GOULD EDU

BackgroundCardiovascular disease remains the leading cause of morbidity and mortality worldwide, with dyslipidemia playing a key role in its progression. Despite advances in lipid-lowering therapy (LLT), LDL-C (Low-Density Lipoprotein Cholesterol) goal achievement remains suboptimal. This study evaluated LDL-C goal attainment in Colombian patients with very high cardiovascular risk (CVR) due to coronary artery disease (CAD) following ESC/EAS guidelines updates.MethodsEDHIPO MARCA (Evaluación De adherencia a la terapia HIPOlipemiante en pacientes de Muy Alto Riesgo CArdiovascular) is a retrospective, multicenter study assessing LDL-C goal achievement in patients with CAD. Data were collected from previous coronary angiogram reports and medical records across 11 Colombian healthcare institutions with certified interventional cardiology services. Patients with CAD who had at least one follow-up LDL-C measurement and an LLT prescription within 12 months post-angiogram were included. LDL-C goal attainment was assessed across three periods—2011–2012, 2016–2017, and 2021–2022—corresponding to the updates of ESC/EAS guidelines (2011, 2016, and 2019, respectively). The LDL-C goals were <70 mg/dL for the first two periods and <55 mg/dL for the most recent one. LDL-C was measured or estimated using the Friedewald equation. Descriptive analyses were performed.ResultsA total of 1,788 patients were included, with a median age of 66 years (IQR: 59–74), and 70.7% were male. Hypertension (67.5%) and overweight (40.8%) were the most common comorbidities. At discharge, statins were prescribed in 84.1% (95% CI: 82.4–85.8%) of patients, increasing to 99.1% (95% CI: 98.6–99.5%) at the end of follow-up (median 6.8 months); PCSK9 inhibitors were prescribed in 1.5%, exclusively in 2019. At the end of follow-up, 36.6% (95% CI: 34.3%, 38.8%) achieved LDL-C goals. By guideline period, goal attainment was 12.1% (95% CI: 5.4%, 18.8%) in 2011, 42.3% (95% CI: 37.9%, 46.8%) in 2016, and 36.2% (95% CI: 33.5%, 38.9%) in 2019. By number of follow-ups, LDL-C goal achievement increased from 32.9% (1 follow-up) to 44.0% (4 follow-ups).ConclusionsDespite widespread LLT use, LDL-C target achievement remains suboptimal. Frequent follow-up and greater use of combination therapy beyond statins may be essential to improve lipid control in very high CVR patients.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12944-025-02657-9.

Objective Guidelines developed by the American College of Cardiology/American Heart Association (ACC/AHA) recommend lipid-lowering therapies (LLTs) to reduce low-density lipoprotein cholesterol (LDL-C) and atherosclerotic cardiovascular disease (ASCVD) risk. This study described LLT utilization patterns and LDL-C goal achievement (to <70 mg/dL) among patients with ASCVD in the United States. Methods This retrospective study was conducted using Optum’s de-identified Clinformatics Data Mart Database (CDM). Patients with their first ASCVD diagnosis (index date) in the CDM database between July 1, 2015, and December 31, 2018, were followed for ≥12 months to assess LLT utilization patterns and change in LDL-C. LLTs included were statins and non-statin LLTs (ezetimibe, fibrates, and proprotein convertase subtilisin/kexin type 9 inhibitors). Adherence was measured as the proportion of days covered (PDC), defined as the number of days with drug on-hand (or number of days exposed to drug) divided by the 12-month follow-up period. Patients with PDC ≥0.8 were considered adherent. Results Among the patients with ASCVD (N = 1,424,893) included in this study, only 621,978 (43.7%) had at least one LDL-C measurement at baseline (6 months prior to and 3 months after the index date). The mean age was 71.5 years, and almost half of the patients were female. Patients were followed for a mean (standard deviation [SD]) duration of 30.6 (11.4) months (median of 29.9 months). During the follow-up, about one-quarter of the patients did not receive any LLT. Among treated patients, 89.5% received statins and 10.5% received non-statin LLT. Less than half (47.6%) of the patients were adherent to the index treatment during the 12-month follow-up. Even in patients receiving combination therapy (statin + non-statin LLT), a sizable proportion (35.8%) showed an increase in LDL-C over the follow-up period. Conclusions This retrospective study highlighted limited LDL-C monitoring in patients with ASCVD, and unmet need in terms of suboptimal utilization of non-stain LLTs, limited adherence to LLTs, and inadequate lipid control after treatment (among those with LDL-C measurements during the follow-up period) need to be addressed to improve outcomes in this patient cohort.

