501 research outputs found
PCSK9 inhibition and inflammation: A narrative review
No full textAtherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality despite excellent pharmacological and revascularization approaches. Low-density lipoproteins (LDL) are undoubtedly the most significant biochemical variables associated with atheroma, however, compelling data identify inflammation as critical for the maintenance of the atherosclerotic process, underlying some of the most feared vascular complications. Although its causal role is questionable, high-sensitivity C-reactive protein (hs-CRP) represents a major biomarker of inflammation and associated risk in CVD. While statin-associated reduced risk may be related to the lowering of both LDL-C and hs-CRP, PCSK9 inhibitors leading to dramatic LDL-C reductions do no alter hs-CRP levels. On the other hand, hs-CRP levels identify groups of patients with a high risk of CV disease achieving better ASCVD prevention in response to PCSK9 inhibition. In the FOURIER study, even in patients with extremely low levels of LDL-C, there was a stepwise risk increment according to the values of hs-CRP: +9% (<1 mg/L), +10.8% (1-3 mg/L) and +13.1% (>3 mg/L). Likewise, in the SPIRE-1 and -2 studies, bococizumab patients with hs-CRP> 3 mg/L had a 60% greater risk of future CV events. Most of the patients enrolled in the PCSK9 trials were on maximally tolerated statin therapy at baseline, and an elevated hs-CRP may reflect residual inflammatory risk after standard LDL-C lowering therapy. Moreover, data on changes in inflammation markers in carriers of PCSK9 loss-of-function mutations are scanty and not conclusive, thus, evidence from the effects of anti-inflammatory molecules on PCSK9 levels might help unravel this hitherto complex tangle
Similarities and differences between European and American guidelines on the management of blood lipids to reduce cardiovascular risk
No full textThe 2018 American Heart Association/American College of Cardiology/Multi-Society (AHA/ACC/MS) Guideline on the Management of Blood Cholesterol and the 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) Guidelines for the Management of Dyslipidemias: Lipid Modification to Reduce Cardiovascular Risk, that were recently released by the United States and Europe, provide new recommendations for the management of blood lipid levels based on the latest evidence. Despite many common points, there are several differences in the recommendations, including the definition of very-high-risk patient category, the recommendations for some categories of patients, such as those with diabetes, familial hypercholesterolemia, chronic kidney disease, and aged patients, and the use of ezetimibe and PCSK9 inhibitors. These differences suggest that multiple approaches can be used to manage lipid abnormalities in the context of cardiovascular risk reduction
Impact of Lipids on Cardiovascular Health : JACC Health Promotion Series
No full textPeople who maintain ideal cardiovascular heath have a low lifetime risk of cardiovascular disease. Therefore, encouraging people to achieve ideal cardiovascular health represents an important opportunity to improve the prevention of cardiovascular disease. However, preventing cardiovascular disease by promoting ideal cardiovascular health requires shifting the focus from treating disease after it develops to preventing cardiovascular events before they happen by slowing the progression of atherosclerosis. Because atherogenic lipoproteins play a central causal role in the initiation and progression of atherosclerosis, maintaining optimal lipid levels is necessary to achieve ideal cardiovascular health. This review describes the cumulative effect of lipid-carrying lipoproteins on the risk of cardiovascular disease, estimates the magnitude of the clinical benefit that can be achieved by maintaining optimal lipid levels, identifies the most effective timing for implementing strategies designed to achieve optimal lipid levels, and provides a clinical pathway to help people achieve the lipid levels necessary for ideal cardiovascular health
The year in cardiovascular medicine 2021: dyslipidaemia
No full textThe past year was an exciting time for clinical lipidology when we learnt more about existing therapies as well as therapies targeting novel pathways discovered through genetic studies. LDL cholesterol remained the main target and a variety of drugs to lower LDL cholesterol through different mechanisms were explored. Emerging evidence on the atherogenity of triglyceride-rich lipoproteins led to renewed interest in lowering them with new treatments. Lp(a) was back in focus with evidence on causality and new targeted therapeutics which dramatically lower Lp(a) levels. We will be able to personalise lipid lowering therapy further with this enriched armamentarium once we have the results of the cardiovascular outcome studies with some of these new agents
Lipid Clinics Network. Rationale and design of the EAS global project
No full textThe evidence of the causal role of low-density lipoprotein cholesterol in the development of atherosclerotic cardiovascular disease is well-established. The clearly identified common position of the European guidelines proclaims necessity to decrease LDL-C concentrations based on a proper risk stratification. However, current worldwide situation with the lipid management still demonstrates inadequate dyslipidemia control, that is probably related to a healthcare system issues. As the need to standardize and implement approaches following the guidelines into clinical practice remains a challenge, the EAS initiates the Lipid Clinics Network project, aiming to provide a structure to establish uniform EU-wide standards of diagnosis, management and treatment of patients with lipid disorders, based on the ESC/EAS Guidelines on management of dyslipidaemias
Updates in Small Interfering RNA for the Treatment of Dyslipidemias
No full textPurpose of Review Atherosclerotic cardiovascular disease (ASCVD) is still the leading cause of death worldwide. Despite
excellent pharmacological approaches, clinical registries consistently show that many people with dyslipidemia do not
achieve optimal management, and many of them are treated with low-intensity lipid-lowering therapies. Beyond the wellknown
association between low-density lipoprotein cholesterol (LDL-C) and cardiovascular prevention, the atherogenicity
of lipoprotein(a) and the impact of triglyceride (TG)-rich lipoproteins cannot be overlooked. Within this landscape, the use
of RNA-based therapies can help the treatment of difficult to target lipid disorders.
