Antonella Lattanzi

Coronary Aging in HIV-Infected Patients

BACKGROUND Human immunodeficiency virus (HIV)-infected patients often demonstrate accelerated aging processes. We investigated whether the vascular age of a cohort of stable HIV-infected patients receiving antiretroviral therapy (ART) was increased and sought out predictors of increased vascular age. METHODS In this cross-sectional study, 400 HIV-infected patients (mean age, 48 years) attending a cardiometabolic clinic underwent cardiac computed tomography imaging to identify coronary artery calcium (CAC). Vascular age was estimated on the basis of the extent of CAC by means of previously published equations. RESULTS Increased vascular age was observed in 162 patients (40.5%), with an average increase of 15 years (range, 1-43 years) over the chronological age. In univariable analyses, chronological age, male sex, systolic blood pressure, duration of ART, fasting glucose level, fasting serum triglyceride level, total cholesterol level, low-density and high-density lipoprotein cholesterol levels, hypertension, and the presence of the metabolic syndrome were associated with increased vascular age. In multivariable linear regression analyses, current CD4+ cell count was the only predictor of increased vascular age (beta = 0.51; P = .005). CONCLUSIONS Increased vascular age is frequent among HIV-infected patients and appears to be associated with CD4+ cell count. If these findings were to be confirmed in prospective trials, a positive response to ART with an increase in CD4+ cell count may become a marker of increased risk of atherosclerosis development.

Lipodystrophy and anti-retroviral therapy as predictors of sub-clinical atherosclerosis in human immunodeficiency virus infected subjects

BACKGROUND AND OBJECTIVE Although anti-retroviral therapy (ART) prolonged survival in HIV-infected persons, an increase in cardiovascular disease has also been observed. A frequent complication of ART is the development of lipodystrophy (LD) with its multiple phenotypes that may be associated with cardiovascular disease. We assessed the contribution of chronic HIV infection, ART use and LD to the presence of sub-clinical atherosclerosis as evaluated by coronary artery calcium (CAC) imaging. METHODS Observational cross-sectional study of 372 HIV-infected patients receiving ART who attended a cardiometabolic clinic (48.2+/-8-year old; 74% men). All patients underwent CAC surveillance with computed tomography and the Agatston score was used to quantitate CAC. Presence of CAC was defined as a score >10. Multivariable logistic regression was used to evaluate associations between HIV clinical factors, ART and LD with the presence of CAC. FINDINGS CAC was found in 134 patients (36%) with a median CAC score of 50 (range 10; 1243). Lipoatrophy alone (OR 3.82, 95% CI: 1.11; 13.1), fat accumulation alone (OR 7.65, 95% CI: 1.71; 37.17) and mixed lipodystrophy phenotypes (OR 4.36, 95% CI: 1.26; 15.01) were strongly associated with presence of CAC after adjusting for age, sex, hypertension and cumulative exposure to ART. CONCLUSION CAC is common among long-term ART users. The association between CAC and LD underscores the potential atherosclerosis risk inherent with ART and the need to undertake routine cardiovascular surveillance in patients treated with these drugs.

Randomized Trial to Evaluate Cardiometabolic and Endothelial Function in Patients with Plasma HIV-1 RNA Suppression Switching to Darunavir/Ritonavir with or without Nucleoside Analogues

Abstract Background: We performed a study to evaluate change in cardiometabolic and endothelial function in HIV-infected patients switching to darunavir/ritonavir (DRV/r) monotherapy versus triple therapy. Methods: The MONARCH trial recruited 30 patients who were taking triple combination therapy and with HIV RNA<40 copies/ mL. Patients were randomized to either DRV/r 800/100 mg once daily (OD) monotherapy or DRV/r 800/100 mg OD plus 2 nucleoside reverse transcriptase inhibitors (NRTIs). The primary objective was to assess endothelial function change from baseline to 24 and 48 weeks in brachial artery flow-mediated dilation (FMD) test; changes in endothelial precursor cells (EPCs) and circulating endothelial cells (CECs) were secondary objectives. Results: At baseline, the median age of participants was 43 years, 77% were men, and median CD4 cell count was 585 cells/μL. The median FMD (%) decreased in both arms in the study period (P > .05), with no statistically significant difference between arms (10.7% at baseline and 6.7% at week 48 in the DRV/r + 2 NRTIs arm; 11.1% at baseline and 8.8% at week 48 in the DRV/r arm). The changes at week 48 were similar in the 2 arms for EPCs and CECs. Total cholesterol and low-density lipoprotein (LDL) cholesterol showed larger rises to week 48 in the DRV/r arm monotherapy group than in the triple-therapy group (+26 vs +9 mg/dL for total cholesterol and +14 vs +5 mg/dL for LDL cholesterol). Conclusions: In the MONARCH trial, switching from triple combination treatment to DRV/r, with or without nucleoside analogues, did not translate into clinically meaningful reductions in endothelial function as measured by FMD.

