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PURPOSE OF REVIEW: This review presents the risks and benefits of very low LDL cholesterol and the safety of using lipid-lowering therapy to achieve these levels. RECENT FINDINGS: A growing body of literature suggests that lower LDL cholesterol levels are associated with a reduced risk of cardiovascular disease. Further, achieving these levels with pharmaceuticals is remarkably safe. Although statins may slightly increase the risk of diabetes mellitus and hemorrhagic stroke, the benefits outweigh the risks. While recommendations from professional societies are increasingly aggressive, additional risk reduction could be achieved by setting more even ambitious LDL cholesterol goals.

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BACKGROUND: Diabetes mellitus (DM) increases the risk of cardiovascular diseases (CVD) significantly. Statins are recommended for all diabetic patients aged ≥ 40 years to alleviate this risk. OBJECTIVES: This study aimed to determine the status of the implementation of the recommendations of lipid management strategies for diabetic patients. METHODS: In this cross-sectional study, 500 patients with DM, aged ≥ 40 referring to a public pharmacy with at least one diabetic medication in their prescription, were enrolled. Patients' demographics, lipid panel data, medications, personal and family history of atherosclerotic cardiovascular disease (ASCVD), and risk factors for ASCVD were documented. The appropriateness of stain dosing intensity was judged based on the American Diabetes Association (ADA) guideline. RESULTS: The mean ± SD of the age of patients was 61.39 ± 10.49 years. Among patients, 238 (47.6) were men. More than half of the patients were subject to receiving primary prevention (59.8%, n = 299). For 80.8% (n = 404) of patients, a statin, most frequently atorvastatin (61.8%), was prescribed. The appropriate statin dose based on the guideline for 470 patients (94%), was high-intensity statin. In 70.6% (n = 353) of patients, lipid management was not in accordance with the guideline. Patients with ASCVD were more likely to receive the statins and the appropriate doses compared to patients without ASCVD (p-value < 0.001). CONCLUSION: Despite a relatively high percentage of patients who received statins, the lipid management in most patients was not in accordance with the guideline. The profound problem was the suboptimal dosage of statins. Investigating the reasons and barriers of the appropriate management can be helpful. Additionally, since patients without ASCVD who should receive statins for primary prevention were significantly less likely to receive statins and evidence-based doses, more attention is needed for this population.

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BACKGROUND: This study investigated whether intensive lipid-lowering therapy with pitavastatin and ezetimibe lowers the incidence of heart failure (HF) events in patients with acute coronary syndrome (ACS). METHODS AND RESULTS: In the HIJ-PROPER study, 1,734 patients with ACS were randomly assigned to either pitavastatin plus ezetimibe therapy (n=864) or pitavastatin monotherapy (n=857). We examined the incidence of HF between these 2 groups over a 3.9-year period after ACS. The primary endpoint of the study was hospitalization for HF. The mean low-density lipoprotein cholesterol levels during the follow-up period were 65.1 mg/dL in the pitavastatin plus ezetimibe group and 84.6 mg/dL in the pitavastatin monotherapy group. The incidence of HF hospitalization was significantly lower in the pitavastatin plus ezetimibe group than in the pitavastatin monotherapy group (19 [2.2%] vs. 40 [4.7%] patients; hazard ratio 0.47, 95% confidence interval 0.27-0.81; P<0.005). This trend was consistent after multivariable analysis using multiple models. CONCLUSIONS: Intensive lipid-lowering therapy with pitavastatin and ezetimibe is associated with a lower incidence of hospitalization for HF in patients with ACS.

