Clinical practice guidelines for cardiovascular disease: how is depression addressed? Protocol for a systematic review.

INTRODUCTION: Depression frequently affects patients with cardiovascular disease (CVD). When these conditions co-occur, outcomes such as quality of life and life expectancy worsen. In everyday practice, this specific and prevalent disease-disease interaction complicates patient management. Clinical practice guidelines (CPGs) aim to provide the best available advice for clinical decision-making to improve patient care. This study will aim to evaluate how CPGs specifically address depression in patients with CVD, and whether they provide any operational guidance for screening and management of depression in the primary care and outpatient setting. METHODS AND ANALYSIS: We will conduct a systematic review of CPGs on CVD management published from 2012 to 2023. A broad literature search for guidelines will be performed through electronic medical databases, grey literature search tools, and websites of national and professional medical organisations.Based on the inclusion criteria, two independent reviewers will evaluate eligible guidelines for screening and management recommendations on depression in patients with CVD. Additional points to be evaluated will be any mention of drug-drug or drug-disease interactions, other aspects of specific relevance to treating physicians, as well as general information on mental health. We will assess the quality of CPGs with a recommendation regarding depression in CVD patients using the Appraisal of Guidelines for Research and Evaluation II. ETHICS AND DISSEMINATION: As this systematic review is based on available published data, ethics approval and consent are not applicable. Our intent is that our results will be published in a peer-reviewed journal, presented at international scientific meetings, and distributed to healthcare providers. PROSPERO REGISTRATION NUMBER: CRD42022384152.

[Unattended automated blood pressure measurement : a valuable tool for the physician]. / Mesure automatique et non observée de la pression artérielle : un outil précieux pour le clinicien.

Three main methods of blood pressure (BP) measurement are routinely used: office-based BP measures (OBPM), 24-hour ambulatory BP measures (ABPM), and home BP measures (HBPM). OBPM can lack precision, ABPM gives exhaustive information but is not comfortable, HBPM requires a device at home and the result is not immediate. The automated (unattended) office blood pressure measurement (AOBP) is a more recent method, simple to implement in the physician's office, permitting to largely avoid the white coat effect. The result is immediate and the readings are similar to those obtained by ABPM, the reference diagnostic method for hypertension. We describe the AOBP for practical application.

Trois méthodes de mesure de la pression artérielle (PA) sont principalement utilisées : la mesure simple de la PA en clinique (MPAC), la mesure ambulatoire de la PA sur 24 h (MAPA) et l'automesure de la PA (AMPA). La MPAC peut manquer de précision, la MAPA donne des informations exhaustives mais n'est pas très confortable, l'AMPA nécessite un appareil à domicile et l'interprétation du résultat n'est pas immédiate. Une méthode plus récente est la mesure automatique et non observée de la PA (MNPA). Il s'agit d'un procédé simple, qui peut être facilement implémenté au cabinet et qui permet d'éviter en grande partie l'effet blouse blanche. Le résultat est immédiat et les valeurs sont similaires aux mesures par MAPA, la méthode de référence de diagnostic de l'hypertension artérielle. Nous décrivons ici la MNPA pour la pratique.

[A practitioner's perspective of the latest lipid guidelines]. / Dernières recommandations européennes sur les dyslipidémies.

The latest ESC recommendations propose several interesting new concepts for the practitioner. The recommendations distinguish between the «apparently healthy¼ patient and the patient at specific cardiovascular risk (diabetes, renal failure, and familial hypercholesterolemia). New risk calculation tools are proposed (SCORE2 and SCORE2-OP). The proposed LDL-C targets are specific to each group, as a general rule, < 1.8 mmol/l for individuals at high risk and < 1.4 mmol/l for individuals at very high risk. Presence of risk modifiers, comorbidities and patient preferences modulates therapeutic approach which is usually based on optimizing lifestyle and statin medication when necessary.

Les dernières recommandations de l'European Society of Cardiology (ESC) introduisent plusieurs nouveaux concepts intéressants pour le praticien. Le patient «en bonne santé apparente¼ est différencié de celui à risque spécifique (diabète, insuffisance rénale et hypercholestérolémie familiale). De nouveaux outils de calcul du risque cardiovasculaire sont proposés (SCORE2 et SCORE2-OP). Les cibles de LDL-C proposées sont spécifiques à chaque groupe avec, en règle générale, une valeur < 1,8 mmol/l pour les patients à haut risque et < 1,4 mmol/l pour ceux à très haut risque. La présence de modificateurs de risque, les comorbidités et les préférences du patient modulent l'approche thérapeutique, qui repose habituellement sur le respect des règles hygiénodiététiques et, au besoin, l'administration d'une statine.

Changes of lipoprotein(a) levels with endogenous steroid hormones.

