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BACKGROUND Omega-3 fatty acids have been proposed to be useful in the prevention of cardiac events. High-risk plaque (HRP) and plaque progression on serial coronary computed tomography angiography (CTA) have been suggested to be the predecessor of acute coronary syndrome (ACS). The purpose of this study was to investigate whether addition of omega-3 fatty acids to statin therapy for secondary prevention would lead to change in plaque characteristics detected by using serial CTA.Methods and Results:This study enrolled 210 patients with ACS: no eicosapentaenoic acid (EPA)/ docosahexaenoic acid (DHA; EPA/DHA), low-dose EPA+DHA, high-dose EPA+DHA, and high-dose EPA alone. HRP was significantly more frequent in patients with plaque progression (P=0.0001). There was a significant interaction between plaque progression and EPA dose regardless of the DHA dose; 20.3% in EPA-none (no EPA/DHA), 15.7% in EPA-low (low-dose EPA+DHA), and 5.6% in EPA-high (high-dose EPA+DHA and high-dose EPA alone). On multivariate logistic regression analysis, HRP (OR 6.44, P

Thoracic endovascular aortic repair (TEVAR) for ruptured thoracic aortic aneurysms is associated with increased perioperative mortality and morbidity compared with intact repair. The purpose of our study was to evaluate the factors associated with the presentation of ruptured aneurysms and adverse outcomes after repair.The Vascular Quality Initiative (VQI) registry was queried (2010-2020) to identify patients who had undergone TEVAR for ruptured and intact thoracic aortic aneurysms. The primary outcome was to identify the factors associated with ruptured thoracic aortic aneurysms. The secondary outcomes included perioperative mortality and morbidity, 5-year survival, and the identification of factors associated with adverse outcomes after TEVAR.Of the 3039 patients identified with a thoracic aortic aneurysm, 2806 (92%) had undergone repair for an intact aneurysm and 233 (8%) had undergone repair for a ruptured aneurysm. Chronic kidney disease was associated with a greater odds of a presentation with a ruptured aneurysm (odds ratio [OR], 3.1; 95% confidence interval [CI], 2.0-4.9; P .001). The factors associated with a lower odds of rupture included prior aortic aneurysm repair (OR, 0.71; 95% CI, 0.49-0.97; P = .05), prior smoker (OR, 0.36; 95% CI, 0.24-0.53; P .001), preoperative beta-blocker therapy (OR, 0.57; 95% CI, 0.41-0.80; P = .001), and preoperative statin therapy (OR, 0.68; 95% CI, 0.49-0.94; P = .020). TEVAR for ruptured thoracic aortic aneurysms was associated with higher perioperative mortality (rupture vs intact, 27% vs 4.6%; OR, 6.6; 95% CI 4.3-10; P .001) and the composite outcome of mortality, new dialysis, paralysis, and stroke (38% vs 9.5%; OR, 5.1; 95% CI, 3.5-7.4; P .001). The 5-year survival was significantly lower after TEVAR for ruptured thoracic aortic aneurysms (50% vs 76%; P .001; hazard ratio, 0.39; 95% CI, 0.29-0.52; P .001). Preoperative statin therapy was associated with higher 5-year survival (hazard ratio, 1.3; 95% CI, 1.0-1.6; P = .021).TEVAR for ruptured thoracic aortic aneurysms results in increased perioperative mortality and morbidity and lower 5-year survival compared with TEVAR for intact aneurysms. Patients with prior aortic aneurysm repair, prior smoking, and preoperative beta-blocker or statin therapy were less likely to present with ruptured thoracic aneurysms. This correlation might be attributed to increased exposure to cardiovascular healthcare providers and, thus, subsequently increased screening and surveillance, allowing for elective repair of thoracic aortic aneurysms.

Aims Lipoprotein(a) [Lp(a)] is a causal and independent risk factor for cardiovascular disease (CVD). People with elevated Lp(a) are often prescribed statins as they also often show elevated low-density lipoprotein cholesterol (LDL-C) levels. While statins are well-established in lowering LDL-C, their effect on Lp(a) remains unclear. We evaluated the effect of statins compared to placebo on Lp(a) and the effects of different types and intensities of statin therapy on Lp(a). Methods and results We conducted a systematic review and meta-analysis of randomized trials with a statin and placebo arm. Medline and EMBASE were searched until August 2019. Quality assessment of studies was done using Cochrane risk-of-bias tool (RoB 2). Mean difference of absolute and percentage changes of Lp(a) in the statin vs. the placebo arms were pooled using a random-effects meta-analysis. We compared effects of different types and intensities of statin therapy using subgroup- and network meta-analyses. Certainty of the evidence was determined using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). Overall, 39 studies (24 448 participants) were included. Mean differences (95% confidence interval) of absolute and percentage changes in the statin vs. the placebo arms were 1.1 mg/dL (0.5–1.6, P Conclusion Statin therapy does not lead to clinically important differences in Lp(a) compared to placebo in patients at risk for CVD. Our findings suggest that in these patients, statin therapy will not change Lp(a)-associated CVD risk.

Background: Statins are the primary therapy in patient with heterozygous familial hypercholesterolemia (HeFH). Non-adherence to statin therapy is associated with increased cardiovascular risk. Objective: We constructed a dynamic prediction model to predict statin adherence for an individual HeFH patient for each upcoming statin prescription. Methods: All patients with HeFH, identified by the Dutch Familial Hypercholesterolemia screening program between 1994 and 2014, were eligible. National pharmacy records dated between 1995 and 2015 were linked. We developed a dynamic prediction model that estimates the probability of statin adherence (defined as proportion of days covered >80%) for an upcoming prescription using a mixed effect logistic regression model. Static and dynamic patient-specific predictors, as well as data on a patient's adherence to past prescriptions were included. The model with the lowest AIC (Akaike Information Criterion) value was selected. Results: We included 1094 patients for whom 21,171 times a statin was prescribed. Based on the model with the lowest AIC, age at HeFH diagnosis, history of cardiovascular event, time since HeFH diagnosis and duration of the next statin prescription contributed to an increased adherence, while adherence decreased with higher untreated LDL-C levels and higher intensity of statin therapy. The dynamic prediction model showed an area under the curve of 0.63 at HeFH diagnosis, which increased to 0.85 after six years of treatment. Conclusion: This dynamic prediction model enables clinicians to identify HeFH patients at risk for non-adherence during statin treatment. These patients can be offered timely interventions to improve adherence and further reduce cardiovascular risk.

Aim. Study the effect of a study video, which was created by researchers and devoted to the atherosclerosis development and the effect of statin therapy on atherosclerotic plaque, on adherence to long-term therapy in patients with high or very high risk of cardiovascular complications.Material and methods. 120 patients admitted to hospital with cardiovascular diseases were included in the study. Patients were randomized into 2 groups: in the main group (n=60), the information video edited by the researchers was shown to patients on the eve of discharge, in addition to a printed brochure on lifestyle and diet modification, and in the control group (n=60), patients were given only a standard brochure. The motivating video shows the damage to the cardiovascular system by the atherosclerotic process and the beneficial effect on the body of constant intake of statins. After 1 and 3 months after discharge from the hospital, telephone calls were made, after which the patients had to visit the center for an objective examination by a researcher and control of laboratory parameters. After 1 month, 110 patients visited the center, after 3 months, 98 respondents visited the center.Results. The group with the information video demonstration noted more frequent adherence to medical recommendations compared to the control: after 1 month, 52 (96%) patients continued treatment versus 48 (86%) patients, 3 months after discharge 48 (96%) patients continued treatment versus 38 (79%) patients (pConclusion. Demonstration of a motivating video about the effect of statins on the atherosclerosis course increases patient adherence to medicinal therapy, including adherence to statins.

Background The 2018 U.S. cholesterol management guideline recommends additional lipid-lowering therapy with ezetimibe for secondary prevention in very high-risk patients with low-density l...