Aims: We sought to investigate the association of remnant cholesterol (remnant-C) and low-density lipoprotein cholesterol (LDL-C) levels with incident atherosclerotic cardiovascular disease (ASCVD) in various subgroups among Koreans. Methods: National Health Information Database, collated by Korean National Health Insurance System, was used for analysis. Among the individuals between 40 and 70 years of age and without history of cerebro-cardiovascular disease, those who had twice or more health screenings between 2009 and 2011 were selected. All subjects were divided into 4 groups by LDL-C level of 3.4 mmol/L (130mg/dL) and remnant-C level of 0.8mmol/L (30mg/dL). The primary outcome was defined as the incidence of ASCVD. Results: 3,686,034 individuals (45.6% women) fulfilled the study requirements. By the end of 2017, 144,004 ASCVD events occurred. High remnant-C and low LDL-C group was 19% of total. Compared with low remnant-C and low LDL-C group, the high remnant-C and high LDL-C group had highest ASCVD risk (HR 1.266, CI 1.243-1.289) and the high remnant-C alone group (HR 1.102, CI 1.087-1.118) had similar ASCVD risk to the high LDL-C alone group (HR 1.098, CI 1.083-1.113). The association of high remnant-C (≥0.8 mmol/L) with an increased ASCVD risk was consistent across various strata. Remnant-C levels remained significantly to associate with ASCVD after adjustment for several confounders, including LDL-C levels. Conclusions: Elevated remnant-C values, apart from LDL-C levels, were independently associated with a risk of incident ASCVD. Combination of high LDL-C and high remnant-C levels better predicted ASCVD incidence than each one alone. Therefore, we might take into account remnant-C measurement in risk stratification for primary prevention of ASCVD.

We sought to investigate the use of lipid-lowering therapy (LLT) and the attainment of low-density lipoprotein cholesterol (LDL-C) goals in patients with atherosclerotic cardiovascular disease (ASCVD) in Australian general practices. The study aimed to investigate the discrepancies between guideline recommendations and clinical practice. This retrospective study used electronic data from Australian general practitioners, extracted from IQVIA's "general practice electronic medical record" data set, covering the period from January 2010 to June 2022. Descriptive statistics examined the relationships between demographics, clinical characteristics, treatment patterns, adherence to LLT, and the achievement of guideline-recommended LDL-C goals, with data stratified by gender, age, and LDL-C levels. Of 13,644 patients with ASCVD identified, 64% of the patients with ASCVD were men, and the overall mean age was 70 years (±13.5 standard deviation). Only 51.9% of patients had a recorded LDL-C test at their most recent general practice physician visit. Of those tested, 60.5% and 50.6% had increased LDL-C levels >1.8 mmol/L and >2.0 mmol/L, respectively. Statin therapy was prescribed to n=11,100 (81.3%) of patients during the study period, but this fell to n=8,918 (65.4%) by the last consult. Of those on treatment at their last review, statin monotherapy was the most common (n=7,861, 57.6%), with a low use of combination therapies (n=1,004, 7.36%). At 1 year, 80.1% of patients on statin monotherapy were adherent (proportion of days covered ≥0.8), but this fell to 47.9% at 5 years. The use of non-high-intensity statins were associated with the highest persistence, being 47.5% adherent at 5 years. There were no significant differences in persistence between females and males nor across age categories <44, 44-65, and>65 years old. The study highlights gaps in the management of ASCVD in Australian general practice, including the lack of monitoring of LDL-C levels, under-prescription of proven LLT, and increasingly poor adherence and persistence with LLT over time.