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Atherosclerosis is characterised by the accumulation of fatty deposits and plaque as a result of a continuously high level of low-density lipoprotein cholesterol (LDL-C) in the blood. The primary objective of this research is to assess the current status of knowledge, research endeavours and developmental trajectories about proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in correlation with atherosclerosis treatment. Additionally, this study aims to compile bibliometric and scientometric investigations within this domain through rigorous scientometric analysis. Analysing the bibliometric landscape and global research trends associated with PCSK9 inhibitors can contribute valuable insights into comprehending atherosclerosis. This is exemplified by examining publications within the Web of Science Core Collection (WOSCC) database from 2008 to 2022. Citespace was used for frequency, co-occurrence, co-citation, grouping and burst analysis, and Microsoft Excel was used to manage descriptive datasets. Eight hundred eighty-five publications available from WOSCC database between the years 2008 and 2022 were extracted and examined. Over the period, 3,138 collaborating institutions from 87 countries, a staggering 7,750 writers involved and 325 distinct journals published about PCSK9 inhibitors studies. Among authors, Sabatine et al. and the journal The New England Journal of Medicine has had the most significant impact. Lipid-lowering therapy and bempedoic acid are the most prominent topical clusters associated with PCSK9 inhibitors, and the most often used keywords are efficacy, safety and PCSK9 inhibitors. We believe this is the first comprehensive analysis of PCSK9 inhibitors research and publications conducted using Scientometric. These results demonstrate the nascence of PCSK9 inhibitors research. They may encourage a wide range of stakeholders, particularly early career researchers from various disciplines, to work together in the future.

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BACKGROUND: Aggressive lipid-lowering therapy is important for secondary prevention of acute myocardial infarction (AMI). The recommended target for low-density lipoprotein cholesterol (LDL-C) of <70 mg/dL is often not achieved. To address this gap, we implemented a clinical pathway in all hospitals that perform percutaneous coronary interventions (PCI) with primary care physicians in Nagasaki and aimed to validate the effectiveness of this pathway in an acute setting. METHODS AND RESULTS: This retrospective cohort study included medical records extracted from 8 hospitals in Nagasaki, Japan, where PCI was performed for patients with AMI. The index date was defined as the date of hospitalization for AMI between July 1, 2021, and February 28, 2023. The primary outcome was the rate of achieving LDL-C <70 mg/dL at discharge. The median baseline LDL-C level at admission was 121 mg/dL (n=226) in the pre-implementation group and 116 mg/dL (n=163) in the post-implementation group. In the post-implementation group, 131 patients were treated using the clinical pathway. The rate of achieving LDL-C <70 mg/dL at discharge increased significantly from 37.2% before implementation to 54.6% after implementation. Logistic regression analysis revealed a positive correlation between the implementation of the clinical pathway and achieving LDL-C <70 mg/dL. CONCLUSIONS: Implementation of a region-wide clinical pathway for LDL-C management significantly improved the rate of intensive lipid-lowering therapy and the achievement of LDL-C targets.

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Peripheral artery disease (PAD) is a common condition characterized by atherosclerosis in the peripheral arteries, associated with concomitant coronary and cerebrovascular diseases. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a class of drugs that have shown potential in hypercholesterolemic patients. This review focuses on the efficacy, safety, and clinical outcomes of PCSK9 inhibitors in PAD based on the literature indexed by PubMed. Trials such as FOURIER and ODYSSEY demonstrate the efficacy of evolocumab and alirocumab in reducing cardiovascular events, offering a potential treatment option for PAD patients. Safety evaluations from trials show few adverse events, most of which are injection-site reactions, indicating the overall safety profile of PCSK9 inhibitors. Clinical outcomes show a reduction in cardiovascular events, ischemic strokes, and major adverse limb events. However, despite these positive findings, PCSK9 inhibitors are still underutilized in clinical practice, possibly due to a lack of awareness among care providers and cost concerns. Further research is needed to establish the long-term effects and cost-effectiveness of PCSK9 inhibitors in PAD patients.