Recent Findings The safety and efficacy of LDL-C lowering with the siRNA inclisiran has been documented in the open-label
ORION-3 trial, with a follow-up of 4 years. While the outcome trial is pending, a pooled analysis of ORION-9, ORION-10,
and ORION-11 has shown the potential of inclisiran to reduce composite major adverse cardiovascular events. Concerning
lipoprotein(a), data of OCEAN(a)-DOSE trial with olpasiran show a dose-dependent drop in lipoprotein(a) levels with an
optimal pharmacodynamic profile when administered every 12 weeks. Concerning TG lowering, although ARO-APOC3
and ARO-ANG3 are effective to lower apolipoprotein(apo)C-III and angiopoietin-like 3 (ANGPTL3) levels, these drugs
are still in their infancy.
Summary In the era moving toward a personalized risk management, the use of siRNA represents a blossoming armamentarium
to tackle dyslipidaemias for ASCVD risk reduction
Lipid-lowering and anti-thrombotic therapy in patients with peripheral arterial disease:European Atherosclerosis Society/European Society of Vascular Medicine Joint Statement
No full textPatients with peripheral arterial disease (PAD) are at very high risk of cardiovascular events, but risk factor management is usually suboptimal. This Joint Task Force from the European Atherosclerosis Society and the European Society of Vascular Medicine has updated evidence on the management on dyslipidaemia and thrombotic factors in patients with PAD. Guidelines recommend a low-density lipoprotein cholesterol (LDLC) goal of more than 50% reduction from baseline and <1.4 mmol/L (<55 mg/dL) in PAD patients. As demonstrated by randomized controlled trials, lowering LDL-C not only reduces cardiovascular events but also major adverse limb events (MALE), including amputations, of the order of 25%. Addition of ezetimibe or a PCSK9 inhibitor further decreases the risk of cardiovascular events, and PCSK9 inhibition has also been associated with reduction in the risk of MALE by up to 40%. Furthermore, statin-based treatment improved walking performance, including maximum walking distance, and pain-free walking distance and duration. This Task Force recommends strategies for managing statin-associated muscle symptoms to ensure that PAD patients benefit from lipid-lowering therapy. Antiplatelet therapy, either daily clopidogrel 75 mg or the combination of aspirin 100 mg and rivaroxaban (2 × 2.5 mg) is also indicated to prevent cardiovascular events. Dual antiplatelet therapy (aspirin and rivaroxaban) may be considered following revascularization, taking into account bleeding risk. This Joint Task Force believes that adherence with these recommendations for lipid-lowering and antithrombotic therapy will improve the morbidity and mortality in patients with PAD.</p
Diagnostic and prognostic role of TFF3, Romo-1, NF-кB and SFRP4 as biomarkers for endometrial and ovarian cancers: a prospective observational translational study
No full textPurpose: This study aimed to evaluate trefoil factor 3 (TFF3), secreted frizzled-related protein 4 (sFRP4), reactive oxygen species modulator 1 (Romo1) and nuclear factor kappa B (NF-κB) as diagnostic and prognostic markers of endometrial cancer (EC) and ovarian cancer (OC). Methods: Thirty-one patients with EC and 30 patients with OC undergone surgical treatment were enrolled together with 30 healthy controls in a prospective study. Commercial ELISA kits determined serum TFF-3, Romo-1, NF-кB and sFRP-4 concentrations. Results: Serum TFF-3, Romo-1 and NF-кB levels were significantly higher in patients with EC and OC than those without cancer. Regarding EC, none of the serum biomarkers differs significantly between endometrial and non-endometrioid endometrial carcinomas. Mean serum TFF-3 and NF-кB levels were significantly higher in advanced stages. Increased serum levels of TFF-3 and NF-кB were found in those with a higher grade of the disease. Regarding OC, none of the serum biomarkers differed significantly among histological subtypes. Significantly increased serum levels of NF-кB were observed in patients with advanced-stage OC than those with stage I and II diseases. No difference in serum biomarker levels was found between those who had a recurrence and those who had not. The sensibility and specificity of these four biomarkers in discriminating EC and OC from the control group showed encouraging values, although no one reached 70%. Conclusions: TFF-3, Romo-1, NF-кB and SFRP4 could represent new diagnostic and prognostic markers for OC and EC. Further studies are needed to validate our results
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