BACKGROUND: Lipoprotein(a) [Lp(a)] is an LDL-like molecule that is likely causal for cardiovascular events and Lp(a) variability has been shown to be mostly of genetic origin. Exogenous hormones (hormone replacement therapy) seem to influence Lp(a) levels, but the impact of endogenous hormone levels on Lp(a) is still unknown. The aim of the study was to assess the effect of endogenous steroid hormone metabolites on Lp(a). METHODS: Lipoprotein(a) levels were measured in 1,021 participants from the Swiss Kidney Project on Genes in Hypertension, a family-based, multicentre, population-based prospective cohort study. Endogenous levels of 28 steroid hormone precursors were measured in 24-h urine collections from 883 individuals. Of the participants with Lp(a) data, 1,011 participants had also genotypes available. RESULTS: The participants had an average age of 51 years and 53% were female. Median Lp(a) levels were 62 mg/L, and the 90th percentile was 616 mg/L. The prevalence of a Lp(a) elevation ≥700 mg/L was 3.2%. Forty-three per cent of Lp(a) variability was explained respectively by: age (2%, p < .001), LDL-C (1%, p = .001), and two SNPs (39%, p value<2⋅10-16 ). Of the 28 endogenous steroid hormones assessed, androstenetriol, androsterone, 16α-OH-DHEA and estriol were nominatively associated with serum Lp(a) levels in univariable analyses and explained 0.4%-1% of Lp(a) variability, but none of them reached significance in multivariable models. CONCLUSIONS: In this contemporary population-based study, the prevalence of a Lp(a) elevation ≥700 mg/L was 3.2%. The effect of endogenous steroid hormone levels of Lp(a) variability was small at best, suggesting a negligible impact on the wide range of Lp(a) variability.

[Long-lasting LDL-C lowering: silence at last]. / Une baisse du cholestérol LDL de longue durée : enfin le silence.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is responsible for the degradation of the LDL-receptor. Inclisiran is a new synthetic interfering ribonucleic acid (siRNA) lowers LDL-cholesterol (LDL-C) levels in the blood by using RNA silencing technology to reduce the production of PCSK9. Inclisiran administered subcutaneously at 0 and 3 months, and then every 6 months has been shown to reduce LDL-C by approximately 50 % in patients at high and very-high cardiovascular risk, or with a diagnosis of familial hypercholesterolemia, but also in patients intolerant to statins. New data are expected, in particular with cardiovascular clinical endpoints, as well as safety for use in adolescents.

La proprotéine convertase subtilisine/kexine de type 9 (PCSK9) est responsable de la dégradation du LDL (Low Density Lipoprotein)-récepteur. L'inclisiran est un nouveau petit ARN interférent synthétique qui baisse les taux de LDL-cholestérol (LDL-C) circulant en utilisant la technologie de silençage ARN pour réduire la production de PCSK9. Administré par voie sous-cutanée à 0 et 3 mois, puis tous les 6 mois, l'inclisiran a démontré une réduction du LDL-C d'environ 50 % chez des patients à haut et très haut risque cardiovasculaire ou avec un diagnostic d'hypercholestérolémie familiale, mais aussi chez des patients intolérants aux statines. De nouvelles données sont attendues, notamment sur les critères de jugement cliniques cardiovasculaires, ainsi que la sécurité d'emploi chez les adolescents.

Apoptotic cells provide an unexpected source of Wnt3 signaling to drive hydra head regeneration.

Decapitated Hydra regenerate their heads via morphallaxis, i.e., without significant contributions made by cell proliferation or interstitial stem cells. Indeed, Hydra depleted of interstitial stem cells regenerate robustly, and Wnt3 from epithelial cells triggers head regeneration. However, we find a different mechanism controlling regeneration after midgastric bisection in animals equipped with both epithelial and interstitial cell lineages. In this context, we see rapid induction of apoptosis and Wnt3 secretion among interstitial cells at the head- (but not foot-) regenerating site. Apoptosis is both necessary and sufficient to induce Wnt3 production and head regeneration, even at ectopic sites. Further, we identify a zone of proliferation beneath the apoptotic zone, reminiscent of proliferative blastemas in regenerating limbs and of compensatory proliferation induced by dying cells in Drosophila imaginal discs. We propose that different types of injuries induce distinct cellular modes of Hydra head regeneration, which nonetheless converge on a central effector, Wnt3.

Silencing of the hydra serine protease inhibitor Kazal1 gene mimics the human SPINK1 pancreatic phenotype.

In hydra, the endodermal epithelial cells carry out the digestive function together with the gland cells that produce zymogens and express the evolutionarily conserved gene Kazal1. To assess the hydra Kazal1 function, we silenced gene expression through double-stranded RNA feeding. A progressive Kazal1 silencing affected homeostatic conditions as evidenced by the low budding rate and the induced animal death. Concomitantly, a dramatic disorganization followed by a massive death of gland cells was observed, whereas the cytoplasm of digestive cells became highly vacuolated. The presence of mitochondria and late endosomes within those vacuoles assigned them as autophagosomes. The enhanced Kazal1 expression in regenerating tips was strongly diminished in Kazal1(-) hydra, and the amputation stress led to an immediate disorganization of the gland cells, vacuolization of the digestive cells and death after prolonged silencing. This first cellular phenotype resulting from a gene knock-down in cnidarians suggests that the Kazal1 serine-protease-inhibitor activity is required to prevent excessive autophagy in intact hydra and to exert a cytoprotective function to survive the amputation stress. Interestingly, these functions parallel the pancreatic autophagy phenotype observed upon mutation within the Kazal domain of the SPINK1 and SPINK3 genes in human and mice, respectively.