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Purpose of Review Since the clinical benefit of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors occurs in a setting of reducing low-density lipoprotein-cholesterol (LDL-C) to unprecedentedly low levels, it becomes of interest to investigate possible adverse effects pertaining to the risk of new-onset diabetes (NOD). Recent Findings While safety results reported in either meta-analyses or cardiovascular outcome trials FOURIER (with evolocumab) and ODYSSEY (with alirocumab) did not rise the incidence of NOD, Mendelian randomization analyses were almost concordant in showing an increased risk of NOD. This evidence was in line with post-marketing safety reports highlighting that evolocumab and alirocumab were primarily related to mild hyperglycaemia rather than diabetes, with most of the hyperglycaemic events occurring during the first 6 months of treatment. Summary Considering the different nature of genetic studies and of randomized controlled trials, with careful monitoring of patients, particularly in the earlier phases of treatment, and the identification of those more susceptible to develop NOD, treatment with PCSK9 inhibitors should be of minimal concern.

Background and aims: Familial hypercholesterolemia (FH) is the most common cause of premature atherosclerotic cardiovascular disease (ASCVD). Türkiye is among the countries with the highest rate of ASCVD. However, no population-based study has been published so far on the prevalence of FH, demographic and clinical characteristics, burden of ASCVD, treatment compliance, and attainment of low-density lipoprotein cholesterol (LDL-C) targets. Methods: We performed a study using the Turkish Ministry of Health's national electronic health records involving 83,063,515 citizens as of December 2021 dating back 2016. Adults fulfilling the diagnostic criteria of definite or probable FH according to the Dutch Lipid Network Criteria (DLNC), and children and adolescents fulfilling the criteria of probable FH according to the European Atherosclerosis Society (EAS) Consensus Panel report formed the study population (n = 157,790). The primary endpoint was the prevalence of FH. Results: Probable or definite FH was detected in 0.63% (1 in 158) of the adults and 0.61% (1 in 164) of the total population. The proportion of adults with LDL-C levels >4.9 mmol/L (190 mg/dL) was 4.56% (1 in 22). The prevalence of FH among children and adolescents was 0.37% (1 in 270). Less than one-third of the children and adolescents, and two-thirds of young adults (aged 18–29) with FH were already diagnosed with dyslipidaemia. The proportion of adults and children and adolescents on lipid-lowering treatment (LLT) was 32.1% and 1.5%, respectively. The overall discontinuation rate of LLT was 65.8% among adults and 77.9% among children and adolescents. Almost no subjects on LLT were found to attain the target LDL-C levels. Conclusions: This nationwide study showed a very high prevalence of FH in Türkiye. Patients with FH are diagnosed late and treated sub-optimally. Whether these findings may explain the high rates of premature ASCVD in Türkiye needs further investigation. These results denote the urgent need for country-wide initiatives for early diagnosis and effective management of FH patients.

Lipoprotein (a) (Lp(a)) attests to be of interest as a new lipoprotein target. However, Lp(a) was discovered in 1963 and since then was recognized as a low-density lipoprotein (LDL)-like lipoprotein with a structurally similar domain to plasminogen. We are increasingly recognizing the importance of Lp(a) and cardiovascular pathologies including atherosclerotic cardiovascular disease, aortic valve stenosis, heart failure, and atrial fibrillation. However, we neither have a standardized measurement method nor an appropriate agent to intervene with this old threat that we have recognized for more than 50 years. Herein, we present an up-to-date review of our knowledge about Lp(a) covering measurement methods, its associates, and summary of the currently available therapies and emerging therapeutic agents for the management of high Lp(a) in the light of recent evidence and guideline recommendations

