Objective.Nontraumatic osteonecrosis (ON) is a well-recognized complication causing disability and affecting quality of life in patients with systemic lupus erythematosus (SLE). The aim of this study was to identify the risk factors for ON, and to identify the minimal investigation(s) needed to optimally monitor the risk of ON in patients with SLE.Methods.A systematic review was conducted using MEDLINE and EMBASE. These databases were searched up to January 2016 using the Medical Subject Heading (MeSH) terms “Osteonecrosis,” “Systemic lupus erythematosus,” and synonymous text words. Randomized controlled trials, case control, cohort, and cross-sectional studies were included. Risk factors for ON in patients with SLE were compiled. The quality of each study was assessed using the Newcastle-Ottawa scale for nonrandomized studies. The quality of evidence of each risk factor was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation method.Results.Of the 545 references yielded, 50 met inclusion criteria. Corticosteroid (CS) use may be strongly associated with ON in patients with SLE. Other clinical variables were moderately associated, including hypertension, serositis, renal disease, vasculitis, arthritis, and central nervous system disease. However, the evidence was low to very low in quality.Conclusion.Based on the best evidence available, CS use may be strongly associated with ON in patients with SLE. Results of this review were considered in the development of recommendations for the diagnosis and monitoring of patients with SLE in Canada and will guide clinicians in their assessment of these patients.

R enin-angiotensin system (RAS) is a key component of cardiovascular and renal system homeostasis. RAS activation during development is well described 1 and contributes to organogenesis and growth, especially in the cardiovascular and renal systems. Among RAS components, angiotensin (Ang) II is the major peptide acting during fetal and neonatal life. Both subtypes of Ang receptors are expressed during fetal development 2,3 but have different patterns of expression during the fetal-neonatal transition. In rats, Ang type 2 (AT2) receptors are upregulated in the heart, large vessels, lungs, and kidneys during fetal development and progressively decline after birth, suggesting their contribution to fetal organogenesis. Ang type 1 (AT1) receptors, on the other hand, are detected late in fetal development, increase soon after birth, and are considered to contribute mainly to tissue maturation, growth, and postnatal adaptation. [2][3][4] This switching pattern of Ang receptors suggests that modifications of AT1/AT2 balance play a key role in different developmental stages. A disruption of this balance, depending on the stage of development, may negatively affect cardiovascular and renal homeostasis and contribute to the establishment of cardiovascular diseases.Deleterious perinatal conditions, including preeclampsia, intrauterine growth restriction, and preterm birth can lead to developmental programming of cardiovascular risk factors and diseases. 5,6 Preterm-born individuals in particular, whose numbers are growing in the population because of recent Abstract-Newborn rats exposed to high oxygen (O 2 ), mimicking preterm birth-related neonatal stress, develop later in life cardiac hypertrophy, dysfunction, fibrosis, and activation of the renin-angiotensin system. Cardiac renin-angiotensin system activation in O 2 -exposed adult rats is characterized by an imbalance in angiotensin (Ang) receptors type 1/2 (AT1/2), with prevailing AT1 expression. To study the role of renin-angiotensin system in the developmental programming of cardiac dysfunction, we assessed Ang receptor expression during neonatal high O 2 exposure and whether AT1 receptor blockade prevents cardiac alterations in early adulthood. Sprague-Dawley newborn rats were kept with their mother in 80% O 2 or room air (control) from days 3 to 10 (P3-P10) of life. Losartan or water was administered by gavage from P8 to P10 (n=9/group). Rats were studied at P3 (before O 2 exposure), P5, P10 (end of O 2 ), and P28. Losartan treatment had no impact on growth or kidney development. AT1 and Ang type 2 receptors were upregulated in the left ventricle by high O 2 exposure (P5 and P10), which was prevented by Losartan treatment at P10. Losartan prevented the cardiac AT1/2 imbalance at P28. Losartan decreased cardiac hypertrophy and fibrosis and improved left ventricle fraction of shortening in P28 O 2 -exposed rats, which was associated with decreased oxidation of calcium/calmodulin-dependent protein kinase II, inhibition of the transforming growth factor-β/SMAD3 pathway...