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Lipid-lowering therapy plays a central role in reducing cardiovascular events. Over the past few decades, clinical trials utilizing several imaging techniques have consistently shown that lipid-lowering therapy can reduce the coronary plaque burden and improve plaque composition. Although intravascular ultrasound has been the most extensively used modality to assess plaque burden, other invasive modalities, such as optical coherence tomography and near-infrared spectroscopy, provide relevant data on plaque vulnerability, and computed tomography angiography detects both plaque volume and characteristics non-invasively. A large body of evidence supports the notion that reducing low-density lipoprotein cholesterol using statins combined with ezetimibe and proprotein convertase subtillisin/kexin type 9 inhibitors consistently shows improvements in plaque burden and favorable morphological changes. This review summarizes previously obtained data on the impact of lipid-lowering treatment strategies on atherosclerotic plaque regression, as assessed using several imaging modalities.

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AIMS: Women are less likely to receive lipid-lowering therapy (LLT) after acute myocardial infarction (AMI). We analysed whether this under-prescription currently persists and has an impact on long-term outcomes. METHODS AND RESULTS: The FAST-MI programme consists of nationwide registries including all patients admitted for AMI ≤ 48 h from onset over a 1 month period in 2005, 2010, and 2015, with long-term follow-up. This analysis focused on high-intensity LLT (atorvastatin ≥ 40 mg or equivalent, or any combination of statin and ezetimibe) in women and men. Women accounted for 28% (N = 3547) of the 12 659 patients. At discharge, high-intensity LLT was significantly less prescribed in women [54 vs. 68% in men, P < 0.001, adjusted odds ratio (OR) 0.78(95% confidence interval (CI) 0.71-0.87)], a trend that did not improve over time: 2005, 25 vs. 35% (P = 0.14); 2010, 66 vs. 79% (P < 0.001); 2015, 67 vs. 79.5% (P = 0.001). In contrast, female sex was not associated with a lack of other recommended treatments at discharge: beta-blockers [adjusted OR 0.98(95% CI 0.88-1.10), P = 0.78], or renin-angiotensin blockers [adjusted OR 0.94(95% CI 0.85-1.03), P = 0.18]. High-intensity LLT at discharge was significantly associated with improved 5 year survival and infarct- and stroke-free survival in women [adjusted hazard ratios (HR) 0.74(95% CI 0.64-0.86), P < 0.001 and adjusted HR: 0.81(95% CI: 0.74-0.89); P < 0.001, respectively]. Similar results were found using a propensity score-matched analysis [HR for 5 year survival in women with high-intensity LLT: 0.82(95% CI 0.70-0.98), P = 0.03]. CONCLUSION: Women suffer from a bias regarding the prescription of high-intensity LLT after AMI, which did not attenuate between 2005 and 2015, with potential consequences on both survival and risk of cardiovascular events.

Lipid-lowering therapy (LLT) is under-prescribed in women after acute myocardial infarction (AMI). Whether this difference persists over time and influences long-term outcomes is unclear. Women still suffer from insufficient prescription of high-intensity LLT at discharge after an AMI, even in the most recent years of the study, with a 5 year survival significantly reduced in women who did not receive high-dose LLT Propensity score matched analysis showed similar results on survival and cardiovascular events.

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We describe a novel use of evolocumab for successful postoperative lipid control in a patient with familial hyperlipidemia who underwent isolated heart transplantation. We believe that this case carries valuable lessons regarding post-transplant proprotein convertase subtilisin kexin 9 inhibitor use with implications for the future of combined organ allocation and transplantation waitlist times.

