Statin Therapy Research Articles

Early Management of Blood Lipid Levels with Non-Statin Lipid-Lowering Drugs in Acute Coronary Syndrome: A Mini Review.

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 < 55mg/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.

Inclisiran Usage in Very High-Risk Patients with Dyslipidemia Resistant to Statins and Ezetimibe Therapy

Background. Complications of systemic atherosclerosis (myocardial infarction, ischemic stroke) are the main causes of mortality and disability in the modern world. The relevance of this problem is determined by its scale: the number of deaths from cardiovascular disease has gradually increased from 12.1 million in 1990 to 18.6 million in 2019 and is on the rise. Today, the standard treatment regimen for dyslipidemia includes statins and ezetimibe. For patients who do not achieve the required lipid lowering, intensification of therapy with a relatively new group of drugs – PCSK9 inhibitors – is available. The aim. To study the effectiveness of inclisiran in the complex therapy of dyslipidemia in patients with very high cardiovascular risk. Materials and methods. The study design was a series of clinical cases, the data of which are described for comparison in dynamics. On the basis of the Department of Cardiometabolic Diseases of the Ukrainian Children’s Cardiac Center, a group of 7 patients with very high cardiovascular risk who did not achieve the target lipid parameters on standard therapy with rosuvastatin and ezetimibe was selected. Results. All the patients in the study group of very high cardiovascular risk with dyslipidemia resistant to standard combination treatment who took inclisiran as part of complex lipid-lowering therapy achieved a significant reduction in total cholesterol, but more importantly, they reached the target low-density lipoprotein cholesterol values. We did not find any side effects when using inclisiran. Conclusions. The present series of clinical cases demonstrates high efficacy of inclisiran as part of complex lipid-lowering therapy in patients with very high cardiovascular risk, who have a combination of coronary heart disease and type 2 diabetes mellitus. These results suggest the possibility of wider use of inclisiran in patients with very high cardiovascular risk to reduce cardiovascular morbidity and mortality.

PCSK9 inhibitor added to high-intensity statin therapy to prevent cardiovascular events in patients with acute coronary syndrome after percutaneous coronary intervention: a randomized, double- blind, placebo-controlled, multicenter SHAWN study

BackgroundIt is currently uncertain whether the combination of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and high-intensity statin treatment can effectively reduce cardiovascular events in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) for culprit lesions. MethodsThis study protocol describes a double-blind, randomized, placebo-controlled, multicenter study aiming to investigate the efficacy and safety of combining a PCSK9 inhibitor with high-intensity statin therapy in patients with ACS following PCI. A total of 1,212 patients with ACS and multiple lesions will be enrolled and randomly assigned to receive either PCSK9 inhibitor plus high-intensity statin therapy or high-intensity statin monotherapy. The randomization process will be stratified by sites, diabetes, initial presentation and use of stable (≥4 weeks) statin treatment at presentation. PCSK 9 inhibitor or its placebo is injected within 4 hours after PCI for the culprit lesion. The primary endpoint is the composite of cardiovascular death, myocardial infarction, stroke, re-hospitalization due to ACS or heart failure, or any ischemia-driven coronary revascularization at 1-year follow-up between 2 groups. Safety endpoints mean PCSK 9 inhibitor and statin intolerance. ConclusionThe SHAWN study has been specifically designed to evaluate the effectiveness and safety of adding a PCSK9 inhibitor to high-intensity statin therapy in patients who have experienced ACS following PCI. The primary objective of this study is to generate new evidence regarding the potential benefits of combining a PCSK9 inhibitor with high-intensity statin treatment in reducing cardiovascular events among these patients.

Association between obesity and statin use on mortality and hospital encounters in atrial fibrillation

