Clinical, behavioral and biomarker predictors of PCSK9 levels in HIV-infected patients naïve of statin therapy: A cross-sectional analysis from the Swiss HIV cohort.

BACKGROUND AND AIMS: Better characterization of Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) profile is currently needed to tailor appropriate lipid-lowering strategies in HIV patients. METHODS: HIV-infected individuals aged ≥ 40 years and naive of statin therapy included in the Swiss HIV cohort study were screened for PCSK9 levels with a routine blood sample collection in 2014 at the Geneva University Hospitals. An exploratory linear regression model was built including clinical (age, sex, ethnicity, cardiovascular risk factors, body mass index, low CD4 defined as ≤200 cells/µl, leucocytes, lymphocytes, platelet, antiretroviral therapy), behavioral (tobacco and marijuana smoking, alcohol use and physical activity) and biomarker (CRP, TNF-α, IL-8, Il-10 and MCP-1) to investigate association with continuous PCSK9 levels. RESULTS: We studied 239 HIV-infected individuals who met inclusion criteria and available PCSK9 levels with a mean age of 49 years. 35 subjects (14.6%) reported marijuana consumption, of whom 20 (57.1%) reported daily consumption and 15 (6.3%) occasional use. PCSK9 levels were correlated with low-density lipoprotein-cholesterol (LDL-C). Our exploratory model identified marijuana consumption (p=0.023) and low CD4 values (p=0.020) as significantly associated factors with higher PCSK9 levels. No association was found with Framingham risk score. Patients with marijuana consumption had significantly higher levels of PCSK9 with a dose-response effect (p < 0.001); the association persisted after adjustment for the calculated Framingham risk score (p=0.003) and additional adjustment for clinical variables (p=0.027). CONCLUSIONS: In HIV-infected individuals naïve of statin treatment, marijuana consumption and low CD4 values are associated with higher PCSK9 levels independently of clinically relevant confounding factors.

Is acute idiopathic pericarditis associated with recent upper respiratory tract infection or gastroenteritis? A case-control study.

OBJECTIVES: The aim of this study was to assess the association of a clinical diagnosis of acute idiopathic pericarditis (AIP), and a reported upper respiratory tract infection (URTI) or gastroenteritis (GE) in the preceding month. DESIGN: Patients who were hospitalised with a first diagnosis of AIP were retrospectively compared with a control group of patients admitted with deep vein thrombosis (DVT), matched by gender and age. SETTING: Primary and secondary care level; one hospital serving a population of about 170,000. PARTICIPANTS: A total of 51 patients with AIP were included, of whom 46 could be matched with 46 patients with control DVT. Only patients with a complete review of systems on the admission note were included in the study. MAIN OUTCOME MEASURE: Conditional logistic regression was used to assess the association of a clinical diagnosis of AIP and an infectious episode (URTI or GE) in the month preceding AIP diagnosis. RESULTS: Patients with AIP had more often experienced a recent episode of URTI or GE than patients with DVT (39.1% vs 10.9%, p=0.002). The multivariate conditional regression showed that AIP was independently associated with URTI or GE in the last month preceding diagnosis (OR=37.18, 95% CI=1.91 to 724.98, p=0.017). CONCLUSIONS: This is, to the best of our knowledge, the first study demonstrating an association between a recent episode of URTI or GE and a clinical diagnosis of AIP.

Lipodystrophy among HIV-infected patients: a cross-sectional study on impact on quality of life and mental health disorders.

BACKGROUND: Lipodystrophy (LD) is a frequent adverse event of combination antiretroviral therapy (ART) and occurs mainly in patients exposed to first-generation antiretroviral drugs. The aim of this study was to explore and measure the interaction between LD, mental health, and quality of life of human immunodeficiency virus (HIV) positive individuals seen in a metabolic clinic. METHODS: We conducted a single-site cross-sectional study including all HIV-infected patients attending the LIPO group and metabolism day clinic at the University Hospitals of Geneva, Switzerland between January 31, 2008 and November 28, 2013. Data on LD were prospectively collected using the HIV Outpatient Study (HOPS) score, the Lipodystrophy Case Definition (LDCD), ART regimens, anthropometric measures, imaging, and standardized questionnaires. Quality of life was evaluated using a visual analog scale of 0-100. Depression and anxiety were assessed using the Beck Depression Inventory and the State Trait Anxiety Inventory scales, respectively. RESULTS: One hundred ninety-four patients (54.6% male; 45.4% female; median age, 50 years) on successful ART (median CD4 cell count, 569.0 cells/mm(3); median viral load, 20 copies/mL) were evaluated. Among these, 62.7, 63.5 and 35.5% of patients reported at least one body site affected by fat hypertrophy, atrophy or both, respectively. Using the LDCD score conservative definition, including imaging and biological values, 57.8% were diagnosed with LD. Of these, 39.7% suffered from severe/very severe LD. Depression was reported by 35.6% of individuals; 51.9% had anxiety symptoms and 49.5% reported poor quality of life (defined as being inferior to 50% on a scale from 0 to 100%). LD (odds ratio (OR = 5.22, 95% confidence interval (CI) 1.07-25.37, p-value: 0.040), depression (OR = 4.67, 95% CI 1.08-20.31, p-value 0.040), and anxiety (OR = 7.83, 95% CI 1.91-32.03, p-value 0.004) all affected significantly the quality of life. CONCLUSIONS: LD, depression and anxiety were frequent features among HIV-infected individuals seen in the metabolic clinic and significantly impacted on their quality of life.