Switching to darunavir/ritonavir monotherapy vs. triple-therapy on body fat redistribution and bone mass in HIV-infected adults: the Monarch randomized controlled trial

Changes in body fat distribution and bone mass in HIV-infected patients may be associated with long-term use of nucleoside reverse transcriptase inhibitors (NRTIs). The Monarch trial recruited 30 patients receiving non-nucleoside reverse transcriptase inhibitor or protease inhibitor−based highly active antiretroviral therapy, with HIV RNA <40 copies/mL. Patients were randomized to either darunavir/ritonavir 800/100 mg once daily monotherapy or darunavir/ritonavir 800/100 mg once daily + two NRTIs. Bone mass, peripheral lipoatrophy and central fat accumulation were assessed using dual-energy X-ray absorptiometry scanning, supplemented by computed tomography scans. Median age was 43 years, 77% were men. Visceral adipose tissue remained stable from baseline to Week 48 in the whole group (p = 0.261) with no significant difference between arms (p = 0.56). There was a significant reduction in insulin resistance (HOMA-IR, p = 0.013) over 48 weeks in the whole group, but not of body mass index (p = 0.24). In the darunavir/ritonavir monotherapy arm, there was a small but significant increase in both lumbar and femur bone mineral density at 48 weeks and was observed after correction for baseline values. The absolute change in lumbar bone mineral density at 48 weeks was more pronounced in the darunavir/ritonavir arm compared with the darunavir/ritonavir + 2NRTIs arm. In this study, discontinuing nucleoside analogues and switching to darunavir/ritonavir monotherapy was associated with a small but statistically significant increase in bone mineral density, but stable levels of limb fat and visceral adipose tissue.

Effects of antihypertensive treatment on endothelial function in postmenopausal hypertensive women. A significant role for aldosterone inhibition

Introduction: Endothelial dysfunction is a well-demonstrated independent predictor of cardiovascular events in hypertensive postmenopausal women. Accordingly, it is plausible that improving endothelial function could represent an adjunctive target for antihypertensive treatment. The aim of our study was to evaluate the effect of pharmacologic treatment on endothelial function in the specific population of hypertensive postmenopausal women. Methods: A total of 320 consecutive hypertensive postmenopausal women underwent a high-resolution ultrasound study of the brachial artery at baseline and after six months, while ‘optimal’ control of blood pressure (maintenance of blood pressure values below 140/90 mmHg at all follow-up visits) was achieved using antihypertensive therapy. Endothelial function was measured as flow-mediated dilation, using ultrasound method. Results: After six months of treatment, flow-mediated dilatation (FMD) had significantly improved in the majority of patients (n = 257 [80.3% of the entire population]; FMD = 8.1 ± 1.0% at baseline vs. 10.6 ± 1.5% after follow-up; p < 0.001), but it had not changed or worsened in others (n = 63 [19.7%]; FMD = 8.2 ± 1.2% at baseline vs. 7.6 ± 1.0% after six months; p = ns). Improvement of endothelial function, at multivariate analysis, resulted independently associated with the use of aldosterone inhibitors (odds ratio = 2.15; 95% confidence interval: 1.55–2.75; p = 0.001). Conclusions: This study demonstrates that a significant improvement in endothelial function may be obtained after six months of an optimal antihypertensive therapy. Among all hypertensive postmenopausal women that achieved an optimal control of blood pressure during follow-up, the use of drugs that inhibit aldosterone receptors was associated with an improvement of endothelial function, beyond the ‘optimal’ blood pressure control.

Metabolic disorders induced by highly active antiretroviral therapy and their relationship with vascular remodeling of the brachial artery in a population of HIV-infected patients

Antiretroviral therapy has positively modified the natural history of HIV infection; but this treatment can induce metabolic abnormalities, including dyslipidemia, fat redistribution, high blood pressure, and insulin resistance. The metabolic syndrome, a clustering of the metabolic disorders, is frequently detected among HIV patients, especially those on antiretroviral treatment. All the arteries can modify their diameter in response to a chronic injury. This process, defined vascular remodeling, was demonstrated for the brachial artery. It is well known that the diameter of the brachial artery was correlated with the number of the elements of the metabolic syndrome and was associated with the severity of coronary artery disease. On this basis, we postulate that brachial arterial enlargement may be a process potentially correlated with the metabolic disorders induced by antiretroviral therapy. We tested this hypothesis in a large population of HIV-infected patients in which we measured brachial artery diameter, as an indicator of artery remodeling, by noninvasive, ultrasonographic technique. Our population consisted of 570 patients, with a mean age of 46.3 +/- 7.1 years. All the patients were chronically treated with highly active antiretroviral therapy. Brachial artery diameter was correlated with insulin resistance, evaluated by the homeostasis model assessment of insulin resistance index (r = 0.18, P < .0001). There was a significant linear increase in brachial artery diameter as the number of components of the metabolic syndrome increased: brachial artery diameter for those with 0, 1, 2, 3, or + characteristics was 39.3 +/- 7.2, 41.0 +/- 6.8, 42.0 +/- 7.3, and 43.8 +/- 7.9 mm, respectively (P < .001 for trend). In multivariable logistic regression analysis, brachial artery diameter was independently correlated with the presence of metabolic syndrome. Our results are in line with the hypothesis that, among HIV-infected patients chronically treated with antiretroviral therapy, those with a larger brachial artery diameter are at high risk for metabolic disorders, including a more severe insulin resistance and the presence of metabolic syndrome.

