Enkhmaa Byambaa, Anuurad Erdembileg, Zhang Wei, Li Chin-Shang, Kaplan Robert, Lazar Jason, Merenstein Dan, Karim Roksana, Aouizerat Brad, Cohen Mardge, Butler Kenneth, Pahwa Savita, Ofotokun Igho, Adimora Adaora A, Golub Elizabeth, Berglund Lars
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.).
Arterioscler Thromb Vasc Biol. 2017 May;37(5):997-1004. doi: 10.1161/ATVBAHA.117.309137. Epub 2017 Mar 23.
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.
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 (=0.029) and allele-specific apo(a) level carried by the smaller apo(a) sizes (=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) (=0.035) and allele-specific apo(a) level carried by the smaller apo(a) sizes (=0.010) in the HIV-infected women. Notably, none of the other lipids/lipoproteins was associated with carotid artery intima-media thickness.
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.
在一般人群中，脂蛋白(a)[Lp(a)]已被确认为心血管疾病的独立因果风险因素。Lp(a)水平在很大程度上受载脂蛋白(a)[apo(a)]基因大小多态性的调节。Lp(a)/apo(a)在人类免疫缺陷病毒(HIV)相关的心血管疾病风险升高中的作用仍不清楚。
在女性机构间HIV研究(WIHS)中，对150名感染HIV的女性和100名未感染HIV的女性评估了总血浆Lp(a)水平、等位基因特异性apo(a)水平、单个apo(a)等位基因携带的Lp(a)水平与颈总动脉内膜中层厚度之间的关联。使用了有调整和无调整的线性回归分析。该队列较为年轻(平均年龄约31岁)，大多数为黑人(约70%)。按HIV感染状况，小尺寸apo(a)(≤22个kringle重复序列)或高Lp(a)水平(≥30mg/dL)的患病率相似。仅在感染HIV的女性中，总血浆Lp(a)水平(=0.029)和较小apo(a)尺寸携带的等位基因特异性apo(a)水平(=0.022)与颈动脉内膜中层厚度显著相关。在考虑混杂因素(年龄、种族、吸烟、体重指数、血压、丙型肝炎病毒合并感染、绝经、血脂、治疗状态、CD4 T细胞计数和HIV/RNA病毒载量)后，感染HIV的女性中Lp(a)(=0.035)和较小apo(a)尺寸携带的等位基因特异性apo(a)水平(=0.010)的关联仍然显著。值得注意的是，其他脂质/脂蛋白均与颈动脉内膜中层厚度无关。
Lp(a)和等位基因特异性apo(a)水平可预测感染HIV的年轻女性的颈动脉内膜中层厚度。需要进一步研究以确定HIV感染中Lp(a)致动脉粥样硬化性增加的潜在机制。