BackgroundObesity increases risk of atrial fibrillation (AF) at least in part due to pro-inflammatory effects, but has been paradoxically associated with improved mortality. Although statins have pleiotropic anti-inflammatory properties, their interaction with obesity and clinical outcomes in AF is unknown. We explored the relationship between BMI, statin use, and all-cause mortality and AF/congestive heart failure (CHF)-related encounters, hypothesizing that statin exposure may be differentially associated with improved outcomes in overweight/obesity. MethodsThis was a single center retrospective cohort study of adults with AF diagnosed between 2011–2018. Patients were grouped by body mass index (BMI) and statin use at time of AF diagnosis. Outcomes included all-cause mortality and ED or inpatient encounters for AF or CHF. Results and ConclusionsA total of 2503 subjects were included (median age 66 years, 43.4 % female, median BMI 29.8 kg/m2, 54.6 % on baseline statin therapy). Increasing BMI was associated with decreased mortality hazard but not associated with AF/CHF encounter risk. Adjusting for statin-BMI interaction, demographics, and cardiovascular comorbidities, overweight non-statin users experienced improved mortality (adjusted hazard ratio [aHR] 0.55, 95 % CI 0.35–0.84) compared to statin users (aHR 0.98, 95 % CI 0.69–1.40; interaction P-value = 0.013). Mortality hazard was consistently lower in obese non-statin users than in statin users, however interaction was insignificant. No significant BMI-statin interactions were observed in AF/CHF encounter risk. In summary, statin use was not differentially associated with improved mortality or hospitalization risk in overweight/obese groups. These findings do not support statins for secondary prevention of adverse outcomes based on overweight/obesity status alone.

Impact of RA treatment strategies on lipids and vascular inflammation in rheumatoid arthritis: a secondary analysis of the TARGET randomized active comparator trial

BackgroundTreatments for rheumatoid arthritis (RA) are associated with complex changes in lipids and lipoproteins that may impact cardiovascular (CV) risk. The objective of this study was to examine lipid and lipoprotein changes associated with two common RA treatment strategies, triple therapy or tumor necrosis factor inhibitor (TNFi), and association with CV risk.MethodsIn this secondary data analysis of the TARGET trial, methotrexate (MTX) inadequate responders with RA were randomized to either add sulfasalazine and hydroxychloroquine (triple therapy), or TNFi for 24-weeks. The primary trial outcome was the change in arterial inflammation measured in the carotid arteries or aorta by FDG-PET/CT at baseline and 24-weeks; this change was described as the target-to-background ratio (TBR) in the most diseased segment (MDS). Routine lipids and advanced lipoproteins were measured at baseline and 24-weeks; subjects on statin therapy at baseline were excluded. Comparisons between baseline and follow-up lipid measurements were performed within and across treatment arms, as well as change in lipids and change in MDS-TBR.ResultsWe studied 122 participants, 61 in each treatment arm, with median age 57 years, 76% female, and 1.5 year median RA disease duration. When comparing treatment arms, triple therapy had on average a larger reduction in triglycerides (15.9 mg/dL, p = 0.01), total cholesterol to HDL-C ratio (0.29, p-value = 0.01), and LDL particle number (111.2, p = 0.02) compared to TNFi. TNFi had on average a larger increase in HDL particle number (1.6umol/L, p = 0.006). We observed no correlation between change in lipid measurements and change in MDS-TBR within and across treatment arms.ConclusionsBoth treatment strategies were associated with improved lipid profiles via changes in different lipids and lipoproteins. These effects had no correlation with change in CV risk as measured by vascular inflammation by FDG-PET/CT.Trial registrationClinicalTrials.gov ID NCT02374021.

Prescription patterns of statins in cirrhotic patients: a survey among primary care physicians and cardiologists

Background Statin therapy is widely utilized for preventing atherosclerotic cardiovascular disease, both as a primary and secondary measure. Despite the American Association for the Study of Liver Diseases’ endorsement of statin use in cirrhotic patients, practitioners exhibit hesitancy, primarily due to concerns regarding hepatotoxicity. This study aimed to evaluate statin prescription patterns in cirrhotic patients by primary care physicians (PCPs) and cardiologists through a survey. Methods A voluntary survey via Survey Monkey with nine objective-type questions was sent to 220 PCPs and 75 cardiologists within Allegheny Health Network. Survey results were collected, and a chi square test was used to compare the two groups. A P value ≤ 0.05 was considered statistically significant. Results A total of 64 PCPs (29.1%) and 15 cardiologists (20%) completed the survey. Overall, 12.6% did not prescribe statins for primary prevention of atherosclerotic cardiovascular disease in compensated cirrhotic patients. While all cardiologists prescribed statins for secondary prevention, over 50% preferred lower-intensity options. Conversely, 14.1% of PCPs avoided statin prescriptions for secondary prevention. Cardiologists were significantly more inclined to prescribe statins, especially for cirrhosis due to metabolic dysfunction-associated steatotic liver disease compared to PCPs (73.3% vs 45.3%, P = 0.05). Conclusions Despite increasing evidence favoring use of statins in cirrhosis for improving portal hemodynamics and decreasing ascites, hepatic encephalopathy, the incidence of hepatocellular carcinoma, and mortality, there is still hesitation on the part of prescribers for the fear of worsening liver disease. Wider dissemination of current guidelines and education practices may help to bridge this gap.

