High Atherosclerotic Cardiovascular Disease Risk Research Articles

Non-HDL cholesterol and residual risk of cardiovascular events in patients with ischemic heart disease and well-controlled LDL cholesterol: a cohort study

Identifying patients at high residual risk of atherosclerotic cardiovascular disease (ASCVD) despite statin-treatment is of paramount clinical importance. We aim to investigate if non-high-density lipoprotein cholesterol (non-HDL-C) identifies residual risk of ASCVD and death in statin-treated patients with ischemic heart disease and low-density lipoprotein cholesterol (LDL-C) ≤ 1.8mmol/L. Leveraging Danish regional and national registries, we identified statin-treated patients with ischemic heart disease who underwent coronary angiography (CAG) and attained LDL-C ≤ 1.8mmol/L within a year post-CAG. Outcomes were myocardial infarction (MI), ASCVD (MI or ischemic stroke), and all-cause death occurring from one year after CAG to end of follow-up. Cox regression analyses obtained adjusted hazard ratios (HR). Between January 1, 2011, and December 31, 2020, we included 23,641 statin-treated patients with ischemic heart disease and LDL-C ≤ 1.8mmol/L. During median follow-up of 4.1 years (IQR 2.4-6.1), 893 (3.8%) patients developed MI, 1207 (5.1%) ASCVD, and 3054 (12.9%) patients died. For ASCVD the adjusted HRs (95% confidence interval) for non-HDL-C < 25th percentile (<1.7mmol/L) versus 25th-74th (1.7-2.1mmol/L), 75th-94th (2.2-2.6mmol/L), and ≥95th (≥2.7mmol/L) percentile were 1.1 (0.9-1.3), 1.4 (1.1-1.7), and 1.8 (1.4-2.4), and for all-cause death 1.0 (0.9-1.1), 1.2 (1.1-1.4), and 1.4 (1.2-1.7), respectively. In a contemporary secondary prevention cohort of patients with well-managed LDL-C, non-HDL-C emerges as an easily accessible marker to detect patients facing high residual risk of ASCVD and death. These findings are important for preventive strategies extending beyond LDL-C targets. Research grant from the Novo Nordisk Foundation.

Redefining the Roles of Aspirin across the Spectrum of Cardiovascular Disease Prevention.

Even before its role in platelet inhibition was fully characterized in the 1980s, aspirin had been incorporated into the cardiovascular disease care algorithm. Early trials examining its use in unstable angina and acute myocardial infarction revealed evidence of its protective role in the secondary prevention of atherosclerotic cardiovascular disease (ASCVD). Large trials assessing use in the primary prevention setting and optimal dosing regimens were studied in the late 1990s and early 2000s. As a cornerstone of cardiovascular care, aspirin was incorporated into primary and secondary ASCVD prevention guidelines in the United States and mechanical heart valve guidelines. However, in recent years, with significant advances in medical and interventional ASCVD therapies, scrutiny has been placed on the bleeding profile of aspirin, and guidelines have adapted to new evidence. Updates in primary prevention guidelines reserve aspirin only for patients at higher ASCVD risk and low bleeding risk - though questions remain in ASCVD risk assessment as risk-enhancing factors have proven difficult to incorporate on a population level. New thoughts regarding aspirin use in secondary prevention - especially with the concomitant use of anticoagulants - have altered recommendations as additional data accrued. Finally, a recommendation for aspirin and vitamin K antagonists with mechanical heart valves has been modified. Despite aspirin losing a foothold in cardiovascular care, new evidence has strengthened claims for its use in women at high risk for preeclampsia.

Impact of anthropometric parameters on outcomes in Asians with metabolic dysfunction-associated fatty liver disease.