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BACKGROUND: Dyslipidemia remains the major cause of atherosclerotic cardiovascular disease (ASCVD). Lipid management in patients with increased cardiovascular (CV) risk needs improvement across Europe, and data gaps are noticeable at the country level. HYPOTHESIS: We described the current treatment landscape in Belgium, hypothesizing that lipid management in patients with ASCVD remains inadequate and aiming to understand the reasons. METHODS: Using data from an anonymized primary care database in Belgium derived from 494 750 individuals, we identified those with any CV risk factor between November 2019 and October 2022 and described the clinical features of patients with ASCVD. The main outcomes were the proportion of patients (i) receiving lipid-lowering therapies (LLTs), (ii) per low-density lipoprotein cholesterol (LDL-C) threshold, stratified per LLT, (iii) reaching the 2021 ESC recommended LDL-C goals, and (iv) LDL-C reduction per type of LLT was also determined. RESULTS: Among 40 888 patients with very high CV risk, 24 859 had established ASCVD. Most patients with ASCVD were either receiving monotherapy (59.6%) or had no documented LLT (25.1%). Further, 64.2% of those with no documented LLT exhibited LDL-C levels ≥ 100 mg/dL. Among common treatment options, one of the greatest improvements in LDL-C levels was achieved with combination therapy of statin and ezetimibe, reducing LDL-C levels by 41.5% (p < 0.0001). Yet, in this group, 24.8% of patients had still LDL-C levels ≥ 100 mg/dL and only 20.7% were at goal. CONCLUSION: Our study emphasizes the importance of developing strategies to help patients achieve their LDL-C goals, with a focus on supporting the implementation of combination LLT in routine clinical practice.

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Lipid-lowering therapy (LLT) is a cornerstone of atherosclerotic cardiovascular disease prevention. Although LLT might lead to different reductions in low-density lipoprotein cholesterol (LDL-C) levels in women and men, LLT diminishes cardiovascular risk equally effectively in both sexes. Despite similar LLT efficacy, the use of high-intensity statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors is lower in women compared to men. Women achieve the guideline-recommended LDL-C levels less often than men. Greater cholesterol burden is particularly prominent in women with familial hypercholesterolemia. In clinical practice, women and men with dyslipidemia present with different cardiovascular risk profiles and disease manifestations. The concentrations of LDL-C, lipoprotein(a), and other blood lipids differ between women and men over a lifetime. Dissimilar levels of LLT target molecules partially result from sex-specific hormonal and genetic determinants of lipoprotein metabolism. Hence, to evaluate a potential need for sex-specific LLT, this comprehensive review (i) describes the impact of sex on lipoprotein metabolism and lipid profile, (ii) highlights sex differences in cardiovascular risk among patients with dyslipidemia, (iii) presents recent, up-to-date clinical trial and real-world data on LLT efficacy and safety in women, and (iv) discusses the diverse medical needs of women and men with dyslipidemia and increased cardiovascular risk.

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Background: Lipid-related risk and residual cardiovascular risk remain high in patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). Significant treatment gaps exist in implementation of pluripotent and effective therapies that reduce these risks. Objective: This study evaluates the efficacy and impact of a dedicated, standalone cardiometabolic clinic designed to address treatment gaps through streamlined management and optimization of treatment strategies. Methods: We retrospectively collected data from the first 400 patients with T2D and ASCVD who underwent treatment at the clinic and presented for at least one follow-up visit. These patients were primarily managed for their cardiometabolic risks and received intensified lipid-lowering therapies, including adjunct non-statin therapies. Results: Significant findings included increased use of glucagon-like peptide-1 receptor agonists (GLP1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) to 84 % and 65 %, respectively, with 94 % of patients eventually on one therapy and 55 % on dual therapy. Increases in lipid-lowering therapies led to 89 % of patients achieving low-density lipoprotein cholesterol levels below patient-specific thresholds for intensification. Conclusion: This care model effectively manages high-risk patient needs, achieving significant intensification of lipid-lowering therapies and broad use of cardiometabolic drugs, and highlights the clinic's potential to serve as a model for similar high-risk populations.