Background: Atherosclerotic cardiovascular diseases (ASCVD) including myocardial infarction, stroke and peripheral arterial disease continue to be major causes of premature death, disability and healthcare expenditure globally. Preventing the accumulation of cholesterol-containing atherogenic lipoproteins in the vessel wall is central to any healthcare strategy to prevent ASCVD. Advances in current concepts about reducing cumulative exposure to apolipoprotein B (apo B) cholesterol-containing lipoproteins and the emergence of novel therapies provide new opportunities to better prevent ASCVD. The present update of the World Heart Federation Cholesterol Roadmap provides a conceptual framework for the development of national policies and health systems approaches, so that potential roadblocks to cholesterol management and thus ASCVD prevention can be overcome.Methods: Through a review of published guidelines and research papers since 2017, and consultation with a committee composed of experts in clinical management of dyslipidaemias and health systems research in low-and-middle income countries (LMICs), this Roadmap identifies (1) key principles to effective ASCVD prevention (2) gaps in implementation of these interventions (knowledge-practice gaps); (3) health system roadblocks to treatment of elevated cholesterol in LMICs; and (4) potential strategies for overcoming these.Results: Reducing the future burden of ASCVD will require diverse approaches throughout the life-course. These include: a greater focus on primordial prevention; availability of affordable cholesterol testing; availability of universal cholesterol screening for inherited dyslipidaemias; risk stratification moving beyond 10-year risk to look at lifetime risk with adequate risk estimators; wider availability of affordable cholesterol-lowering therapies which should include statins as essential medications globally; use of adequate doses of potent statin regimens; and combination therapies with ezetimibe or other therapies in order to attain and maintain robust reductions in LDL-C in those at highest risk. Continuing efforts are needed on health literacy for both the public and healthcare providers, utilising multi-disciplinary teams in healthcare and applications that quantify both ASCVD risk and benefits of treatment as well as increased adherence to therapies.Conclusions: The adverse effects of LDL-cholesterol and apo B containing lipoprotein exposure are cumulative and result in ASCVD. These are preventable by implementation of different strategies, aimed at efficiently tackling atherosclerosis at different stages throughout the human life-course. Preventive strategies should therefore be updated to implement health policy, lifestyle changes and when needed pharmacotherapies earlier with investment in, and a shift in focus towards, early preventive strategies that preserve cardiovascular health rather than treat the consequences of ASCVD.

In this second part of the review of the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), the findings in relation to patients with stroke, the ACS phenotype, history of coronary artery bypass graft surgery, heart failure, concurrent polyvascular atherosclerotic cardiovascular disease (ASCVD) and diabetes mellitus, and different levels of expression of selected cardiovascular biomarkers, are discussed. The combination therapy was proven safe, and drug discontinuation rates were not increased by adding ezetimibe. Since both statins and ezetimibe are now almost globally generically available, it can be concluded that for secondary prevention of ASCVD, adding ezetimibe to high-intensity statin therapy further reduces low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk, cost-effectively.

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality in the United States (U.S.) and incurs significant cost to the healthcare system. Management of cholesterol remains central for ASCVD prevention and has been the focus of multiple national guidelines. In this review, we compare the American Heart Association (AHA)/American College of Cardiology (ACC) and the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) Cholesterol guidelines. We review the evidence base that was used to generate recommendations focusing on 4 distinct themes: 1) the threshold of absolute 10-year ASCVD risk to start a clinician-patient discussion for the initiation of statin therapy in primary prevention patients; 2) the utility of coronary artery calcium score to guide clinician-patient risk discussion pertaining to the initiation of statin therapy for primary ASCVD prevention; 3) the use of moderate versus high-intensity statin therapy in patients with established ASCVD; and 4) the utility of ordering lipid panels after initiation or intensification of lipid lowering therapy to document efficacy and monitor adherence to lipid lowering therapy. We discuss why the VA/DoD and AHA/ACC may have reached different conclusions on these key issues.

Background Although statins reduce cardiovascular morbidity and mortality, only about one-half of eligible patients receive treatment. Safe and appropriate consumer access to statins could have a significant positive public health impact. Objectives This study compares the concordance between a participant and clinician assessment of eligibility for statin therapy using a technology-assisted approach. Methods A total of 500 participants, 83 with limited literacy, completed an at-home Web-based application to assess appropriateness for treatment with rosuvastatin 5 mg. The Web application is designed to assess eligibility for a moderate-intensity statin based on current guidelines and deny access to individuals with contraindications to rosuvastatin. Subsequently, participants visited a research site where clinicians, blinded to the information the participant entered, performed an independent Web application assessment. The Web application is programmed for 1 of 3 rosuvastatin treatment outcomes: “OK to use,” “not right for you,” or “ask a doctor.” The primary endpoint was the percent of participants whose self-selected eligibility for nonprescription rosuvastatin was concordant with clinician assessment. Results For the primary endpoint, participant selection for statin therapy was concordant with clinician selection in 481 (96.2%) of 500 participants (95% confidence interval: 94.1%-97.7%), of whom 23 (4.6%) were deemed appropriate and 458 (91.6%) were deemed inappropriate for treatment. Discordance was due to incorrect self-selection (“OK to use”) in 3 cases, incorrect rejection (“not right for you”) in 14 cases and an incorrect “ask a doctor” outcome in 2 cases. Conclusions The use of a technology-assisted approach to consumer self-selection for statin therapy resulted in participant self-selection that showed substantial agreement with clinician selection.

Statins, a class of lipid-lowering drugs, reduce morbidity and mortality in patients with established atherosclerosis-related cardiovascular disease. Early initiation of statin therapy after admission for acute coronary syndromes (ACS), stroke, or transient ischemic attack (TIA) is associated with improved cardiovascular outcomes. Moreover, high-dose statin treatment prior to coronary or carotid revascularization has been shown to reduce cardiovascular events in these patients. However, many patients may be undertreated, and a residual cardiovascular risk remains in current clinical practice. Despite the beneficial role of statins, their discontinuation rate among patients is still elevated leading to severe adverse cardiovascular events due to atherosclerotic plaque destabilization. In this review, we summarized the impact of statin treatment among patients, focusing on the initiation time-points as well as the potential harm derived by their discontinuation.

Background: The mevalonate pathway generates endogenous cholesterol and intermediates including geranylgeranyl pyrophosphate (GGPP). By reducing GGPP production, statins exert pleiotropic or cholesterol-independent effects. The potential regulation of GGPP homeostasis through dietary intake and the interaction with concomitant statin therapy is unknown. Methods: We developed a sensitive high-pressure liquid chromatography technique to quantify dietary GGPP and conducted proteomics, qualitative real-time polymerase chain reaction screening, and Western blot to determine signaling cascades, gene expression, protein–protein interaction, and protein membrane trafficking in wild-type and transgenic rats. Results: GGPP contents were highly variable depending on food source that differentially regulated blood GGPP levels in rats. Diets containing intermediate and high GGPP reduced or abolished the effects of statins in rats with hypoxia- and monocrotaline-induced pulmonary hypertension: this was rescuable by methyl-allylthiosulfinate and methyl-allylthiosulfinate–rich garlic extracts. In human pulmonary artery smooth muscle cells treated with statins, hypoxia activated RhoA in an extracellular GGPP-dependent manner. Hypoxia-induced ROCK2 (Rho associated coiled-coil containing protein kinase 2)/Rab10 (Ras-related protein rab-10) signaling was prevented by statin and recovered by exogenous GGPP. The hypoxia-activated RhoA/ROCK2 pathway in rat and human pulmonary artery smooth muscle cells upregulated the expression of Ca 2+ -sensing receptor (CaSR) and HIMF (hypoxia-induced mitogenic factor), a mechanism attenuated by statin treatment and regained with exogenous GGPP. Rab10 knockdown almost abrogated hypoxia-promoted CaSR membrane trafficking, a process diminished by statin and resumed by exogenous GGPP. Hypoxia-induced pulmonary hypertension was reduced in rats with CaSR mutated at the binding motif of HIMF and the interaction between dietary GGPP and statin efficiency was abolished. In humans fed a high GGPP diet, blood GGPP levels were increased. This abolished statin-lowering effects on plasma GGPP, and also on hypoxia-enhanced RhoA activity of blood monocytes that was rescued by garlic extracts. Conclusions: There is important dietary regulation of GGPP levels that interferes with the effects of statin therapy in experimental pulmonary hypertension. These observations rely on a key and central role of RhoA-ROCK2 cascade activation and Rab10-faciliated CaSR membrane trafficking with subsequent overexpression and binding of HIMF to CaSR. These findings warrant clinical investigation for the treatment of pulmonary hypertension and perhaps other diseases by combining statin with garlic-derived methyl-allylthiosulfinate or garlic extracts and thus circumventing dietary GGPP variations.