During the COVID-19 pandemic, all countries implemented lockdown to prevent transmission of coronavirus. The prolonged stay-at-home process created some unfavourable effects like unhealthy lifestyle, physical inactivity and sedentary behaviour especially in patients with cardiovascular risk. Hypertensive individuals are also affected in the pandemic because of limited access to healthcare services, screening, and altered lifestyles. We aimed to investigate physical activity (PA) level, sedentary behaviour, mental health and healthy lifestyle behaviours in patients with hypertension and compare these parameters with healthy controls. This prospective, cross-sectional study included 40 hypertensive and 40 age-sex matched healthy controls. We assessed PA with the International Physical Activity Questionnaire long-form, quality of life with Short-Form 36 (SF-36) questionnaire, anxiety and depression with Hospital Anxiety and Depression Scale (HADS) and lifestyle behaviours with Health-Promoting Lifestyle Profile Scale-II (HPLP-II). Moderate and vigorous PA levels of hypertensives' were statistically lower than healthy controls (P = 0.001; P = 0.003, respectively). Hypertensive patients exhibited lower SF-36 physical function (P = 0.001), energy/vitality (P = 0.042), body pain scores than those of healthy controls (P = 0.007). Although HADS-anxiety, depression scores were similar (P 0.05), the depression ratio (45%) was more common in the hypertensive group during the lockdown. The main findings are that hypertensive patients have lower PA levels and worse quality of life than healthy controls during the pandemic. In addition, the presence of depression is more common among hypertensive patients. Considering unhealthy lifestyles, governments, and health professionals should take some precautions and plan interventions against physical inactivity. As known, providing regular physical activity is a keystone to fighting against cardiovascular disease.

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.

Therapeutic advances in hereditary amyloid transthyretin (ATTRv) amyloidosis with polyneuropathy extended life expectancy and delayed symptom progression especially in patients with early disease. Thus, detection and monitoring of asymptomatic carriers gained importance. However, there is still limited consensus on genetic screening of ATTRv-polyneuropathy patients' family members and diagnostic tests that must be done in the follow-up. In this study, we followed prospectively five asymptomatic carriers of a family with ATTRV30M (p.Val50Met) mutation by different diagnostic tests for three years. The carriers were followed by neurological examination, nerve conduction studies, sympathetic skin response test, heart rate variability, SFN-SIQ and DN4 questionnaires, quantitative sensory testing (QST), skin biopsy and in vivo corneal confocal microscopy. Nerve conduction studies, sympathetic skin response test and heart rate variability were normal in all for three years. Baseline QST and SFN-SIQ were normal but became abnormal during follow-up of two individuals who developed small fiber neuropathy symptoms. Baseline intraepidermal nerve fiber density was low in three carriers and decreased to below normative values in all during follow-up, while corneal sub-basal nerve density was low in all carriers compared to controls during the entire follow-up. Thus, our study showed that SFN-SIQ and QST are useful diagnostic tools to detect the transition to symptomatic ATTRv-polyneuropathy.

Summary: Patients 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

The dyslipidemia guidelines of the three major societies have been revised recently in light of new evidence. LDL-C is the primary target in the ESC, AHA/ACC/Multisociety and Canadian Cardiovascular Society (CCS) guidelines. These guidelines uniformly recommend intensifying lipid-lowering treatment with increased risk; however, the risk estimation systems are different across the guidelines. The ESC guidelines have LDL-C goals which have become more stringent over the years and advocate the use of statin and, if necessary, non-statin therapies to obtain these goals. AHA/ACC/Multisociety guidelines have LDL-C thresholds and advocate combination therapy less liberally and for selected patients. All three guidelines acknowledge the importance of shared decision making. Despite some divergent approaches and recommendations, the main principles and messages are the same across the guidelines. To combat the epidemic of cardiovascular disease, our focus should be not on the differences but on implementing the guidelines in our region.

