Search

Prevention of cardiovascular disease remains a key-objective from a health care point of view. The present article focuses on primary prevention, i.e. to prevent a first cardiovascular event among at-risk people. The first step is to evaluate the cardiovascular risk level (low to moderate, high, very high), which allows to fix target goals. It is especially the case regarding the management of dyslipidaemias. Lipid abnormalities are considered as a major coronary risk factor (especially, LDL or even better non-HDL cholesterol according to recent guidelines). Theoretically, it is quite easy to control this risk factor thanks to available lipid-lowering drugs, yet this goal remains insufficiently reached in clinical practice. The second step is to prescribe, in addition to life-style measures, the best pharmacological treatment. In most cases, it is a statin that should be well titrated, eventually combined with ezetimibe and/or bempedoic acid, to reach the set objectives. Finally, it is important to convince the at-risk individual by providing the valuable information regarding the benefits/risks ratio of the therapy and to verify a good drug compliance in the long run. Indeed, as dyslipidaemia is asymptomatic, people in primary prevention too easily tend to neglect (and eventually stop) the valuable therapy, also because statins have been widely (yet unfairly) criticized by some people in recent years.

Evolocumab is a monoclonal antibody that blocks PCSK9 («Proproteine Convertase Subtilisine/Kexine type 9»). It exerts a rapid, potent and sustained reduction of LDL cholesterol (LDL-c) levels in combination with statin therapy. It was first reimbursed for the treatment of familial hypercholesterolaemia. The FOURIER trial and its extension FOURIER-OLE among patients with atherosclerotic cardiovascular disease and residual hypercholesterolaemia despite statin therapy demonstrated that evolocumab significantly reduces the incidence of major cardiovascular adverse events (- 15 %, P <0.001). There was a monotonic relationship between the reduction in clinical events and the diminution of LDL-c levels even down to the lowest concentrations. The safety profile of evolocumab was excellent, also in patients with very low LDL-c levels. Because of these favorable results, evolocumab (Repatha®) is now reimbursed, under conditions, for the secondary prevention of atherosclerotic cardiovascular disease.

PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9) inhibition has proven its interest to potentiate the cholesterol-lowering effects of statins. Indeed, this protein contributes to the intracellular degradation of LDL cholesterol receptors and thereby reduces their recycling and expression at the hepatocyte membrane. PCSK9 inhibition allows a major and sustained reduction of LDL cholesterol (LDL-c) in patients with familial hypercholesterolaemia or with established cardiovascular disease. Two monoclonal antibodies that inhibit the effect of PCSK9 are currently commercialized, alirocumab and evolocumab. Another approach consists in the inhibition of PCSK9 synthesis. Inclisiran is a novel small interfering RNA-based therapy (anti-sense). By binding to the messenger RNA (mRNA) precursor of PCSK9, inclisiran inhibits the PCSK9 gene expression, resulting in increased hepatocyte recycling and membrane expression of LDL receptors and decreased levels of LDL-c. This article summarizes the mode of action, pharmacokinetics, efficacy, safety profile, indications and reimbursement conditions of inclisiran. This novel cholesterol-lowering drug is indicated as add-on therapy in adults with atherosclerotic cardiovascular disease or with heterozygous familial hypercholesterolaemia in whom LDL-c level is ? 100 mg/dl and does not reach target LDL-c levels despite statin and ezetimibe or without statin or ezetimibe in case of intolerance or contra-indication for one of these medications.

Patients at high or very high cardiovascular risk should have a LDL cholesterol level as low as possible, a target that may be difficult to be reached with statin monotherapy, especially when this treatment is not well tolerated. It is generally recommended to use pharmacological combinations to reach more and more strict objectives. Bempedoic acid is a new oral cholesterol-lowering medication that reduces hepatic cholesterol synthesis by inhibiting the enzyme adenosine triphosphate (ATP)-citrate lyase enzyme. Because this medication is a prodrug that is selectively activated in the liver, it is deprived of any muscular adverse effect. This article summarizes the mode of action, pharmacokinetics, efficacy, safety profile, indications and reimbursement conditions of bempedoic acid. This novel cholesterol-lowering drug is indicated in combination with statins (with or without ezetimibe) in patients who do not attain LDL goals despite administration of a statin at the maximum tolerated dose or in case of statin intolerance.