Should Lipoprotein(a) be Measured in Youth?

DA VINCI study: Change in approach to cholesterol management will be needed to reduce the implementation gap between guidelines and clinical practice in Europe

Purpose: The change in coronary physiology from lipid-lowering therapy (LLT) lacks an appropriate method of examination. Quantitative flow ratio (QFR) is a novel angiography-based approach allowing rapid assessment of coronary physiology. This study sought to determine the impact of low-density lipoprotein cholesterol (LDL-C) goal achievement on coronary physiology through QFR.Methods: Cases involving percutaneous coronary intervention (PCI) and 1-year angiographic follow-up were screened and assessed by QFR analysis. Patients were divided into two groups according to the LDL-C level at the 1-year follow-up: (1) goal-achievement group (LDL-C < 1.8 mmol/L or reduction of ≥50%, n = 146, lesion = 165) and (2) non-achievement group (n = 286, lesion = 331). All QFR data and major adverse cardiovascular and cerebrovascular events (MACCEs) at 1 year were compared between groups.Results: No differences between the groups in quantitative coronary angiography (QCA) data or QFR post-PCI were found. At the 1-year follow-up, lower percentage diameter stenosis (DS%) and percentage area stenosis (AS%) were recorded in the goal-achievement group (27.89 ± 10.16 vs. 30.93 ± 12.03, p = 0.010, 36.57 ± 16.12 vs. 41.68 ± 17.39, p = 0.003, respectively). Additionally, a better change in QFR was found in the goal-achievement group (0.003 ± 0.068 vs. −0.018 ± 0.086, p = 0.007), with a lower incidence of physiological restenosis and MACCEs (2.1 vs. 8.4%, p = 0.018, 5.4 vs. 12.6%, p = 0.021, respectively).Conclusion: Evaluated by QFR, patients who achieved the LDL-C goal appear to have a better coronary physiological benefit. This group of patients also has a better clinical outcome.

Guidelines for patients with atherosclerotic cardiovascular disease (ASCVD) recommend intensive statin therapy and adding nonstatin therapy if low-density lipoprotein cholesterol (LDL-C) levels are 70 mg/dL or more. Compliance with guidelines is often low. To track LDL-C treatment patterns in the US over 2 years. GOULD is a prospective observational registry study involving multiple centers. Patients with ASCVD receiving any lipid-lowering therapy (LLT) were eligible. Between December 2016 and July 2018, patients were enrolled in 1 of 3 cohorts: (1) those currently receiving proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) and 2 groups not receiving PCSK9i drugs, with (2) LDL-C levels of 100 mg/dL or more or (3) LDL-C levels of 70 to 99 mg/dL. Patients had medical record reviews and telephone interviews every 6 months. Analysis was done on data collected as of October 5, 2020. The primary outcome was the change in LLT use in 2 years. Secondary outcomes included the number of LDL-C measurements, LDL-C levels, and responses to structured physician and patient questionnaires over 2 years. A total of 5006 patients were enrolled (mean [SD] age, 67.8 [9.9] years; 1985 women [39.7%]; 4312 White individuals [86.1%]). At 2 years, 885 (17.1%) had LLT intensification. In the cohorts with LDL-C levels of 100 mg/dL or more and 70 to 99 mg/dL, LLT intensification occurred in 403 (22.4%) and 383 (14.4%), respectively; statins were intensified in 115 (6.4%) and 168 (6.3%), ezetimibe added in 123 (6.8%) and 118 (4.5%), and PCSK9i added in 114 (6.3%) and 58 (2.2%), respectively. In the PCSK9i cohort, 508 of 554 (91.7%) were still taking PCSK9i at 2 years. Lipid panels were measured at least once over 2 years in 3768 patients (88.5%; PCSK9i cohort, 492 [96.1%]; LDL-C levels ≥100 mg/dL or more, 1294 [85.9%]; 70-99 mg/dL, 1982 [88.6%]). Levels of LDL-C fell from medians (interquartile ranges) of 120 (108-141) mg/dL to 95 (73-118) mg/dL in the cohort with LDL-C levels of 100 mg/dL or more, 82 (75-89) to 77 (65-90) mg/dL in the cohort with LDL-C levels of 70 to 99 mg/dL, and 67 (42-104) mg/dL to 67 (42-96) mg/dL in the PCSK9i cohort. Levels of LDL-C less than 70 mg/dL at 2 years were achieved by 308 patients (21.0%) and 758 patients (33.9%) in the cohorts with LDL-C levels of 100 mg/dL or more and 70 to 99 mg/dL, respectively, and 272 patients (52.4%) in the PCSK9i cohort. At 2 years, practice characteristics were associated with more LLT intensification (teaching vs nonteaching hospitals, 148 of 589 [25.1%] vs 600 of 3607 [16.6%]; lipid protocols or none, 359 of 1612 [22.3%] vs 389 of 2584 [15.1%]; cardiology, 452 of 2087 [21.7%] vs internal or family medicine, 204 of 1745 [11.7%] and other, 92 of 364 [25.3%]; all P < .001) and achievement of LDL-C less than 70 mg/dL (teaching vs nonteaching hospitals, 173 of 488 [35.5%] vs 823 of 2986 [27.6%]; lipid protocols vs none, 451 of 1411 [32.0%] vs 545 of 2063 [26.4%]; both P < .001; cardiology, 523 of 1686 [30.1%] vs internal or family medicine, 377 of 1472 [25.6%] and other, 96 of 316 [30.4%]; P = .003). Of patients with ASCVD, most with suboptimal LDL-C levels at baseline, only 17.1% had LLT intensification after 2 years, and two-thirds remained at an LDL-C level greater than 70 mg/dL. Further intensive efforts are needed to achieve optimal LDL-C management in patients with ASCVD.

