Atherosclerotic Cardiovascular Disease In Patients Research Articles

Abstract 16164: Lipoprotein (a) Testing in Patients With Atherosclerotic Cardiovascular Disease in Five Large U.S. Health Systems

Introduction: Lipoprotein (a) [Lp(a)] is an independent, causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Screening patterns remain variable and it is unclear what factors are associated with Lp(a) testing, and whether knowing the Lp(a) value changes management. Research Question: To better understand the proportion of Lp(a) testing, factors predicting Lp(a) testing, and impact on management in ASCVD patients. Methods: A retrospective study using electronic medical record data from five health systems in the CardioHealth Alliance and PCORnet® identified a cohort with an ASCVD diagnosis in 5 years prior to the index date. The index date was defined as the date of the first Lp(a) test result in 2019-2021 for those with a Lp(a) test, or the date of a randomly selected outpatient encounter in 2019-2021 for those without a Lp(a) test. Initiation of lipid lowering therapy (LLT) was assessed within 6 months after the index date. Multivariable regression modeling was used to determine factors associated with Lp(a) testing. Results: Among 595,685 ASCVD participants, only 2,588 (0.4%) were tested for Lp(a). In adjusted models, those who were older, Black, or Hispanic were less likely to have Lp(a) testing, while those with familial hypercholesterolemia, ischemic stroke/TIA, PAD, prior LLT, or LDL-C ≥130mg/dL were more likely to be tested (table). Those with elevated Lp(a) (>50mg/dL or >125 nmol/L) were more likely to initiate any LLT (43.9% vs 34.6%, p=0.03), particularly PCSK9i (10.9% vs 4.8%, p<0.01) and ezetimibe (11.5% vs 5.9%, p <0.01) compared to those without elevated Lp(a). Statin initiation remained similar between those with and without elevated Lp(a) (32.1% vs 29.5%, p=0.47). Conclusion: Lp(a) testing in ASCVD patients is infrequent, with evidence of disparities by race and ethnicity. Having elevated Lp(a) was associated with higher initiation of non-statin LLT. However, overall initiation of any LLT after an elevated Lp(a) test was low.

Abstract 18677: Residual Cardiovascular Risk Reduction Through a Digital App

Introduction: atherosclerotic cardiovascular disease (ASCVD) is the first cause of disability and death globally and represents the main etiological agent of myocardial infarction and ischemic stroke. The causal association between LDL cholesterol (LDL chol) and ASCVD is one of the most consolidated topics of modern medicine: it has gone from the demonstration that high levels of LDL Chol are a necessary condition for atherogenesis to the awareness that "the lower the better" and "the earlier the better" to underline the need for secondary and primary prevention to reduce atherosclerotic burden. Hypothesis: we hypothesized that motivational alerts sent through telemedicine to patients could affect escalation therapy in ASCVD patients. Aim: we evaluated the impact of a digital-APP in dyslipidemia management, and other CV risk factors, but focusing mainly on LDL chol. Methods: fifty dyslipidemic patients (APP_pts; 40 males; mean age 62±9 years; age range 40÷81 yrs) were followed through telemedicine-based APP from March 2022 to May 2023, in comparison with additional 50 dyslipidemic patients (ST_pts; 43 males; mean age 63±9 years; age range 40÷81 yrs) who underwent standard outpatient visits. Patients’ access to digital APP was remotely monitored and reports were used for therapy adjustments. Statistical analysis was performed with GraphPad Prism 7; comparisons were carried out by two-way ANOVA and by chi-square test. Results: baseline LDL chol values were 93,3±36,4 mg/dL, and 90,8±43,8 mg/dL, in APP_pts and in, ST_pts, respectively; six months after enrollment, both cohorts experienced significant reductions (APP_pts, 72,1±35,2 mg/dL, p=0,024; ST_pts, 76,7±38,6 mg/dL, p=0,008) vs baseline. We further subdivided both groups into ischemic and non-ischemic subjects (APP_pts: 26 vs 24; ST_pts : 33 vs 17). Remarkably, telemedicine control showed a 32% reduction in LDL chol for ischemic pts, while ischemic ST_pts gained only 11%. Overall, dyslipidemic control in non-ischemic pts appeared less beneficial (17 vs 15%). Finally, telemedicine-based APP resulted more effective than standard monitoring (p=0,04). Conclusion: aggressive lipid lowering therapies should be implemented with remote patients monitoring, mostly in the post-ischemic setting.