REDUCE-IT demonstrated that adding 4 g/day of icosapent ethyl (IPE; purified ethyl ester of eicosapentaenoic acid [EPA]) to statins substantially reduced cardiovascular disease (CVD) events, with few adverse effects. These data prompted numerous leading medical societies across five continents, including the American College of Cardiology, the European Society of Cardiology, and the Japanese Circulation Society, to update their guidelines or scientific/consensus statements to recommend use of IPE for primary and secondary prevention of CVD events.This review discusses the incorporation of IPE into international guidelines and scientific statements, noting areas of consensus and distinction. As background, this review also describes the CVD benefits and risks of IPE as a statin adjunct, and outlines current data regarding the potential mechanisms of CVD risk reduction by EPA (as IPE) beyond triglyceride reduction.IPE is unique among 'triglyceride-lowering' treatments in having strong CVD outcomes data and, therefore, a broad international consensus among professional medical society guidelines and statements endorsing its use for CVD risk reduction in patients generally meeting REDUCE-IT inclusion criteria. IPE should be considered for CVD prevention as a statin adjunct in all such patients.Plain Language SummaryCardiovascular disease (CVD) remains the leading cause of death worldwide. Statin monotherapy is conventionally used first-line to reduce the risk of CV events, such as heart attacks and strokes, in patients with elevated cholesterol. However, considerable risk remains despite appropriate control of cholesterol levels with a statin. Consequently, research has focused on treatment of additional therapeutic targets to reduce this remaining CV risk. One such target is elevated blood triglyceride levels. Unfortunately, most drugs that lower triglyceride levels, such as niacin, fibrates, and mixed omega-3 fatty acids, have not reduced the risk of cardiovascular events in clinical trials when added to statin therapy. However, the omega-3 fatty acid eicosapentaenoic acid ('EPA') administered in highly purified form as icosapent ethyl (IPE) has emerged as the first omega-3 fatty acid, and the first triglyceride-lowering agent to prevent CV events when added to statins. This was demonstrated most notably in the pivotal REDUCE-IT trial, in which IPE reduced the risk of major CV events by 25% in high-risk patients with mildly to moderately elevated triglyceride levels despite statin-controlled cholesterol levels. The mechanisms responsible for this reduction in CV events appear to go far beyond lowering triglyceride levels alone. In light of the positive results from the REDUCE-IT trial, IPE was approved for CV disease risk reduction globally, including in the United States, Canada, European Union, and the United Kingdom, and its use is being increasingly endorsed in United States and international statements and guidelines for managing CV risk. Despite minor differences among guidelines, there is strong consensus that IPE should be considered for use in CVD prevention in all patients who meet the proposed criteria.

International audience; The healthcare system of Ukraine was already suffering from several shortfalls before February 2022, but the war of aggression started by the Russian leadership is poised to inflict a further severe blow that will have long-lasting consequences for the health of all Ukrainians. In pre-war Ukraine, noncommunicable diseases (NCDs) contributed to 91% of deaths, especially cardiovascular diseases (67%). Ukrainians have a high prevalence of risk factors for NCDs ranking among the highest levels reported by the World Health Organization (WHO) in the European (EU) Region. Cardiovascular disease is one of the key health risks for the conflict-affected Ukrainian population due to significant limitations in access to health care and interruptions in the supply of medicines and resources. The excess mortality observed during the COVID-19 pandemic, due to a combination of viral illness and chronic disease states, is bound to increase exponentially from poorly treated NCDs. In this report, we discuss the impact of the war on the public health of Ukraine and potential interventions to provide remote health assistance to the Ukrainian population.

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 ( 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.

