HIV-associated lipodystrophy: from fat injury to premature aging

Combination antiretroviral therapy (cART) against HIV infection dramatically reduces AIDS-related morbidity. However, many patients under cART display HIV-associated lipodystrophy. Moreover, some develop early agerelated comorbidities. Thymidine analog reverse transcriptase inhibitors (tRNTIs) are mainly responsible for peripheral lipoatrophy, and protease inhibitors (PIs) for fat hypertrophy and metabolic complications. Longterm HIV infection probably also causes fat alterations. Severe mitochondrial toxicity and oxidative stress cause lipoatrophy, whereas the hypertrophy of upper body fat depots could result from mild oxidative stress, cortisol activation and inflammation. The metabolic complications associated with lipodystrophy are responsible for increased cardiovascular and hepatic risks and could also participate in premature aging. We propose that adipose tissue injury by HIV and cART induces fat hypertrophy or atrophy and contributes to premature aging

228 Blood pressure in HIV-infected patients

ObjectifveTo determine the prevalence of hypertension in a cohort of HIV-infected patients (HIV+).MethodsHIV+ patients were enrolled consecutively at ambulatory cardiology consultation. We evaluated:cardiovascular risk factors,office blood pressure,24 hours ambulatory blood pressure monitoring (ABPM).We identified patients with known hypertension, masked hypertension and white-coat effect.Results258 HIV+ patients (mean age 49±7 ans, 91% men) were consecutively included in this study between 2005 and 2009. Cardiovascular risk factors were as follows: 52% had dyslipidemia, 51% were active smokers, 40% with known hypertension and 9% were diabetics. Body mass index of the entire cohort was 24±4kg/mΣ and 89% were under antiretrovirals. Data on blood pressure are depicted in Table 1. 19% (29) were discovered to have hypertension.ConclusionHypertension is frequent in HIV-infected patients and more and more common with aging. The number of non-dipper HIV+ was high in this cohort. Studies on the impact of HIV infection and antiretrovirals on the autonomic nervous system should be performed.ParametersN=258Office systolic BP, mmHg131±19Office diastolic BP, mmHg81±10Mean 24h-systolic BP, mmHg125±13Mean 24-diastolic BP, mmHg77±9Daytime systolic BP, mmHg129±13Daytime diastolic BP, mmHg80±9Nighttime systolic BP, mmHg115±17Nighttime diastolic BP, mmHg68±10BP profile in known hypertensive patientsN=103Number of patients with appropriate BP control, %45%Number of patients with white-coat effect, %17%Non dipper, %43% in known hypertensive patients 39% in unknown hypertensive patient

Is Impact of Statin Therapy on All-Cause Mortality Different in HIV-Infected Individuals Compared to General Population? Results from the FHDH-ANRS CO4 Cohort

French Hospital Database on HIVInternational audienceBackgroundThe effect of statins on all-cause mortality in the general population has been estimated as 0.86 (95%CI 0.79-0.94) for primary prevention. Reported values in HIV-infected individuals have been discordant. We assessed the impact of statin-based primary prevention on all-cause mortality among HIV-infected individuals.MethodsPatients were selected among controls from a multicentre nested case-control study on the risk of myocardial infarction. Patients with prior cardiovascular or cerebrovascular disorders were not eligible. Potential confounders, including variables that were associated either with statin use and/or death occurrence and statin use were evaluated within the last 3 months prior to inclusion in the case-control study. Using an intention to continue approach, multiple imputation of missing data, Cox’s proportional hazard models or propensity based weighting, the impact of statins on the 7-year all-cause mortality was evaluated.ResultsAmong 1,776 HIV-infected individuals, 138 (8%) were statins users. During a median follow-up of 53 months, 76 deaths occurred, including 6 in statin users. Statin users had more cardiovascular risk factors and a lower CD4 T cell nadir than statin non-users. In univariable analysis, the death rate was higher in statins users (11% vs 7%, HR 1.22, 95%CI 0.53-2.82). The confounders accounted for were age, HIV transmission group, current CD4 T cell count, haemoglobin level, body mass index, smoking status, anti-HCV antibodies positivity, HBs antigen positivity, diabetes and hypertension. In the Cox multivariable model the estimated hazard ratio of statin on all-cause mortality was estimated as 0.86 (95%CI 0.34-2.19) and it was 0.83 (95%CI 0.51-1.35) using inverse probability treatment weights.ConclusionThe impact of statin for primary prevention appears similar in HIV-infected individuals and in the general population