Abstract 15850: Low Rates of Achievement of Low-Density Lipoprotein Cholesterol Levels <55 mg/dL Among Patients With Atherosclerotic Cardiovascular Disease in the United States: Findings From the Cardiovascular Multicenter Observational Investigation of Lipid Care in the United States-2 Registry

Introduction: Guidelines are increasingly recommending a goal LDL-C <55 mg/dL in persons with atherosclerotic cardiovascular disease (ASCVD). The proportion and characteristics of US adults with ASCVD with an LDL-C <55 mg/dL remains unclear. Aims: To evaluate lipid management in ASCVD patients and factors associated with achieving an LDL-C <55mg/dL. Methods: Using electronic health record data from 8 US health systems, we evaluated LDL-C levels and treatment patterns in persons with prevalent ASCVD seen as outpatients between 1/1/2021-12/31/2021 with an LDL-C level within the prior year. Multivariable logistic regression modeling with generalized estimating equations was used to evaluate factors associated with an LDL-C <55 mg/dL. Results: Among 178,240 eligible ASCVD patients, 43.5% (77,472) had an LDL- C <70 mg/dL and 22.0% (39,270) had an LDL-C <55 mg/dL. Older age was associated with higher odds of LDL-C <55 mg/dL (OR 1.10 per 10 years, 95% CI 1.07-1.13), while female sex (OR 0.71, 95% CI 0.68-0.64) Black race (OR 0.77, 95% CI 0.70-0.86), and non-coronary artery disease forms of ASCVD including peripheral artery disease (PAD, OR 0.61, 95% CI 0.58-0.64) and cerebrovascular disease (CeVD, OR 0.72, 95% CI 0.66-0.79) were associated with lower odds of LDL-C <55 mg/dL in multivariable modeling. Overall, while 75.0% were on a statin, only 36.9% were on a high-intensity statin, 5.7% were on ezetimibe, and 1.7% were on a PCSK9i. Combination therapy was rare: only 4.2% were on a statin+ezetimibe, 0.5% on statin+PCSK9i, and 0.3% on all three. Conclusions: Less than a quarter of US patients with ASCVD achieve an LDL <55 mg/dL. Achieving this goal is even less common among younger adults, women, Black persons, and those with PAD and CeVD. Current therapeutic regimens often fail to use high-intensity statins, and markedly underutilize combinations of statins with ezetimibe and/or PCSK9 inhibitors.

Abstract 13043: LDL-C, Lp(a) and Hs-CRP Each Predict Future Cardiovascular Events After ACS on High-Intensity Statin Therapy. An Analysis of the ODYSSEY OUTCOMES Trial

Background: Atherosclerotic cardiovascular disease (ASCVD) risk has been jointly associated with levels of LDL cholesterol (LDL-C), lipoprotein [Lp](a)] and the inflammatory marker high-sensitivity C reactive protein (hsCRP). It is unclear whether and to what extent each of these biomarkers predict ASCVD risk after acute coronary syndrome (ACS), particularly in the era of intensive LDL-C lowering. Recent analysis of 3 trials in stable ASCVD patients with hypertriglyceridemia suggested that hsCRP may be a stronger predictor for recurrent events than LDL-C; however, only 52% received high-intensity statin. Methods: The ODYSSEY OUTCOMES trial enrolled post-ACS patients not at goal for atherogenic lipoproteins a median of 2.6 months after ACS and on treatment with maximum tolerated (89% high-intensity) atorvastatin or rosuvastatin. Absolute risk of major adverse cardiovascular events (MACE, the primary composite outcome of coronary heart disease death, nonfatal myocardial infarction, fatal/nonfatal ischemic stroke or unstable angina hospitalization) and all-cause death were analyzed as a function of baseline LDL-C, hs-CRP, and Lp(a) values in patients randomized to the placebo arm via natural cubic splines from Poisson regression models, adjusted for age, sex, diabetes, BMI, current smoking, and the other 2 predictor variables. Results: Among 9149 evaluable patients, median (Q1-Q3) LDL-C, hsCRP, and Lp(a) were 81 (71-97) mg/dL, 1.7 (0.8-3.9) mg/L, and 21.4 (6.6-60.1) mg/dL, respectively. For each parameter, a higher baseline value was associated with a substantial increase in risk of MACE ( Figure , all spline p<0.0001). LDL-C and hsCRP were associated with all-cause death (p<0.0001), but not Lp(a) (p>0.05). Conclusion: In ACS patients receiving intensive statin therapy and not at goal for atherogenic lipoproteins, LDL-C, hs-CRP, and Lp(a) were independent predictors of MACE. LDL-C and hsCRP were independent predictors of all-cause death.

