Masiá Mar, Padilla Sergio, Bernal Enrique, Almenar Maria V, Molina Juan, Hernández Ildefonso, Graells Mafia L, Gutiérrez Félix
Infectious Diseases Unit, Hospital General Universitario de Elche, Universidad Miguel Hernández, Elche, Spain.
Clin Ther. 2007 Jul;29(7):1448-55. doi: 10.1016/j.clinthera.2007.07.025.
Oxidative stress (OS) results from excessive free radical production, exceeding endogenous antioxidant defense mechanisms, which can damage a wide variety of cellular components. One of the main consequences is the attack of free radicals on polyunsaturated fatty acids contained in low-density lipoprotein (LDL) lipids, causing lipid peroxidation and subsequent elevated concentrations of lipid peroxides and their metabolites, which are strongly suggestive of oxidative damage. OS is increased among HIV-infected patients, but whether it implicates a higher risk for cardiovascular disease or the influence of antiretroviral therapy (ART) on OS remains unknown.
The aim of this study was to assess the relationship of OS with established cardiovascular risk factors and with ART as measured by total peroxide concentration.
A prospective cross-sectional study was conducted in 245 consecutive HIV-infected patients during a 2-month period (September 15, 2003-November 15, 2003) at the HIV clinic of the Infectious Disease Unit, Hospital General Universitario de Elche, Universidad Miguel Hernández, Elche, Spain. Laboratory measurements included total peroxide concentrations, C-reactive protein (CRP) levels, fasting lipid levels, white blood cell type CD4(+) T-lymphocyte counts, plasma HIV RNA, and routine blood tests. To measure OS, total peroxide concentration was determined quantitatively with a colorimetric assay. The association of peroxide concentrations with HIV-related variables and cardiovascular risk factors was examined using univariate and multivariate analyses.
Two hundred forty-five patients were screened and enrolled in the study; no patients refused enrollment. Median (interquartile range [IQR]) age of the patients was 40.2 (35.4-46.2) years; 194 (79.2%) were male, and 238 (97.1%) white. Median (IQR) weight was 67.5 (60.4-76.0). Ninety-five (38.8%) patients were receiving a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen at the time of enrollment; 52 (21.2%) were on a protease inhibitor (PI)-based regimen. Peroxide concentrations were above reference values (< 400 micromol/L) in 121 (49.4%) patients. Peroxide levels correlated positively with CRP (P < 0.001) and LDL-cholesterol (LDL-C) (P = 0.003), and negatively with age (P = 0.002) and body mass index (P < 0.001). Among patients on ART, peroxide concentrations were significantly lower in those treated with NNRTI-based regimens than in those receiving PIs (median [IQR], 331.2 [196.2-495.7] vs 472.8 [302.5-586.5] micromol/L; P = 0.003). In multivariate analysis, when peroxide concentration was dichotomized according to reference values (< 400 micromol/L), age (odds ratio [OR], 0.96; 95% CI, 0.93-0.99; P = 0.007) and ART including NNRTI (OR, 0.52; 95% CI, 0.28-0.95; P = 0.03) were associated with low peroxide concentrations, while LDL-C (OR, 1.01; 95% CI, 1.00-1.02; P = 0.03) predicted the highest values.
The results from this study suggest that, among this cohort of HIV-infected patients, peroxide concentration used as a marker of OS was associated with other established cardiovascular risk factors. Antiretroviral regimens based on NNRTIs were associated with low peroxide concentrations. In contrast, high peroxide levels were found in patients receiving PI-based regimens.
氧化应激（OS）是由于自由基产生过多，超过内源性抗氧化防御机制，从而可损害多种细胞成分。主要后果之一是自由基攻击低密度脂蛋白（LDL）脂质中所含的多不饱和脂肪酸，导致脂质过氧化以及随后脂质过氧化物及其代谢产物浓度升高，这强烈提示存在氧化损伤。HIV感染患者的氧化应激增加，但它是否意味着心血管疾病风险更高或抗逆转录病毒疗法（ART）对氧化应激的影响仍不清楚。
本研究旨在评估氧化应激与既定心血管危险因素以及与通过总过氧化物浓度衡量的抗逆转录病毒疗法之间的关系。
在西班牙埃尔切米格尔·埃尔南德斯大学埃尔切综合大学医院传染病科的HIV诊所，于2003年9月15日至2003年11月15日的2个月期间，对245例连续的HIV感染患者进行了一项前瞻性横断面研究。实验室测量包括总过氧化物浓度、C反应蛋白（CRP）水平、空腹血脂水平、白细胞类型CD4(+)T淋巴细胞计数、血浆HIV RNA和常规血液检查。为了测量氧化应激，采用比色法对总过氧化物浓度进行定量测定。使用单变量和多变量分析研究过氧化物浓度与HIV相关变量和心血管危险因素之间的关联。
筛选并纳入了245例患者；无患者拒绝入组。患者的中位（四分位间距[IQR]）年龄为40.2（35.4 - 46.2）岁；194例（79.2%）为男性，238例（97.1%）为白人。中位（IQR）体重为67.5（60.4 - 76.0）。95例（38.8%）患者在入组时接受基于非核苷类逆转录酶抑制剂（NNRTI）的方案；52例（21.2%）接受基于蛋白酶抑制剂（PI）的方案。121例（49.4%）患者的过氧化物浓度高于参考值（<400微摩尔/升）。过氧化物水平与CRP（P < 0.001）和低密度脂蛋白胆固醇（LDL-C）（P = 0.003）呈正相关，与年龄（P = 0.002）和体重指数（P < 0.001）呈负相关。在接受抗逆转录病毒治疗的患者中，接受基于NNRTI方案治疗的患者过氧化物浓度显著低于接受PI治疗的患者（中位[IQR]，331.2 [196.2 - 495.7]对472.8 [302.5 - 586.5]微摩尔/升；P = 0.003）。在多变量分析中，当过氧化物浓度根据参考值（<400微摩尔/升）进行二分法划分时，年龄（优势比[OR]，0.96；95%可信区间，0.93 - 0.99；P = 0.007）和包括NNRTI的抗逆转录病毒疗法（OR，0.52；95%可信区间，0.28 - 0.95；P = 0.03）与低过氧化物浓度相关，而LDL-C（OR，1.01；95%可信区间，1.00 - 1.02；P = 0.03）预测了最高值。
本研究结果表明，在这组HIV感染患者中，用作氧化应激标志物的过氧化物浓度与其他既定心血管危险因素相关。基于NNRTI的抗逆转录病毒方案与低过氧化物浓度相关。相反，接受基于PI方案治疗的患者过氧化物水平较高。
