, Department of Radiology, UTSW Medical Center, Dallas, Texas, USA fBiochimie et Hormonologie, Hôpital Tenon AP-HP Paris, CDR Saint-Antoine, Inserm UMR_S938, Université Paris 6-UPMC, Institute of Cardiometabolism and Nutrition, Paris gDepartment of Cardiology, Saint Antoine Hospital, Inserm U938, Université Paris 6-UPMC, Faculté de Médecine Pierre et Marie Curie, Paris, France.
Abstract
OBJECTIVE: 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. DESIGN/ METHODS: 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. RESULTS: 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. CONCLUSION: 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.
OBJECTIVE: 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. DESIGN/ METHODS: 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. RESULTS: Young, asymptomatic HIV-infectedpatients (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-infectedpatients, 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. CONCLUSION: 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.
Authors: W H Wilson Tang; Zeneng Wang; Bruce S Levison; Robert A Koeth; Earl B Britt; Xiaoming Fu; Yuping Wu; Stanley L Hazen Journal: N Engl J Med Date: 2013-04-25 Impact factor: 91.245
Authors: Jun Zhang; Madhusudana R Chaluvadi; Rob Reddy; Meike S Motika; Terrilyn A Richardson; John R Cashman; Edward T Morgan Journal: Drug Metab Dispos Date: 2008-12-16 Impact factor: 3.922
Authors: Duy M Dinh; Gretchen E Volpe; Chad Duffalo; Seema Bhalchandra; Albert K Tai; Anne V Kane; Christine A Wanke; Honorine D Ward Journal: J Infect Dis Date: 2014-07-23 Impact factor: 5.226
Authors: Aurelian Bidulescu; Lloyd E Chambless; Anna Maria Siega-Riz; Steven H Zeisel; Gerardo Heiss Journal: BMC Cardiovasc Disord Date: 2007-07-13 Impact factor: 2.298
Authors: Chris deFilippi; Janet Lo; Robert Christenson; Ida Grundberg; Lauren Stone; Markella V Zanni; Hang Lee; Steven K Grinspoon Journal: AIDS Date: 2018-04-24 Impact factor: 4.177
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 Elliott Miller; Sabina A Haberlen; Todd T Brown; Joseph B Margolick; Joseph A DiDonato; Stanley L Hazen; Mallory D Witt; Lawrence A Kingsley; Frank J Palella; Matthew Budoff; Lisa P Jacobson; Wendy S Post; Cynthia L Sears Journal: J Acquir Immune Defic Syndr Date: 2016-05-01 Impact factor: 3.731