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PURPOSE OF REVIEW: Current guidelines for primary and secondary prevention of cardiovascular events in adults up to age 75 years are well-established. However, recommendations for lipid-lowering therapies (LLT), particularly for primary prevention, are inconclusive after age 75. In this review, we focus on adults ≥ 75 years to assess low-density lipoprotein-cholesterol (LDL-C) as a marker for predicting atherosclerotic cardiovascular disease (ASCVD) risk, review risk assessment tools, highlight guidelines for LLT, and discuss benefits, risks, and deprescribing strategies. RECENT FINDINGS: The relationship between LDL-C and all-cause mortality and cardiovascular outcomes in older adults is complex and confounded. Current ASCVD risk estimators heavily depend on age and lack geriatric-specific variables. Emerging tools may reclassify individuals based on biologic rather than chronologic age, with coronary artery calcium scores gaining popularity. After initiating LLT for primary or secondary prevention, target LDL-C levels for older adults are lacking, and non-statin therapy thresholds remain unknown, relying on evidence from younger populations. Shared decision-making is crucial, considering therapy's time to benefit, life expectancy, adverse events, and geriatric syndromes. Deprescribing is recommended in end-of-life care but remains unclear in fit or frail older adults. After an ASCVD event, LLT is appropriate for most older adults, and deprescribing can be considered for those approaching the last months of life. Ongoing trials will guide statin prescription and deprescribing among older adults free of ASCVD. In the interim, for adults ≥ 75 years without a limited life expectancy who are free of ASCVD, an LLT approach that includes both lifestyle and medications, specifically statins, may be considered after shared decision-making.

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Reducing low-density lipoprotein cholesterol levels lowers the risk of atherosclerotic cardiovascular disease. With the current and future portfolios of emerging lipid-lowering therapies included in various national and international guidelines, the objectives of this study were (i) to investigate the perceptions of UK prescribers', including doctors, pharmacists, and nurses, on current lipid management for cardiovascular diseases and prescriptions of novel lipid-lowering therapies, and (ii) to explore the challenges and facilitating factors of prescribing novel lipid-lowering therapies through qualitative interviews. Qualitative semi-structured interviews with twelve medical and non-medical prescribers were conducted, around 20-30 min in length. The interviews were audio-recorded and transcribed on an online platform. A thematic analysis was deployed. Four major themes emerged from the analysis: (1) prescribing barriers; (2) prescribing enablers; (3) inter-profession variability; and (4) health literacy. These themes highlighted the contrast between the need for optimal shared decision making and the various constraints in practice. Participants expressed their inexperience with novel lipid-lowering therapies and acknowledged the requirement and importance of these agents for primary cardiovascular disease prevention. Participants recognised confidence and competence as key drivers for prescribing therapies and welcomed further education and training to enhance their skillset. Patients' misconceptions towards current lipid-lowering therapies contributed to their refusal of newer agents, highlighting a requirement to improve patient education. Targeting communities through awareness campaigns was identified as a viable solution.

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Background: The purpose of this study was to analyze the major cardiovascular risk (CVR) factors and their trends in the study population. Methods: The results of subjects in the Polish Prospective Urban and Rural Epidemiological Study (PURE) study group were interpreted. CVR was calculated for each participant according to the Systematic Coronary Risk Evaluation (SCORE2) scale or the Systematic Coronary Risk Evaluation-Older Persons (SCORE2-OP) scale. Data from the beginning of the analysis (2013) and nine years later (2022) were included. In addition, the use of lipid-lowering therapy (LLT) and meeting the low-density lipoprotein cholesterol (LDL-c) target criterion at the beginning and end of the study were analyzed. Results: Patients in the high and very high CVR groups who had abnormal LDL-c results accounted for 64% and 91% of their group in 2013 and 70% and 92% in 2022, respectively. Conclusions: Regardless of age, patients using LLT at the start of the analysis had a greater increase in future CVR, especially if they had lipid abnormalities at the start of the study. This may be due to reverse causality and multimorbidity in these patients, highlighting the importance of appropriate treatment of lipid abnormalities.

