Angeles Muñoz

El fenotipo «hipertrigliceridemia-cintura abdominal aumentada» es un factor de riesgo de aterosclerosis subclinica en pacientes con infeccion por el virus de la inmunodeficiencia humana

BACKGROUND AND OBJECTIVE To study the association between hypertriglyceridemic waist phenotype and the presence of subclinical atherosclerosis in human immunodeficiency virus (HIV) infected patients. PATIENTS AND METHODS Cross sectional study. Hypertriglyceridemic waist phenotype was considered if the waist was ≥90cm and triglycerides ≥2.0mmol/l (178mg/dl) in men and ≥85cm and ≥1.5mmol/L (133mg/dl) in women, respectively. We used the intima-media thickness (IMT) to detect carotid subclinical atherosclerosis. RESULTS We analyzed 152 patients, of whom 128 (84.2%) were receiving antiretroviral therapy, 40.7% were receiving protease inhibitors and 38.1% were treated with non-nucleoside reverse transcriptase inhibitors. The prevalence of hypertriglyceridemic waist phenotype was 23.6% (95% confidence interval [CI] 16.8-30.3%). Patients with hypertriglyceridemic waist phenotype had higher cardiovascular risk according to the Framingham score (11.09 [7.6] vs 3.88 [4], P=0.001) and lipodystrophy (33.3 vs. 13.7%, P=0.032) and metabolic syndrome (69.4 vs. 1.9%, P<0.001) were more frequent. The IMT was elevated in 21 (13.8%) patients. Hypertriglyceridemic waist phenotype (odds ratio [OR] 4.66 [95%CI 1.05-20.6; P = 0.043]) and metabolic syndrome (OR 3.74 [95%CI 1.25-11.23; P = 0.018]) were independently associated with higher IMT. CONCLUSIONS The hypertriglyceridemic waist phenotype is a risk factor for subclinical atherosclerosis in HIV infected patients and it is useful to detect patients with lipodystrophy, metabolic syndrome and high cardiovascular risk.

Improvement of endothelial function after switching previously treated HIV-infected patients to an NRTI-sparing bitherapy with maraviroc.

Nucleoside reverse transcriptase inhibitor (NRTI) is associated with endothelial dysfunction and proinflammatory effects. Maraviroc (MVC) is an antagonist of CCR5 receptor. CCR5 is the receptor of RANTES (Regulated on Activation, Normal T Cell Expressed and Secreted), a mediator of chronic inflammation and endothelial function. Our aim was to evaluate the maintenance of viral suppression and improvement of endothelial function in virologically suppressed HIV‐infected patients switched to an NRTI‐sparing combined antiretroviral therapy (cART) with MVC.

The CD4:CD8 ratio is associated with IMT progression in HIV-infected patients on antiretroviral treatment

Inversion of the CD4:CD8 ratio (<1) has been identified as a hallmark of immunosenescence and an independent predictor of mortality in the general population. We aimed to assess the association between the CD4:CD8 ratio and intima‐media thickness (IMT) progression in treated HIV‐infected patients as a marker of early atherosclerosis.

High Prevalence of Subclinical Atherosclerotic Disease in Spanish HIV-Infected Patients with Low Cardiovascular Risk