[No abstract available], Sanofi Genzyme Actelion Pharmaceuticals Abbott Laboratories Pfizer Bayer Schering Amgen Fondazione Internazionale Menarini, COI statement: M.K. has received honoraria (for lectures and consultancy) from Abbott, Actelion, Astra-Zeneca, Abdi Ibrahim, Aegerion, Bayer Schering, Menarini, Sanofi Genzyme, and Pfizer, and research funding from Aegerion, Amryt Pharma, Amgen, Pfizer, and Sanofi and has participated in clinical trials with Amgen, Bayer Schering, and Sanofi for the last 3 years. O.K.T. and L.H.C. had no conflicts of interest. L.T. has received honoraria/consultancy fees from Merck, Amgen, Astra, Novartis, Abbott, Daiichi Sankyo, Nova Nordisk, Pfizer, Actelion, Servier, Sanofi, Boehringer Ingelheim, Menarini, Kowa, Aegerion, and Abbott. Editorial

This study is aimed at investigating gender differences in the medical management of patients with coronary heart disease (CHD). Analyses were based on the ESC EORP EUROASPIRE V (European Survey Of Cardiovascular Disease Prevention And Diabetes) survey. Consecutive patients between 18 and 80 years, hospitalized for a coronary event, were included in the study. Information on cardiovascular medication intake at hospital discharge and at follow-up (≥ 6 months to 0.01) at discharge and follow-up respectively. However, a statistically significant difference was found in the use of statins at follow-up, in disfavor of women (82.8% vs. 77.7%; P 0.01). Furthermore, women were less likely than men to have received a CABG (20.4% vs. 13.2%; P

Atherosclerosis is initiated by functional changes in the endothelium accompanied by accumulation, oxidation, and glycation of LDL-cholesterol in the inner layer of the arterial wall and continues with the expression of adhesion molecules and release of chemoattractants. PCSK9 is a proprotein convertase that increases circulating LDL levels by directing hepatic LDL receptors into lysosomes for degradation. The effects of PCSK9 on hepatic LDL receptors and contribution to atherosclerosis via the induction of hyperlipidemia are well defined. Monoclonal PCSK9 antibodies that block the effects of PCSK9 on LDL receptors demonstrated beneficial results in cardiovascular outcome trials. In recent years, extrahepatic functions of PCSK9, particularly its direct effects on atherosclerotic plaques have received increasing attention. Experimental trials have revealed that PCSK9 plays a significant role in every step of atherosclerotic plaque formation. It contributes to foam cell formation by increasing the uptake of LDL by macrophages via scavenger receptors and inhibiting cholesterol efflux from macrophages. It induces the expression of inflammatory cytokines, adhesion molecules, and chemoattractants, thereby increasing monocyte recruitment, inflammatory cell adhesion, and inflammation at the atherosclerotic vascular wall. Moreover, low shear stress is associated with increased PCSK9 expression. PCSK9 may induce endothelial cell apoptosis and autophagy and stimulate the differentiation of smooth muscle cells from the contractile phenotype to synthetic phenotype. Increasing evidence indicates that PCSK9 is a molecular target in the development of novel approaches toward the prevention and treatment of atherosclerosis. This review focuses on the molecular roles of PCSK9 in atherosclerotic plaque formation.

A meeting entitled ‘Current Perspective on the Use of Statins in the Treatment of Dyslipidemic Patients’ was held in Stresa, Italy, on 27–28th June 2019. The presentations covered the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines on dyslipidaemia, with discussion about the importance of controlling low-density lipoprotein cholesterol (LDL-C) and the pharmacological opportunities to reach the novel lipid goals. The roles of statins to manage dyslipidaemia in patients with different cardiovascular risks were also discussed. In particular, the efficacy and safety of pitavastatin for the treatment of dyslipidaemia were reviewed, highlighting its further advantages beyond LDL-C reduction. Therefore, the impact of statins on the glycaemic profile was discussed in view of the null/lower effect of pitavastatin as compared with other statins, as well as the interaction profile with other drugs commonly used. This meeting report summarizes the main messages of the discussion with a special focus on pitavastatin, whose main features in different settings are described.

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 importan...