Abstract 16059: Real-World Exploration of Low Density Lipoprotein Cholesterol Management in Patients With Atherosclerotic Cardiovascular Disease

Introduction: Although guidelines recommend low-density lipoprotein cholesterol (LDL-C) to bel <70mg/dL in patients with atherosclerotic cardiovascular disease (ASCVD), implementation of these recommendations remains low. Research Question: To understand LDL-C management nationally and identify gaps or disparities in guideline directed care. Methods: A retrospective cohort study utilizing electronic medical record data from five health systems participating in the CardioHealth Alliance and PCORnet® was performed on patients with a LDL-C measurement in 2021 and prior ASCVD. Multivariable regression modeling was used to determine the relationship of clinical factors with guideline directed LDL-C targets. Results: Among 216,074 ASCVD participants, only 86,188 (40%) had LDL-C <70 mg/dL. Compared with participants with uncontrolled LDL-C (≥70mg/dL), those with LDL-C <70 mg/dL tended to be male (64.9% vs 49.1%), White (87.3% vs 83.9%), had coronary artery disease (83.5% vs 73.0%), heart failure (29.1% vs 21.3%), diabetes (48.2% vs 34.1%), and atrial fibrillation (26.1% vs 19.3%). Among those with LDL-C ≥70 mg/dL not on lipid lowering therapy (LLT) at baseline (n=53,957 [41%]), only 20% were initiated on any LLT within 6 months of the elevated LDL-C value. Several factors were associated with not achieving LDL-C <70 mg/dL (Figure) including female sex (RR 1.13 [95% CI 1.12-1.14] p <0.001), Black race (1.15 [1.14-1.16] p <0.001), and Hispanic ethnicity (1.04 [1.01-1.06] p=0.007). Additionally, prior Lp(a) testing was associated with reaching LDL-C target (0.87 [0.82-0.92], p<0.001). Conclusions: Within five large U.S. health systems, only 40% of ASCVD patients achieved target LDL-C of <70 mg/dL. Patients who were female, Black, and/or Hispanic were particularly unlikely to achieve target, highlighting significant disparities. Multidisciplinary and inclusive approaches from health system to community may be needed to improve LDL-C care nationally.

Comparison of Effects of Injectable Semaglutide and Dulaglutide on Oxidative Stress and Glucose Variability in Patients with Type 2 Diabetes Mellitus: A Prospective Preliminary Study.

Recent trials have shown that glucagon-like peptide-1 receptor agonists considerably reduce atherosclerotic cardiovascular disease in patients with type 2 diabetes mellitus (T2DM). Oxidative stress, a surrogate marker of cardiovascular risk, is associated with glucose variability. However, to the best of our knowledge, no studies have compared the effects of injectable semaglutide and dulaglutide therapies on oxidative stress and glucose variability assessed via continuous glucose monitoring (CGM). This study aimed to analyze and compare the effects of semaglutide and dulaglutide therapies on oxidative stress and glucose variability as assessed through CGM. This is an open-label, multicenter, randomized, prospective, parallel-group comparison study. Overall, 37 patients with T2DM treated with dulaglutide for at least 12weeks were randomized into two groups: one receiving continuous dulaglutide therapy (n = 19) and one receiving injectable semaglutide therapy (n = 18) groups. The coprimary endpoints were changes in the results of the diacron-reactive oxygen metabolites test, an oxidative stress marker, and CGM-evaluated glucose variability after 24weeks. The secondary endpoint was changes in the Diabetes Treatment Satisfaction Questionnaire (DTSQ) scores. Switching to semaglutide therapy was better than continuous dulaglutide therapy in reducing oxidative stress, glucose variability, and glycated hemoglobin levels. Conversely, continuous dulaglutide therapy was better than semaglutide therapy in terms of DTSQ scores for "Convenience" and "Recommend." Injectable semaglutide therapy may be more effective than dulaglutide therapy in ameliorating oxidative stress and regulating glucose metabolism, including glucose variability, in patients with T2DM, while dulaglutide therapy may be more effective in terms of treatment satisfaction. UMIN-CRT ID: UMIN000042670 (registered 7 December 2020).