Epidemiologists have claimed for decades that about 50% of predisposition for coronary artery disease (CAD) is genetic. Advances in technology made possible the discovery of hundreds of genetic risk variants predisposing to CAD. Multiple clinical trials have shown that cardiac events can be prevented by drugs to lower plasma low‐density lipoprotein cholesterol (LDL‐C). A major barrier to primary prevention is the lack of markers to identify those individuals at risk prior to the development of symptoms of the disease. Conventional risk factors are age‐dependent, occurring mostly in the sixth or seventh decade, which is less than desirable for early primary prevention. A polygenic risk score, derived from the number of genetic risk variants predisposing to CAD inherited by an individual, has been evaluated in over 1 million individuals. The risk for CAD is stratified into high, intermediate, and low. Polygenic risk scores derived from retrospective genotyping of several clinical trials evaluating the effect of statin therapy or PCSK9 inhibitors show the genetic risk is reduced 40%–50% by decreasing plasma LDL‐C. Prospective randomized placebo‐controlled clinical trials document a 40%–50% reduction in cardiac events in individuals at high genetic risk associated with favorable lifestyle changes and increased physical activity. The polygenic risk score is not age‐dependent and remains the same throughout life. Thus, the GRS is superior to conventional risk factors in identifying asymptomatic individuals at risk for CAD early in life for primary prevention. These results indicate clinical embracement of the GRS in primary prevention would be a paradigm shift in the treatment of the number one killer, CAD.

Therapeutic intervention should be determined by the risk of developing atheromatous cardiovascular disease (CVD). The higher the risk, the more intense the action should be. This is the reason for the stratification of patient risk. In primary prevention, the two main guidelines used, the American Heart Association and the American College of Cardiology (ACC/AHA) use the Pooled cohort equations (PCE) and the guidelines of the European societies use the SCORE tables. The PCE calculates the risk of fatal and non-fatal CVD, and the SCORE calculates risk of fatal CVD only. In young people, it is useful to consider the lifetime risk calculation. The Spanish Society of Arteriosclerosis (SEA) recommends the SCORE system in Spain. SCORE and PCE calculate the risk for people up to 70 and 75 years of age. Prediction and potentials are available for 80 years of age and above, with the data available being much more scarce. Risk stratification in secondary prevention may be useful to identify the subgroup of patients who may benefit from more intensive treatment. Imaging tests, especially coronary calcium scans and vascular ultrasound, can help to better the profile risk. European guidelines identify LDL cholesterol as a therapeutic target. They recommend initiating treatment with statins, and increasing dose and potency until targets are achieved, and then to treatment with potent statins at a maximum tolerated dose, and ezetimibe if targets are not achieved. As a third step, PCSK9 inhibitors are indicated. They set very ambitious targets, as low as 40 mg/dL in those subjects with recurrences before two years of CVD despite high-intensity statin therapy, and below 55 mg/dL for all very high-risk subjects.

Despite trial evidence, high intensity statins are underutilized in routine clinical practice. This study sought to assess the individual and joint contributions of the TRS2P score as a measure of residual risk and LDL-C levels to benefits from further LDL-C lowering in the TNT trial.A total of 9980 patients were divided into 4 groups based on TRS2P and LDL-C at baseline:median TRS2P andmedian LDL-C (group 1),median TRS2P and ≥median LDL-C (group 2), ≥median TRS2P andmedian LDL-C (group 3), ≥median TRS2P and ≥median LDL-C (group 4). The effect of atorvastatin 80 mg vs. 10 mg on the risk of any cardiovascular event was assessed among the groups.Percentage reductions in LDL-C with atorvastatin 80 mg were consistent across groups, whereas absolute reductions were approximately 11 mg/dL greater when LDL-C was ≥median. Despite atorvastatin 10 mg, either TRS2P ≥ median or LDL-C ≥ median were associated with more events and highest when both were ≥median (groups 1-4; 21.5%, 28.1%, 36.3%, and 40.5%, respectively; p-trend0.0001. Although relative benefits were similar, absolute risk reduction from atorvastatin 80 mg was lowest when both scores weremedian (1.3%, group 1) and highest when both weremedian (7.2%, group 4), NNT 78 vs. 14 (p-interaction0.0001).Measures of residual risk as well LDL-C identify patients who remain at high risk despite statins with the combination identifying those who derive the greatest benefits from even modest additional LDL-C lowering. Attention to residual risk as well as LDL-C may further help to optimize guideline implementation.

Purpose of review Triglycerides (TGs) are measured as part of routine lipid profiles but their relationship to cardiovascular disease (CVD) risk has been controversial and overshadowed by high-density lipoprotein cholesterol (HDL-C). Recent findings Epidemiological studies show a clear relationship of TG-containing lipoproteins including remnant particles with CVD risk with the effect being most clearly demonstrated through the excess risk captured by non-HDL-C compared with low-density lipoprotein-cholesterol (LDL-C). Mendelian randomisation studies show a consistent relationship of gene variants linked to TG metabolism with rates of CVD. Furthermore, meta-analyses of intervention trials with statins and other nonstatin drugs also suggest that reducing TGs is associated with benefits on rates of CVD events. Historical subgroup data from fibrate trials suggest benefits in patients with high TG:HDL ratios but seem to add little to optimized statin therapy. Recent trials with omega-3 fatty acids (specifically eicosapentaenoic acid) have suggested that high-dose formulations in contrast to low dose formulations have benefits on CVD outcomes. Summary Further studies with newer agents are required to determine the place of TG-lowering drugs in therapeutic pathways. Trials with agents such as pemafibrate and vupanorsen may finally answer these questions.

Background: Patients with elevated triglycerides despite statin therapy have increased risk for ischemic events, including coronary revascularizations. Methods: REDUCE-IT (The Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial), a multicenter, double-blind, placebo-controlled trial, randomly assigned statin-treated patients with elevated triglycerides (135–499 mg/dL), controlled low-density lipoprotein (41–100 mg/dL), and either established cardiovascular disease or diabetes plus other risk factors to receive icosapent ethyl 4 g/d or placebo. The primary and key secondary composite end points were significantly reduced. Prespecified analyses examined all coronary revascularizations, recurrent revascularizations, and revascularization subtypes. Results: A total of 8179 randomly assigned patients were followed for 4.9 years (median). First revascularizations were reduced to 9.2% (22.5/1000 patient-years) with icosapent ethyl versus 13.3% (33.7/1000 patient-years) with placebo (hazard ratio, 0.66 [95% CI, 0.58–0.76]; P P P P =0.0005). Conclusions: Icosapent ethyl reduced the need for first and subsequent coronary revascularizations in statin-treated patients with elevated triglycerides and increased cardiovascular risk. To our knowledge, icosapent ethyl is the first non–low-density lipoprotein–lowering treatment that has been shown to reduce coronary artery bypass grafting in a blinded, randomized trial. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.

