title: Plaque burden in HIV-infected patients is associated with serum intestinal microbiota-generated trimethylamine.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Suman
authors.initials: S
authors.lastname: Srinivasa
authors.forename: Kathleen V
authors.initials: KV
authors.lastname: Fitch
authors.forename: Janet
authors.initials: J
authors.lastname: Lo
authors.forename: Hanane
authors.initials: H
authors.lastname: Kadar
authors.forename: Rachel
authors.initials: R
authors.lastname: Knight
authors.forename: Kimberly
authors.initials: K
authors.lastname: Wong
authors.forename: Suhny
authors.initials: S
authors.lastname: Abbara
authors.forename: Dominique
authors.initials: D
authors.lastname: Gauguier
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Capeau
authors.forename: Franck
authors.initials: F
authors.lastname: Boccara
authors.forename: Steven K
authors.initials: SK
authors.lastname: Grinspoon
mesh_terms: D002794:Choline / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D064806:Dysbiosis / Q000276:immunology* / Q000503:physiopathology; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D007410:Intestinal Diseases / Q000276:immunology* / Q000503:physiopathology; D008297:Male; D008744:Methylamines / Q000097:blood; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000276:immunology / Q000473:pathology / Q000821:virology*; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D008744:Methylamines; C005855:trimethyloxamine; C023336:trimethylamine; D002794:Choline