We examined the incidence and predictors of clinical outcomes in metabolic dysfunction-associated fatty liver disease (MAFLD), focusing on anthropometric parameters. Adult patients with MAFLD were identified in nationwide databases and a hospital cohort. Primary endpoints were atherosclerotic cardiovascular disease (ASCVD) and advanced fibrosis. Logistic and Cox regression analyses were used to analyse the association between anthropometric parameters and endpoints. In total, 4407 of 15256 (28.9%) and 6274 of 25784 subjects (24.3%) had MAFLD in the nationwide database; of these, 403 (9.2%) and 437 (7.0%) subjects were of lean/normal weight, respectively. Compared to the overweight/obese group, the lean/normal weight group had a significantly lower muscle mass (15.0 vs. 18.9kg) and handgrip strength (31.9 vs. 35.1kg) and had a higher ASCVD risk (9.0% vs. 6.3% and 15.9% vs. 8.5%; Ps<0.001). Sarcopenia (odds ratio [OR], 6.66; 95% confidence interval [CI], 1.79-24.80) and handgrip strength (OR, 0.92; 95% CI, 0.86-0.97; Ps=0.005) were associated with the ASCVD risk in the lean/normal weight group. In a hospital cohort (n=1363), the ASCVD risk was significantly higher in the lean/normal weight group than in the overweight/obese group (median follow-up, 39.1months). Muscle mass was inversely correlated with the ASCVD risk (hazard ratio [HR], 0.72; 95% CI, 0.56-0.94), while visceral adiposity was associated with advanced fibrosis (HR, 1.36; 95% CI, 1.10-1.69; Ps<0.05). Muscle mass/strength was significantly associated with the ASCVD risk in patients with MAFLD. Visceral adiposity was an independent predictor of advanced fibrosis.

Expanding the therapeutic landscape: ezetimibe as non-statin therapy for dyslipidemia.

Dyslipidemia is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD), and statins are the primary therapeutic options for reducing low-density lipoprotein cholesterol (LDL-C) levels. However, it can be challenging to achieve optimal LDL-C goals with statin monotherapy. Ezetimibe, a cholesterol absorption inhibitor, offers a potential non-statin therapy to optimize LDL-C management. Key clinical trials, such as IMPROVE-IT and RACING, have demonstrated that the addition of ezetimibe to statin therapy leads to further decreases in LDL-C or significant decreases in major adverse cardiovascular events (MACEs), particularly in patients with high ASCVD risk. Subsequent meta-analyses and clinical trials have further supported the beneficial effect of ezetimibe, suggesting additive decreases in LDL-C and MACEs, as well as pleiotropic effects. This review provides a comprehensive analysis of the clinical implications of ezetimibe for managing dyslipidemia; it also evaluates the available evidence that supports the role of ezetimibe as an adjunct non-statin therapy for long-term use. However, the long-term pleiotropic effects of ezetimibe remain controversial because of limited clinical data. Therefore, additional research is needed to clarify its potential benefits beyond LDL-C reduction. Nonetheless, an understanding of the role of ezetimibe in dyslipidemia management will help clinicians to develop effective treatment strategies.

Serum proteomic profiling of carotid arteriopathy: A population outcome study

Background and aimsCirculating proteins reflecting subclinical vascular disease may improve prediction of atherosclerotic cardiovascular disease (ASCVD). We applied feature selection and unsupervised clustering on proteomic data to identify proteins associated with carotid arteriopathy and construct a protein-based classifier for ASCVD event prediction. Methods491 community-dwelling participants (mean age, 58 ± 11 years; 51 % women) underwent carotid ultrasonography and proteomic profiling (CVD II panel, Olink Proteomics). ASCVD outcome was collected (median follow-up time: 10.2 years). We applied partial least squares (PLS) to identify proteins linked to carotid intima-media thickness (cIMT). Next, we assessed the association between future ASCVD events and protein-based phenogroups derived by unsupervised clustering (Gaussian Mixture modelling) based on proteins selected in PLS. ResultsPLS identified 19 proteins as important, which were all associated with cIMT in multivariable-adjusted linear regression. 8 of the 19 proteins were excluded from the clustering analysis because of high collinearity. Based on the 11 remaining proteins, the clustering algorithm subdivided the cohort into two phenogroups. Compared to the first phenogroup (n = 177), participants in the second phenogroup (n = 314) presented: i) a more unfavorable lipid profile with higher total cholesterol and triglycerides and lower HDL cholesterol (p ≤ 0.014); ii) higher cIMT (p = 0.0020); and iii) a significantly higher risk for future ASCVD events (multivariable-adjusted hazard ratio (95 % CI) versus phenogroup 1: 2.05 (1.26–3.52); p = 0.0093). The protein-based phenogrouping supplemented ACC/AHA 10-year ASCVD risk scoring for prediction of a first ASCVD event. ConclusionsFocused protein-based phenogrouping identified individuals at high risk for future ASCVD and may complement current risk stratification strategies.