Limited evidence supports the association between low-density lipoprotein cholesterol (LDL-C) and mortality across different atherosclerotic cardiovascular disease (ASCVD) risk stratifications. To explore the associations between LDL-C levels and mortality and to identify the optimal ranges of LDL-C with the lowest risk of mortality in populations with diverse ASCVD risk profiles. The ChinaHEART project is a prospective cohort study that recruited residents aged 35 to 75 years from 31 provinces in mainland China between November 2014 and December 2022. Participants were categorized into low-risk, primary prevention, and secondary prevention cohorts on the basis of their medical history and ASCVD risk. Data analysis was performed from December 2022 to October 2023. The primary end point was all-cause mortality, and secondary end points included cause-specific mortality. Mortality data were collected from the National Mortality Surveillance System and Vital Registration. The association between LDL-C levels and mortality was assessed by using Cox proportional hazard regression models with various adjusted variables. A total of 4 379 252 individuals were recruited, and 3 789 025 (2 271 699 women [60.0%]; mean [SD] age, 56.1 [10.0] years) were included in the current study. The median (IQR) LDL-C concentration was 93.1 (70.9-117.3) mg/dL overall at baseline. During a median (IQR) follow-up of 4.6 (3.1-5.8) years, 92 888 deaths were recorded, including 38 627 cardiovascular deaths. The association between LDL-C concentration and all-cause or cardiovascular disease (CVD) mortality was U-shaped in both the low-risk cohort (2 838 354 participants) and the primary prevention cohort (829 567 participants), whereas it was J-shaped in the secondary prevention cohort (121 104 participants). The LDL-C levels corresponding to the lowest CVD mortality were 117.8 mg/dL in the low-risk group, 106.0 mg/dL in the primary prevention cohort, and 55.8 mg/dL in the secondary prevention cohort. The LDL-C concentration associated with the lowest all-cause mortality (90.9 mg/dL vs 117.0 mg/dL) and CVD mortality (87 mg/dL vs 114.6 mg/dL) were both lower in individuals with diabetes than in individuals without diabetes in the overall cohort. This study found that the association between LDL-C and mortality varied among different ASCVD risk cohorts, suggesting that stricter lipid control targets may be needed for individuals with higher ASCVD risk and those with diabetes.