Background Statin persistence and adherence are low among US adults. Most individuals with HIV in the US have high adherence to antiretroviral therapy (ART), but less is known about their statin persistence and adherence. Objectives We analyzed persistence and adherence to statin therapy among adults with and without HIV. Methods We analyzed claims data from adults in the MarketScan database who initiated statin therapy between 2007 and 2016. People with HIV (n = 5619) were frequency matched 1-to-4 to those without HIV (n = 22,476) based on age, sex, and calendar year of statin initiation. Statin persistence was defined by having dispensed statin medication during the last 90 days of the 365 days following initiation. High statin adherence was defined as a proportion of days covered (PDC) ≥0.80 during the 365 days following initiation. Among people with HIV, the PDC for each ART was calculated. Results The mean age of the study population was 51 years and 85.8% were men. Statin persistence was higher among adults with versus without HIV (72.8% versus 65.2%, multivariable-adjusted prevalence ratio 1.13, 95%CI 1.11–1.15). Among those who were persistent, a higher proportion of people with versus without HIV had high statin adherence (69.6% versus 59.9%, multivariable-adjusted prevalence ratio 1.16, 95%CI 1.13–1.19). Among people with HIV and high ART adherence (minimum PDC ≥0.90), 34.6% had a PDC for statin therapy Conclusion Adults with HIV were more persistent and adherent to statin medications versus those without HIV. However, a high proportion of adults with HIV had low statin adherence.

Background and aims In familial hypercholesterolemia (FH), statin treatment should be considered from 8 to 10 years of age, but the prevalence of statin use among children is not known. Methods Statin use (2008–2018) among children aged 10–14 and 15–19 years was obtained from the national prescription databases in Norway, Sweden and Denmark. We assumed that all statin users in these age groups had FH, and that the estimated prevalence of FH is 1 in 250 inhabitants. Changes in prevalence rates of statin use between 2008 and 2018 by country, age and sex were estimated using the Joinpoint Regression Program version 4.8.0.1. Differences in prevalence rate ratio each year between countries were analyzed using Poisson regression. Results Among children aged 10–14 years, there was a significant increase in statin use in Norway and Denmark between 2008 and 2018, while in Sweden an increase was only seen after 2014. Among children aged 15–19 years, an increase in statin use was only observed in Norway and Sweden between 2008 and 2018. Statin use was significantly more prevalent in Norway than in Sweden and Denmark each year, and in 2018 the proportion of children using statins was 4–5 times (10–14 years) and 3 times (15–19 years) higher in Norway compared with Sweden and Denmark. In 2018 in Norway, 19% and 35% of children aged 10–14 years and 15–19 years estimated to have FH used statins respectively; corresponding percentages in Sweden were 4.5% and 10%, and in Denmark 3% and 12%. In Norway, the increase in statin use between 2008 and 2018 roughly corresponded to the increase in children with genetically verified FH. Conclusions Between 2008 and 2018, statin use increased in children aged 10–19 years in Norway, Sweden and Denmark, but with large differences between the countries; statin use was 3–5 times more prevalent in Norway than in Sweden and Denmark, which may be due to a more widespread use of genetic testing for FH in Norway.

Background and aims: Statins suppress hepatic mRNA expression of ANGPTL3 encoding angiopoietin-like 3 in healthy subjects, but it is unknown if plasma ANGPTL3 concentrations are affected by statins prescribed to hypercholesterolemic patients in clinical practice. We therefore investigated the effect of statin treatment on plasma ANGPTL3 concentrations in hypercholesterolemic patients. In addition, we explored the underlying mechanism by which statins regulate ANGPTL3 in vitro. Methods: Plasma ANGPTL3 concentrations were measured in 93 genetically confirmed familial hypercholesterolemia (FH) patients who were using statin therapy and 61 statin naïve FH patients. Moreover, concentrations were measured in 14 hypercholesterolemic patients who discontinued their statin treatment for 4 weeks. In vitro studies were performed with Huh7 human hepatoma cells. Results: Plasma ANGPTL3 concentrations were 15% lower in statin treated FH patients compared to statin naïve FH patients (145 (120-193) vs. 167 (135-220) ng/ml, p = 0.012). Statin discontinuation resulted in a 21% (p

Statin therapy reduces low-density lipoprotein cholesterol (LDL-C), inflammation, and atherosclerotic cardiovascular disease. We investigated the association between LDL-C and statin therapy on the prevalence of plaque rupture (PR). Patients with acute coronary syndromes who underwent optical coherence tomography imaging of the culprit lesion were divided into 4 groups based on LDL-C level and statin use (Group 1: LDL-C ≤ 100 without statin; Group 2; LDL-C ≤ 100 with statin; Group 3: LDL-C > 100 with statin; Group 4: LDL-C > 100 without statin), and the prevalence of PR was compared between the groups. Among 896 patients, PR was diagnosed in 444 (49.6%) patients. The prevalence of PR was significantly different among the 4 groups (p = 0.007): it was highest in the high LDL-C without statin group and lowest in the low LDL-C without statin group (53.9% and 39.2%, respectively). Compared with the high LDL-C without statin group, the low LDL-C without statin and low LDL-C with statin groups had a significantly lower prevalence of PR (p = 0.001, p = 0.040, respectively), and the low LDL-C with statin group had a significantly higher prevalence of calcification (p = 0.037). The patients with naturally low LDL-C have the lowest risk of PR. The patients with low LDL-C achieved by statin therapy had a higher prevalence of calcification. When LDL-C level is elevated, early and aggressive treatment with statin may help to prevent PR by stabilizing plaques through calcification.

Background Guidelines recommend adults who discontinue statin therapy because of statin-associated symptoms be reinitiated. Low-density lipoprotein cholesterol (LDL-C) levels achieved after statin reinitiation are unknown. Objective The objective of this study was to determine LDL-C levels after statin reinitiation. Methods We analyzed data from 5498 participants in the REasons for Geographic And Racial Differences in Stroke study who reported ever taking a statin. We categorized participants according to their pattern of statin use including those taking a statin who did not experience statin-associated symptoms and continued treatment, and those who discontinued statins because of statin-associated symptoms and were not reinitiated, reinitiated and remained on treatment, and discontinued treatment after being reinitiated. Mortality and vascular event reduction with statin reinitiation was estimated using data from the Cholesterol-Lowering Treatment Trialists Collaboration. Results After multivariable adjustment, LDL-C was 14.1 (95% CI: 9.9–18.3) mg/dL higher among participants reinitiated and taking a statin compared with those without statin-associated symptoms who continued statin therapy. Mean LDL-C was 18.1 mg/dL (95% CI: 13.0–23.1) and 27.5 mg/dL (95% CI: 20.7–34.4) lower among participants reinitiated and taking a statin compared with those who discontinued statin therapy and were not reinitiated and those who discontinued statins after being reinitiated, respectively. An LDL-C reduction of 18.1 mg/dL with statin reinitiation was projected to reduce all-cause and coronary heart disease mortality by 5.6% and 8.9%, respectively, and myocardial infarction or coronary heart disease death and major vascular events by 10.7% and 9.8%, respectively, over 5 years. Conclusion Reinitiating individuals who discontinue statin therapy may reduce LDL-C and cardiovascular risk.

Background Rates of statin use among minority women are unclear. Hypothesis We hypothesized that statin use would vary by race/ethnicity with lower rates among minority women compared with Whites. Methods Data from the study of women's health across the nation, a multiethnic cohort of women collected between 2009 to 2011 were used to examine reported statin use by race/ethnicity and risk profile. Multivariable logistic modeling was performed to estimate the odds ratio (OR) of statin treatment. Results Of the 2399 women included, 234 had a diagnosis of atherosclerotic disease (ASCVD), 254 were diabetic (without ASCVD), 163 had an LDL ≥190 mg/dL, and 151 had a 10 year ASCVD pooled risk score ≥7.5%. Statins were used by 49.6% of women with CVD; 59.8% of women with diabetes without known ASCVD; 42.3% of women with an LDL ≥190 mg/dL; and 19.9% of women with an ASCVD risk ≥7.5%. Rates of statin use were 43.8% for women with ≥ two prior ASCVD events and 69.4% for women with ≥ one prior ASCVD event plus multiple high‐risk conditions. Among women eligible for statins, Black women had a significantly reduced adjusted odds of being on a statin (OR 0.53, 95% confidence interval [CI] 0.36‐0.78) compared with White women. Conclusions In this cohort of multiethnic women, rates of statin use among women who would benefit were low, with Black women having lower odds of statin use than White women.

