European Heart Journal

Low-density lipoprotein cholesterol (LDL-C) is a proven causative factor for developing atherosclerotic cardiovascular disease. Individuals with genetic conditions associated with lifelong very low LDL-C levels can be healthy. We now possess the pharmacological armamentarium (statins, ezetimibe, PCSK9 inhibitors) to reduce LDL-C to an unprecedented extent. Increasing numbers of patients are expected to achieve very low (<30 mg/dL) LDL-C. Cardiovascular event reduction increases log linearly in association with lowering LDL-C, without reaching any clear plateau even when very low LDL-C levels are achieved. It is still controversial whether lower LDL-C levels are associated with significant clinical adverse effects (e.g. new-onset diabetes mellitus or possibly haemorrhagic stroke) and long-term data are needed to address safety concerns. This review presents the familial conditions characterized by very low LDL-C, analyses trials with lipid-lowering agents where patients attained very low LDL-C, and summarizes the benefits and potential adverse effects associated with achieving very low LDL-C. Given the potential for cardiovascular benefit and short-term safe profile of very low LDL-C, it may be advantageous to attain such low levels in specific high-risk populations. Further studies are needed to compare the net clinical benefit of non-LDL-C-lowering interventions with very low LDL-C approaches, in addition to comparing the efficacy and safety of very low LDL-C levels vs. current recommended targets.

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Lipoproteins in chronic kidney disease: from bench to bedside

Thimoteus Speer, Paul M Ridker, Arnold von Eckardstein, Stefan J Schunk, Danilo Fliser

doi : 10.1093/eurheartj/ehaa1050

European Heart Journal, Volume 42, Issue 22, 7 June 2021, Pages 2170–2185

Chronic kidney disease (CKD) is associated with high cardiovascular risk. CKD patients exhibit a specific lipoprotein pattern termed ‘uraemic dyslipidaemia’, which is characterized by rather normal low-density lipoprotein cholesterol, low high-density lipoprotein cholesterol, and high triglyceride plasma levels. All three lipoprotein classes are involved in the pathogenesis of CKD-associated cardiovascular diseases (CVDs). Uraemia leads to several modifications of the structure of lipoproteins such as changes of the proteome and the lipidome, post-translational protein modifications (e.g. carbamylation) and accumulation of small-molecular substances within the lipoprotein moieties, which affect their functionality. Lipoproteins from CKD patients interfere with lipid transport and promote inflammation, oxidative stress, endothelial dysfunction as well as other features of atherogenesis, thus contributing to the development of CKD-associated CVD. While, lipid-modifying therapies play an important role in the management of CKD patients, their efficacy is modulated by kidney function. Novel therapeutic agents to prevent the adverse remodelling of lipoproteins in CKD and to improve their functional properties are highly desirable and partially under development.

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Lipoprotein(a) is associated with large artery atherosclerosis stroke aetiology and stroke recurrence among patients below the age of 60 years: results from the BIOSIGNAL study

Markus Arnold, Juliane Schweizer, Christos T Nakas, Valerie Schütz, Laura P Westphal, Corinne Inauen, Thomas Pokorny, Andreas Luft, Alexander Leichtle, Marcel Arnold, Antonela Bicvic, Urs Fischer, Gian Marco De Marchis, Leo H Bonati, Mandy D Müller, Timo Kahles, Krassen Nedeltchev, Carlo W Cereda, Georg K?gi, Alejandro Bustamante, Joan Montaner, George Ntaios, Christian Foerch, Katharina Spanaus, Arnold von Eckardstein, Mira Katan

doi : 10.1093/eurheartj/ehab081

European Heart Journal, Volume 42, Issue 22, 7 June 2021, Pages 2186–2196

Lipoprotein(a) [Lp(a)] is a recognized causal risk factor for atherosclerotic cardiovascular disease but its role for acute ischaemic stroke (AIS) is controversial. In this study, we evaluated the association of Lp(a) with large artery atherosclerosis (LAA) stroke and risk of recurrent cerebrovascular events in AIS patients.

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Elevated lipoprotein(a) and the risk of stroke in children, young adults, and the elderly

Sotirios Tsimikas

doi : 10.1093/eurheartj/ehab251

European Heart Journal, Volume 42, Issue 22, 7 June 2021, Pages 2197–2200

no abstract

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Lipoprotein(a), LDL-cholesterol, and hypertension: predictors of the need for aortic valve replacement in familial hypercholesterolaemia

Leopoldo Pérez de Isla, Gerald F Watts, Rodrigo Alonso, José Luis D?az-D?az, Ovidio Mu?iz-Grijalvo, Daniel Zamb?n, Francisco Fuentes, Raimundo de Andrés, Teresa Padr?, José L?pez-Miranda, Pedro Mata

doi : 10.1093/eurheartj/ehaa1066

European Heart Journal, Volume 42, Issue 22, 7 June 2021, Pages 2201–2211

Familial hypercholesterolaemia (FH) and elevated lipoprotein(a) [Lp(a)] are inherited disorders associated with premature atherosclerotic cardiovascular disease (ASCVD). Aortic valve stenosis (AVS) is the most prevalent valvular heart disease and low-density lipoprotein cholesterol (LDL-C) and Lp(a) may be involved in its pathobiology. We investigated the frequency and predictors of severe AVS requiring aortic valve replacement (AVR) in molecularly defined patients with FH.

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