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Introduction: European guidelines recommend the implementation of lipid-lowering therapies (LLTs) in adults (≥ 65 years) with established atherosclerotic cardiovascular disease (ASCVD) and for risk-based primary prevention in older adults (≤ 75 years), yet their use in very-old adults (> 75 years) is controversial, discretionary, and oriented on the presence of risk factors. The aim of this retrospective study is to assess guideline-directed LLT implementation and low-density lipoprotein cholesterol (LDL-C) target achievement in high-/very-high-risk older/very-old adults (65-74 and ≥ 75 years) at presentation for ST-segment elevation myocardial infarction (STEMI) and also to assess evidence-based care delivery to older adults in our region. Methods: All STEMI patients with available LDL-C and total cholesterol presenting for treatment at a large tertiary center in Salzburg, Austria, 2018-2020, were screened (n = 910). High-risk/very-high-risk patients (n = 369) were classified according to European guidelines criteria and divided into cohorts by age: < 65 years (n = 152), 65-74 years (n = 104), and ≥ 75 years (n = 113). Results: Despite being at high-/very-high-risk, prior LLT use was < 40% in the total cohort, with no significant difference by age. Statin monotherapy predominated; 20%-23% of older/very-old adults in the entire cohort were using low-/moderate-intensity stains, 11%-13% were using high-intensity statins, 4% were on ezetimibe therapy, and none were taking proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. In the secondary prevention cohort, 53% of older/very-old patients used prior LLTs. Significantly higher percentages of older/oldest ASCVD patients (43% and 49%) met LDL-C targets < 70 mg/dL compared to patients < 65 years (29%; p = 0.033), although just 22% and 30% of these older groups attained stricter LDL-C targets of < 55 mg/dL. Low LLT uptake (16%) among older adults aged 64-74 years for primary prevention resulted in 17% and 10% attainment of risk-based LDL-C targets < 70 mg/dL and < 55 mg/dL, respectively. Oldest adults (≥ 75 years) in both primary and secondary prevention groups more often met risk-based targets than older and younger adults, despite predominantly receiving low-/moderate-intensity statin monotherapy. Conclusion: Secondary prevention was sub-optimal in our region. Less than half of older/very-old adults with established ASCVD met LDL-C targets at the time of STEMI, suggesting severe care-delivery deficits in LLT implementation. Shortcomings in initiation of risk-based LLTs were also observed among high-/very-high-risk primary prevention patients < 75 years, with the achievement of risk-based LDL-C targets in 10%-48% of these patients.

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Elevated low-density lipoprotein cholesterol (LDL-C) is a major causal factor for atherosclerotic cardiovascular disease (ASCVD), the leading cause of mortality worldwide. Statins are the recommended first-line lipid-lowering therapy (LLT) for patients with primary hypercholesterolemia and established ASCVD, with LLT intensification recommended in the substantial proportion of patients who do not achieve levels below guideline-recommended LDL-C thresholds with statin treatment alone. The proprotein convertase subtilisin/kexin type 9 inhibitor monoclonal antibody evolocumab has demonstrated significant LDL-C reductions of > 60% in the clinical trial and open-label extension settings, with LDL-C reductions observed early post-evolocumab initiation and maintained long term, during up to 8.4 years of follow-up. Evolocumab therapy, when added to a statin, also conferred a significant reduction in major cardiovascular (CV) events, including a 20% reduction in the composite of CV death, myocardial infarction (MI), or stroke. The absolute benefits were enhanced among various patient types at high and very high risk for secondary ASCVD (e.g., with recent MI, multiple events or peripheral artery disease). Importantly, evolocumab treatment resulted in incremental CV risk reductions during the extended follow-up, including a 23% reduction in CV mortality and no apparent LDL-C level below which there is no further CV risk reduction. Hence, the evolocumab clinical data support the need for early and significant LDL-C lowering, especially in vulnerable ASCVD patients, in order to derive the greatest benefit in the long term. Importantly, evolocumab had no impact on any treatment emergent adverse events apart from a small increase in local injection site reactions. A growing body of real-world evidence (RWE) for evolocumab in heterogeneous populations is consistent with the trial data, including robust LDL-C reductions below guideline-recommended thresholds, a favourable safety profile even at the lowest levels of LDL-C achieved, and a high treatment persistence rate of > 90%. Altogether, this review highlights findings from 50 clinical trials and RWE studies in > 51,000 patients treated with evolocumab, to demonstrate the potential of evolocumab to address the healthcare gap in LDL-C reduction and secondary prevention of ASCVD in a variety of high- and very high-risk patients.