BACKGROUND Statins have an important and well-established role in the prevention of atherosclerotic cardiovascular disease (ASCVD). However, several studies have reported widespread underuse of statins in various practice settings and populations. Review of relevant literature reveals opportunities for improvement in the implementation of guideline-directed statin therapy (GDST). AIM To examine the impact of cardiologist intervention on the use of GDST in the ambulatory setting. METHODS Patients with at least one encounter at the adult Internal Medicine Clinic (IMC) and/or Cardiology Clinic (CC), who had an available serum cholesterol test performed, were evaluated. The 2 comparison groups were defined as: (1) Patients only seen by IMC; and (2) Patients seen by both IMC and CC. Patients were excluded if variables needed for calculation of ASCVD risk scores were lacking, and if demographic information lacked guideline-directed treatment recommendations. Data were analyzed using student t-tests or χ2, as appropriate. Analysis of Variance was used to compare rates of adherence to GDST. RESULTS A total of 268 patients met the inclusion criteria for this study; 211 in the IMC group and 57 in the IMC-CC group. Overall, 56% of patients were female, mean age 56 years (± 10.65, SD), 22% Black or African American, 56% Hispanic/Latino, 14% had clinical ASCVD, 13% current smokers, 66% diabetic and 63% hypertensive. Statin use was observed in 55% (n = 147/268) of the entire patient cohort. In the IMC-CC group, 73.6% (n = 42/57) of patients were prescribed statin therapy compared to 50.7% (n = 107/211) of patients in the IMC group (P = 0.002). In terms of appropriate statin use based on guidelines, there was no statistical difference between groups [IMC-CC group 61.4% (n = 35/57) vs IMC group, 55.5% (n = 117/211), P = 0.421]. Patients in the IMC-CC group were older, had more cardiac risk factors and had higher proportions of non-white patients compared to the IMC group (P < 0.02, all). CONCLUSION Although overall use of GDST was suboptimal, there was no statistical difference in appropriate statin use based on guidelines between groups managed by general internists alone or co-managed with a cardiologist. These findings highlight the need to design and implement strategies to improve adherence rates to GDST across all specialties.

Background:The use of statins in children, although not frequent, is recommended in specific clinical contexts, namely, familial hypercholesterolaemia, conditions carrying a moderate-high cardiovascular risk and sub-optimal cholesterol levels after implementation of lifestyle modifications. The aim of this study is to characterise children with dyslipidaemia managed with statins, followed at a tertiary referral centre in central Portugal.Methods and results:The authors carried out a retrospective and descriptive study made up of 66 patients (50% males, mean age of therapy onset 11.9 years) followed up at the Cardiovascular Clinic of a tertiary referral centre between January, 2012, and May, 2018. Clinical, analytical, and echocardiographic parameters were analysed. About 60.6% had clinical and/or molecular diagnosis of familial hypercholesterolaemia. On average, each patient had three cardiovascular risk factors, obesity (31%) being most prevalent, followed by arterial hypertension (14%). Statin therapy showed a statistically significant reduction in the lipid profile, particularly in the total cholesterol (23%) and low-density lipoprotein cholesterol (30%) levels, as well as in the carotid intima-media thickness (p = 0.015). Hepatic and muscle integrity markers were within normal range.Conclusions:Statins are safe and efficient in the management of children with hypercholesterolaemia. Our study showed that apart from its lipid-lowering properties, it also reduced significantly the carotid intima-media thickness and, implicitly, the cardiovascular risk of these patients.

Purpose of review Lipid-lowering therapies play a major role in reducing atherosclerotic cardiovascular disease (ASCVD). This article reviews the most recent lipid-lowering therapy trials, many of which provide a unique opportunity to further reduce low-density lipoprotein cholesterol (LDL-C) levels and ASCVD risk on top of statin therapy, and in doing so further decrease the number of future major adverse cardiovascular events. Recent findings Although statin therapy has been the mainstay of treatment for lowering LDL-C levels for many years, many individuals require additional or alternative options for further reducing their risk. Trials on previously studied therapies, such as PCSK9 inhibitors, and new therapies, including inclisiran, bempedoic acid and icosapent ethyl demonstrate significant potential for further lowering of LDL-C levels and risk for events on top of maximally tolerated statin therapy with favourable side effect profiles. Summary As therapies for ASCVD prevention continue to emerge, clinicians will need to identify the appropriate treatment for individuals based on their estimated risk and risk-enhancing factors. When statin therapy is either not sufficient or patients do not tolerate adequate statin therapy, relying on newer therapies, such as PCSK9-inhibitors, inclisiran, bempedoic acid and icosapent ethyl, will be critical to maximize risk factor profiles to reduce adverse outcomes.

Familial hypercholesterolaemia (FH) is caused by a major genetic defect in the low-density lipoprotein (LDL) clearance pathway. Characterised by LDL-cholesterol elevation from birth, FH confers a significant risk for premature coronary artery disease (CAD) if overlooked and untreated. With risk exposure beginning at birth, early detection and intervention is crucial for the prevention of CAD. Lowering LDL-cholesterol with lifestyle and statin therapy can reduce the risk of CAD. However, most individuals with FH will not reach guideline recommended LDL-cholesterol targets. FH has an estimated prevalence of approximately 1:250 in the community. Multiple strategies are required for screening, diagnosing and treating FH. Recent publications on FH provide new data for developing models of care, including new therapies. This review provides an overview of FH and outlines some recent advances in the care of FH for the prevention of CAD in affected families. The future care of FH in Australia should be developed within the context of the National Health Genomics Policy Framework.

Publisher Copyright: © 2022 The Author(s) Background and Purpose: We aimed to assess the association between covert atherosclerosis, arterial stiffness, and early-onset cryptogenic ischemic stroke (CIS) in a prospective case-control study. Methods: We enrolled 123 young CIS patients (median age 41 years; 42% women) and 123 age- and sex-matched controls. Carotid intima-media thickness (CIMT), Augmentation Index (AIx), central pulse wave velocity (PWV), and subendocardial viability ratio (SEVR) were compared between patients and controls. Conditional logistic regression was used adjusting for age, systolic blood pressure, diastolic blood pressure, current smoking, total cholesterol/high-density lipoprotein cholesterol (Total-C/HDL-C) ratio, and glycated albumin to assess the independent association between CIMT, arterial stiffness and CIS. Results: Patients with higher CIMT and PWV were older, more often men and they had more frequently well-documented risk factors, lower HDL and higher Total-C/HDL-C ratio compared to other tertiles. In univariate comparisons, we found no differences between patients and controls regarding CIMT, AIx, or PWV. In the entire cohort, patients had a significantly lower SEVR compared to controls (146.3%, interquartile range [IQR] 125.7-170.3 vs. 158.0%, IQR 141.3-181.0, P=0.010). SEVR was lower also in women compared to their controls (132.0%, IQR 119.4-156.1 vs. 158.7%, IQR 142.0-182.8, P=0.001) but no significant difference appeared between male patients and male controls. However, after adjusting for comorbidities and laboratory values these significant differences were lost (odds ratio [OR] 1.52, 95% confidence interval [CI] 0.47-4.91) in the entire cohort and OR 3.89, 95% CI 0.30-50.80 in women). Conclusions: Higher CIMT and PWV were associated to higher age, male sex, and several well-documented cardiovascular risk factors. However, in this study we could not prove that either covert atherosclerosis or arterial stiffness contribute to pathogenesis of early-onset CIS.