Long Term Prognostic Value of Subclinical Carotid and Femoral Arterial Wall Lesions in Patients With ST-Elevation-Myocardial Infarction Having Percutaneous Coronary Intervention

The presence of clinical peripheral arterial disease (PAD) is associated with an increased risk for adverse cardiovascular outcomes in patients with coronary artery disease. However, there are few data regarding the impact of the presence and degree of the subclinical PAD on outcomes in patients with coronary artery disease. The aim of this study was to assess prospectively the grade of subclinical PAD in the setting of patients who underwent primary percutaneous coronary intervention for the prediction of intermediate- and long-term clinical outcomes. A total of 971 consecutive patients without histories of clinical PAD who under went primary percutaneous coronary intervention for ST-segment elevation myocardial infarction were included in a prospective follow-up. Subclinical PAD severity was blindly assessed on the basis of an ultrasound arterial morphologic classification defined with the assessment of wall carotid and femoral artery bifurcations. This classification included 4 increasing classes of subclinical carotid and femoral arterial wall lesions, and the total group was divided accordingly. Death and major cardiovascular and cerebrovascular events were evaluated. During a median follow-up period of 40 months, a total of 109 patients (11.2%) died, 9 (2.8%) in class I, 12 (3.1%) in class II, 37 (23.7%) in class III, and 51 (49.0%) in class IV (p <0.001). On multivariate analysis, mortality in class IV was sevenfold higher (hazard ratio [HR] 7.34, 95% confidence interval [CI] 3.3 to 16.33, p <0.001) compared to class I and was also increased in class III (HR 5.38, 95% CI 2.42 to 11.92, p <0.001). Similar results were obtained for major adverse cardiovascular and cerebrovascular events in class IV (HR 7.50, 95% confidence interval 5.36 to 10.50, p <0.0001), class III (HR 6.44, 95% CI 4.45 to 9.32, p <0.001), and class II (HR 1.73, 95% CI 1.23 to 2.43, p = 0.002). In conclusion, ultrasound arterial morphologic classification may be applied in patients with ST-segment elevation myocardial infarctions who undergo primary percutaneous coronary intervention and can stratify patients for poor clinical outcomes during long-term follow-up.

Effects of pregnancy on endothelial function and cardiovascular disease risk in HIV-infected women

OBJECTIVE This study assessed flow-mediated vasodilation (FMD) and brachial artery diameter (BAD) in HIV-infected pregnant women compared to healthy pregnant controls, and determined their relationships to variables of interest, including the HIV status. METHODS Subjects were enrolled prospectively for this longitudinal, observational study. Body mass index (BMI), blood pressure (BP), fasting lipoprotein profiles, homeostasis model assessment of insulin resistance (HOMA-IR), FMD, and BAD were assessed at 10-12, 20-22, and 32-35weeks gestation in HIV-infected women and healthy controls aged 18-45years with singleton pregnancies. RESULTS Fourteen HIV-infected women and 19 controls were enrolled. Groups were similar at baseline except there were more Caucasians in the control group (P<0.01). FMD and BAD did not change during pregnancy in either group, and there were no differences between groups. In multivariable regression analysis, FMD was associated with BAD (P=0.002), but not with age, BMI, BP, TC, TG, HOMA-IR, or HIV status. No variables were associated with BAD. CONCLUSION No differences were observed in FMD or BAD between HIV-infected and healthy pregnant women, and neither measure changed significantly during pregnancy. HIV status did not affect endothelial function or brachial artery diameter. Pregnancy does not appear to further increase the CVD risk associated with HIV infection.

Impairment of functional integrity of the vasculature is not changed in patients starting abacavir

Abstracts of the Ninth International Congress on Drug Therapy in HIV Infection Meeting abstracts – A single PDF containing all abstracts in this Supplement is available here . http://www.biomedcentral.com/content/pdf/1758-2652-11-S1-info.pdf