Over the past 10 years, meta-analyzes of statins, randomized clinical trials using ezetimibe and anti-PCSK9 antibodies, and Mendelian randomization studies have strengthened the central and causal role of LDL-c in the development of cardiovascular disease. The LDL-c target has been gradually lowered and to date there is no LDL-c threshold below which the benefit of the reduction disappears. The decrease in cardiovascular risk is proportional to the absolute reduction in the concentration of LDL-c regardless of the means by which this reduction is obtained. These data led to the formulation of new guidelines for the management of dyslipidemias relating in particular to a lowering of the LDL-c target and to the complementary use of ezetimibe and anti-PCSK9 antibodies after statins.

LDL cholesterol targets are increasingly strict in recent international guidelines, especially in patients at very high or high cardiovascular risk. To reach these targets, it is recommended to use a potent statin, with a titration up to the maximal tolerated dose and, if not sufficient, to combine ezetimibe, a medication that blocks the intestinal absorption of cholesterol. This association allows reduce the dose of statin, while keeping an excellent cholesterol-lowering efficacy and favouring a good tolerance profile. This article describes the characteristics of a fixed-dose combination of rosuvastatin, the most potent statin, and ezetimibe, commercialized in Belgium under the trade name Myrosor®.

It has been well established that low-density lipoproteins (LDL) and other apolipoprotein B-containing lipoproteins are causally related to atherosclerotic cardiovascular disease (ASCVD) and that lowering these lipoproteins reduces the risk of ASCVD. By lowering LDL particles as much as possible, ASCVD can be prevented. There seems to be no LDL-cholesterol (LDL-C) threshold below which no further ASCVD prevention can be achieved. Furthermore, a low (an even very low) LDL-C appears to be safe. The new ESC/EAS guidelines based on these concepts are a step towards a benefit-based strategy by focusing on the clinical benefit that can be achieved by treating the cause of ASCVD. It is recommended to lower LDL-C as much as possible to prevent ASCVD, especially in high and very high-risk patients. With these new recommendations come recognition of the importance of combination therapies in high and very high-risk patients, first with statins and ezetimibe, and if needed with a PCSK9 inhibitor. The present paper is a review of some new concepts arising during the past 10 years in the field of lipidology and the description of what is new in the 2019 EAS/ESC guidelines.

Statins are the most commonly prescribed cholesterol-lowering drugs for cardiovascular prevention. Data from randomized clinical trials have shown an increased risk of diabetes mellitus type 2 (DT2) on statin treatment. These findings have been confirmed in genetic Mendelian randomization studies and in observational cohorts. The molecular mechanisms remain partly unknown. The risk of TD2 is higher with high doses of statins and in people with preexisting risk factors for T2D (prediabetes, metabolic syndrome). The cardiovascular benefit of statins overdrive by far the risk of diabetes and the prescription of statins in high risk cardiovascular subjects should not be questioned. Glycaemic monitoring and the adaptation of lifestyle and dietary measures are recommended for subjects at risk of T2D., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Hypertriglyceridaemia is a common finding in medical practice. The reduction of triglyceride levels may contribute to reduce the cardiovascular risk (at least in patients with low HDL cholesterol) and to avoid the occurrence of acute pancreatitis (in case of severe hypertriglyceridaemia). The discovery of causes of hypertriglyceridaemia (comorbidities, medications) may lead to specific measures. Otherwise, the focus should be put on dietary advises first (reduced caloric intake to promote weight loss, less alcohol, less sucrose), which, if well conducted, may result in spectacular results. If they fail, some pharmacological approaches may be considered, but with generally a limited success rate. Among them, fenofibrate is the best studied and has been shown to be useful for cardiovascular prevention, especially if low HDL cholesterol is associated with hypertriglyceridaemia in patients with type 2 diabetes.