SAT658 Tirzepatide Reduces The Predicted Risk Of Developing Atherosclerotic Cardiovascular Disease: A Post-hoc Analysis Of The Surmount-1 Trial

Abstract Disclosure: E.R. Hankosky: Employee; Self; Eli Lilly &amp; Company. Stock Owner; Self; Eli Lilly &amp; Company. H. Wang: Other; Self; Eli Lilly &amp; Company. N.M. Lisa: Employee; Self; Eli Lilly &amp; Company. Stock Owner; Self; Eli Lilly &amp; Company. H. Kan: Employee; Self; Eli Lilly &amp; Company. Stock Owner; Self; Eli Lilly &amp; Company. F. Wang: Employee; Self; Eli Lilly &amp; Company. Stock Owner; Self; Eli Lilly &amp; Company. N.N. Ahmad: Employee; Self; Eli Lilly &amp; Company. Stock Owner; Self; Eli Lilly &amp; Company. A. Stefanski: Grant Recipient; Self; Eli Lilly &amp; Company. Employee; Self; Eli Lilly &amp; Company. Stock Owner; Self; Eli Lilly &amp; Company. W. Garvey: Consulting Fee; Self; Eli Lilly &amp; Company, Novo Nordisk, Boehringer Ingelheim, Pfizer, Inc., Fractyl Laboratories, Merck. Grant Recipient; Self; Eli Lilly &amp; Company, Novo Nordisk, Pfizer, Inc. Background: Tirzepatide (TZP) resulted in substantial and sustained body weight reduction among participants with obesity or overweight in SURMOUNT-1, a phase 3 randomized clinical trial. Using predictive modelling, the current study assessed the impact of TZP treatment on the 10-year risk of developing atherosclerotic cardiovascular disease (ASCVD) among SURMOUNT-1 participants. Methods: The American College of Cardiology/American Heart Association (ACC/AHA) risk engine was applied to data from SURMOUNT-1 participants free of ASCVD at baseline. ASCVD risk scores were calculated at baseline, 24, and 72 weeks. The model inputs were age, total cholesterol, high density lipoprotein, systolic blood pressure, hypertension treatment, diabetes, and smoking status. Mean percent change in the 10-year risk score from baseline to week 72 was compared between TZP groups and placebo (PBO) using Mixed Model for Repeated Measures (MMRM), adjusted for baseline risk scores and country; risk scores were analyzed on log-scale. Since the risk score was low in the overall SURMOUNT-1 population, a subgroup analysis was conducted in participants with higher ASCVD risk at baseline (score≥7.5%, ACC/AHA intermediate-to-high risk). Results: A total of 2461 participants (TZP 5 mg, n=614; 10 mg, n=616; 15 mg, n=609; PBO, n=622) were included (mean age=45 years; female=68%; White=70%). At baseline, the median 10-year predicted risk score ranged from 1.5%–1.6% and did not differ across treatment groups. Median absolute risk scores for TZP 5/10/15 mg and PBO groups were 1.4%, 1.2%, 1.3%, and 1.6% at week 24, and 1.3%, 1.2%, 1.1%, and 1.7% at week 72, respectively. At week 72, MMRM-estimated relative change in risk from baseline was -16.4%, -23.5%, -22.4%, and 12.7% for TZP 5/10/15mg and PBO, leading to significantly greater reduction for TZP groups compared to PBO (TZP 5 mg: -25.8%; 10 mg: -32.1%; 15 mg: -31.1%; p≤0.001). Among 272 participants (TZP 5 mg, n=83; 10 mg, n=66; 15 mg, n=55; PBO, n=68) with intermediate-to-high baseline ASCVD risk, median risk scores for TZP 5/10/15 mg and PBO groups were: baseline: 11.3%, 10.5%, 10.9%, 10.1%; week 72: 11.3%, 9.0%, 10.3%, 11.7%, respectively. MMRM-estimated relative risk reduction at week 72 was -10.3%, -20.6%, -16.1%, and 6.4% for TZP 5/10/15 mg and PBO groups, respectively. Consistent with the primary analysis, relative risk reduction was significantly greater in TZP groups compared to PBO (TZP 5 mg = -15.7%; 10 mg = -25.3%; 15 mg = -21.1%; p≤0.01). Conclusion: TZP treatment significantly reduced the 10-year predicted risk of developing ASCVD compared to PBO, though the magnitude of reduction in absolute risk scores was small due to low baseline risk in the overall population. Among participants with higher ASCVD risk at baseline, TZP treatment resulted in larger absolute reductions in risk along with significant relative risk reduction consistent with the primary analysis. Presentation: Saturday, June 17, 2023