Community Pharmacists Identification of Gaps in Care - Statin Utilization for Primary Prevention.

Background: Statins are a highly effective lipid-lowering therapy associated with significant reductions in atherosclerotic cardiovascular disease (ASCVD) events and death. Despite these benefits, statins are underutilized. Pharmacist-led interventions to increase statin prescribing are effective. To our knowledge, no prior studies implemented a comprehensive cardiovascular risk assessment utilizing point-of-care (POC) testing in community pharmacies. Objectives: The primary objective was to determine if community pharmacists can be utilized to identify gaps in care regarding appropriate use of statin therapy for prevention of ASCVD events in HPSAs. Secondary objectives were to assess public interest in ASCVD risk assessment and statin prescribing by the pharmacist, and to identify factors associated with statin gaps in care. Methods: A cross-sectional study was conducted at three independent community pharmacies. Participants were identified based on age and medication history and were scheduled at their pharmacy to receive a comprehensive ASCVD risk screening consisting of POC measurement of a complete lipid panel, blood glucose or A1C, and blood pressure. Participants were informed of their statin candidacy at the screening. Participants completed a survey regarding perceptions of the services provided and opinions of statin prescribing by pharmacists. Results: Of the 57 participants, 43 (75.4%) were possible statin candidates. Most indicated trusting their pharmacist to prescribe a cholesterol-lowering medication and felt insurance should pay for these screenings. Conclusion: ASCVD risk assessment conducted within the community pharmacy setting for can be utilized to identify treatment gaps in status use. Participants indicated trusting pharmacists to provide this service and found the service valuable.

The Effect of Statin Therapy on Bone Metabolism Markers and Mineral Density: Aa GRADE-Assessed Systematic Review and Dose-Response Meta-Analysis of Randomized Controlled Trials.

Statin therapy is widely used for the management of dyslipidemia and the prevention of cardiovascular diseases (CVDs). However, there is a growing concern about its potential effects on bone metabolism markers and mineral density. The aim of this systematic review and meta-analysis was to investigate the effect of statin therapy on these parameters. PubMed/MEDLINE, Scopus, and Clarivate Analytics Web of Science databases were searched from inception to August 2023, using MESH terms and keywords. After screening 2450 articles, 16 studies that met the inclusion criteria were included, of which 12 randomized controlled trials (RCTs) were used for meta-analysis. The findings showed that statin therapy significantly reduced bone-specific alkaline phosphatase (B-ALP) levels (WMD=-1.1 U/L; 95% CI -2.2 to -0.07; P=0.03; I2=0%,), and bone mineral density (BMD) at different sites (WMD=-0.06 g/cm2; 95% CI -0.08 to -0.04; P<0.001; I2=97.7%, P<0.001). However, this treatment did not have a significant effect on osteocalcin, serum C-terminal peptide of type I collagen (S-CTx), serum N-telopeptides of type I collagen (NTx) concentration, or overall fracture risk. This systematic review and meta-analysis provide evidence that statin therapy is associated with a significant reduction in B-ALP levels and BMD at different sites of the skeleton. Further studies are needed to investigate the long-term effects of statin therapy on bone health and to identify the potential underlying mechanisms.

Prescribing patterns of statins and associated factors among type 2 diabetes mellitus patients in Africa: A systematic review and meta-analysis

