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Purpose 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 well-known 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. In the era moving toward a personalized risk management, the use of siRNA represents a blossoming armamentarium to tackle dyslipidaemias for ASCVD risk reduction., (© 2023. The Author(s).)

The 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., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: We sought to evaluate physicians' opinions and practices in lipid management., Methods and Results: A web-based survey by the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) was distributed to 70 696 individuals at two time points, before and after publication of the 2019 ESC/EAS dyslipidaemia guidelines. Respondents (1271 in the first and 1056 in the second part) were most commonly cardiologists in Europe. More than 90% of participants reported that they regularly measure lipid levels and discuss lipid-lowering treatment with patients. More than 87% found the use of LDL-C goals useful or potentially useful, although it was acknowledged that recommended goals are frequently not achieved. Regarding the LDL-C goal according to the 2019 guidelines (<1.4 mmol/L for very high-risk patients), more than 70% of respondents felt that it is based on solid scientific evidence, but 31% noted that implementation should also consider available local resources and patient preferences. Statin intolerance was perceived as infrequent, affecting 1-5% of patients according to most respondents but was the main reason for not prescribing a statin to secondary-prevention patients, followed by patient non-adherence. Although most respondents reported that 11-20% of secondary-prevention patients have an indication to add a non-statin medication, fewer patients (<10% according to most respondents) receive these medications., Conclusions: This survey shows a high level of acceptance of the LDL-C treatment goals recommended by current ESC/EAS guidelines. Although patient-related factors were the main reported reasons for suboptimal lipid-lowering therapy, physician inertia to intensify treatment cannot be excluded as an additional contributing factor., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Purpose of Review: Recent evidence has shaped the new guidelines for the management of dyslipidemia. The importance of accurate risk estimation, subclinical disease detection, and contemporary dyslipidemia management approaches are discussed in this review., Recent Findings: Risk prediction helps determine the intensity of management strategies and identify high-risk patients. To overcome the pitfalls of the current risk prediction systems, incorporating genetic scores, biomarkers, and imaging is being explored. Key initiating event in atherogenesis is low-density lipoprotein cholesterol (LDL-C) retention in the arterial wall. Recent dyslipidemia guidelines agree that LDL-C is the primary target, but management approaches vary. Guidelines are shaped by new studies that show the benefits of high-intensity lipid lowering, especially for patients at very high-risk. Global risk assessment should be performed in all individuals for cardiovascular disease prevention. Main target should be the causal risk factors, particularly LDL-C which is one of the most important modifiable causal factors. Lower LDL-C goals will help prevent further events in very high-risk patients.

Objectives : Dyslipidemia is one of the risk factors for atherosclerotic cardiovascular disease. Cardiovascular events decrease with decreasing LDL-C levels and all guidelines emphasize the importance of LDL-C lowering. However, implementation in real life is suboptimal. This study aimed to evaluate the treatment approaches to the dyslipidemia of physicians. Methods : This study was conducted as an online survey for internal medicine specialists and residents. The survey included questions on the physicians' demographics, their attitudes toward dyslipidemia management in three different case scenarios and questions. The physicians were asked to indicate their treatment and guideline preferences in the three cases. Results : Among the 366 participants 67.5% were internal medicine specialists and 18.9% were internal medicine residents. Fourteen percent of physicians did not use guidelines in clinical practice. Five percent of specialists and 10.1% of residents doubted the necessity of dyslipidemia treatment, 30% of both specialists and residents were affected by the patient's reluctance. The specialists were more likely to state that reaching the target LDL-C should be a priority compared to the residents (p = 0.003). Most physicians (58.7%) treated the patients according to the guideline recommendations if the patients were at high risk. They were less likely to get to guideline recommendation goals if the patients were at low risk (29.8%). Conclusion : Despite overwhelming evidence, some physicians did not use guidelines and some physicians doubted the necessity of dyslipidemia treatment. A significant proportion of physicians were affected by the patient's reluctance. There is a clear need to educate physicians about the importance of guidelines.

