Lipoprotein(a) and HIV: Allele-Specific Apolipoprotein(a) Levels Predict Carotid Intima-Media Thickness in HIV-Infected Young Women in the Women's Interagency HIV Study

Byambaa Enkhmaa; Erdembileg Anuurad; Wei Zhang; Chin-Shang Li; Robert Kaplan; Jason Lazar; Dan Merenstein; Roksana Karim; Brad Aouizerat; Mardge Cohen; Kenneth Butler; Savita Pahwa; Igho Ofotokun; Adaora A Adimora; Elizabeth Golub; Lars Berglund

doi:10.1161/ATVBAHA.117.309137

Lipoprotein(a) and HIV: Allele-Specific Apolipoprotein(a) Levels Predict Carotid Intima-Media Thickness in HIV-Infected Young Women in the Women's Interagency HIV Study

Arterioscler Thromb Vasc Biol. 2017 May;37(5):997-1004. doi: 10.1161/ATVBAHA.117.309137. Epub 2017 Mar 23.

Authors

Affiliations

¹ From the Departments of Internal Medicine (B.E., E.A., W.Z., L.B.) and Public Health Sciences (C.-S.L.), University of California, Davis; Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY (R. Kaplan); Department of Cardiovascular Disease, SUNY Downstate Medical Center, Brooklyn, NY (J.L.); Department of Family Medicine, Georgetown University Medical Center, Washington, DC (D.M.); Department Preventive Medicine, University of Southern California, Los Angeles (R. Karim); Department of Oral and Maxillofacial Surgery, New York University (B.A.); Stroger Hospital, Cook County Bureau of Health Services, Chicago, IL (M.C.); Division of Geriatric Medicine/Gerontology, University of Mississippi Medical Center, Jackson (K.B.); Miami Center for AIDS Research, University of Miami, FL (S.P.); Department of Medicine, Infectious Diseases, Emory School of Medicine, Atlanta, GA (I.O.); Division of Infectious Diseases, University of North Carolina, Chapel Hill (A.A.A.); and Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (E.G.).
² From the Departments of Internal Medicine (B.E., E.A., W.Z., L.B.) and Public Health Sciences (C.-S.L.), University of California, Davis; Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY (R. Kaplan); Department of Cardiovascular Disease, SUNY Downstate Medical Center, Brooklyn, NY (J.L.); Department of Family Medicine, Georgetown University Medical Center, Washington, DC (D.M.); Department Preventive Medicine, University of Southern California, Los Angeles (R. Karim); Department of Oral and Maxillofacial Surgery, New York University (B.A.); Stroger Hospital, Cook County Bureau of Health Services, Chicago, IL (M.C.); Division of Geriatric Medicine/Gerontology, University of Mississippi Medical Center, Jackson (K.B.); Miami Center for AIDS Research, University of Miami, FL (S.P.); Department of Medicine, Infectious Diseases, Emory School of Medicine, Atlanta, GA (I.O.); Division of Infectious Diseases, University of North Carolina, Chapel Hill (A.A.A.); and Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD (E.G.). lberglund@ucdavis.edu.

Abstract

Objective: In the general population, lipoprotein(a) [Lp(a)] has been established as an independent causal risk factor for cardiovascular disease. Lp(a) levels are to a major extent regulated by a size polymorphism in the apolipoprotein(a) [apo(a)] gene. The roles of Lp(a)/apo(a) in human immunodeficiency virus (HIV)-related elevated cardiovascular disease risk remain unclear.

Approach and results: The associations between total plasma Lp(a) level, allele-specific apo(a) level, an Lp(a) level carried by individual apo(a) alleles, and common carotid artery intima-media thickness were assessed in 150 HIV-infected and 100 HIV-uninfected women in the WIHS (Women's Interagency HIV Study). Linear regression analyses with and without adjustments were used. The cohort was young (mean age, ≈31 years), with the majority being Blacks (≈70%). The prevalence of a small size apo(a) (≤22 Kringle repeats) or a high Lp(a) level (≥30 mg/dL) was similar by HIV status. Total plasma Lp(a) level (P=0.029) and allele-specific apo(a) level carried by the smaller apo(a) sizes (P=0.022) were significantly associated with carotid artery intima-media thickness in the HIV-infected women only. After accounting for confounders (age, race, smoking, body mass index, blood pressure, hepatitis C virus coinfection, menopause, plasma lipids, treatment status, CD4⁺ T cell count, and HIV/RNA viral load), the association remained significant for both Lp(a) (P=0.035) and allele-specific apo(a) level carried by the smaller apo(a) sizes (P=0.010) in the HIV-infected women. Notably, none of the other lipids/lipoproteins was associated with carotid artery intima-media thickness.

Conclusions: Lp(a) and allele-specific apo(a) levels predict carotid artery intima-media thickness in HIV-infected young women. Further research is needed to identify underlying mechanisms of an increased Lp(a) atherogenicity in HIV infection.

Keywords: antiretroviral therapy; apo(a) size, HIV treatment; apolipoprotein(a); cardiovascular risk; carotid artery intima–media thickness; lipoprotein(a).

Publication types

Multicenter Study
Research Support, N.I.H., Extramural

MeSH terms

Adult
Alleles*
Apoprotein(a) / blood*
Apoprotein(a) / genetics*
Biomarkers / blood
Carotid Artery Diseases / blood
Carotid Artery Diseases / diagnostic imaging
Carotid Artery Diseases / etiology*
Carotid Artery Diseases / genetics
Carotid Artery, Common / diagnostic imaging*
Carotid Intima-Media Thickness*
Case-Control Studies
Female
HIV Infections / blood
HIV Infections / complications*
HIV Infections / diagnosis
HIV Infections / genetics
Humans
Linear Models
Predictive Value of Tests
Prospective Studies
Risk Assessment
Risk Factors
United States
Young Adult

Substances

Biomarkers
Apoprotein(a)

Abstract

Publication types

MeSH terms

Substances

Grants and funding