Dear Editor: Patients with HIV infection have an increased mortality, largely attributable to cardiovascular disease (CVD). In addition to traditional and not traditional cardiovascular risk factors, HIV infection and antiretroviral therapy (ART) have also been implicated in the premature development of atherosclerosis and coronary heart disease. There is the need to stratify the risk of coronary events in HIV patients. Framingham risk score is an extensively studied index to predict cardiovascular risk in the general population. It includes current smoking status, gender, age, cholesterol concentrations and blood pressure, and estimates the risk of coronary events by stratifying individuals into three risk categories: low ( < 10% risk of an event in 10 years), intermediate (10– 20%), and high ( > 20%). Framingham risk score could underestimate prediction in HIV-infected patients because there are many aspects that contribute to it. A inflammatory reaction associated with HIV infection may play a role in the atherosclerotic process. In addition, ART is associated with metabolic abnormalities that increase cardiovascular risk. Endothelial dysfunction and increased intima medial thickness (IMT) are considered an early event in the development of atherosclerosis. In general population have shown to correlate with coronary atherosclerosis, and have been directly associated with an increased risk of myocardial infarction and stroke in older adults without a history of CVD. We aimed to investigate whether Framingham risk score predict subclinical atherosclerotic disease (SAD) in HIV infected patients with low cardiovascular risk. We also studied the prevalence of SAD, the association of SAD with cardiovascular risk factors and HIV-related factors, and its relationship with plasma levels of several proatherosclerotic biomarkers. The study was conducted at the HIV outpatient clinic of the University Hospital Reina Sofia of Murcia, Spain. Consecutive healthy HIV-infected adults visiting from January 2009 to June 2009 were invited to participate. The investigation was approved by the Ethics Committee for Clinical Research and the patients’ informed consent was obtained. Details were taken for age, HIV transmission category, stage of HIV infection according to Center for Disease Control and Prevention (CDC) criteria, duration of ART, current antiretroviral medication, coinfection with hepatitis B or C virus, cardiovascular risk factors and pharmacologic treatment of dyslipidemia, diabetes, or hypertension. Blood samples were collected after an 8-h overnight fast for measurement of glycemia, total cholesterol, high-density lipoprotein (HDL) cholesterol, direct low-density lipoprotein (LDL) cholesterol, triglycerides, creatinine, insulinemia, CD4 + T-cell count, and HIV plasma viral load. An additional sample was processed by centrifugation. Plasma aliquots obtained were stored at 80 C. All frozen samples were subsequently defrosted and plasma levels of several proatherosclerotic biomarkers were simultaneously measured. More precisely, we determined levels of vascular cell adhesion molecule (VCAM), secretory phospholipase A2 (SPLA2), thiobarbituric acid reactive species (TBARS), superoxide dismutases (SOD), resistin, adiponectin, high-sensitivity Creactive protein (hsCRP), and antioxidant capacity. Plasma concentrations of sVCAM-1, SPLA-2, adiponectin, and hsCRP were measured using commercially available enzyme-linked immunosorbent assay (ELISA) kits. TBARS, SOD, and antioxidant capacity were measured using colorimetric assay. The 10-year risk of developing myocardial infarction or coronary death was calculated for each patient with the Framingham equation. To determine SAD we measured endothelial function and common and bulb carotid intima media thickness (c-IMT). SAD was considered if common c-IMT >0.8 mm or bulb cIMT >1 mm or flow-mediated dilatation (FMD) <5%. Endothelial function was evaluated measuring FMD. Patients were required to fast and not use any tobaccocontaining products for 8 h before the study. Patients were placed in a supine position and a blood pressure cuff was placed on the widest part of the proximal right forearm, approximately 1 cm distal to the antecubital fossa. Using a high-resolution ( ‡ 7 MHz) linear array vascular ultrasound transducer (Philips iE33, Philips, Andover, MA), the brachial artery was located above the elbow and scanned in longitudinal sections. Baseline vessel diameter was determined with the mean of three measures. The forearm cuff was inflated to 240 mm Hg for 5 min to induce reactive hyperemia. FMD

The CD4/CD8 ratio is inversely associated with cIMT progression in HIV infected patients on antiretroviral treatment

Abstract Inversion of the CD4/CD8 ratio (<1) has been identified as a surrogate marker of immunosenescence and an independent predictor of AIDS events in HIV-infected patients and mortality in the general population. We aimed to assess the association between the CD4/CD8 ratio and carotid intima-media thickness (cIMT) progression in treated HIV-infected patients as a marker of coronary heart disease. A longitudinal study was conducted during 3 years in 96 virally suppressed HIV-infected patients receiving antiretroviral treatment (ART). We analyzed the associations between the CD4/CD8 ratio, cardiovascular risk factors, and antiretroviral treatment (ART) and progression of subclinical atherosclerosis assessed using cIMT at baseline and after 3 years. Finally, 96 patients completed the study. Seventy six (79.1%) patients were male, aged 44 ± 10 years; 39 (40.6%) were on treatment with protease inhibitors; 49 (51.04%) with nonnucleoside reverse transcriptase inhibitors, 6 (6.25%) with integrase inhibitors, ...

Use of high-volume outdoor smog chamber photo-reactors for studying physical and chemical atmospheric aerosol formation and composition

The atmospheric particulate matter has a large impact on climate, biosphere behaviour and human health. Its study is complex because of large number of species are present at low concentrations and the continuous time evolution, being not easily separable from meteorology, and transport processes. Closed systems have been proposed by isolating specific reactions, pollutants or products and controlling the oxidizing environment. High volume simulation chambers, such as EUropean PHOtoREactor (EUPHORE), are an essential tool used to simulate atmospheric photochemical reactions. This communication describes the last results about the reactivity of prominent atmospheric pollutants and the subsequent particulate matter formation. Specific experiments focused on organic aerosols have been developed at the EUPHORE photo-reactor. The use of on-line instrumentation, supported by off-line techniques, has provided well-defined reaction profiles, physical properties, and up to 300 different species are determined in particulate matter. The application fields include the degradation of anthropogenic and biogenic pollutants, and pesticides under several atmospheric conditions, studying their contribution on the formation of secondary organic aerosols (SOA). The studies performed at the EUPHORE have improved the mechanistic studies of atmospheric degradation processes and the knowledge about the chemical and physical properties of atmospheric particulate matter formed during these processes.

Particulate matter formation from photochemical degradation of organophosphorus pesticides

Several experiments were performed in the European Photo-reactor - EUPHORE - for studying aerosol formation from organophosphorus pesticides such as diazinon, chlorpyrifos, chlorpyrifos-methyl and pirimiphos-methyl. The mass concentration yields obtained (Y) were in the range 5 - 44% for the photo-oxidation reactions in the presence and the absence of NOx. These results confirm the importance of studying pesticides as significant precursors of atmospheric particulate matter due to the serious risks associated to them.The studies based on the use of EUPHORE photoreactor provide useful data about atmospheric degradation processes of organophosphorus pesticides to the atmosphere. Knowledge of the specific degradation products, including the formation of secondary particulate matter, could complete the assessment of their potential impact, since the formation of those degradation products plays a significant role in the atmospheric chemistry, global climate change, radiative force, and are related to health effects.