Cardiovascular disease (CVD) is the leading cause of death. Although once considered merely as a lipid storage disease, studies indicate the role of inflammation in initiation and progression of atherosclerotic CVD, as well as the development of thrombotic complications. Despite significant advances in treatment of atherosclerosis, there still exists a residual risk for CVD-related morbidity and mortality. Even with optimal treatment, the rate of a new event after an index acute coronary syndrome event, such as myocardial ischemia or infarction, in the first three years has been reported to be as high as 20%. In the last decades, inflammation due to apoB-lipoproteins and other traditional risk factors, such as hypertension, diabetes and smoking, is accepted as a new target for CVD prevention. Up to now, several anti-inflammatory drugs have been tested for use in atherosclerosis. This review focuses on the current status of anti-inflammatory drug therapy for atherosclerotic CVD in humans.

Patients 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

Familial hypercholesterolemia (FH) is the most common genetic metabolic disorder characterized by markedly elevated LDL-C levels from birth leading to atherosclerotic cardiovascular disease (ASCVD) and premature deaths. The purpose of this review is to share the current knowledge in the diagnosis, risk estimation, and management of patients with FH in the light of recent evidence and guideline recommendations. Recent registries underscored the prevalence of FH as 1/200–250 translating to an almost 1500 million subjects suffering from FH worldwide. However, only a minority of FH patients are identified early and effectively treated. In most cases, mutations in the LDL-receptor (LDLR) gene and to a lesser degree in the apolipoprotein B-100 (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9), and the LDL-receptor adaptor protein 1 (LDLRAP1) genes cause FH. Diagnostic scores such as Dutch Lipid Clinic Network criteria using clinical manifestations are helpful in identifying FH. Traditional risk factors and high lipoprotein(a) affect the course of the disease. Vascular ultrasound imaging and coronary calcium scoring are helpful for further risk estimation of these patients. Getting to LDL-C goals is possible with currently available treatments including statins, ezetimibe, and PCSK9 inhibitors, as well as lipoprotein apheresis, lomitapide, and mipomersen in more severe phenotypes. Additionally, novel agents bempedoic acid, inclisiran, and evinacumab expanded the treatment choices for some patients with FH. Early diagnosis and initiation of LDL-C lowering are still required to achieve the greatest reduction in ASCVD morbidity and mortality in patients with FH. FH is a common genetic disorder characterized by markedly elevated LDL-C levels from birth onward, resulting in significantly increased risk for ASCVD. Despite major advances in our understanding of the disease and effective therapies, FH is still underdiagnosed and undertreated. Early initiation of LDL-C lowering by increased awareness of FH among the healthcare professionals, patients, and the public is necessary to achieve meaningful reduction in ASCVD morbidity and mortality in these patients.

Recent advances in human genetics, together with a large body of epidemiologic, preclinical, and clinical trial results, provide strong support for a causal association between triglycerides (TG), TG-rich lipoproteins (TRL), and TRL remnants, and increased risk of myocardial infarction, ischaemic stroke, and aortic valve stenosis. These data also indicate that TRL and their remnants may contribute significantly to residual cardiovascular risk in patients on optimized low-density lipoprotein (LDL)-lowering therapy. This statement critically appraises current understanding of the structure, function, and metabolism of TRL, and their pathophysiological role in atherosclerotic cardiovascular disease (ASCVD). Key points are (i) a working definition of normo- and hypertriglyceridaemic states and their relation to risk of ASCVD, (ii) a conceptual framework for the generation of remnants due to dysregulation of TRL production, lipolysis, and remodelling, as well as clearance of remnant lipoproteins from the circulation, (iii) the pleiotropic proatherogenic actions of TRL and remnants at the arterial wall, (iv) challenges in defining, quantitating, and assessing the atherogenic properties of remnant particles, and (v) exploration of the relative atherogenicity of TRL and remnants compared to LDL. Assessment of these issues provides a foundation for evaluating approaches to effectively reduce levels of TRL and remnants by targeting either production, lipolysis, or hepatic clearance, or a combination of these mechanisms. This consensus statement updates current understanding in an integrated manner, thereby providing a platform for new therapeutic paradigms targeting TRL and their remnants, with the aim of reducing the risk of ASCVD., Graphical Abstract Formation of triglyceride-rich lipoprotein remnants and their role in atherogenesis. Metabolic scheme for the generation and clearance of triglyceride-rich lipoprotein remnant particles (A). In hypertriglyceridaemia, overproduction and inefficient lipolysis of both very low-density lipoprotein and chylomicrons lead to increased remnant formation. Triglyceride-rich lipoprotein remnants contribute to the initiation and progression of atherosclerotic lesions (B). Particle retention in the subendothelial space is followed by inflammation, cholesterol deposition, and macrophage foam cell formation.