Atherosclerotic cardiovascular disease risk stratification and management in type 2 diabetes: review of recent evidence-based guidelines.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality and morbidity in individuals with type 2 diabetes mellitus (T2DM). Accordingly, several scientific societies have released clinical practice guidelines to assist health professionals in ASCVD risk management in patients with T2DM. However, some recommendations differ from each other, contributing to uncertainty about the optimal clinical management of patients with T2DM and established ASCVD or at high risk for ASCVD. Thus, the purpose of this paper is to discuss recent evidence-based guidelines on ASCVD risk stratification and prevention in patients with T2DM, in terms of disparities and similarities. To close the gap between different guidelines, a multidisciplinary approach involving general practitioners, endocrinologists, and cardiologists may enhance the coordination of diagnosis, therapy, and long-term follow-up of ASCVD in patients with T2DM.

Serum branch-chained amino acids are increased in type 2 diabetes and associated with atherosclerotic cardiovascular disease

Background and aimCirculating biomarkers of metabolic and cardiovascular diseases can help in the early detection and prevention of those diseases. Using proton nuclear magnetic resonance (1H-NMR), we aimed to study the plasma levels of low-molecular-weight metabolites (LMWMs) in a cohort of 307 patients with metabolic diseases to assess their relationships with type-2 diabetes (T2D) and incident atherosclerotic cardiovascular disease (ASCVD).MethodsWe conducted a cross-sectional and prospective study. We included 307 patients attending the Lipid Unit of our University Hospital for the treatment of the following metabolic disturbances and associated disorders: T2D (73.9%), obesity (58.7%), and hypertension (55.1%). 1H-NMR was used to study the plasma levels of 13 LMWMs. LMWM serum concentrations were evaluated in patients with and without T2D. and the correlations with several parameters and their associations with T2D were analyzed. The association between LMWM levels at baseline and the development of ASCVD in patients with T2D after 10 years of follow-up was also evaluated.ResultsAmong the LMWMs measured, the branched-chain amino acids (BCAAs) valine, leucine and isoleucine showed a positive association with several clinical and lipid-related biochemical parameters and inflammatory markers (p < 0.05). Likewise, these three BCAAS were associated with diabetes even after adjusting for covariates (p < 0.05). During the follow-up period of 10 years, 29 of the 185 patients with diabetes at baseline (15.68%) developed ASCVD. After adjusting for clinical covariates, baseline levels of valine and alanine were associated with the development of ASCVD (p < 0.05).ConclusionOverall, our results indicated that plasma levels of LMWMs measured by 1H-NMR could be potential biomarkers associated with T2D. Moreover, alanine and valine can help in the early detection of the cardiovascular risk associated with this metabolic disease.

Circulating Th17/Treg as a promising biomarker for patients with rheumatoid arthritis in indicating comorbidity with atherosclerotic cardiovascular disease.

Immune and inflammatory responses have a pivotal role in the pathogenesis of rheumatoid arthritis (RA) and atherosclerotic cardiovascular disease (ASCVD). This study aims to explore the change of peripheral lymphocytes, especially the absolute and relative changes in peripheral T cells in RA patients with and without ASCVD. The changes in the lymphocyte subsets were assessed to provide a novel insight in diagnosing and preventing ASCVD in patients with RA. A propensity score matching system (1:1) was conducted to perform a matched case-control study with 169 pairs RA-ASCVD and RA participants. Univariate and multivariate analyses were performed to determine the association between peripheral lymphocytes and RA-ASCVD. Multivariate logistic regression analysis demonstrated that Th17 cell absolute, Th17 cell Ratio, Th17/Treg were associated with a significantly higher risk of ASCVD after model adjustment. Then we focused on Th17/Treg, multivariate logistic analyses in tri-sectional Th17/Treg groups showed that the odds of ASCVD is gradually increasing with Th17/Treg rank's rising after model adjustment. Finally, the restricted cubic spline of Th17/Treg and odds ratio of RA-ASCVD was conducted. Interestingly, we found a critical point of Th17/Treg (critical point = 0.2399). Th17/Treg shows a protective role in the odds of ASCVD when Th17/Treg < 0.2399. With smaller Th17/Treg, the protective efficiency is more obvious when Th17/Treg < 0.2399. Our study suggested that increasing absolute and percentage of Th17 cells in the peripheral blood of patients with RA was associated with the development of ASCVD. And Th17/Treg may be a promising biomarker for patients with RA in indicating comorbidity with ASCVD.