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Acute coronary syndrome (ACS) remains a major cause of morbidity and mortality, despite many improvements in its prevention and management. Lipid management is an important aspect of secondary prevention after ACS. Previous studies indicate that the early use of intensive statin therapy in patients with ACS may alleviate the risk of recurrent cardiovascular events and mortality. However, many patients do not reach the target low-density lipoprotein cholesterol (LDL-C) level of < 55 mg/dL with statin monotherapy, and muscle-related adverse effects caused by statins hinder adherence to treatment. Novel non-statin agents are recommended for patients who cannot achieve the target LDL-C levels with high-intensity statin therapy and those with statin intolerance. The combination of statins and non-statins may synergistically affect intensively lowering LDL-C through different mechanisms, which could lead to better cardiovascular outcomes than statin monotherapy. However, it remains uncertain whether the early use of combination lipid-lowering therapy is more beneficial. The present review summarizes the benefits of intensive statin monotherapy and their early combination with non-statin medications including ezetimibe, PCSK9 inhibitors, inclisiran, and bempedoic acid (BDA) in the management of ACS.

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AIMS: To estimate the proportion eligible for lipid-lowering therapy (LLT) when using the systemic coronary risk estimation 2 (SCORE2) on apparently healthy individuals. METHODS: Individuals aged 50-64 years were randomly invited to the Swedish cardiopulmonary bioimage study (SCAPIS, n=30,154). Participants with previous atherosclerotic cardiovascular disease (CVD), diabetes mellitus, or chronic kidney disease were excluded. The 10-year risk of CVD was estimated using the SCORE2 equation and the multicell chart. Eligibility for LLT was estimated according to the 2021 European Society of Cardiology CVD prevention guidelines. Presence of coronary atherosclerosis was determined using coronary computed tomography angiography (CCTA). RESULTS: Among 26,570 apparently healthy individuals, 32% had high, and 4% had very-high 10-year CVD risk, according to the SCORE2 equation. Among high and very-high risk individuals, 99% had LDL-C levels above guideline goals making 35% of the total population eligible for LLT. Of those eligible, undergoing imaging, 38% had no signs of coronary atherosclerosis according to CCTA. Using the SCORE2 chart, 52% of the population were eligible for LLT, of which 44% had no signs of coronary atherosclerosis. In those with high or very-high risk, ongoing LLT was reported in 7% and another 11% received LLT within six months after study participation. CONCLUSIONS: Nearly all apparently healthy individuals with high and very-high CVD risk, or 35% of the total population, were eligible for LLT according to guidelines, and a large proportion had no signs of atherosclerosis. Compared with the SCORE2 equation, the SCORE2 chart resulted in more individuals being eligible for LLT.

KEY QUESTIONS: What proportion of an apparently healthy middle-aged population would be eligible for lipid-lowering therapy (LLT) according to the 2021 ESC guidelines when using SCORE2? What proportion of those eligible for LLT have atherosclerosis according to coronary imaging? KEY FINDING: According to the guidelines, nearly all individuals categorized as high and very-high risk according to the SCORE2 equation, or 35% of the total population, were eligible for LLT, of which 38% had no signs of coronary atherosclerosis. These proportions increased when the SCORE2 multicell chart was used. TAKE-HOME MESSAGE: Implementing SCORE2 and the ESC guidelines would result in more than one in three apparently healthy middle-aged individuals being eligible for LLT. A significant proportion would have no signs of coronary atherosclerosis.