BackgroundIn sub-Saharan African nations, there's a documented shortfall in the utilization of statins, despite established clinical guidelines advocating their use for reducing cardiovascular risks and overall mortality among Type 2 diabetes patients aged 40–75 years old. Most clinical guidelines recommend prescribing statins to individuals with type 2 diabetes to reduce the chances of cardiovascular disease. There is currently a lack of extensive research on statin utilization specifically for primary prevention of cardiovascular disease in Africa. Thus, this study aimed to assess the prescription patterns of statins for preventing cardiovascular disease in type 2 diabetes patients. MethodsThe findings of the review were presented following the guidelines outlined in the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA-2020) checklist. We conducted searches on electronic databases including PubMed, EMBASE, Cochrane Library, Science Direct, African Journal Online, and Google Scholar. This systematic review and meta-analysis included articles that met specific inclusion criteria: observational studies such as cross-sectional, cohort, and case-control studies focusing on determinants, risk factors, or correlates associated with statin prescription within Africa. Only published articles up to June 2, 2024, published in English, and conducted in either community or healthcare facility settings were considered. Data import was initially conducted using Microsoft Excel, and statistical analysis was performed using STATA software. Cochran's Q test was employed to assess whether there was a significant variance in prevalence among the studies. Additionally, the I2 statistic was utilized to quantify the extent of heterogeneity. A funnel plot, a visual tool, was utilized to evaluate publication bias. ResultsThe search strategy resulted in 7695 published original articles. The full texts of the 89 papers were assessed for eligibility and quality. Moreover, some articles were rejected due to inaccuracies in the outcome variable. Ultimately, only ten studies focusing on the prevalence of statin prescription were examined. The research suggests that the pooled prevalence of statin prescription among Type 2 diabetic individuals in Africa is found to be 48.82% (95% CI: 35.41–63.24). Age greater than 65 years (AOR = 3.56, 95% CI: 1.70–7.45; I2 = 54.7%), comorbidity (AOR = 1.13, 95% CI: 0.27–4.63, I2 = 96.4%), dyslipidemia (AOR = 3.15, 95% CI: 1.54–6.44, I2 = 61.7%), DM duration greater than ten years (AOR = 1.36, 95% CI: 0.81–2.28, I2 = 77.3%), and government insurance (AOR = 8.85, 95% CI: 2.72–28.76, I2 = 81.5%) were factors associated with statin prescription among type 2 diabetic patients. ConclusionsIn general, the extent of statin prescriptions for individuals with type 2 diabetes who are eligible for statin therapy was below the target outlined by clinical practice guidelines. Being over 65 years old, having comorbidities, experiencing dyslipidemia, having type 2 diabetes for more than ten years, and having government insurance were all identified as independent factors predicting the prescription of statins. This finding is concerning and underscores the urgent need to enhance adherence to clinical practice guidelines for the well-being of this vulnerable population at high risk.

Real-world use of medical therapy in moderate asymptomatic carotid stenosis

ObjectiveDespite level 1 evidence demonstrating the benefit of carotid endarterectomy for the prevention of stroke in patients with severe asymptomatic carotid stenosis (ACS), there has been a trend toward recommending optimal medical therapy (OMT) alone. This recommendation has been promulgated based on the observation that modern advances in OMT reduce the overall stroke risk in the general population, but the success of this treatment strategy is dependent on patient and provider adherence. In current practice, patients with moderate ACS are nearly all treated with OMT alone. The objective of this study was to evaluate adherence to OMT in a cohort of patients with moderate ACS undergoing treatment with OMT alone. MethodsConsecutive carotid duplex ultrasound examinations were reviewed for the years 2019 and 2020. Those with moderate (50%-69%) ACS based on Society for Vascular Surgery guidelines were included in the study. Patients were assessed for OMT at the time of the index duplex, the first follow-up visit, and at each subsequent follow-up visit until the end of the study. OMT was defined as abstinence from smoking, aspirin or other antiplatelet use, and statin or other lipid-lowering therapy. Patients were stratified based on their ability to achieve OMT, and each component was evaluated to identify shortfalls in therapy. ResultsA total of 323 duplex ultrasound examinations with moderate ACS in 255 patients were identified. Of the 255 patients, 143 (56.1%) were on OMT at the time of the first duplex; that number increased to 163 (63.9%) by the first follow-up visit and 175 (68.6%) by the completion of the study. There were 112 (43.9%) patients who were not on OMT at the time of the index duplex, 43 (38.4%) of whom achieved OMT over a median follow-up time of 2.7 years. By the end of follow-up, 86 (76.8%) were taking aspirin or another antiplatelet medication, 93 (83.0%) were on statin or other lipid-lowering therapy, and 74 (66.1%) were abstinent from smoking. Pre-duplex smoking was independently associated with failure to achieve OMT (hazard ratio: 0.452, P = .017). ConclusionsAmong patients with moderate ACS who were not previously on OMT, the rate of OMT achievement is poor. Although advances in lipid management through statin therapy have been praised for their role in improving the effectiveness of OMT, smoking cessation represents an important target for improving uptake and as a result effectiveness of OMT.