Is there a benefit of aspirin therapy for primary prevention to reduce the risk of atherosclerotic cardiovascular disease in patients with elevated Lipoprotein (a)—A review of the evidence

Aspirin has long been recognized as a beneficial treatment for atherosclerotic cardiovascular disease (ASCVD) due to its antiplatelet effects. However, there is a need to more precisely identify individuals who would benefit from aspirin therapy for primary prevention in order to reduce the risk of ASCVD. Those with elevated lipoprotein (a) [Lp(a)] levels are at increased risk of ASCVD. In this article, we provide an overview of studies that have explored the use of aspirin therapy in individuals with elevated Lp(a). We discuss the potential mechanisms by which aspirin therapy may reduce ASCVD risk, and present a review of the data on the effectiveness of aspirin therapy in reducing ASCVD risk in individuals with elevated Lp(a). The presented evidence suggests that individuals with elevated Lp(a) benefit more from aspirin therapy for reduction of ASCVD events than the general population.

Guidelines Oriented Approach to Lipid (GOAL) Lowering Quality Improvement International Program

Background: Despite practice guidelines, strategies for lowering LDL-C are often poorly adopted in clinical practice. Materials and Methods: Five countries (Brazil, Kuwait, Mexico, Saudi Arabia, and UAE) enrolled 2,422 patients with atherosclerotic cardiovascular disease (ASCVD) or familial hypercholesterolemia (FH) with low density lipoprotein cholesterol level (LDL-C) above 1.4 mmol/L. Patients were followed at 6 ± 2 months intervals to assess LDL-C level and treatment with ezetimibe and/or proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i). Results: 2422 patients 60.4 ± 11.7 years old and 29% women were enrolled from 87 participating cardiology sites. Overall, 91.1% of patients had coronary artery disease and FH in 12.3%. At baseline LDL-C was 2.96 ± 1.36 mmol/L and 1.87 ± 1.28 mmol/L (p&lt;0.0001) at last available observation (n=2014). Proportion of patients achieving LDL&lt;1.4 mmol/L (primary endpoint) increased from zero to 41.4% (p&lt;0.0001). At baseline, 99.2% of patients were on statin (81.3% high intensity statin), 34.4% on ezetimibe and its use increased significantly (62.9%, p&lt;0.0001). PCSK9i use increased to 35.0% from baseline to last follow up (p&lt;0.0001). Clinical outcomes such as ACS, CVA/TIA, PCI, CABG, or hospitalization for ASCVD reasons were recorded in 10.7% of patients during the follow up. Patients with no event had an overall LDL-C of 1.90 ± 1.3 mmol/L while those with an event had LDL-C significantly higher at the visit immediately prior to event (2.70 ± 1.35, p=0.0001). Conclusion: The results indicate the feasibility of overcoming treatment inertia and improving LDL-C control which should help to achieve reduction in cardiovascular morbidity and mortality in ASCVD patients.

Translating Evidence-based Approaches into optimal Care for individuals at High-risk of ASCVD: Pilot testing of case-based e-learning modules and design of the TEACH-ASCVD study

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death in the United States. Case-based learning using electronic delivery of the modules can educate clinicians and improve translation of evidence-based guidelines into practice for high-risk ASCVD patients. To develop and optimize module design, content, and usability of e-learning modules to teach clinicians evidence-based management in accordance with multi-society guidelines for high-risk ASCVD patients that will be implemented and evaluated in U.S. health systems in the TEACH-ASCVD study. Seven e-learning modules were created by a committee of lipid experts. Focus groups were conducted with lipid experts to elicit feedback on case content followed by interviews with a target audience of clinicians to assess usability of the online module platform. Responses from both groups were evaluated, and appropriate changes were made to improve the e-learning modules. Design of the TEACH-ASCVD study is presented. Feedback regarding case content by lipid experts included providing more detailed patient histories, clarifying various diagnostic criteria, and emphasizing clinical best practices based on evidence-based guidelines. The target audience clinician group reported an agreeable experience with the e-learning modules but noted a discordance between the evidence-based guidelines and clinical decision-making in their own practices. Participants felt the modules would help educate clinicians in managing high-risk ASCVD patients. Clinicians must be informed of best practices as the field of lipidology continues to evolve. E-learning modules provide a concise, valuable, and accessible mechanism for educating clinicians regarding changes in the field to deliver the best patient care.

