Restricted accessResearch articleFirst published online 2019-5
Prevalence,Incidence,and Contributors of Subclinical Atheromatosis,Arteriosclerosis,and Arterial Hypertrophy in HIV-Infected Individuals: A Single-Center,3-Year Prospective Study
Cardiovascular disease (CVD) is an important comorbidity for people living with HIV infection (PLWH) in the combined antiretroviral therapy era. We prospectively examined the presence of subclinical arterial disease in 138 consecutive CVD-free, HIV-infected individuals compared to 664 HIV-negative individuals. We studied 10 arterial sites in 4 beds using 5 distinct biomarkers of subclinical atheromatosis, arteriosclerosis, and hypertrophy and evaluated the association of subclinical arterial damage with CVD-related and HIV-related factors at baseline and at 3-year follow-up. Atheromatosis, arteriosclerosis, and arterial hypertrophy were present in 36.1%, 59.7%, and 34.3% of HIV-infected individuals, respectively, at baseline. HIV infection was independently associated with carotid atheromatosis and hypertrophy. The presence of carotid atheromatosis was independently associated with age, years of smoking, and exposure to nonnucleoside reverse transcriptase inhibitors (NNRTIs). The annual incidence of atheromatosis, arteriosclerosis, and arterial hypertrophy was 5.5, 18.6, and 12.5 cases/100 patients, respectively. Carotid atheromatosis progression was significantly associated with NNRTI exposure. People living with HIV infection exhibited high prevalence and incidence of subclinical arterial damage and site-specific predilection for the carotids. These investigations may help optimize HIV-specific CVD prediction models. The NNRTIs may contribute to atheromatosis, emphasizing the need to consider the atherogenic potential of antiretroviral drugs in management strategies.
Concerted Action on SeroConversion to AIDS and Death in Europe) Collaboration. Changes in the uptake of antiretroviral therapy and survival in people with known duration of HIV infection in Europe: results from CASCADE. HIV Med. 2000;1(4):224–231.
2.
LouieJKHsuLCOsmondDH. Trends in causes of death among persons with acquired immunodeficiency syndrome in the era of highly active antiretroviral therapy, San Francisco, 1994-1998. J Infect Dis. 2002;186(7):1023–1027.
3.
SmithCJRyomLWeberR. D:A:D Study Group. Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration. Lancet.2014;384(9939):241–248.
4.
LewdenCMayTRosenthalE. ANRS EN19 mortalité study group and mortavic. changes in causes of death among adults infected by HIV between 2000 and 2005: The “Mortalité 2000 and 2005” surveys (ANRS EN19 and Mortavic). J Acquir Immune Defic Syndr. 2008;48(5):590–598.
5.
PalellaFJJrBakerRKMoormanAC. HIV outpatient study investigators. Mortality in the highly active antiretroviral therapy era: changing causes of death and disease in the HIV outpatient study. J Acquir Immune Defic Syndr. 2006;43(1):27–34.
6.
PearceDAniCEspinosa-SilvaY. Comparison of in-hospital mortality from acute myocardial infarction in HIV sero-positive versus sero-negative individuals. Am J Cardiol. 2012;110(8):1078–1084.
7.
NdukaCSarkiAUthmanO. Impact of antiretroviral therapy on serum lipoprotein levels and dyslipidemias: a systematic review and meta-analysis. Int J Cardiol. 2015;199:307–318.
8.
ParaskevasKIKatsikiNTzovarasAAKoupidisSAMikhailidisDP. Peripheral arterial disease and HIV-positive patients. Angiology. 2011;62(1):7–9.
9.
SimonAChironiGLevensonJ. Comparative performance of subclinical atherosclerosis tests in predicting coronary heart disease in asymptomatic individuals. Eur Heart J. 2007;28(24):2967–271.
10.
VlachopoulosCXaplanterisPAboyansV. The role of vascular biomarkers for primary and secondary prevention. A position paper from the European Society of Cardiology Working Group on peripheral circulation: endorsed by the Association for Research into Arterial Structure and Physiology (ARTERY) society. Atherosclerosis. 2015;241(2):507–532.
11.
FitchKVStavrouELoobySE. Associations of cardiovascular risk factors with two surrogate markers of subclinical atherosclerosis: endothelial function and carotid intima media thickness. Atherosclerosis. 2011;217(2):437–440.
12.
LorenzMWStephanCHarmjanzA. Both long-term HIV infection and highly active antiretroviral therapy are independent risk factors for early carotid atherosclerosis. Atherosclerosis. 2008;196(2):720–726.
13.
ZhuHYuanJWangY. Long-term use of first-line highly active antiretroviral therapy is not associated with carotid artery stiffness in human immunodeficiency virus-positive patients. Braz J Infect Dis. 2014;18(5):496–500.
14.
ZormpalaASipsasNVMoyssakisI. Impaired distensibility of ascending aorta in patients with HIV infection. BMC Infect Dis. 2012;12:167.
15.
CurrierJSKendallMAZackinR. AACTG 5078 study team. Carotid artery intima-media thickness and HIV infection: traditional risk factors overshadow impact of protease inhibitor exposure. AIDS. 2005;19(9):927–933.
16.
SteinJHCurrierJSHsuePY. Arterial disease in patients with human immunodeficiency virus infection: what has imaging taught us?. JACC Cardiovasc Imaging. 2014;7(5):515–525.
17.
ESH/ESC Task Force for the Management of Arterial Hypertension. 2013 Practice guidelines for the management of arterial hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC): ESH/ESC Task Force for the Management of Arterial Hypertension. J Hypertens. 2013;31(10):1925–1938.
18.
