title: Association between human immunodeficiency virus infection and stiffness of the common carotid artery.
abstract: OBJECTIVE
  Individuals with human immunodeficiency virus (HIV) who use highly active antiretroviral therapy (HAART) may have an increased risk for cardiovascular-related events, although the underlying mechanism remains unclear. We tested the hypothesis that carotid arterial stiffness was higher among persons using HAART compared to HAART-naïve and HIV-uninfected persons.
  
  
  METHODS
  Between 2004 and 2006, we performed high-resolution B-mode ultrasound on 2789 HIV-infected and HIV-uninfected participants of the Women's Interagency HIV Study (1865 women) and the Multicenter AIDS Cohort Study (924 men) and determined carotid arterial distensibility, which is a direct measure of carotid arterial stiffness. We used generalized estimating equations to evaluate the association between distensibility and HIV infection, CD4(+) cell count, and exposure to HAART adjusted for demographic, behavioral, and clinical characteristics.
  
  
  RESULTS
  In multivariable analysis, distensibility was 4.3% lower (95% confidence interval, -7.4% to -1.1%) among HIV-infected vs uninfected participants. Among HIV-infected participants with <200 CD4(+) cells, distensibility was 10.5% lower (95% confidence interval, -14.5% to -6.2%) than that among HIV-uninfected participants, and this effect did not differ significantly by cohort or race. Concurrent HAART use was independently associated with lower distensibility among Multicenter AIDS Cohort Study participants but not among Women's Interagency HIV Study participants.
  
  
  CONCLUSIONS
  Our finding that advanced HIV-related immunosuppression was associated with increased carotid arterial stiffness independent from the effects of traditional atherosclerosis risk factors suggests that the etiologic mechanism underlying reports of an increased cardiovascular disease risk among HIV-infected individuals might involve HIV-related immunosuppression leading to vascular dysfunction and arterial stiffening.
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. eseaberg@jhsph.edu
authors.forename: Eric C
authors.initials: EC
authors.lastname: Seaberg
authors.forename: Lorie
authors.initials: L
authors.lastname: Benning
authors.forename: A Richey
authors.initials: AR
authors.lastname: Sharrett
authors.forename: Jason M
authors.initials: JM
authors.lastname: Lazar
authors.forename: Howard N
authors.initials: HN
authors.lastname: Hodis
authors.forename: Wendy J
authors.initials: WJ
authors.lastname: Mack
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Siedner
authors.forename: John P
authors.initials: JP
authors.lastname: Phair
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Kingsley
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kaplan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D050197:Atherosclerosis / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000821:virology*; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000821:virology*; D016009:Chi-Square Distribution; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000821:virology; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D014463:Ultrasonography; D019562:Viral Load
references.citation: J Acquir Immune Defic Syndr. 2008 Mar 1;47(3):338-41
references.pmid: 18176330
references.citation: Clin Diagn Lab Immunol. 2005 Sep;12(9):1013-9
references.pmid: 16148165
references.citation: N Engl J Med. 1998 Mar 26;338(13):853-60
references.pmid: 9516219
references.citation: AIDS. 2005 Jun 10;19(9):953-60
references.pmid: 15905677
references.citation: Am J Hypertens. 2002 May;15(5):445-52
references.pmid: 12022247
references.citation: Lancet. 1997 Sep 6;350(9079):713-4
references.pmid: 9291911
references.citation: N Engl J Med. 2005 Jan 6;352(1):48-62
references.pmid: 15635112
references.citation: Circulation. 2003 Jan 7;107(1):139-46
references.pmid: 12515756
references.citation: Arterioscler Thromb Vasc Biol. 2005 Nov;25(11):2381-5
references.pmid: 16123321
references.citation: AIDS. 2003 Nov 21;17(17):2529-31
references.pmid: 14600526
references.citation: AIDS. 2005 Jun 10;19(9):927-33
references.pmid: 15905673
references.citation: Circulation. 2001 Jul 17;104(3):257-62
references.pmid: 11457741
references.citation: Med Clin North Am. 2009 May;93(3):583-604, Table of Contents
references.pmid: 19427493
references.citation: Am J Epidemiol. 1995 Aug 1;142(3):323-30
references.pmid: 7631636
references.citation: N Engl J Med. 2007 Apr 26;356(17):1723-35
references.pmid: 17460226
references.citation: AIDS. 2004 Apr 30;18(7):1037-41
references.pmid: 15096807
references.citation: J Antimicrob Chemother. 2007 Oct;60(4):724-32
references.pmid: 17715125
references.citation: AIDS. 1998 May 7;12(7):F51-8
references.pmid: 9619798
references.citation: Ann Intern Med. 2001 Dec 4;135(11):939-53
references.pmid: 11730394
references.citation: J Am Coll Cardiol. 2008 Aug 12;52(7):569-76
references.pmid: 18687253
references.citation: Epidemiology. 1998 Mar;9(2):117-25
references.pmid: 9504278
references.citation: Am J Med. 1997 Mar;102(3):227-31
references.pmid: 9217589
references.citation: N Engl J Med. 2006 Nov 30;355(22):2283-96
references.pmid: 17135583
references.citation: Circulation. 2004 Apr 6;109(13):1603-8
references.pmid: 15023877
references.citation: Am J Hypertens. 2003 May;16(5 Pt 1):356-62
references.pmid: 12745196
references.citation: Curr Opin HIV AIDS. 2007 Jul;2(4):324-31
references.pmid: 19372907
references.citation: JAMA. 1998 Nov 4;280(17):1497-503
references.pmid: 9809730
references.citation: Am J Cardiol. 1994 Oct 1;74(7):691-5
references.pmid: 7942527
references.citation: AIDS. 2003 Nov 21;17(17):2479-86
references.pmid: 14600519
references.citation: Am J Epidemiol. 1987 Aug;126(2):310-8
references.pmid: 3300281
references.citation: AIDS. 2008 Aug 20;22(13):1615-24
references.pmid: 18670221
references.citation: Circulation. 1989 Jan;79(1):1-7
references.pmid: 2642753
references.citation: N Engl J Med. 2003 Nov 20;349(21):1993-2003
references.pmid: 14627784
references.citation: Ultrasound Med Biol. 1997;23(2):157-64
references.pmid: 9140173
references.citation: Hypertension. 2006 Mar;47(3):365-70
references.pmid: 16432047
references.citation: Ann Med. 2002;34(1):55-63
references.pmid: 12014436
references.citation: Lancet. 2002 Nov 30;360(9347):1747-8
references.pmid: 12480430