Laboratory diagnosis of severe hypertriglyceridaemia. Cases from the dyslipidaemia regristy of the spanish atherosclerosis society

Background and Aims Severe hypertriglyceridaemia (sHTG) increases the risk of cardiovascular disease and acute pancreatitis episodes. Patients with sHTG fit mainly into two clinical entities: Familial or Multifactorial Chylomicronemia Syndromes (FCS and MCS, respectively). FCS and MCS exhibit clinical differences but also separate genetic and biochemical characteristics that can be assessed in the laboratory. The aim of this work has been to implement a laboratory workflow to help diagnose sHTG patients with either FCS or MCS. Methods Patients with two fasting triglycerides >1000mg/dL determinations were sequenced with a capture probe panel of 24 triglycerides-related genes using massive parallel sequencing (n=200). Two-step sequential ultracentrifugation was performed (n= 159) to diagnose Type I hyperlipoproteinemia (HLP I) and post heparin lipoprotein lipase activity was measured to discard or confirm its deficiency (n=60). Results Most patients had MCS as they: (i) did not exhibit HLPI and/or (ii) their genetic profile was not compatible with FCS and (iii) were not deficient in LPL activity. FCS cases were identified as they had: (i) HLPI, and/or (ii) biallelic pathogenic variants in LPL (n=5), GPIHBP1 (n=3), or LMF1 (n=2) genes and/or (iii) LPL activity deficiency. We identified 4 FCS patients with HLPI, biallelic pathogenic variants in APOA5 but a rescued LPL activity. An additional study of Apo-AV functionality was designed to confirm the FCS diagnosis in these cases. Conclusions Laboratory studies, in patients with severe hypertriglyceridaemia, provide with information of clinical utility to distinguish between Familial and Multifactorial Chylomicronemia Syndromes.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Influence of high cardiovascular risk in asymptomatic people on the duration and cost of sick leave: results of the ICARIA study.

AIMS: We investigated the potential influence of a moderate-to-high cardiovascular (CV) risk (CVR) (defined as a Systematic COronary Risk Evaluation model, or SCORE ≥ 4%), in the absence of an established CV disease, on the duration and cost of CV and non-CV sick leave (SL) resulting from common and occupational accidents or diseases. METHODS AND RESULTS: We conducted a prospective cohort study on 690 135 workers with a 1-year follow-up and examined CV- and non-CV-related SL episodes. To obtain baseline values, CVR factors were initially assessed at the beginning of the year during routine medical examination. The CVR was calculated with the SCORE charts for all subjects. Moderate-to-high CVR was defined as SCORE ≥ 4%. A baseline SCORE ≥ 4% was associated with a higher risk for long-term CV and non-CV SL, as revealed by follow-up assessment. This translated into an increased cost, estimated at euro5 801 464.18 per year. Furthermore, pharmacological treatment for hypertension or hyperlipidaemia was significantly associated with longer SL duration. CONCLUSION: Moderate-to-high CVR in asymptomatic subjects was significantly associated with the duration and cost of CV and non-CV SL. These results constitute the first body of evidence that the SCORE charts can be used to identify people with a non-established CV disease, which might ultimately translate into more lost workdays and therefore increased cost for society

A search for pair production of new light bosons decaying into muons in proton-proton collisions at 13 TeV

A search for new light bosons decaying into muon pairs is presented using a data sample corresponding to an integrated luminosity of 35.9fb−1 of proton-proton collisions at a center-of-mass energy √s=13TeV, collected with the CMS detector at the CERN LHC. The search is model independent, only requiring the pair production of a new light boson and its subsequent decay to a pair of muons. No significant deviation from the predicted background is observed. A model independent limit is set on the product of the production cross section times branching fraction to dimuons squared times acceptance as a function of new light boson mass. This limit varies between 0.15 and 0.39 fb over a range of new light boson masses from 0.25 to 8.5 GeV. It is then interpreted in the context of the next-to-minimal supersymmetric standard model and a dark supersymmetry model that allows for nonnegligible light boson lifetimes. In both cases, there is significant improvement over previously published limits