Purpose Low-density lipoprotein cholesterol (LDL-C) recommendations differ between the 2018 American College of Cardiology/American Heart Association (ACC/AHA) and 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines for patients with atherosclerotic cardiovascular disease (ASCVD) (vs. Methods DA VINCI was a cross-sectional observational study of patients prescribed lipid-lowering therapy (LLT) across 18 European countries. Ten-year cardiovascular risk (CVR) was predicted among ASCVD patients receiving stabilized LLT. For patients with LDL-C ≥ 70 mg/dl, the absolute LDL-C reduction required to achieve an LDL-C of Results Of the 2039 patients, 61% did not achieve LDL-C Conclusion In ASCVD patients, achieving ESC/EAS LDL-C goals could result in a 2% additional ARR over 10 years versus the ACC/AHA approach. Graphical abstract

Aim Assessing the effect of statin therapy (ST) at hospital admission for COVID-19 on in-hospital mortality. Methods and results Retrospective observational study. Patients taking statins were 11 years older and had significantly more comorbidities than patients who were not taking statins. A genetic matching (GM) procedure was performed prior to analysis of the mortality risk. A Cox proportional hazards model was used for the cause-specific hazard (CSH) function, and a competing-risks Fine and Gray (FG) model was also used to study the direct effects of statins on risk. Data from reverse transcription-polymerase chain reaction-confirmed 2157 SARS-CoV-2-infected patients [1234 men, 923 women; age: 67 y/o (IQR 54–78)] admitted to the hospital were retrieved from the clinical records in anonymized manner. Three hundred and fifty-three deaths occurred. Five hundred and eighty-one patients were taking statins. Univariate test after GM showed a significantly lower mortality rate in patients on ST than the matched non-statin group (19.8% vs. 25.4%, χ2 with Yates continuity correction: P = 0.027). The mortality rate was even lower in patients (n = 336) who maintained their statin treatments during hospitalization compared with the GM non-statin group (17.4%; P = 0.045). The Cox model applied to the CSH function [HR = 0.58(CI: 0.39–0.89); P = 0.01] and the competing-risks FG model [HR = 0.60 (CI: 0.39–0.92); P = 0.02] suggest that statins are associated with reduced COVID-19-related mortality. Conclusions A lower SARS-CoV-2 infection-related mortality was observed in patients treated with ST prior to hospitalization. Statin therapy should not be discontinued due to the global concern of the pandemic or in patients hospitalized for COVID-19.

Background The debate about statins in primary prevention of cardiovascular (CV) disease is still alive, especially in old and very old adults. Purpose We undertook a propensity match-weighted cohort study to investigate whether statin treatment recommendations translate into improved cardiovascular (CV) outcomes in the current routine clinical care of the elderly. Methods We included in our analysis 5,619 people aged 65 years or older from the ISACS (International Survey of Acute Coronary Syndrome) Archives (NCT04008173) who presented to hospital with a first manifestation of CV disease. Participants were stratified as statin users versus nonusers and as old (65 to 75 years) versus very old (76 years or over) adults. We estimated the effects of statins on the most severe clinical manifestation of CV disease, namely ST segment elevation myocardial infarction (STEMI), using inverse probability of treatment weighting models. Estimates were compared by test of interaction on the log scale. Results The risk of STEMI was much lower in statin users than in nonusers in both patients aged 65 to 75 years (14.7% absolute risk reduction; relative risk [RR] ratio: 0.55, 95% CI 0.45 to 0.66) and those aged 76 years and older (13.3% absolute risk reduction; RR ratio: 0.58, 95% CI 0.46 to 0.72). Estimates were similar in patients with and without history of hypercholesterolemia (interaction test; p value= 0.2408). Proportional reductions in STEMI diminished with female sex in the old (p for interaction=0.002), but not in the very old age (p for interaction=0.26). We also observed a remarkable reduction in the risk of 30- day mortality from STEMI with statin therapy in both age groups (10.2% absolute risk reduction; RR ratio: 0.39; 95% CI 0.23 – 0.68 for patients aged 76 or over and 3.8% absolute risk reduction; RR ratio 0.37; 95% CI 0.17 – 0.82 for patients aged 65 to 75 years old; interaction test, p value=0.4570). Conclusion Preventive statin therapy in the elderly reduces the risk of STEMI with benefits in mortality from STEMI, irrespective of the presence of a history of hypercholesterolemia. This effect persists after the age of 76 years. Benefits are less pronounced in women. Funding Acknowledgement Type of funding sources: None.

Introduction High-dose statin therapy (HIST) halts coronary plaque progression and reduces the risk of cardiovascular events by increasing atheroma calcification. The Agatston score is well established in the clinical routine for assessment of coronary artery calcification using non-contrast computed tomography. However, randomized controlled trials failed to detect an influence of HIST vs. low-to-intermediate statin therapy (LIST) on the Agatston and CAC volume score after one year. Coronary plaques with lower density including spotty calcifications may represent dynamic and early stages of atherosclerosis. We evaluated whether CAC density differentiates in HIST- vs. LIST-treated patients after one year. Methods The meta-analysis contains data from two prospective, randomized, double-blind studies (BELLES, EBEAT) that were designed to detect CAC changes after one year comparing HIST vs. LIST. In both studies, patient's coronary calcification burden was measured at baseline and one-year follow-up using electron beam computed tomography (EBCT). Patients data were pooled and stratified by intensity of statin therapy. Furthermore, the cohort was divided into several subgroup analyses, accounting for LDL-Cholesterol reduction, initial Agatston score and a consistent number of lesions. Results Data from 852 patients, 66% female were included. The amount of CAC overall increased after 1 year [Agatston score: 169.3 (80.0, 377.1) vs. 214.9 (95.4, 450.0); p Conclusion HIST vs. LIST leads to a higher reduction in cholesterol levels, which does not translate into relevant differences in the change of CAC density at one-year follow-up. Funding Acknowledgement Type of funding sources: None.

Aim. To study lipid-lowering therapy in patients with high and very high risk of cardiovascular events (CVEs) at the outpatient and inpatient care stages in Irkutsk.Material and methods. We analyzed 260 discharge summaries of patients with hypertension of high and very high risk of CVEs for the second half of 2019: 145 — from a hospital; 115 — from outpatient records. Patient adherence to statin therapy, achievement of target lowdensity lipoprotein cholesterol (LDL-C) levels in each patient subgroup was assessed.Results. The proportion of patients who reached the recommended LDL-C levels in accordance with the 2017 guidelines tends to increase in comparison with prior data. High adherence to lipid-lowering therapy was accompanied by an increase in the proportion of patients reaching the recommended LDL-C levels. In most cases, regardless of cardiovascular risk, low-dose statin therapy were used. A detailed analysis of adherence to statin therapy using questionnaires revealed that more than half of patients in high-risk categories (64%) did not comply with lipid-lowering therapy.Conclusion. Favorable trends were revealed in relation to an increase in the proportion of high-risk patients reaching target LDL-C levels. Adherence to statin therapy remains low. Previously established problems in managing such patients remains: stereotyped lipid-lowering therapy prescriptions without taking into account cardiovascular risk, the use of low-dose therapy, and the frequent prescription of statins with a lower lipid-lowering effect. Inpatients use higher statin doses than outpatients.