A risk stratification analysis of atherosclerotic cardiovascular disease events post-statin discontinuation in patients who underwent sleeve gastrectomy or Roux-en-Y gastric bypass bariatric/metabolic surgeries

BackgroundCardiovascular disease remains a leading cause of mortality globally, and its prevalence is notably elevated in individuals with obesity. Bariatric surgery is an effective intervention to reduce obesity-related health risks. However, the implications of discontinuing statin therapy, particularly post-bariatric surgery, among those with a history of atherosclerotic cardiovascular disease have yet to be clarified. We aimed to ascertain the risk of atherosclerotic cardiovascular disease events following statin cessation after bariatric surgery and to delineate the variance in outcomes between primary and secondary prevention cohorts. MethodsThe TriNetX database, encompassing electronic medical records from 69 United States healthcare institutions, spanning 2012 to 2021. Using a retrospective cohort design, patients aged ≥18 years who underwent bariatric surgery and were concurrently on statin therapy were selected. Discontinuation was defined as a 90-day lapse after the last statin prescription. Patients were categorized as "primary" or "secondary" prevention based on their atherosclerotic cardiovascular disease history. The primary outcome was the occurrence of an atherosclerotic cardiovascular disease event post-statin cessation. Multivariable Cox proportional hazards models discerned factors influencing this outcome. ResultsOf the 453 statin users who underwent bariatric surgery, 332 (73.1%) were in the primary prevention group and 121 (26.7%) in the secondary prevention group. At 1-year post-surgery, atherosclerotic cardiovascular disease event-free rates were 93% for primary and 68% for secondary prevention groups. Primary prevention patients showed an 82% reduced risk of post-statin cessation atherosclerotic cardiovascular disease events than secondary prevention patients (hazard ratio, 0.181; 95% confidence interval, 0.119–0.274). Additionally, Hispanic/Latino patients had heightened post-statin cessation atherosclerotic cardiovascular disease risks compared to non-Hispanic/Latino peers. ConclusionPost-bariatric surgery statin discontinuation can pose significant risks, especially for those with atherosclerotic cardiovascular disease history and certain demographic groups, such as those over age 40 with diabetes. Ethnic disparities in outcomes necessitate individualized, equitable healthcare strategies. Optimal decisions about statin cessation necessitate comprehensive evaluations of cardiovascular determinants, with future research crucial to refine therapeutic approaches based on these insights.

Association between Estimated Small Dense Low-Density Lipoprotein Cholesterol and Occurrence of New Lesions after Percutaneous Coronary Intervention in Japanese Patients with Stable Angina and Receiving Statin Therapy.

Low-density lipoprotein cholesterol (LDL-C) is considered the most important risk factor for coronary artery disease (CAD). Although lipid-lowering therapy using high-intensity statins for patients with stable CAD is one of the cornerstones of medication therapy, there is still a risk of residual cardiovascular events, even after controlling for LDL-C. Recently, attention has focused on the association between small dense LDL-C as a residual risk factor for CAD, and it has been reported that a formula can be used to calculate the small LDL-C. We investigated the association between estimated small dense LDL-C (Esd LDL-C) and the occurrence of new lesions with myocardial ischemia 2 years after percutaneous coronary intervention (PCI) in 537 patients with stable angina who underwent PCI. In this study, all patients had been prescribed statins. This study was based on previously reported data regarding the relationship between non-high-density lipoprotein cholesterol levels and stable angina pectoris after PCI. Revascularization, including new lesions and in-stent restenosis, and new lesions appeared in 130 and 90 patients, respectively, 2 years after PCI. Age, diabetes mellitus (DM), LDL-C, and Esd LDL-C were associated with the occurrence of revascularization and new lesions 2 years after PCI. Multivariate logistic regression analysis models revealed that Esd LDL-C [odds ratio (OR) 1.03, 95% confidence interval (CI) 1.004-1.048, p = 0.020; and OR 1.03, 95% CI 1.009-1.057, p = 0.007, respectively] were associated with the revascularization and occurrence of new lesions 2 years after PCI. As well as total cholesterol and LDL-C, Esd LDL-C was an independent risk factor for the revascularization and occurrence of new lesions 2 years after PCI for stable angina in Japanese patients receiving statin therapy. In patients with stable angina who are on lipid-lowering therapy with statins, calculating the Esd LDL-C may provide useful information for predicting revascularization and the occurrence of new lesions.

Effect of Pravastatin on Kidney Function in Patients with Dyslipidemia and Type2 Diabetes Mellitus: A Multicenter Prospective Observational Study.