Tobacco-stained fingers: a clue for smoking-related disease or harmful alcohol use? A case-control study.

OBJECTIVE: Tobacco stain on fingers is frequent. However, there is scarce description of this clinical sign. We aimed to explore tobacco stain on fingers as a marker of tobacco-related disease independent of cumulative tobacco exposure, and to find behavioural and environmental characteristics associated with those stains. DESIGN: Case-control study. SETTING: A Swiss community hospital of 180 beds. PARTICIPANTS: 49 adults presenting tobacco-tars staining on fingers were matched to 49 control smokers by age, gender, height and pack-year (PY). OUTCOME MEASURES: Documented smoking-related carcinoma, ischaemic heart disease, peripheral arterial disease, stroke and chronic obstructive pulmonary disease (COPD), also determined by lung function, were compared between groups. Association between harmful alcohol use, mental disorders or unemployment and tar-staining was adjusted for smoking behaviour through conditional logistic regression. RESULTS: Overall cigarette-related disease was high in the case group (84%), and symptomatic peripheral arterial disease was more frequent compared to controls (OR 3.5, CI 95% 1.1 to 14.6). Smoking-related carcinoma, ischaemic heart disease, stroke and COPD were not statistically different for control smokers. Harmful alcohol use was strongly associated with stains and this association persists after adjustment for smoking unfiltered cigarettes, smoking more than one pack of cigarettes in a day and age at smoking onset (adjusted OR 4.6, CI 95% 1.2 to 17.2). Mental disorders and unemployment were not statistically significant. CONCLUSIONS: Patients with tobacco-tar-stained fingers frequently have cigarette-related disease, however statistically not more than control smokers matched for PY, except for symptomatic peripheral arterial disease. This study suggests a link between stained fingers and addictive behaviour or concomitant high alcohol consumption.

Is bone mineral mass truly decreased in teenagers with a first episode of forearm fracture? A prospective longitudinal study.

BACKGROUND: Forearm fractures are common in the pediatric population and are mostly treated by cast immobilization. The purposes of this study were first to determine whether forearm fractures in adolescents are associated with abnormal bone mineral density (BMD) or content (BMC) at the time of fracture, and second, to quantify the bone mineral loss at various sites due to cast-mediated immobilization. METHODS: This longitudinal case-control study recruited 50 adolescents (age, 12.8 ± 1.8 y) who underwent cast-mediated immobilization for a forearm fracture and 50 healthy controls (13.0 ± 1.8 y). Using 2 dual-energy x-ray absorptiometries, BMD and BMC were measured at various skeletal sites (total body, lumbar spine, total upper limb, and forearm) at fracture time and at cast removal. RESULTS: At the fracture time, BMD/BMC Z-scores at the lumbar spine and areal BMD at the peripheral wrist were not different among the injured and the healthy subjects. At cast removal, significant BMD decreases were observed in adolescents with fracture at the level of the radial and the ulnar diaphyses (-5.6% and -3.8%, respectively) and the total upper limb (-5.6%) compared with the noninjured side. Significant decreases in the BMC values were observed at the level of the radial diaphysis (-6.4%), ultradistal ulna (-10.2%), total upper limb, and total ulna (-8.2% and -4.9%, respectively). CONCLUSIONS: These data demonstrate that total body, lumbar spine, or wrist bone mineral mass and density (BMC and BMD) are not reduced at the fracture time in adolescents sustaining a first episode of upper limb fracture when compared with healthy subjects. These findings suggest that forearm fractures are not related to osteopenia in youth. In addition, cast-mediated immobilization results in a significant bone mineral loss at the upper limb, which may explain the increased risk of sustaining a second fracture. Finally, bone callus formation may interfere when assessing bone mineral mass after cast removal and may lead to an erroneous underestimation of bone mineral mass decrease. LEVEL OF EVIDENCE: Level IV.