Lipoprotein(a) operates in causal pathways to promote atherosclerosis, arterial thrombosis, and aortic stenosis. It has been associated with rare cases of nonatherosclerotic arterial thrombotic stroke at any age. Inherited variation of lipoprotein(a) levels substantially increases cardiovascular risk in 20% of people worldwide. Recent progress in identifying the risk associated with lipoprotein(a) and in pursuing effective treatment has led to a recent Global Think Tank including representatives from the European Atherosclerosis Society, American Heart Association, Preventive Cardiovascular Nurses Association, National Lipid Association, and other groups. The need for standardized laboratory measurement in nanomoles per liter met with unanimous consensus. Atherosclerotic risk is linearly associated with plasma lipoprotein(a) levels, so that persons with the highest levels may have risk similar to other severe inherited lipoprotein disorders. Universal once-in-lifetime screening has been recommended by European and Canadian cardiovascular societies, but not by U.S. organizations. Current pharmacologic therapies are limited to 20-30% lowering of lipoprotein(a) levels, and no pharmacologic treatment for lowering lipoprotein(a) has yet been proven to reduce risk in a cardiovascular outcomes trial. Treatment for high-risk patients focuses on reducing low density lipoprotein cholesterol and other risk factors. New therapies targeting messenger RNA for apolipoprotein(a) can achieve 80-90% reduction of lipoprotein(a) levels. One such therapy using a liver-directed antisense oligonucleotide is currently being tested in a large cardiovascular outcomes trial. Increased recognition of lipoprotein(a)-associated risk and emergence of potentially effective therapy together lead to a mandate for a unified global effort on education, standardization, and clinical management.

Pulmonary hypertension is a group of diseases, including pulmonary arterial hypertension associated with congenital heart disease (APAH-CHD), characterized by progressive deterioration in pulmonary hemodynamics associated with substantial morbidity and mortality risk. THALES is a national multicenter, prospective observational registry, providing data on patients with APAH-CHD. The study comprised APAH-CHD patients (>3 months of age) with confirmed diagnosis of right heart catheterization or echocardiographic findings. Initial and follow-up data were collected via regular hospital visits. Descriptive statistics are used for definitive purposes. Overall, 1034 patients aged 3 months–79 years (median 11.2 [Q1–Q3: 2.2–24.3] years) with APAH-CHD were enrolled at 61 centers, 50.3% being retrospectively enrolled. Most had either Eisenmenger's syndrome (49.2%) or systemic-to-pulmonary shunts (42.7%). Patients were mostly in functional class I–II at the time of diagnosis (46.6%). Mean 6-min walk distance (6MWD) was 369 ± 120 m. Mean pulmonary arterial pressure was 54.7 ± 22.2 mmHg for the whole group, and was highest in patients with Eisenmenger's syndrome. Targeted therapies were noted in 398 (38.5%) patients (monotherapy in 80.4%). Follow-up data were available in 506 patients. Survival at 140 months was 79% and was associated with baseline 6MWD >440 m (p = 0.009), brain natriuretic peptide level < 300 ng/L (p < 0.001). Follow-up 6MWD >165 m (p < 0.0001), brain natriuretic peptide level, Actelion Pharmaceuticals