Overweight/obesity and prevalent atherosclerotic cardiovascular disease in patients with heterozygous familial hypercholesterolemia: An analysis from HELLAS-FH registry

Overweight/obesity and prevalent atherosclerotic cardiovascular disease in patients with heterozygous familial hypercholesterolemia: An analysis from HELLAS-FH registry

Apolipoprotein B compared with low-density lipoprotein cholesterol in the atherosclerotic cardiovascular diseases risk assessment

The subendothelial retention of apolipoprotein B (apoB)-containing lipoproteins is a critical step in the initiation of pro-atherosclerotic processes. Recent genetic and clinical evidence strongly supports the concept that the lipid content of the particles is secondary to the number of circulating atherogenic particles that are trapped within the arterial lumen. Since each low-density lipoproteins (LDL) particle contains one apoB molecule, as do intermediate density lipoprotein (IDL) and very low-density lipoprotein (VLDL) particles, apoB level represents the total number of atherogenic lipoproteins, which is independent of particle density, and not affected by the heterogeneity of particle cholesterol content (clinically evaluated by LDL-cholesterol level). From this perspective, apoB is proposed as a better proxy to LDL-cholesterol for assessing atherosclerotic cardiovascular disease risk, especially in specific subgroups of patients, including subjects with diabetes mellitus, with multiple cardiometabolic risk factors (obesity, metabolic syndrome, insulin resistance, and hypertension) and with high triglyceride levels and very low LDL-cholesterol levels. Therefore, given the causal role of LDL-cholesterol in atherosclerotic cardiovascular disease (ASCVD) development, routine measurement of both LDL-cholesterol and apoB is of utmost importance to properly estimate global cardiovascular risk and to determine the 'residual' risk of ASCVD in patients receiving therapy, as well as to monitor therapeutic effectiveness.

Cardiometabolic risk management: insights from a European Society of Cardiology Cardiovascular Round Table.

Metabolic comorbidities are common in patients with cardiorenal disease; they can cause atherosclerotic cardiovascular disease (ASCVD), speed progression, and adversely affect prognosis. Common comorbidities are Type 2 diabetes mellitus (T2DM), obesity/overweight, chronic kidney disease (CKD), and chronic liver disease. The cardiovascular system, kidneys, and liver are linked to many of the same risk factors (e.g. dyslipidaemia, hypertension, tobacco use, diabetes, and central/truncal obesity), and shared metabolic and functional abnormalities lead to damage throughout these organs via overlapping pathophysiological pathways. The COVID-19 pandemic has further complicated the management of cardiometabolic diseases. Obesity, T2DM, CKD, and liver disease are associated with increased risk of poor outcomes of COVID-19 infection, and conversely, COVID-19 can lead to worsening of pre-existing ASCVD. The high rates of these comorbidities highlight the need to improve recognition and treatment of ASCVD in patients with obesity, insulin resistance or T2DM, chronic liver diseases, and CKD and equally, to improve recognition and treatment of these diseases in patients with ASCVD. Strategies to prevent and manage cardiometabolic diseases include lifestyle modification, pharmacotherapy, and surgery. There is a need for more programmes at the societal level to encourage a healthy diet and physical activity. Many pharmacotherapies offer mechanism-based approaches that can target multiple pathophysiological pathways across diseases. These include sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, selective mineralocorticoid receptor antagonists, and combined glucose-dependent insulinotropic peptide/glucagon-like peptide-1 receptor agonist. Non-surgical and surgical weight loss strategies can improve cardiometabolic disorders in individuals living with obesity. New biomarkers under investigation may help in the early identification of individuals at risk and reveal new treatment targets.

The Gulf Achievement of Cholesterol Targets in Out-Patients Study (GULF ACTION): Design, Rationale, and Preliminary Results.