StoneNJRobinsonJGLichtensteinAH. American College of Cardiology/American Heart Association task force on practice guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(25 Pt B):2889–2934.
19.
Reference Values for Arterial Stiffness’ Collaboration. Determinants of pulse wave velocity in healthy people and in the presence of cardiovascular risk factors: “establishing normal and reference values”. Eur Heart J. 2010;31(19):2338–2350.
20.
LaurentSCockcroftJVan BortelL. European network for non-invasive investigation of large arteries. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006;27(21):2588–2605.
21.
EngelenLBossuytJFerreiraI. Reference values for arterial measurements collaboration. Reference values for local arterial stiffness. Part A: carotid artery. J Hypertens. 2015;33(10):1981–1996.
22.
RomanMJNaqviTZGardinJM. American Society of Echocardiography.; Society for vascular medicine and biology. American society of echocardiography report. Clinical application of noninvasive vascular ultrasound in cardiovascular risk stratification: a report from the American Society of Echocardiography and the Society for Vascular Medicine and Biology. Vasc Med. 2006;11(3):201–211.
23.
AndersonJLHalperinJLAlbertNM. Management of patients with peripheral artery disease (compilation of 2005 and 2011 ACCF/AHA guideline recommendations): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127(13):1425–1443.
24.
EngelenLFerreiraIStehouwerCD. Reference values for arterial measurements collaboration reference intervals for common carotid intima-media thickness measured with echotracking: relation with risk factors. Eur Heart J. 2013;34(30):2368–2380.
25.
So-ArmahKFreibergMS. Cardiovascular disease risk in an aging HIV population: not just a question of biology. Curr Opin HIV AIDS. 2014;9(4):346–354.
26.
FitchKVLoobySERopeA. Effects of aging and smoking on carotid intima-media thickness in HIV-infection. AIDS. 2013;27(1):49–57.
27.
Fernández-MonteroJVBarreiroPde MendozaC. Hepatitis C virus coinfection independently increases the risk of cardiovascular disease in HIV-positive patients. J Viral Hepat. 2016;23(1):47–52.
28.
MavroudisCAMajumderBLoizidesS. Coronary artery disease and HIV; getting to the HAART of the matter. Int J Cardiol. 2013;167(4):1147–1153.
29.
KarmochkineMAnkriACalvezV. Plasma hypercoagulability is correlated to plasma HIV load. Thromb Haemost. 1998;80(1):208–209.
30.
de Gaetano DonatiKRabagliatiRIacovielloL. HIV infection, HAART, and endothelial adhesion molecules: current perspectives. Lancet Infect Dis. 2004;4(4):213–222.
31.
TorrianiFJKomarowLParkerRA. For the ACTG 5152s Study Team. Endothelial function in human immunodeficiency virus-infected antiretroviral-naive subjects before and after starting potent antiretroviral therapy: The ACTG (AIDS Clinical Trials Group) Study 5152s.J Am Coll Cardiol. 2008;52(7):569–576.
32.
WangXChaiHYaoQ. Molecular mechanisms of HIV protease inhibitor-induced endothelial dysfunction. J Acquir Immune Defic Syndr. 2007;44(5):493–499.
33.
LoJLoobySEWeiJ. Increased aldosterone among HIV-infected women with visceral fat accumulation. AIDS. 2009;23(17):2366–2370.
34.
AlbuquerqueVMZírpoliJCde Barros Miranda-FilhoD. Risk factors for subclinical atherosclerosis in HIV-infected patients under and over 40 years: a case-control study. BMC Infect Dis. 2013;13:274.
35.
WormSWSabinCWeberR. Risk of myocardial infarction in patients with HIV infection exposed to specific individual antiretroviral drugs from the 3 major drug classes: the data collection on adverse events of anti-HIV drugs (D:A:D) study. J Infect Dis. 2010;201(3):318–330.
36.
RosenblattLFarrAMJohnstonSS. Risk of cardiovascular events among patients initiating efavirenz-containing versus efavirenz-free antiretroviral regimens. Open Forum Infect Dis. 2016;3(2):ofw061.
37.
DesaiMJoyceVBendavidE. Risk of cardiovascular events associated with current exposure to HIV antiretroviral therapies in a US veteran population. Clin Infect Dis. 2015;61(3):445–452.
38.
RyomLLundgrenJDEl-SadrW. Association between cardiovascular disease and contemporarily used protease inhibitors[abstract]. Paper presented at: Conference on Retroviruses and Opportunistic Infections (CROI 2017), 13–16 February 2017, Seattle, WA.
39.
ProtogerouADFransenJZampeliE. The additive value of femoral ultrasound for subclinical atherosclerosis assessment in a single center cohort of 962 adults, including high risk patients with rheumatoid arthritis, human immunodeficiency virus infection and type 2 diabetes mellitus. PLoS One. 2015;10(7):e0132307.
40.
ShaikhSBrittendenJLahiriR. Macrophage subtypes in symptomatic carotid artery and femoral artery plaques. Eur J Vasc Endovasc Surg. 2012;44(5):491–497.
41.
YarasheskiKELacinyEOvertonET.18FDG PET-CT imaging detects arterial inflammation and early atherosclerosis in HIV-infected adults with cardiovascular disease risk factors. J Inflamm (Lond). 2012;9(1):26.
42.
HannaDBLinJPostWS. Association of macrophage inflammation biomarkers with progression of subclinical carotid artery atherosclerosis in hiv-infected women and men. J Infect Dis. 2017;215(9):1352–1361.
43.
PeyracchiaMDe LioGMontrucchioC. Evaluation of coronary features of HIV patients presenting with ACS: The CUORE, a multicenter study. Atherosclerosis. 2018;274:218–226.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