Background Patients with risk factors or established atherosclerotic cardiovascular disease remain at high‐risk for ischemic events. Triglyceride levels may play a causal role. Methods and Results We performed a retrospective study of adults aged ≥45 years receiving statin therapy, with a low‐density lipoprotein cholesterol of 41 to 100 mg/dL, and ≥1 risk factor or established atherosclerotic cardiovascular disease between 2010 and 2017. Outcomes included death, all‐cause hospitalization, and major adverse cardiovascular events (myocardial infarction, stroke, or peripheral artery disease). The study sample included 373 389 primary prevention patients and 97 832 secondary prevention patients. The primary prevention cohort had a mean age of 65±10 years, with 51% women and 44% people of color, whereas the secondary prevention cohort had a mean age of 71±11 years, with 37% women and 32% people of color. Median triglyceride levels for the primary and secondary prevention cohorts were 122 mg/dL (interquartile range, 88–172 mg/dL) and 116 mg/dL (interquartile range, 84–164 mg/dL), respectively. In multivariable analyses, primary prevention patients with triglyceride levels ≥150 mg/dL were at lower adjusted risk of death (hazard ratio [HR], 0.91; 95% CI, 0.89–0.94) and higher risk of major adverse cardiovascular events (HR, 1.14; 95% CI, 1.05–1.24). In the secondary prevention cohort, patients with triglyceride levels ≥150 mg/dL were at lower adjusted risk of death (HR, 0.95; 95% CI, 0.92–0.97) and higher risk of all‐cause hospitalization (HR, 1.03; 95% CI, 1.01–1.05) and major adverse cardiovascular events (HR, 1.04; 95% CI, 1.05–1.24). Conclusions In a contemporary cohort receiving statin therapy, elevated triglyceride levels were associated with a greater risk of atherosclerotic cardiovascular disease events and lower risk of death.

Background Conflicting data suggest that statins could cause hepatitis in certain group of patients, while improving prognosis in patients affected by some chronic liver diseases. Therefore, we aimed to quantify the potential protective role of statins on some main liver-related health outcomes in clinical studies on patients affected by hepatitis. Methods We applied fixed-effects or random-effects meta-analyses with inverse variance weighting to calculate pooled estimates and confidence intervals (95% confidence intervals [CI]). We calculated the odds ratios (OR) and 95% CI for the targets of mortality and hepatocellular carcinoma, fibrosis, and cirrhosis. Results Nine studies (N: 195,602 patients) reported data on mortality of patients affected by chronic viral hepatitis, six studies (N: 72,960) reported data on the risk to develop hepatocellular carcinoma, two studies on fibrosis progression (N: 9678) and two studies (N: 85,205) on cirrhosis development. Statins reduce the risk to develop hepatocarcinoma (OR (95% CI) = 0.47 (0.28, 0.81), p=0.005) (Figure 1), liver fibrosis (OR (95% CI) = 0.55 (0.34, 0.87), p Conclusion Long-term treatment with statins seems to be safe in patients affected by hepatitis, while significantly improving their prognosis. Extensive education should be continued in order to avoid discontinuing statin therapy in patients with liver diseases. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Background and Aims: Statin therapy is an essential component of cardiovascular preventive care. In recent years, various vessel wall MRI (VW-MRI) techniques have been used to monitor atherosclerosis progression or regression in patients with extracranial or intracranial large-artery atherosclerosis. We aimed to perform a systematic review and meta-analysis on the effects of statin therapy on plaque evolution as assessed by VW-MRI.Materials and Methods: Prospective studies investigating carotid and intracranial atherosclerotic plaques in patients on statin therapy monitored by serial VW-MRI were systematically identified in the literature. The plaque burden and lipid-rich necrotic core (LRNC) volume of carotid plaque and the imaging features of intracranial plaques were extracted and summarized. For studies investigating carotid artery wall volume and LRNC volume, combined estimates were derived by meta-analysis.Results: The study identified 21 studies of carotid plaque and two studies of intracranial plaque. While 16 studies investigating carotid plaques that included 780 patients by High-resolution VW-MRI were included in the meta-analysis. There was no significant change in carotid wall volume from baseline to 12 months. A significant change in LRNC volume was observed at > 12 months compared with baseline (Effect = −10.69, 95% CI = −19.11, −2.28, P < 0.01), while no significant change in LRNC volume at 3–6 months or 7–12 months after statin therapy initiation in 6 studies. Increases in fibrous tissue and calcium and reduction in neovascularization density of the plaque were seen in 2/3 studies (including 48/59 patients), 1/3 studies (including 17/54 patients), and 2/2 studies (including 71 patients) after statin therapy, respectively. Two studies with 257 patients in intracranial atherosclerosis showed that statins could effectively decrease wall volume and plaque enhancement volume.Conclusions: Collective data indicated that statins could potentially stabilize carotid plaques by significantly reducing LRNC with 1 year of therapy as shown on serial carotid VW-MRI. There was no significant decrease in wall volume, which nonetheless indicated that plaque composition changes might be more sensitive to response monitoring than wall volume. It is likely that more sensitive, clinically relevant, and preferably quantitative indicators of therapeutic effects on intracranial vessel plaque morphology will be developed in the future.

Background Globalisation has seen a shift towards international multicentre randomised controlled trials (RCTs). The amalgamation of heterogenous patient populations is thought to be responsible for the geographic variation in treatment effect noted in recent trials. Furthermore, there is significant underrepresentation of lower- income countries in cardiovascular disease (CVD) research. These issues raise important questions about the generalisability of these trial results. Given the central role of statin therapy in CVD risk reduction, we evaluated for geographic variation in treatment effect in the primary and secondary prevention statin RCTs. Methods We conducted a comprehensive literature search using the terms: “statin”, “coronary disease”, “reduce” and “cholesterol”. We included statin RCTs with >1000 participants, therapy >2 years and CVD outcomes. We analysed each study for regional recruitment data and geographic subgroup analysis. Results From an initial 2154 studies, we identified 20 eligible for inclusion. This amounted to 138,612 participants across multiple continents including Europe 69,086 (49.8%), Asia 14,672 (10.6%), South America 5128 (3.7%), North America 33,393 (24.1%), Oceania 9445 (6.8%) and Africa 2801 (2%). Data were unavailable for 4087 (2.9%) participants. Despite together comprising 35% of the world's population, China and India represented only 2.7% and 1.3% of the studied population respectively. None of the 6 multi-continent trials provided regional analysis. Conclusion We were unable to identify significant geographic variation in the outcomes of the statin RCTs, primarily due to a lack of data. We also observed regarding statin RCT data, there is limited involvement of countries with the greatest burden of CVD.

Aims To estimate the proportion of patients with a recent myocardial infarction (MI) who would be eligible for additional lipid-lowering therapy according to the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines for the management of dyslipidaemias, and to simulate the effects of expanded lipid-lowering therapy on attainment of the low-density lipoprotein cholesterol (LDL-C) target as recommended by the guidelines. Methods and results Using the nationwide SWEDEHEART register, we included 25 466 patients who had attended a follow-up visit 6–10 weeks after an MI event, 2013–17. While most patients (86.6%) were receiving high-intensity statins, 82.9% of the patients would be eligible for expanded lipid-lowering therapy, as they had not attained the target of an LDL-C level of

Statin-induced necrotizing autoimmune myopathy (SINAM) is an exceptionally rare yet devastating complication of statin therapy that can occur at any time after initiation. It should be considered in patients who develop proximal muscle weakness and marked elevated creatine phosphokinase while taking statin therapy. (Level of Difficulty: Beginner.), Graphical abstract, Statin-induced necrotizing autoimmune myopathy (SINAM) is an exceptionally rare yet devastating complication of statin therapy that can occur at any…

In the ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, 18,924 patients with a recent acute coronary syndrome (ACS) not at lipid goals despite maximally tolerated statin therapy were randomized to alirocumab or placebo

Background and aims For children with heterozygous familial hypercholesterolaemia (HeFH), European guidelines recommend consideration of statin therapy by age 8–10 years for those with a low density lipoprotein cholesterol (LDL-C) >3.5 mmol/l, and dietary and lifestyle advice. Here we compare the characteristics and lipid levels in HeFH children from Norway, UK, Netherlands, Belgium, Czech Republic, Austria, Portugal and Greece. Methods Fully-anonymized data were analysed at the London centre. Differences in registration and on treatment characteristics were compared by standard statistical tests. Results Data was obtained from 3064 children. The median age at diagnosis differed significantly between countries (range 3–11 years) reflecting differences in diagnostic strategies. Mean (SD) LDL-C at diagnosis was 5.70 (±1.4) mmol/l, with 88% having LDL-C>4.0 mmol/l. The proportion of children older than 10 years at follow-up who were receiving statins varied significantly (99% in Greece, 56% in UK), as did the proportion taking Ezetimibe (0% in UK, 78% in Greece). Overall, treatment reduced LDL-C by between 28 and 57%, however, in those >10 years, 23% of on-treatment children still had LDL-C>3.5 mmol/l and 66% of those not on a statin had LDL-C>3.5 mmol/l. Conclusions The age of HeFH diagnosis in children varies significantly across 8 countries, as does the proportion of those >10 years being treated with statin and/or ezetimibe. Approximately a quarter of the treated children and almost three quarters of the untreated children older than 10 years still have LDL-C concentrations over 3.5 mmol/l. These data suggest that many children with FH are not receiving the full potential benefit of early identification and appropriate lipid-lowering treatment according to recommendations., Graphical abstract Image 1, Highlights • The age of HeFH diagnosis varies significantly between 8 European countries. • The proportion of HeFH children being treated varies across 8 European countries. • A quarter of FH children on statins have LDL-C above the target (>3.5 mmol/L). • Many FH children are not getting the full benefit of early diagnosis and treatment.