To assess the current dyslipidemia management in the Arabian Gulf region by describing the demographics, study design, and preliminary results of out-patients who achieved low-density lipoprotein cholesterol (LDL-C) goals at the time of the survey. The Arabian Gulf population is at high risk for atherosclerotic cardiovascular disease at younger ages. There is no up-to-date study regarding dyslipidemia management in this region, especially given the recent guideline-recommended LDL-C targets. Up-to-date comprehensive assessment of the current dyslipidemia management in the Arabian Gulf region, particularly in view of the recent evidence of the additive beneficial effects of ezetimibe and proprotein convertase subtilisin/kexin-9 (PCSK-9) inhibitors on LDL-C levels and cardiovascular outcomes. The Gulf Achievement of Cholesterol Targets in Out-Patients (GULF ACTION) is an ongoing national observational longitudinal registry of 3000 patients. In this study, adults ≥18 years on lipid-lowering drugs for over three months from out-patients of five Gulf countries were enrolled between January 2020 and May 2022 with planned six-month and one-year follow-ups. Of the 1015 patients enrolled, 71% were male, aged 57.9±12 years. In addition, 68% had atherosclerotic cardiovascular disease (ASCVD), 25% of these patients achieved the LDL-C target, and 26% of the cohort were treated using combined lipid-lowering drugs, including statins. The preliminary results of this cohort revealed that only one-fourth of ASCVD patients achieved LDL-C targets. Therefore, GULF ACTION shall improve our understanding of current dyslipidemia management and "guideline gaps" in the Arabian Gulf region.

Role of Different Low-Density Lipoprotein-Lowering Medications on Secondary Prevention of Atherosclerotic Cardiovascular Disease in Patients With Diabetes Mellitus.

Purpose The objective of this study was to explore the optimal cholesterol-lowering therapy for diabetic patients categorized as having a very high risk for future atherosclerotic cardiovascular disease (ASCVD) events. The primary medications under investigation were statins, ezetimibe, and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors (PCSK9-Is). The efficacy of different medication regimens helped to draw conclusions regarding the evolution of cholesterol management recommended under the American College of Cardiology's (ACC) 2013 and 2018 guidelines. Methods A retrospective chart review was conducted on a cohort of patients from a large, community-based cardiology practice. Inclusion criteria specified patients aged 30-82 with a past medical history of two or more ASCVD events or one ASCVD event and at least two high-risk comorbidities. Acquired data included demographics, all lipid panels, medications used, and ASCVD events between December 1, 2013, and December 31, 2019. The data were stored and encrypted on a REDCap account. Sub-group analysis was conducted on only diabetic patients, who were then categorized by medication regimen. The statistical analysis was completed using Fisher's exact test. A p-value <0.05 was considered significant. Results A total of 102 diabetic patients met the inclusion criteria. Our primary analysis determined the percentage of patients who achieved their goals on each medication regimen. The goal was defined as a low-density lipoprotein cholesterol (LDL-C) level of less than 70 mg/dL or at least a 50% reduction from baseline levels. The results are as follows: none (0%), statin (33.9%), ezetimibe (21.1%), statin + ezetimibe (73.5%), PCSK9-Is ± statin (83.3%), and PCSK9-Is and ezetimibe ± statin (100%). There proved to be a significant difference favoring all combination regimens over statins alone; however, there was no significant difference between these advanced regimens. A follow-up analysis determined if these patients were able to maintain their goals in the subsequent lipid panel after achieving their goals. The results are as follows: none (0%), statin (61.5%), ezetimibe (50%), statin + ezetimibe (77.8%), PCSK9-Is ± statin (100%), and PCSK9-Is and ezetimibe ± statin (66.6%). The only significant difference found was between PCSK9-Is ± statins and statins alone. Conclusions Our study revealed that regimens using PCSK9 inhibitors and ezetimibe, in addition to maximally tolerated statin therapy, were more effective than statin therapy alone in achieving the goal. On extended analysis, only PCSK9 inhibitors showed superior ability in terms of maintaining the goals for diabetic patients at very high risk for future ASCVD events. This implies that statins alone may be inadequate to properly treat this specific patient population. In the context of clinical practice, physicians could have heightened consideration for dual therapy consisting of maximally tolerated statins and a secondary agent in accordance with the 2018 ACC guidelines.

Effects of intensive lipid lowering compared with moderate-intensity lipid lowering on coronary atherosclerotic plaque phenotype and major adverse cardiovascular events in adults with low to intermediate 10-year ASCVD risk (ILLUMINATION study): protocol for a multicentre, open-label, blinded-endpoint, randomised controlled trial

IntroductionCurrent guidelines recommend moderate-intensity lipid lowering (low-density lipoprotein cholesterol, LDL-C of <2.6 mmol/L or 30%–49% reduction from the baseline) for patients with intermediate 10-year atherosclerotic cardiovascular disease (ASCVD) risk. The...