Background and Aims: Familial hypercholesterolaemia (FH) is an autosomal dominant lipoprotein disorder characterized by significant elevation of low-density lipoprotein cholesterol (LDL-C) and markedly increased risk of premature cardiovascular disease (CVD). Because of the very high coronary artery disease risk associated with this condition, the prevalence of FH among patients admitted for CVD outmatches many times the prevalence in the general population. Awareness of this disease is crucial for recognizing FH in the aftermath of a hospitalization of a patient with CVD, and also represents a unique opportunity to identify relatives of the index patient, who are unaware they have FH. This article aims to describe a feasible strategy to facilitate the detection and management of FH among patients hospitalized for CVD., Methods: A multidisciplinary national panel of lipidologists, cardiologists, endocrinologists and cardio-geneticists developed a three-step diagnostic algorithm, each step including three key aspects of diagnosis, treatment and family care., Results: A sequence of tasks was generated, starting with the process of suspecting FH amongst affected patients admitted for CVD, treating them to LDL-C target, finally culminating in extensive cascade-screening for FH in their family. Conceptually, the pathway is broken down into 3 phases to provide the treating physicians with a time-efficient chain of priorities., Conclusions: We emphasize the need for optimal collaboration between the various actors, starting with a "vigilant doctor" who actively develops the capability or framework to recognize potential FH patients, continuing with an "FH specialist", and finally involving the patient himself as "FH ambassador" to approach his/her family and facilitate cascade screening and subsequent treatment of relatives., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Evolocumab is a fully human monoclonal antibody (mAb) targeting ProProtein Convertase Subtilisin/Kexin 9 (PCSK9). PCSK9 is a circulating enzyme secreted by the liver and plays a key role in the LDL-Receptors (LDL-R) turnover. Binding of PCSK9 on the extracellular part of LDL-R is responsible for its degradation in the lysosome instead of its recycling to the cell surface, thereby producing a reduction in the number of LDL-R on the cell surface, a decreased LDL-C uptake and increased levels of LDL-C. Inhibiting PCSK9 is a new way to markedly reduce LDL-C. The development of mAbs that bind the extracellular PCSK9 and prevent its interaction with LDL-R is the most advanced and tested approach to PCSK9 inhibition to date. The clinical efficacy and safety of evolocumab have been studied in a number of controlled trials versus placebo or versus active comparator (ézétimibe) during 12 to 76 weeks. Added on statin, evolocumab reduced LDL-C up to 50 to 60 % from baseline. Evolocumab also reduced LCL-C in monotherapy in statin-intolerant patients. Evolocumab also significally reduced total cholesterol, non-HDL cholesterol, apoprotein B and lipoprotein(a). Safety and tolerance were good. Evolocumab is commercialized under the trade name Repatha® and administrated subcutaneously at the dose of 140 mg every 2 weeks or 420 mg once per month. Repatha® is approved in Belgium, with conditions, for the treatment of hypercholesterolemia in patients with heterozygous (HFe) and homozygous (HFo) familial hypercholesterolemia.

Two clinical trials demonstrate the superiority versus a placebo of two antidiabetic drugs in patients with type 2 diabetes and high cardiovascular risk. Empagliflozin, an inhibitor of sodium-glucose type 2 (SGLT2) cotransporters, in EMPA-REG OUTCOME, and liraglutide, an agonist of glucagon-like peptide-1 (GLP-1) receptors, in LEADER, showed a significant reduction in major cardiovascular events (- 14 and - 13 %, respectively), cardiovascular mortality (- 38 and - 22 %, respectively) and all-cause mortality (- 32 and - 15 %, respectively). A lower progression of kidney disease and less renal events were also reported. The underlying protective mechanisms remain controverted as the discussion whether the benefits are specific to each medication or could be extended to other molecules of these two pharmacological classes., Competing Interests: Le Pr A. J. Scheen déclare avoir reçu des honoraires comme orateur, membre d’un conseil scientifique ou investigateur clinicien de la part des firmes AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, Merck Sharp & Dohme, Novartis, NovoNordisk, et Sanofi. Il a également été investigateur clinicien dans les études EMPA-REG OUTCOME et LEADER. Le Dr Philippe Ernest a été co-investigateur dans l’étude EMPA-REG OUTCOME. Les autres auteurs de cet article n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Type 2 diabetes mellitus is a common chronic disease whose economic impact on both patients and society is constantly increasing. "The Cost of Diabetes in Europe--Type 2 study" is the first coordinated attempt to measure total healthcare costs of type 2 diabetes mellitus in Europe. On average, 3% of the population with type 2 diabetes accounted for 5% of the total healthcare expenditure. Complications have a substantial impact on the costs of managing type 2 diabetes. The prevention of complications, especially cardiovascular disease, will potentially reduce overall healthcare expenditure.

Colloid cysts of the third ventricle are rare, benign cysts of endodermal origin. Between 1989 and 1999, eight patients with this lesion (five females, three males), with a mean age of 40.5 years (range 20-54), were identified out of 1354 operated for tumours of the central nervous system. Among the eight, two were familial. They were half sisters 38 and 28 years-old, who were diagnosed to have colloid cysts of the third ventricle on CT scanning. Transcortical excision yielded 10 and 15 mm sized colloid cysts, respectively. Moreover, both sisters developed a multinodular goiter associated with these congenital tumours. The second sibling developed hyperprolactinemia associated with macroprolactinemia. Pregnancy was only possible after bromocriptine treatment. These cases provide further evidences that colloid cysts probably have an autosomic recessive pattern of inheritance with variable penetrance.