Background Indonesia, the world's largest archipelago, faces significant challenges in equitable healthcare delivery due to its geographical and infrastructural disparities. Atherosclerotic Cardiovascular Disease (ASCVD) remains the leading cause of mortality, with over 659,000 deaths recorded in 2019. Effective dyslipidemia management is crucial for preventing adverse ASCVD events. Unfortunately, the lack of implementation of an updated national lipid management registry might hinder optimal strategy for the adverse events. This study evaluated dyslipidemia cholesterol management practices among high- and very high-risk patients across the country. Methods The study recruited 322 patients from eight centers across six provinces in Indonesia between May 2022 and March 2023. Patients were stratified based on the ASCVD risk and followed over three visits. Baseline clinical characteristics, lipid profiles, and treatment regimens were analyzed. Descriptive statistics summarized continuous and categorical variables, and low-density lipoprotein cholesterol (LDL-C) achievement was assessed. Results Of the 322 patients, 98.8% were very high-risk, with only 4.9% achieving &lt;55 mg/dL and 21.2% achieving &lt;70 mg/dL. Moderate-intensity statins were the most prescribed (51.2%), followed by high-intensity (36.6%). LDL-C reduction was most pronounced in private insurance patients, achieving a mean LDL-C of 69.8 mg/dL at the third visit compared to 98.9 mg/dL in National Health Insurance (Jaminan Kesehatan Nasional/JKN) participants. Missed visit rates increased over time, with 57.5% of patients missing the third visit, predominantly among JKN participants and low-income groups. Conclusion Majority of the population failed to achieve the recommended target of LDL-C levels. Dyslipidemia management in Indonesia remains suboptimal, with disparities driven by socioeconomic factors. Improved policies addressing medication availability, national lipid registry establishment, and equitable healthcare access are essential to enhance lipid management and reduce the burden of ASCVD in Indonesia.

United Kingdom and European guidelines recommend that patients with atherosclerotic carotid artery disease should be commenced on optimal cardioprotective medical therapy, specifically antiplatelet agents and lipid lowering therapy (LLT). This single centre cohort study explored the peri-operative prescription and titration of guideline directed medical therapy (GDMT) alongside low density lipoprotein cholesterol (LDL-C) levels in patients undergoing carotid intervention. The study included 260 patients who underwent carotid intervention from 1 January 2017 to 31 December 2021. Electronic hospital records were checked for data on demographics, comorbidities, antiplatelet and LLT prescriptions, and cholesterol results. Data from four time points were obtained: prior to the index event; at the time of admission for carotid intervention; at discharge following intervention; and at one year. Antiplatelet therapy was indicated in one fifth and high intensity LLT in 39% of patients who were not on cardioprotective medications prior to the index event. From the time of admission for carotid intervention to discharge, the proportion of patients who were prescribed antithrombotic therapy (82% vs. 100%; p < .001) and LLT (88% vs. 94%; p = .004) statistically significantly increased. Mean LDL-C levels statistically significantly reduced from 2.2 mmol/L pre-admission to 1.8 mmol/L at one year follow up (p = .026). However, only 53% of patients achieved an LDL-C target of < 1.8 mmol/L one year following intervention. All patients who did not achieve the LDL-C target had scope for uptitration of statin or co-prescription of adjuvant LLT agents, including ezetimibe, inclisiran, and PCSK9i. Underutilisation of LLT prior to incident stroke was identified as a key tractable problem. Admission for carotid intervention is associated with an increase in GDMT and reduction in LDL-C levels. There is scope for improvement and a need for long term community based management of cardiovascular risk, specifically risk assessment, initiation and ongoing uptitration of LLT, and regular monitoring of LDL-C levels.