Risk of atherosclerotic cardiovascular disease in patients with premature ASCVD: A study from approximately 1 million young adults

Abstract Funding Acknowledgements Type of funding sources: None. Background Risk of atherosclerotic cardiovascular disease (ASCVD) attributable to premature ASCVD remains poorly understood. Purpose To evaluate the risk of ASCVD among those with premature ASCVD versus those without in a large contemporary population. Methods This observational cohort study included young adults (ages 30-55 years) with and without prior ASCVD (as of January 1, 2006) who were members of an integrated healthcare delivery system in Northern California. Adjusted multivariate models were specified to estimate risk ratios (RRs) for incident ASCVD events by ASCVD status at baseline. Incident ASCVD events were defined as a composite of nonfatal myocardial infarction, ischemic stroke, or coronary heart disease death through December 31, 2020. Results A total of 929,214 individuals met the selection criteria of no prior ASCVD and 5,703 with prior ASCVD. Mean age was 43.9 (±7.3) years and 50.0 (±5.2) years, respectively. Fifty-two and thirty percent were women in each cohort, and the median follow-up was 11.8 and 8.3 years, respectively. Crude ASCVD rate was 2.1 and 24.5 events per 1,000 person-years, respectively. Age-adjusted Kaplan-Meier curves for ASCVD in individuals with and without prior ASCVD in Figure. In models adjusted for demographics (sex, age, race) and traditional risk factors (diabetes, hypertension, LDL-cholesterol, HDL-cholesterol, total cholesterol, smoking), individuals with prior ASCVD had RR of 4.6 (95% CI 4.3-5.0) for CHD, RR of 3.0 (95% CI 2.7-3.4) for stroke and RR of 4.1 (95% CI 3.8-4.3) for ASCVD. Conclusions Risk of ASCVD among those with prior ASCVD was several-fold greater compared to those without prior ASCVD. Continued efforts for secondary prevention are needed in this vulnerable high-risk population.

Potential for optimizing management of overweight and obesity in patients with established atherosclerotic coronary artery disease

Abstract Funding Acknowledgements Type of funding sources: None. Obesity and overweight play a key role in the development of cardiovascular disease or myocardial ischemia, particularly today, as does their relationship to traditional and non-traditional risk factors. Despite, diet and weight management are grossly under-met per desired body mass index (BMI) threshold goals among very high-risk patients with established atherosclerotic cardiovascular disease (ASCVD). Thus, we aimed to investigate the presence of overweight and obesity in patients with established atherosclerotic cardiovascular disease who were admitted to our center. Patients and methods: Out of 790 patients admitted in our center between May and October 2021, we analyzed 341 patients who underwent isolated coronary artery by-pass surgery. Risk factors were noted as well as previous drug therapy, previous COVID 19 infection and vaccination. Anthropometric data were measured and BMI was determined. Obesity was defined as a BMI &amp;gt;_30 kg/m2 and overweight as a BMI between 25 and 30 kg/m2 . Patients with a BMI &amp;gt;_40 kg/m2 were considered morbidly obese. Early cardiac rehabilitation (phase 1) was performed by using personalized approach in all patients. Results Out of 341 patients (64.68±7.91 years of age), 275 were males (80.6%). The total of 97 (28.44%) had previous myocardial infarction. Blood pressure was well controlled. Majority of the patients reached the step 2 goals according to EAPC Guidelines on prevention (130.7±6.45/75.27±6.54mmHg), and were adherent to prescribed drugs. Mean heart rate was 65±5.65/minute. Only 27% of females and 22% of males had normal weight with BMI between 18.5 and 24.9.kg/m2. The mean BMI was 27.76 kg/m2. 50% of males and females were overweight. Obesity was noted in 23% of females and 27% of males (0.7% morbidly obese. Early cardiac rehabilitation was performed in all patients and they were all referred to participate the phase 2 programs. Conclusions Diet and body weight reduction in overweight and obese ASCVD patients should continue to be a priority given the impact on cardiovascular risk. There is a potential for optimizing management of overweight and obesity in patients. In addition to a better risk factor profile, weight loss also leads to a better quality of life. Cardiovascular prevention and rehabilitation programs should include weight loss intervention. Different forms of self-support and use of digital health might be used as a specific component of a comprehensive intervention to reduce total cardiovascular risk, extend life expectancy, and improve quality of life.