Hyper-inflammation and Endothelial Activation in HIV Infected Patients with Detectable and Undetectable Viral Load

Although HIV and antiretroviral therapy (ART) have been linked with an increased cardiovascular risk, the pathological pathways remain unknown. We assessed whether secretory phospholipase A2 (sPLA2), high-sensitivity C-reactive protein (hs-CRP), vascular cell adhesion molecule (VCAM), thiobarbituric acid reactive species (TBARS), Superoxide dismutases (SOD), adiponectin and resistin were elevated in HIV infected patients with detectable and undetectable viral load compared to a control group matched for age, sex and cardiovascular risk factors. We evaluated its correlation with traditional and no traditional cardiovascular risk factors and carotid intima-media thickness. Levels of sPLA2 (median [IQR]) were 8.35 (5.36, 9.6) pg/ml, hsCRP were 3.3 (IQR, 1.27, 5.28) mg/L, VCAM 945.6 (IQR, 655.9, 1404.05) ng/ml and TBARS 1.69 (IQR, 1.39, 1.97) uM/L in HIV infected group compared to levels of sPLA2 1.22 (IQR, 0.69, 2.62) pg/ml (p<0.001), hsCRP 3.05 (IQR, 2.68, 3.27) mg/L (p=0.05), VCAM 678.35 (IQR, 530.39, 831.04) ng/ml (p<0.001) and TBARS 7.47 (IQR, 5.03, 10.4) uM/L (p<0.001) in control group. Levels of VCAM (median [IQR]) were 1047.19 (IQR, 609.06, 1084.1) ng/ml (p=0.015) and sPLA2 were 7.6 (IQR, 5.25, 9.6) pg/ml (p<0.001) in HIV infected patients with undetectable viral load compared to control group. There was a good correlation between all analyzed biomarkers and cardiovascular risk factors. In conclusion, HIV infection induces chronic inflammation and endothelial activation that is not completely suppressed by the treatment.

Factores asociados con la estancia media hospitalaria prolongada en pacientes con neumonía por el virus de la gripe A H1N1

Pneumonia is the main complication after infection by the H1N1 influenza virus and it is usually the most common cause of hospital admission.1,2 Prevalence rates of pneumonia in hospitalized patients range from 39% to 66%.1,3,4 These differences can be attributed to the varied nature of the admission criteria used and the sensitivity of the case detection system. The unfavorable evolution of hospitalized patients has been linked to delay in starting antiviral treatment, use of corticosteroids, age of the patients, and presence of neuromuscular diseases.1 We describe a prospective, observational, descriptive study conducted from 25 April to 31 December 2009 in the Hospital General Universitario Reina Sofia, Murcia, Spain. This hospital has 250 adult beds for a population of 200 000 inhabitants. The aim of the study was to estimate the frequency of pneumonia in patients hospitalized with infection by the H1N1 influenza virus and to determine the factors linked to prolonged hospital stay. The pneumonia severity index (PSI) was used to assess the severity of the patients.5 The diagnosis of H1N1 influenza was confirmed by nasopharyngeal exudate culture and real time PCR using Roche’s RealTime ready Influenza A/H1N1 Detection test. The international guidelines6 and, since September 2009, the Spanish Ministry of Health’s recommendations7 were followed for hospitalizing patients. Infection with H1N1 influenza virus was diagnosed in 537 patients and 97 patients were hospitalized. There was a 37.1% prevalence of pneumonia (95% confidence interval [CI], 27.4%-46.6%) among the hospitalized patients. The main characteristics of the 36 patients with pneumonia are shown in the Table. The mean hospital stay was 6.43 days (SD, 4.83). Taking mean hospital stay to be a dependent variable, a multivariate linear analysis was performed which included age, sex, presence of risk factors for complicated H1N1 influenza7 and/or underlying diseases, smoking habit, multilobular and bilateral pneumonia, coinfection, oxygen saturation on admission to hospital, leukopenia, LDH levels, use of corticosteroids, time interval until Oseltamivir treatment was started, admission to the ICU, and PSI. The best predictors (r2=0.765; P.001) of prolonged hospital stay were PSI (standardized beta coefficient [SBC], +0.317), coinfection (SBC, +0.276), and oxygen saturation on admission to hospital (SBC, ?0.676). The findings of our study showed an elevated prevalence of pneumonia in patients hospitalized due to H1N1 influenza.1,3,4 Severity of the patient’s condition, respiratory failure on admission and coinfection are known severity factors that can have a negative impact on the outcome of pneumonia and therefore prolong the hospital stay. Fine et al5 found a mean hospital stay of 5 days for