0578: Valvular atrial fibrillation and the risk of stroke and deaths: additional prognostic value of the CHA2DS2-VASc score

PurposeThe CHA2DS2-VASc score has been validated and is widely used to stratify the risk of thromboembolism in patients with non-valvular atrial fibrillation (AF). We sought to investigate whether this score could also be useful to predict the risk of stroke and death in patients with valvular AF.MethodsBetween 1998 and 2011, 1,592 consecutive patients, hospitalised for AF, 300 with valvular AF (mitral and/or aortic valve disease) and 1,292 with non-valvular AF were enrolled in the cohort. All patients were followed-up at least 6 months and cardiovascular events recorded. The end-point was defined as the first occurrence of stroke or death. The Cox analysis was adjusted on warfarin, antiplatelet and antiarrhythmic treatments at discharge.ResultsMean age was 73±14 years in valvular AF and 68±15 in non-valvular AF (p=0.0001). At baseline, in the valvular AF group CHA2DS2-VASc score were = 0 for 14 (5%) patients, = 1 for 28 (9%), ? 2 for 258 (86%). Non-valvular AF CHA2DS2-VASc scores were = 0 for 158 (12%), = 1 for 189 (15), ?2 for 945 (73%). The difference was statistically significant (p<0.0001). During a mean follow-up of 4.6±3.5 years, the patients with valvular AF experienced 154 (51%) and the patients with non-valvular AF experienced 409 (32%) strokes or deaths. The Kaplan-Meier curves (figure) show that patients with a CHA2DS2-VASc score ?2 were at higher risk of stroke or death. The adjusted Cox model, showed that valvular AF (HR, 1.57, 95%CI 1.30-1.89, p<0.0001) and a CHA2DS2-VASc score ?2 (HR, 5.30, 95%CI 3.77-7.45, p<0.0001) were predictors of risk of stroke or death.ConclusionThese results suggest that a CHA2DS2-VASc score ?2 is associated with a higher risk of stroke and deaths, at mid-term follow-up, in patients with valvular AF (figure next page).Abstract 0578 - Figure: Kaplan-Meier survival curve

Long-term effects of evolocumab in participants with HIV and dyslipidemia: results from the open-label extension period

Objectives: People with HIV (PWH) are at an increased risk of atherosclerotic cardiovascular disease. Suboptimal responses to statin therapy in PWH may result from antiretroviral therapies (ARTs). This open-label extension study aimed to evaluate the long-term safety and efficacy of evolocumab up to 52\u200aweeks in PWH. Design: This final analysis of a multinational, placebo-controlled, double-blind, randomized phase 3 trial evaluated the effect of monthly subcutaneous evolocumab 420\u200amg on low-density lipoprotein cholesterol (LDL-C) during the open-label period (OLP) following 24\u200aweeks of double-blind period in PWH with hypercholesterolemia/mixed dyslipidemia. All participants enrolled had elevated LDL-C or nonhigh-density lipoprotein cholesterol (non-HDL-C) and were on stable maximally tolerated statin and stable ART. Methods: Efficacy was assessed by percentage change from baseline in LDL-C, triglycerides, and atherogenic lipoproteins. Treatment-emergent adverse events (TEAEs) were examined. Results: Of the 467 participants randomized in the double-blind period, 451 (96.6%) received at least one dose of evolocumab during the OLP (mean age of 56.4\u200ayears, 82.5% male, mean duration with HIV of 17.4\u200ayears). By the end of the 52-week OLP, the overall mean (SD) percentage change in LDL-C from baseline was -57.8% (22.8%). Evolocumab also reduced triglycerides, atherogenic lipid parameters (non-HDL-C, apolipoprotein B, total cholesterol, very-low-density lipoprotein cholesterol, and lipoprotein[a]), and increased HDL-C. TEAEs were similar between placebo and evolocumab during the OLP. Conclusion: Long-term administration of evolocumab lowered LDL-C and non-HDL-C, allowing more PWH to achieve recommended lipid goals with no serious adverse events. Trail registration: NCT02833844. Video abstract: http://links.lww.com/QAD/C441

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Anomalies échocardiographiques chez le sujet adulte porteur de l'infection par le virus de l'immunodéficience humaine (revue de la litterature)

PARIS7-Xavier Bichat (751182101) / SudocSudocFranceF

PERICARDITE TUBERCULEUSE (ETUDE PERSONNELLE A PROPOS DE 7 OBSERVATIONS ET REVUE DE LA LITTERATURE)

PARIS12-CRETEIL BU Médecine (940282101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Génétique moléculaire des plantes

National audienc