Aims Recent European guidelines recommend in patients with atherosclerotic cardiovascular disease to achieve a reduction of low-density lipoprotein-cholesterol of at least 50% if the baseline low-density lipoprotein-cholesterol level is between 1.8 and 3.5 mmol/L. Systematic reviews have associated a given statin/dose combination with a fixed percentage low-density lipoprotein-cholesterol response. Algorithms for detecting cases and estimating the prevalence of familial hypercholesterolaemia often rely on such fixed percentage reductions. Methods and results We used data from 915 coronary patients participating in the EUROASPIRE V study in whom atorvastatin or rosuvastatin therapy was initiated at hospital discharge and who were still using these drugs at the same dose at a follow-up visit 6 or more months later. Pre and on-treatment low-density lipoprotein-cholesterol levels were compared across the full low-density lipoprotein-cholesterol range. The prevalence of FH was estimated using the Dutch Lipid Clinic Network criteria, once using observed pre-treatment low-density lipoprotein-cholesterol and once using imputed pre-treatment low-density lipoprotein-cholesterol by following the common strategy of applying fixed correction factors to on-treatment low-density lipoprotein-cholesterol. Inter-individual variation in the low-density lipoprotein-cholesterol response to a fixed statin and dose was considerable, with a strong inverse relation of percentage reductions to pre-treatment low-density lipoprotein-cholesterol. The percentage low-density lipoprotein-cholesterol response was markedly lower at the left end of the pre-treatment low-density lipoprotein-cholesterol range especially for levels less than 3 mmol/L. The estimated prevalence of familial hypercholesterolaemia was 2% if using observed pre-treatment low-density lipoprotein-cholesterol and 10% when using imputed low-density lipoprotein-cholesterol. Conclusion The inter-individual variation in the percentage low-density lipoprotein-cholesterol response to a given dose of a statin is largely dependent on the pre-treatment level: the lower the pre-treatment low-density lipoprotein-cholesterol level the smaller the percentage low-density lipoprotein-cholesterol reduction. The use of uniform correction factors to estimate pre-treatment low-density lipoprotein-cholesterol is not justified.

Fingolimod, a sphingosine-1-phosphate receptor agonist, is used for treatment of relapsing-remitting multiple sclerosis (RRMS). S1P receptors that fingolimod acts upon have also been shown to be expressed on atrial myocytes. This expression pattern has been linked with the drug's cardiovascular effects, such as bradycardia. We aimed to evaluate the clinical and electrocardiographic predictors of heart rate (HR) reduction in patients receiving first-dose fingolimod.We retrospectively analyzed subjects diagnosed with RRMS who were allocated to fingolimod treatment. HR, systolic and diastolic blood pressure values and electrocardiography during the first dose of fingolimod were accessed.A total of 114 RRMS patients (65.8% female, 33.58 ± 8.63 years) were included. After the initial dose of fingolimod, the heart rate decreased significantly at each hour (each p 0.001). Nadir heart rate was reached at 4 h. The multivariate binary logistic regression analysis revealed that BMI (OR: 0.878, p = 0.045), optic nerve involvement (OR: 3.205, p = 0.018), baseline HR (OR: 1.079, p = 0.002) and T-peak-T-end interval (OR: 1.046, p = 0.030) were independent predictors of greater HR reduction. During 6-h monitorization, none of the patients had relevant adverse reactions.Our findings provide an insight on clinical and electrocardiographic predictors of HR reduction that occurs in RRMS patients receiving first dose of fingolimod.

People 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.