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Background: Familial hypercholesterolemia (FH) is a monogenic disease characterized by a high concentration of low-density lipoprotein cholesterol. This population is considered to be at high cardiovascular risk; however, disease evolution remains heterogeneous among individuals. The coronary artery calcium (CAC) score is currently the best predictor of incidental major cardiovascular events in primary prevention in the general population. Few studies have described the CAC score in FH populations. Methods: The objective of our study was to determine the predictors of the CAC score in FH patients. We retrospectively studied FH patients followed at the Montreal Clinical Research Institute (IRCM) Lipid Clinic CJC Open 3 (2021) 41e47

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Severe hypertriglyceridemia is defined by triglycerides levels reaching 11,3 mmol/L (1000 mg/dL) or when chylomicrons are present in the circulation (1). Severe hypertriglyceridemia increases the risk of acute pancreatitis, a serious complication that can be recurrent and fatal. Severe hypertriglyceridemia is most often caused by an underlying primary chylomicronemia disease, either monogenic of multifactorial. Familial chylomicronemia syndrome is a rare autosomal recessive disease that can result from mutations in lipoprotein lipase in more than 90% of cases. Multifactorial chylomicronemia is an oligogenic or polygenic disorder characterized by a reduction in lipoprotein lipase activity. Primary chylomicronemia should be managed in a specialized lipid clinic before acute pancreatitis occur. However, primary chylomicronemia is underdiagnosed (2). This is why hospitalization for an acute episode of hypertriglyceridemia-induced pancreatitis is a window of opportunity to investigate these patients. The first objective of our study was to investigate retrospectively the quality of the follow-up of patients hospitalized for hypertriglyceridemia-induced acute pancreatitis, specifically looking at specialized lipid clinic referrals. The second objective was to correlate triglyceride (TG) levels with severity of the pancreatitis. A total of 1063 patients were hospitalized for acute pancreatitis at our center between 2012 and 2019. Twenty-five patients (2.35%) were diagnosed with hypertriglyceridemia-induced pancreatitis. Of those 25 patients, one died of pancreatitis complications, two were already diagnosed with primary chylomicronemia, and of the remaining twenty-two, 11 (50%) had a referral for an evaluation at a specialized lipid clinic. Those referrals resulted in three diagnoses of primary chylomicronemia, with a multidisciplinary follow-up. Regarding severity of pancreatitis, TG levels were positively correlated with patients being hospitalized in the intensive care unit (ICU) and also having longer stays in the ICU. Only half of patients hospitalized for a hypertriglyceridemia-induced pancreatitis at our center had a referral for lipid disorder evaluation upon hospital discharge. We believe it is important to raise awareness concerning primary chylomicronemia to avoid recurrent acute pancreatitis preceding diagnosis, seeing this pathology increases morbidity and mortality. 1. Valdivielso et al. Eur J Intern Med. 2014;25(8):689-94. 2. Brown et al. J Clin Lipidol. 2018;12(2):254-263.

Neonatal oxidative stress is a major postnatal deleterious factor predisposing preterm born infants to classical complications of prematurity (retinopathy, bronchopulmonary dysplasia) which are characterized by impaired vascular development. Our group has previously shown that rats transiently exposed to high O2 as newborns (mimicking human preterms oxidative stress conditions) develop high blood pressure (BP), cardiac remodeling and dysfunction later in life, in part mediated by the renin angiotensin system (RAS). Cardiac RAS activation is characterized by AT1/AT2 receptors imbalance, with increased AT1R at adult age. In order to study the role of RAS at early stages of the developmental programming of cardiac dysfunction caused by high O2 exposure, we assessed whether an early and short-term treatment with AT1R blocker Losartan, prevents cardiac alterations at young male 4 wks-old rats (prior to the elevation of BP in this model). Sprague-Dawley newborns rats were kept with their mother in 80% O2 (O2 group, n=9) or room air (Ctrl, n=9) from days 3-10 of life (P3-P10). Losartan (LOS, n=10, 20 mg/Kg) or water was administered by gavage in O2 rats from P8-P10 (last 2 days of O2 to avoid impact on nephrogenesis). At 4 wks, echocardiography reveals that O2 rats have decreased fraction of shortening compared to Ctrl (FS: 37±2 vs 42±2 %), suggesting impaired systolic function in O2. Cardiac hypertrophy evaluated by heart/body weight and cardiomyocyte surface area (CSA) is also increased in O2 vs Ctrl (141±13 vs 118±4 μm2). LOS treatment prevented the impairment of systolic function in O2 by ameliorating FS (43±2 %) and reducing CSA (121±11 μm2). LOS treatment also modulated RAS genes expression (RT-PCR): LOS restored AT1/AT2 balance in O2 hearts by decreasing AT1b subunit (0.8±0.2 O2 vs 1.3±0.3 O2+LOS vs 0.9±0.2 Ctrl) as well as increasing ACE2 (1.5±0.4 O2 vs 0.8±0.1 O2+LOS vs 1.1±0.4 Ctrl) expressions. In conclusion, a short-term treatment with LOS during neonatal O2 exposure prevents the impairment of cardiac systolic function and hypertrophy at young age. This data reinforces the key role of RAS in the developmental programming of cardiac dysfunction and reveals LOS as an effective strategy to prevent early cardiac alterations caused by neonatal high O2 exposure.

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