Dataset Information

Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons.

ABSTRACT:

Background

Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection.

Methods

In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Using the Metabochip, we genotyped 1875 HIV-positive, white individuals enrolled in 24 HIV observational studies, including 571 participants with a first CAD event during the 9-year study period and 1304 controls matched on sex and cohort.

Results

A genetic risk score built from 23 CAD-associated SNPs contributed significantly to CAD (P = 2.9 × 10(-4)). In the final multivariable model, participants with an unfavorable genetic background (top genetic score quartile) had a CAD odds ratio (OR) of 1.47 (95% confidence interval [CI], 1.05-2.04). This effect was similar to hypertension (OR = 1.36; 95% CI, 1.06-1.73), hypercholesterolemia (OR = 1.51; 95% CI, 1.16-1.96), diabetes (OR = 1.66; 95% CI, 1.10-2.49), ? 1 year lopinavir exposure (OR = 1.36; 95% CI, 1.06-1.73), and current abacavir treatment (OR = 1.56; 95% CI, 1.17-2.07). The effect of the genetic risk score was additive to the effect of nongenetic CAD risk factors, and did not change after adjustment for family history of CAD.

Conclusions

In the setting of HIV infection, the effect of an unfavorable genetic background was similar to traditional CAD risk factors and certain adverse antiretroviral exposures. Genetic testing may provide prognostic information complementary to family history of CAD.

SUBMITTER: Rotger M

PROVIDER: S-EPMC3669528 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Publications

Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons.

Rotger Margalida M Glass Tracy R TR Junier Thomas T Lundgren Jens J Neaton James D JD Poloni Estella S ES van 't Wout Angélique B AB Lubomirov Rubin R Colombo Sara S Martinez Raquel R Rauch Andri A Günthard Huldrych F HF Neuhaus Jacqueline J Wentworth Deborah D van Manen Danielle D Gras Luuk A LA Schuitemaker Hanneke H Albini Laura L Torti Carlo C Jacobson Lisa P LP Li Xiuhong X Kingsley Lawrence A LA Carli Federica F Guaraldi Giovanni G Ford Emily S ES Sereti Irini I Hadigan Colleen C Martinez Esteban E Arnedo Mireia M Egaña-Gorroño Lander L Gatell Jose M JM Law Matthew M Bendall Courtney C Petoumenos Kathy K Rockstroh Jürgen J Wasmuth Jan-Christian JC Kabamba Kabeya K Delforge Marc M De Wit Stephane S Berger Florian F Mauss Stefan S de Paz Sierra Mariana M Losso Marcelo M Belloso Waldo H WH Leyes Maria M Campins Antoni A Mondi Annalisa A De Luca Andrea A Bernardino Ignacio I Barriuso-Iglesias Mónica M Torrecilla-Rodriguez Ana A Gonzalez-Garcia Juan J Arribas José R JR Fanti Iuri I Gel Silvia S Puig Jordi J Negredo Eugenia E Gutierrez Mar M Domingo Pere P Fischer Julia J Fätkenheuer Gerd G Alonso-Villaverde Carlos C Macken Alan A Woo James J McGinty Tara T Mallon Patrick P Mangili Alexandra A Skinner Sally S Wanke Christine A CA Reiss Peter P Weber Rainer R Bucher Heiner C HC Fellay Jacques J Telenti Amalio A Tarr Philip E PE

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20130326 1

<h4>Background</h4>Persons infected with human immunodeficiency virus (HIV) have increased rates of coronary artery disease (CAD). The relative contribution of genetic background, HIV-related factors, antiretroviral medications, and traditional risk factors to CAD has not been fully evaluated in the setting of HIV infection.<h4>Methods</h4>In the general population, 23 common single-nucleotide polymorphisms (SNPs) were shown to be associated with CAD through genome-wide association analysis. Usi ...[more]

PMID: 23532479

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Project description:BackgroundPeople with HIV (HIV+) may have increased cardiovascular event rates compared with HIV-negative (HIV-) persons. Cross-sectional data from the United States and Switzerland, based on coronary artery calcium scan (CAC) and coronary computed tomography angiography (CCTA), suggest, respectively, increased and similar prevalence of subclinical atherosclerosis in HIV+ vs HIV- persons.MethodsWe repeated CAC/CCTA in 340 HIV+ and 90 HIV- study participants >2 years after baseline CAC/CCTA. We assessed the association of HIV infection, Framingham risk score (FRS), and HIV-related factors with the progression of subclinical atherosclerosis.ResultsHIV+ were younger than HIV- participants (median age, 52 vs 56 years; P < .01) but had similar median 10-year FRS (8.9% vs 9.0%; P = .82); 94% had suppressed HIV viral load. In univariable and multivariable analyses, FRS was associated with the incidence rate ratio (IRR) of new subclinical atherosclerosis at the follow-up CAC/CCTA, but HIV infection was not: any plaque (adjusted IRR for HIV+ vs HIV- participants, 1.21; 95% CI, 0.62-2.35), calcified plaque (adjusted IRR for HIV+ vs HIV- participants, 1.06; 95% CI, 0.56-2), noncalcified/mixed plaque (adjusted IRR for HIV+ vs HIV- participants, 1.24; 95% CI, 0.69-2.21), and high-risk plaque (adjusted IRR for HIV+ vs HIV- participants, 1.46; 95% CI, 0.66-3.20). Progression of CAC score between baseline and follow-up CAC/CCTA was similar in HIV+ (median annualized change [interquartile range {IQR}], 0.41 [0-10.19]) and HIV- participants (median annualized change [IQR], 2.38 [0-16.29]; P = .11), as was progression of coronary segment severity score (HIV+: median annualized change [IQR], 0 [0-0.47]; HIV-: median annualized change [IQR], 0 [0-0.52]; P = .10) and coronary segment involvement score (HIV+: median annualized change [IQR], 0 [0-0.45]; HIV-: median annualized change [IQR], 0 [0-0.41]; P = .25).ConclusionsIn this longitudinal CAC/CCTA study from Switzerland, Framingham risk score was associated with progression of subclinical atherosclerosis, but HIV infection was not.

Dataset Information

Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons.

Background

Methods

Results

Conclusions

Publications

Contribution of genetic background, traditional risk factors, and HIV-related factors to coronary artery disease events in HIV-positive persons.

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