Several studies have reported that pravastatin can mitigate the progression of kidney disease, but limited evidence exists regarding its effects on kidney function in Asian patients. This multicenter prospective observational study aimed to assess the effect of pravastatin on kidney function in Korean patients with dyslipidemia and type2 diabetes mellitus (T2DM) in clinical practice. This 48-week prospective multicenter study included 2604 of 2997 eligible patients with dyslipidemia and T2DM who had available estimated glomerular filtration rate (eGFR) measurements. The primary endpoint was eGFR percent change at week24 from baseline. We also assessed secondary endpoints, which included percent changes in eGFR at weeks12 and 48 from baseline, as well as changes in eGFR, metabolic profiles (lipid and glycemic levels) at 12, 24, and 48weeks from baseline, and safety. We noted a significant improvement in eGFR, with mean percent changes of 2.5%, 2.5%, and 3.0% at 12, 24, and 48weeks, respectively (all adjusted p < 0.05). The eGFR percent changes significantly increased in subgroups with baseline eGFR 30-90mL/min/1.73m2, glycated hemoglobin (HbA1c) ≥ 7 at baseline, no hypertension history, T2DM duration > 5years, or previous statin therapy. Lipid profiles were improved and remained stable throughout the study, and interestingly, fasting glucose and HbA1c were improved at 24weeks. Our findings suggest that pravastatin may have potential benefits for improving eGFR in Korean patients with dyslipidemia and T2DM. This could make it a preferable treatment option for patients with reduced kidney function. NCT05107063 submitted October 27, 2021.

The Effect of Eicosapentaenoic and Docosahexaenoic Acid Supplementation on Coronary Artery Calcium Progression in Subjects With Diabetes and Coronary Artery Disease: A Secondary Analysis of a Randomized Trial

Higher coronary artery calcium (CAC) scores and progression of CAC are associated with higher mortality. We previously reported that subjects with coronary artery disease randomly allocated to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation or none had similar significant increases in CAC score over 30 months. Whether these findings are influenced by diabetes status is unknown. A total of 242 subjects with coronary artery disease who were on statin therapy were randomly allocated to to 1.86 g EPA and 1.5 g DHA daily or none (control). The CAC score was measured at baseline and 30-month follow-up using noncontrast, cardiac computed tomography. A significant interaction term between diabetes status and treatment arm was noted in the prediction of the CAC score (p <0.001). A total of 176 subjects (85.8% men) had no diabetes and 66 subjects (80.3% men) had diabetes. The mean age was 62.9 ± 7.9 versus 63.2 ± 7.1 years, respectively. The mean low-density lipoprotein cholesterol and median triglyceride levels were not significantly different between those without and with diabetes: 77.7 ± 25.9 versus 77.1 ± 30.2 mg/100 ml, respectively, and 117.0 (78.0 to 158.0) versus 119.0 (84.5 to 201.5) mg/100 ml, respectively. Subjects with diabetes on EPA+DHA had a greater increase in CAC score than subjects with diabetes in the control group (median 380.7 vs 183.5, respectively, p = 0.021). In contrast, no difference occurred between the EPA+DHA and control groups in subjects without diabetes (175.7 vs 201.1, respectively, p = 0.41). In conclusion, EPA+DHA supplementation was associated with greater CAC progression in subjects with diabetes than subjects with diabetes in the control group over a 30-month period; whether this indicates progression of the disease burden or plaque stabilization requires further study.

Statins as a Combatant for Treatment of Glioblastoma

The competitive HMG-CoA reductase (HMGCR) inhibitors, commonly referred to as "statins," have been shown in preclinical tests to have promise anticancer characteristics in addition to being potent medications that lower cholesterol and lower cardiovascular risk. When combined with other cancer treatment strategies, statins seem to improve the treatment outcome for a variety of malignancies. After surgical resection followed by concomitant radiation and chemotherapy, the median overall survival (OS) for glioblastoma multiforme (GBM), a particularly lethal cerebral tumour, is only about one year. Due to their capacity to inhibit cell growth, survival, migration, metastasis, inflammation, and angiogenesis in both in vitro and in vivo investigations, statins have recently come to light as prospective adjuvant medications for the treatment of GBM. Statins' therapeutic effects on the survival of GBM patients are still debatable, though. When just focusing on the treatment of cancer, specifically GBM, this study intends to analyse and address some of the known effects of statin medicines, including concurrent statin therapy with chemotherapeutic agents. Keywords: statin, glioblastoma, brain tumor, antitumor, cholesterol, apoptosis.