International audience; Background and aimsThis European Atherosclerosis Society (EAS) Task Force provides practical guidance for combination therapy for elevated low-density lipoprotein cholesterol (LDL-C) and/or triglycerides (TG) in high-risk and very-high-risk patients.MethodsEvidence-based review.ResultsStatin-ezetimibe combination treatment is the first choice for managing elevated LDL-C and should be given upfront in very-high-risk patients with high LDL-C unlikely to reach goal with a statin, and in primary prevention familial hypercholesterolaemia patients. A proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor may be added if LDL-C levels remain high. In high and very-high-risk patients with mild to moderately elevated TG levels (>2.3 and < 5.6 mmol/L [>200 and < 500 mg/dL) on a statin, treatment with either a fibrate or high-dose omega-3 fatty acids (icosapent ethyl) may be considered, weighing the benefit versus risks. Combination with fenofibrate may be considered for both macro- and microvascular benefits in patients with type 2 diabetes mellitus.ConclusionsThis guidance aims to improve real-world use of guideline-recommended combination lipid modifying treatment.

OBJECTIVE To determine the possible alterations of retinal microcirculation associated with right-sided intracardiac pressures in patients with IPAH. METHODS Twenty patients with IPAH and 20 age- and sex-matched healthy controls were included in the study. Hemodynamic data were obtained from the most recent right heart catheterization. Echocardiographic examination was performed within 24 h of ophthalmological examination. For the right eyes of all participants, high-resolution scans of chorioretinal microvascular networks at different depths of the retina were captured via OCT angiography. RESULTS The perfusion of the superficial and deep capillary plexus (SCP and DCP), and choriocapillaris (CCP) flow area were significantly lower than those in healthy control subjects (p

The widespread use of statins has largely improved the treatment of hypercholesterolemia, but many patients still fail to achieve the LDL-C targets recommended by guidelines. Furthermore, some patients continue to present a very high cardiovascular (CV) risk or even an extreme risk despite being well treated, mainly due to the presence of co-morbidities such as diabetes or peripheral artery disease, which significantly increase their global CV risk. For these very high CV risk patients, the most recent European guidelines have reviewed the LDL-C goals and recommend an LDL-C reduction of at least 50% and a goal of55 mg/dL or even40 mg/dL. Recent clinical trials have shown that patient stratification based on the presence or absence of atherothrombotic risk factors may represent a valuable tool to identify patients at extremely high CV risk who may benefit more from an aggressive LDL-C-lowering approach. In these patients it may be appropriate to aim for the lowest LDL-C level, independently of recommended goals, with all the available pharmacological approaches.

To better understand the level of knowledge and interest in ‘diet and lifestyle’ for cholesterol management and CVD prevention, European Atherosclerosis Society (EAS) members were invited to take part in an online survey. In total, 269 EAS members participated of which 64 (24%) were students/postdocs, 102 (38%) researchers involved with CVD-related research and 103 (38%) doctors and clinicians who directly interact with patients. All (99%) of the participants either agreed or strongly agreed that ‘diet and lifestyle’ have a role to play in cholesterol management, with 80% indicating that ‘diet and lifestyle’ is very or extremely important. Of the clinicians, 75% indicated that their patients voluntarily ask for ‘diet and lifestyle’ advice and over 80% said they continuously provide ‘diet and lifestyle advice’ to their patients. Of the surveyed clinicians, 91% feel sufficiently educated and confident to provide expert advice and over 90% recommend medication, diet change, frequent exercise and smoking cessation to their patients. In view of more specific dietary advice, clinicians reportedly recommend a ‘Mediterranean diet’, and advise to avoid high-fat foods, and to increase intake of high-fibre foods. Interestingly, smoking cessation and alcohol avoidance were mentioned less frequently. In view of educational needs, over half of the surveyed EAS members use the internet and ‘guidelines’ to learn about ‘diet and lifestyle’ in relation to cholesterol and CVD risk management. Clinicians tend to use ‘guidelines’ more often, while students/postdocs tend to use the internet significantly more than clinicians and CVD researchers. Regarding unmet needs for educational tools addressing specifically ‘diet and lifestyle’, clinicians feel that patient-oriented leaflets and pocket guidelines would be most beneficial materials to introduce, while students/postdocs would prefer an app. In summary, the role of ‘diet and lifestyle’ as a cornerstone of cholesterol management and CVD risk prevention seems well recognised amongst EAS members surveyed.