According to the Japan Atherosclerosis Society Guidelines for the Prevention of Atherosclerotic Cardiovascular Diseases 2017, standard statin therapy for hyper-low-density lipoprotein cholesterol cholesterolemia in elderly patients may be effective for the secondary prevention of coronary artery disease, as in non-elderly adults. On the other hand, high-intensity statin therapy may not be recommended in all elderly cardiovascular disease patients with dyslipidemia, and particularly in elderly patients aged ≥ 85 years. In any case, tailor-made medical care with use of statin is required that matches the background of each patient.

HMG coenzyme A reductase inhibitors (statins) significantly decrease low-density lipoprotein-cholesterol, resulting in stabilization, and in some cases regression, of atherosclerotic plaque with subsequent reduction in atherosclerotic cardiovascular disease (ASCVD) events. To date, there remains a paucity of data to guide the use of statins in young adults (20-49 years old). We herein aim to summarize the potential benefits and risks for statin therapy in younger adults, outlining a possible approach to statin use in young adults. Early identification and treatment of young individuals at risk for ASCVD offers the potential to significantly reduce the lifetime risk of ASCVD. However, there is a paucity of data on the potential side effects of long-term statin use over many decades. Comprehensive risk assessment, including calculation of life-time ASCVD risk, as well as incorporating non-traditional risk factors including lipoprotein (a), strong family history of premature ASCVD, familial hypercholesterolemia, LDL-C level and presence of underlying systemic inflammatory disorders can be helpful in identifying young adults who stand to benefit the most from statin therapy. Selective use of coronary artery calcium (CAC) assessment, as well as potentially polygenic risk scores, can be considered in situations where there remains uncertainty regarding risk assessment. Importantly, the decision for statin treatment should occur in the context of a patient centered shared decision-making process.

Aims We hypothesized that adherence to statin therapy determines survival in patients with peripheral artery disease (PAD). Methods and results Single-centre longitudinal observational study with 691 symptomatic PAD patients. Mortality was evaluated over a mean follow-up of 50 ± 26 months. We related statin adherence and low-density lipoprotein cholesterol (LDL-C) target attainment to all-cause mortality. Initially, 73% of our PAD patients were on statins. At follow-up, we observed an increase to 81% (P Conclusion Our data suggest that adherence to statin therapy is associated with reduced mortality in symptomatic PAD patients. A strategy of intensive and sustained statin therapy is recommended.

Hypertriglyceridemia (HTG) is associated with increased cardiovascular disease (CVD) risk. However, the cost burden of HTG-related CVD in high-risk US adults on statins has not been well characterized.We estimated the HTG-related health care cost burden among US adults with CVD or diabetes taking statin therapy.We estimated population sizes and annual health care costs among US adults aged ≥45 years with diabetes or CVD taking statin therapy with normal triglycerides (TGs) defined as TG 150 mg/dL compared with those with HTG defined as TG ≥ 150 mg/dL. Population sizes were estimated from the 2007-2014 National Health and Nutrition Examination Surveys. Adjusted mean total annual health care costs in 2015 US dollars were estimated using the Optum Research Database. The annual total health care cost burden was estimated by multiplying the population size by the mean annual total incremental health care costs overall and within subgroups.There were 6.2 (95% confidence interval [CI], 5.4 - 7.1) million and 12.0 (95% CI, 11.1 - 12.9) million US adults aged ≥45 years with diabetes and/or CVD on statin therapy with TG ≥ 150 mg/dL and TG 150 mg/dL, respectively. The mean adjusted incremental total one-year health care costs in adults with TG ≥ 150 mg/dL compared with those with TG 150 mg/dL was $1730 (95% CI, $1160 - $2320). This leads to a projected annual incremental cost burden associated with HTG in patients with diabetes or CVD on statins of $10.7 billion (95% CI, $6.8 B - $14.6 B).In US adults on statins and at high risk for CVD, the health care costs associated with HTG are substantial.

Aims The aim of this study was to evaluate the low-density lipoprotein cholesterol lowering efficacy and safety of a bempedoic acid 180 mg and ezetimibe 10 mg fixed-dose combination in patients with hypercholesterolemia and a high risk of cardiovascular disease receiving maximally tolerated statin therapy. Methods This phase 3, double-blind clinical trial enrolled adult patients at high risk of cardiovascular disease due to atherosclerotic cardiovascular disease, heterozygous familial hypercholesterolemia, or multiple cardiovascular disease risk factors. Patients were randomly assigned (2:2:2:1) to treatment with the fixed-dose combination, bempedoic acid 180 mg, ezetimibe 10 mg or placebo added to stable background statin therapy for 12 weeks. The primary efficacy endpoint was the percentage change from baseline to week 12 in low-density lipoprotein cholesterol. Results Among the 301 patients included in the primary analysis, the mean baseline low-density lipoprotein cholesterol level was 3.87 mmol/L (149.8 mg/dL). At week 12, the fixed-dose combination lowered low-density lipoprotein cholesterol (–36.2%) significantly more than placebo (1.8% (placebo-corrected difference –38.0%); P Conclusion The bempedoic acid and ezetimibe fixed-dose combination significantly lowered low-density lipoprotein cholesterol versus placebo or other oral monotherapies and had a favourable safety profile when added to maximally tolerated statin therapy in patients with hypercholesterolemia and high cardiovascular disease risk. Trial Registration ClinicalTrials.gov identifier: NCT03337308.

Background and aims The beneficial effect of statin therapy has been well established for both primary and secondary prevention of cardiovascular disease. Nevertheless, it remains under-used among patients with chronic kidney disease (CKD). We aimed to investigate the impact of statin therapy across a wide spectrum of CKD patients presenting with acute coronary syndrome (ACS). Methods We included all patients with ACS enrolled in the Acute Coronary Syndrome Israel Survey (ACSIS) between the years 2006 and 2016, and allocated them to 3 groups according to their renal function based on an estimated glomerular filtration rate (eGFR) calculation on admission (MDRD formula): eGFR 60 ml/min/1.73 m2 (n = 6501, 73%). Primary outcome included in-hospital, 30-day, and 1-year major adverse cardiovascular events (MACE), and the independent prognostic effect of statins among CKD patients with ACS, by Cox regression analysis. Results All 8945 consecutive ACS patients were included in our analysis. On hospital discharge, statin prescriptions were negatively associated with eGFR ]eGFR>60 ml/min/1.73 m2 -95%, eGFR 30–59 ml/min/1.73 m2 -90%, eGFR Conclusions In our study, the beneficial effect of statins was maintained among CKD patients presenting with ACS. Therefore, these patients should be treated with statins regardless of their eGFR.

Background: Considering the increasing burden of cardiovascular risk factors and recent advances on the management of acute coronary syndromes (ACS), we studied the epidemiological characteristics ...