: Obesity is a key factor for cardiovascular diseases and complications. Obesity is associated with hypertension, dyslipidemia and type II diabetes, which are the major predictors of cardiovascular disease in the future. It predisposes for atrial fibrillation, heart failure, sudden cardiac death, renal disease and ischemic stroke that are the main causes of cardiovascular hospitalization and mortality. As obesity and the cardiovascular effects on the vessels and the heart start early in life, even from childhood, it is important for health policies to prevent obesity very early before the disease manifestation emerge. Key roles in the prevention are strategies to increase physical exercise, reduce body weight and to prevent or treat hypertension, lipids disorders and diabetes earlier and efficiently to prevent cardiovascular complications.Epidemiology and mechanisms of obesity-induced hypertension, diabetes and dyslipidemia will be reviewed and the role of lifestyle modification and treatment strategies in obesity will be updated and analyzed. The best treatment options for people with obesity, hypertension, diabetes and dyslipidemia will discussed.

Background: The PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor evolocumab reduced low-density lipoprotein cholesterol and cardiovascular events in the FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk). We investigated the efficacy and safety of evolocumab in patients with peripheral artery disease (PAD) as well as the effect on major adverse limb events., Methods: FOURIER was a randomized trial of evolocumab versus placebo in 27 564 patients with atherosclerotic disease on statin therapy followed for a median of 2.2 years. Patients were identified as having PAD at baseline if they had intermittent claudication and an ankle brachial index of <0.85, or if they had a prior peripheral vascular procedure. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, hospital admission for unstable angina, or coronary revascularization. The key secondary end point was a composite of cardiovascular death, myocardial infarction, or stroke. An additional outcome of interest was major adverse limb events defined as acute limb ischemia, major amputation, or urgent peripheral revascularization for ischemia., Results: Three thousand six hundred forty-two patients (13.2%) had PAD (1505 with no prior myocardial infarction or stroke). Evolocumab significantly reduced the primary end point consistently in patients with PAD (hazard ratio [HR] 0.79; 95% confidence interval [CI], 0.66-0.94; P =0.0098) and without PAD (HR 0.86; 95% CI, 0.80-0.93; P =0.0003; P interaction =0.40). For the key secondary end point, the HRs were 0.73 (0.59-0.91; P =0.0040) for those with PAD and 0.81 (0.73-0.90; P <0.0001) for those without PAD ( P interaction =0.41). Because of their higher risk, patients with PAD had larger absolute risk reductions for the primary end point (3.5% with PAD, 1.6% without PAD) and the key secondary end point (3.5% with PAD, 1.4% without PAD). Evolocumab reduced the risk of major adverse limb events in all patients (HR, 0.58; 95% CI, 0.38-0.88; P =0.0093) with consistent effects in those with and without known PAD. There was a consistent relationship between lower achieved low-density lipoprotein cholesterol and lower risk of limb events ( P =0.026 for the beta coefficient) that extended down to <10 mg/dL., Conclusions: Patients with PAD are at high risk of cardiovascular events, and PCSK9 inhibition with evolocumab significantly reduced that risk with large absolute risk reductions. Moreover, lowering of low-density lipoprotein cholesterol with evolocumab reduced the risk of major adverse limb events., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01764633., (© 2017 American Heart Association, Inc.)

A meeting of European experts in cardiovascular (CV) disease and lipids was convened in Paris, France, on 10 November 2014 to discuss lipid profile, and in particular atherogenic dyslipidaemia (AD), and associated CV risk. Key points that were raised and discussed during the meeting are summarised in this paper, which also accounts for further discussion and agreement on these points by the group of experts. Elevated levels of low-density lipoprotein cholesterol (LDL-c) are commonly associated with a greater CV risk than low LDL-c levels, and are routinely managed with statins. However, even for patients controlled on statins and achieving low LDL-c levels, abnormal lipid profiles observed in some patients (i.e. elevated triglyceride levels, with/without low levels of high-density lipoprotein cholesterol [HDL-c]) have been linked to the presence of a residual CV risk. Therefore, it is recommended that both triglyceride and HDL-c levels be measured, to allow for the overall CV residual risk to be adequately managed. Favourable safety and clinical data support the combination of statins with other lipid-lowering agents, such as fenofibrate. Patients who have elevated triglyceride levels plus low levels of HDL-c are most likely to achieve clinical benefit from fenofibrate-statin combination therapy. In these patients with AD, achieving target non-HDL-c levels should be a key focus of CV risk management, and the use of non-HDL-c was advocated to provide a better measure of CV risk than LDL-c levels., (© 2015 Elsevier Ireland Ltd. All rights reserved.)