1446-P: Gender Inequalities in Cardiovascular Risk Factors in Primary Prevention Adults Living with Type 1 Diabetes in Germany and France—Findings from DPV and SFDT1

Introduction &amp; Objectives: To evaluate whether medical care for and level of cardiovascular risk factors differ in primary prevention between adult men and women with type 1 diabetes (T1D) in two European countries in 2020-2022. Methods: We included 2657 participants from the DPV registry (Germany, mean age 40±15, diabetes duration 23±14 years; 50.9% men) and 1172 from the SFDT1 study (France, age 39±14, diabetes duration 22±13 years; 53.2% men). Results: HbA1c levels and body mass indexes were similar in women and men with similar proportions of HbA1c&amp;lt;7% (DPV: 36.6 vs. 33.0%, respectively; SFDT1: 22.8 vs. 24.9%; both n.s.). Women had less overweight in DPV (55.4 vs. 61.0%, p&amp;lt;0.05) but not in SFDT1 (48.0 vs. 44.9%, n.s.) and were less prone to smoke (DPV: 19.7 vs. 25.8%, p&amp;lt;0.05; SFDT1: 21.0 vs. 26.0%, n.s.). Systolic blood pressure was lower in women than men (DPV: 124±15 vs. 129±15; SFDT1: 121±16 vs. 126±14mmHg, both p&amp;lt;0.05) with similar rates of antihypertensive therapy in case of systolic/diastolic blood pressure ≥140/90mmHg (DPV: 70.5 vs. 63.6%; SFDT1: 73.3 vs. 68.6%, both n.s.). In case of microalbuminuria, ACEi-ARB were less prescribed in women than men in DPV (21.4 vs 37.6%, p&amp;lt;0.05) but not SFDT1 (70.6 vs 62.0%, n.s.). In women compared to men, HDL-cholesterol levels were higher; triglycerides lower and LDL-cholesterol similar in DPV and SFDT1. In those with LDL-cholesterol &amp;gt;130 mg/dL (DPV: 19.9 vs. 23.9%; SFDT1 17.0 vs. 19.2%, both n.s.), statin therapy was less prescribed in women than men in DPV (7.9 vs. 17.0%, p&amp;lt;0.05), SFDT1 (18.2 vs. 21.0%, n.s.). Conclusion: Women in primary prevention have a better cardiovascular risk profile than men in both studies. We observed a high rate of therapeutic inertia, which might be higher in women for statin and nephroprotection with ACEi-ARB especially in Germany. Disclosure E. Cosson: Advisory Panel; Abbott, AstraZeneca, Lilly Diabetes, Novo Nordisk, Sanofi, Roche Diagnostics, Novartis AG, Amgen Inc. M. Auzanneau: Other Relationship; Insulet Corporation. G.A. Aguayo: None. W. Karges: None. J. Riveline: Board Member; Abbott, Novo Nordisk A/S, Sanofi, Eli Lilly and Company, Medtronic, Dexcom, Inc., Insulet Corporation, Air Liquide, AstraZeneca. P. Augstein: None. L. Sablone: None. P.M. Jehle: None. G. Fagherazzi: Speaker's Bureau; Sanofi. Advisory Panel; Timkl, SAB Biotherapeutics, Inc., Vitalaire, Roche Diabetes Care. R.W. Holl: None.

Epicardial fat modifies the relationship between coronary calcium score and all-cause mortality: The St. Francis Heart Study

ObjectiveEpicardial fat is associated with cardiovascular risk factors and adverse outcomes. However, it is not clear if epicardial fat remains to be a mortality risk when coronary calcium score (CAC) is taken into account. MethodsWe studied the 1005 participants from the St. Francis Heart Study who were apparently healthy with CAC scores at 80th percentile or higher for age and gender, randomly assigned to placebo or statin therapy. At baseline, lipid profiles and non-contrast CT images were obtained where the epicardial fat volume was analyzed. Likelihood ratio testing was used to assess the additional prognostic value of epicardial fat to CAC for the risk of all-cause mortality. ResultsIncreased epicardial fat volume was associated with higher CAC. For each unit increase in lnCAC, the average epicardial fat volume increased by 3.34 mL/m2. After a mean follow-up period of 17 years, 179 (18%) participants died. Increased epicardial fat volume was associated with an adjusted hazard ratio of 1.11 (95% CI: 1.02 to 1.20) predicting all-cause mortality. In the stratified analysis testing strata of epicardial fat and CAC, those with increased epicardial fat and increased CAC had the highest risk of death. Compared with a model containing lnCAC and traditional risk factors, a model additionally containing epicardial fat volume yielded a better model fit (likelihood ratio test p < 0.001). ConclusionIncreased epicardial fat volume is associated with increased all-cause mortality risk. In addition, it portends incremental prognostic value to CAC score in mortality prediction.

Effects of omega-3 fatty acids on coronary revascularization and cardiovascular events: a meta-analysis.