Joint statement from the European Atherosclerosis Society and European Society of Vascular Medicine focuses on patients with peripheral arterial disease

Low-density lipoprotein cholesterol (LDL-C) is an important causal risk factor for atherosclerotic cardiovascular disease (ASCVD). However, a sizable proportion of middle-aged individuals with elevated LDL-C level have not developed coronary atherosclerosis as assessed by coronary artery calcification (CAC). Whether presence of CAC modifies the association of LDL-C with ASCVD risk is unknown. We evaluated the association of LDL-C with future ASCVD events in patients with and without CAC. The study included 23 132 consecutive symptomatic patients evaluated for coronary artery disease using coronary computed tomography angiography (CTA) from the Western Denmark Heart Registry, a seminational, multicenter-based registry with longitudinal registration of patient and procedure data. We assessed the association of LDL-C level obtained before CTA with ASCVD (myocardial infarction and ischemic stroke) events occurring during follow-up stratified by CAC>0 versus CAC=0 using Cox regression models adjusted for baseline characteristics. Outcomes were identified through linkage among national registries covering all hospitals in Denmark. We replicated our results in the National Heart, Lung, and Blood Institute-funded Multi-Ethnic Study of Atherosclerosis. During a median follow-up of 4.3 years, 552 patients experienced a first ASCVD event. In the overall population, LDL-C (per 38.7 mg/dL increase) was associated with ASCVD events occurring during follow-up (adjusted hazard ratio [aHR], 1.14 [95% CI, 1.04-1.24]). When stratified by the presence or absence of baseline CAC, LDL-C was only associated with ASCVD in the 10 792/23 132 patients (47%) with CAC>0 (aHR, 1.18 [95% CI, 1.06-1.31]); no association was observed among the 12 340/23 132 patients (53%) with CAC=0 (aHR, 1.02 [95% CI, 0.87-1.18]). Similarly, a very high LDL-C level (>193 mg/dL) versus LDL-C <116 mg/dL was associated with ASCVD in patients with CAC>0 (aHR, 2.42 [95% CI, 1.59-3.67]) but not in those without CAC (aHR, 0.92 [0.48-1.79]). In patients with CAC=0, diabetes, current smoking, and low high-density lipoprotein cholesterol levels were associated with future ASCVD events. The principal findings were replicated in the Multi-Ethnic Study of Atherosclerosis. LDL-C appears to be almost exclusively associated with ASCVD events over ≈5 years of follow-up in middle-aged individuals with versus without evidence of coronary atherosclerosis. This information is valuable for individualized risk assessment among middle-aged people with or without coronary atherosclerosis.

Effects of Fixed-dose Combination of Low-intensity Rosuvastatin and Ezetimibe Versus Moderate-intensity Rosuvastatin Monotherapy on Lipid Profiles in Patients With Hypercholesterolemia: A Randomized, Double-blind, Multicenter, Phase III Study

Background and Objectives: Patients with atherosclerotic cardiovascular disease (ASCVD) remain at high risk of recurrent events. REALITY aims to analyse the actual levels of low-density lipoprotein cholesterol (LDL-C), the modalities of lipid-lowering therapies (LLT) used, and ASCVD patient outcomes in a real-world setting in Spain. Methods: REALITY is a retrospective observational study conducted using a healthcare database of 1.8 million patients representative of the Spanish population. The study included 26,976 patients with new or recurrent ASCVD events recruited from 2017 to 2019 and followed up for two years. Results: Management of ASCVD involved the utilisation of high-intensity (53%) or very high-intensity (36%) LLT. After two years, a decrease in total cholesterol (from 228.7 to 176.7 mg/dL), LDL-C (from 126.4 to 99.0 mg/dL), and triglycerides (from 216.7 to 163.7 mg/dL), accompanied by a moderate increase in HDL-C levels was observed. However, LDL-C goals of ESC/EAS guidelines were only reached by a minority of patients. Less than 15% of ASCVD patients achieved their LDL-C goals of <70, as stated in contemporary guidelines (3% if the present <55 mg/dL threshold in the ESC/EAS guidelines is considered). During the follow-up period, 9% of ASCVD patients died and 25% experienced a new ASCVD event. Conclusions: In the REALITY study, most patients did not achieve their target LDL-C goals despite receiving high- or very high-intensity LLT. Increasing the utilisation of extreme LLT is crucial to reducing recurrent ASCVD events and mitigating these patients' high morbidity and mortality risk.