ABC | Volume 110, Nº5, May 2018

Original Article Salmazo et al Frequency of subclinical atherosclerosis in Brazilian HIV-infected patients Arq Bras Cardiol. 2018; 110(5):402-410 Carotid intima-media thickness rate (CIMT) and the presence of atherosclerotic plaque (PL) in the carotid have been associated with the Framingham coronary heart disease risk score (FCRS); individuals with this index elevated have a higher risk of developing CVD. 17-24 Another marker of CVD is high-sensitivity C-reactive protein (hs-CRP). In HIV-positive patients, hs-CRP, although low in sensitivity, is known to be a possible marker of disease progression and atherosclerosis. 25-28 Arterial stiffness by pulse wave velocity (PWV), augmentation index (AIx), and ascending aortic pressure (AP) have been studied as promising indices of early endothelial dysfunction diagnosis. 29-32 Few publications have evaluated these indices in HIV-positive patients and the number of cases has been limited. 16,29-32 The objectives of the present study were: 1- To identify the frequency of subclinical atherosclerosis in HIV-positive patients, comparing it with that of control subjects; 2- To associate the diagnosis of subclinical atherosclerosis with viral load, CD4 levels and antiretroviral treatment inHIV‑positivepatients; 3- To associate the presence of carotid atherosclerosis with cardiovascular risk factors and with the FCRS in HIV‑positive patients. Methods Written informed consent was obtained fromall participants, and the study protocol was approved by the Ethics Committee of the university. This is a prospective cross-sectional case-control study with consecutively selected patients. All HIV-infected patients from the Infectious Diseases outpatient clinic were included in the study. Exclusion criteria were evidence of atherosclerosis (interview, chart review and physical examination), age under 18 years, pregnancy, evidence of other causes of immunosuppression, and data acquisition failure due to technical difficulties. Healthy controls were prospectively included. Data source Invitation to participate in the studywas offered after exposure to the project in the waiting room during a routine visit. Those who accepted were referred to a clinic where they received more information, had their doubts clarified, and underwent an interview guided by a structured questionnaire, a physical examination, and a carotid ultrasound assessment followed by a referral to collect a blood sample for laboratory tests. HAART information, time since diagnosis and treatment, HIV-RNA viral load, and CD4 + and CD8 + cell counts were obtained from a review of medical records. Cardiovascular risk was calculated by FCRS. 12 Carotid artery ultrasound Carotid artery ultrasound was performed by the same appropriately trained expert using a Vivid I or Vivid S6 (General Electric Healthcare, USA) equipped with 7.0 MHz linear transducer and an image acquisition system. Images were obtained and analyzed according to the Consensus Statement from the American Society of Echocardiography and Mannheim Carotid Intima-Media Thickness Consensus recommendations. 21,22 Carotid intima-media images were obtained by an automated method using GE developed software, to determine average thickness of the left and right carotid arteries. A PL was defined as a focal structure that encroached into the arterial lumen at least 0.5 mm, or 50% of surrounding CIMT, or carotid thickness > 1.5 mm. 21 Arterial stiffness Arterial stiffness indices (PWV, AIx, and AP) were obtained by the same experienced operator using Sphygmocor CPV System equipment (AtCor Medical, Australia) and following current recommendations. 29 Laboratory tests A sample of 12-hour fasting peripheral blood was obtained from all patients to analyze hs-CRP, glucose, albumin, complete blood count, urea, creatinine, total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-c), and triglycerides (TGL). LDL-c was estimated using the Friedewald equation when TGL were lower than 400 mg/dL. 7 Statistical analyses All statistical analysis was performed using SAS/STAT (SAS Institute Inc., Cary, North Carolina, USA). Continuous variables with normal distribution were presented as mean and standard deviation, and continuous variables with non-normal distribution were presented as medians and interquartile ranges. Categorical variables were presented as proportions. The Shapiro-Wilk test was performed as a normality test. Multivariate logistic regression was used to estimate associations between carotid atherosclerosis and clinical variables. Multiple linear regression was utilized to analyze associations between arterial stiffness and clinical variables or the presence of carotid atherosclerosis. TheWilcoxon-Mann-Whitney test was used to compare two groups of non-parametric results. The unpaired Student t test was applied for parametric results. One-way ANOVA was employed to compare the groups in FCRS classification. All tests were two-tailed, and significance was set at p < 0.05. Results Study population The study included264HIV-infectedpatients and279healthy volunteers (control group). In the HIV-infected group, median time since HIV diagnosis was 96 months (35‑149 months) and treatment duration was 78 months (15‑142 months). Viral load ranged from undetectable to 397,155 copies/mL (median: undetectable; 75 th percentile: 253 copies/mL). 403