Benefits of pharmacologic omega-3 fatty acid administration in cardiovascular prevention are controversial. Particularly, effects on coronary revascularization are unclear; also debated are specific benefits of eicosapentaenoic acid (EPA). We investigated incident coronary revascularizations, myocardial infarction (MI), stroke, heart failure (HF), unstable angina, and cardiovascular death, in subjects randomized to receive EPA or EPA + docosahexaenoic acid (EPA + DHA) vs. control. Meta-analysis of randomized controlled trials (RCTs) was conducted after MEDLINE, Embase, Scopus, Web of Science, and Cochrane Library search. Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines were followed for abstracting data and assessing data quality and validity. Data were pooled using a random effects model. Eighteen RCTs with 134 144 participants (primary and secondary cardiovascular prevention) receiving DHA + EPA (n = 52 498), EPA alone (n = 14 640), or control/placebo (n = 67 006) were included. Follow-up ranged from 4.5 months to 7.4 years. Overall, compared with controls, omega-3 supplementation reduced the risk of revascularization [0.90, 95% confidence interval (CI) 0.84-0.98; P = 0.001; P-heterogeneity = 0.0002; I2 = 68%], MI (0.89, 95% CI 0.81-0.98; P = 0.02; P-heterogeneity = 0.06; I2 = 41%), and cardiovascular death (0.92, 95% CI 0.85-0.99; P = 0.02; P-heterogeneity = 0.13; I2 = 33%). Lower risk was still observed in trials where most participants (≥60%) were on statin therapy. Compared with DHA + EPA, EPA alone showed a further significant risk reduction of revascularizations (0.76, 95% CI 0.65-0.88; P = 0.0002; P-interaction = 0.005) and all outcomes except HF. Omega-3 fatty acid supplementation reduced the risk of cardiovascular events and coronary revascularization, regardless of background statin use. Eicosapentaenoic acid alone produced greater benefits. The role of specific omega-3 molecules in primary vs. secondary prevention and the potential benefits of reduced revascularizations on overall health status and cost savings warrant further research.

Artificial Intelligence in Coronary Artery Calcium Scoring.

Cardiovascular disease (CVD), particularly coronary heart disease (CHD), is the leading cause of death in the US, with a high economic impact. Coronary artery calcium (CAC) is a known marker for CHD and a useful tool for estimating the risk of atherosclerotic cardiovascular disease (ASCVD). Although CACS is recommended for informing the decision to initiate statin therapy, the current standard requires a dedicated CT protocol, which is time-intensive and contributes to radiation exposure. Non-dedicated CT protocols can be taken advantage of to visualize calcium and reduce overall cost and radiation exposure; however, they mainly provide visual estimates of coronary calcium and have disadvantages such as motion artifacts. Artificial intelligence is a growing field involving software that independently performs human-level tasks, and is well suited for improving CACS efficiency and repurposing non-dedicated CT for calcium scoring. We present a review of the current studies on automated CACS across various CT protocols and discuss consideration points in clinical application and some barriers to implementation.

LDLR c.89_92dup: a novel frameshift variation in familial hypercholesterolemia

BackgroundFamilial hypercholesterolemia (FH) is a common inherited metabolic disease that causes premature atherosclerosis, cardiovascular disease, and even death at a young age. Approximately 95% of FH-causing genetic variants that have been identified are in the LDLR gene. However, only 10% of the FH population worldwide has been diagnosed and adequately treated, due to the existence of numerous unidentified variants, uncertainties in the pathogenicity scoring of many variants, and a substantial number of individuals lacking access to genetic testing.ObjectiveThe aim of this study was to identify a novel variant in the LDLR gene that causes FH in a Chinese family, thereby expanding the spectrum of FH-causing variants.MethodsPatients were recruited from Beijing Anzhen Hospital, Capital Medical University. FH diagnosis was made according to the Dutch Lipid Clinical Network (DLCN) criteria. Whole-exome sequencing (WES) was conducted to identify the FH-causing variant in the proband, and amplicon sequencing was used to verify the variant in his family members.ResultsA three-generation Chinese family was recruited, and two FH patients were clinically diagnosed, both without known FH-causing variants. These two FH patients and another possible patient carried a novel variant, NC_000019.9(NM_000527.5):c.89_92dup (NP_000518.1:p.Phe32Argfs*21), in the ligand-binding domain of the low-density lipoprotein (LDL) receptor that led to a frameshift. The FH adults in the family showed severe clinical symptoms and statin therapy resistance.ConclusionThis study identified a novel pathogenic LDLR variant, c.89_92dup, associated with severe FH clinical manifestations and statin therapy resistance.