FRI085 Lipid Lowering Therapy Deficits In Secondary Cardiovascular Prevention In A Large Cohort From Eight Busy Clinics In Greece Over 12 Years

Abstract Disclosure: R.D. Paparodis: None. I. Androulakis: None. D.P. Askitis: None. I. Perogamvros: None. N. Angelopoulos: None. A. Rizoulis: None. S. Livadas: None. A. Boniakos: None. Background: The increasing availability of aggressive lipid lowering therapies (LLTs) worldwide is expected to produce a significant decline in cholesterol concentrations worldwide and a more successful attainment of LDL lowering goals (LLGs), especially in those who need them most: patients with established atherosclerotic cardiovascular disease (ASCVD). Aims: To assess the long-term changes in the rate of attainment of LGs according to the European Society of Cardiology Guidelines nationwide, with the use of different LLTs during 12 consecutive years. Methods: We reviewed the charts of all patients initially seen between 2010-2022 who returned for care follow up at our 8 busy Endocrinology clinics, located in 6 cities in Greece, between Sep-1-2022 and Nov-30-2022. We enrolled those with recorded diagnosis of ASCVD [coronary artery disease (CAD), peripheral arterial disease (PAD) or carotid stenosis &amp;gt;50% (CS)] prior to our initial visit. For the present work, we reviewed data on tobacco use, intake of LLTs, and LDL-cholesterol concentrations as recorded during our initial clinic visit. We excluded all patients referred to our clinics for lipids management. Data are presented as means ± standard deviation. Means are compared with Kruskal Wallis test and p&amp;lt;0.05 is deemed significant. Results: We enrolled n=890 consecutive patients, age 63.9 ± 11.4 years, n=339 were women (38.1%), n=529 (59.4%) had diabetes, n=672 (75.5%) had hypertensions and all had ≥1 forms of established ASCVD: n=630 with CAD, n=279 with CS and n=151 with PAD. Out of these, n=144 (16.2%) were on no LLTs, n=334 (37.5%) continued to smoke, n=381 (42.8%) were on guidelines-based appropriate LLT strategy, n=248 (27.9%) reached LLGs and n=318 (35.7%) fulfilled the year-specific guidelines requirements. Of note is, that this rate dropped to 2.4-20.4% in the years 2019-2022. The likelihood of achieving LDL goals was not statistically significantly different among patients with different forms of ASCVD (p=0.42). Overall, the mean LDL was 88.2 ± 32.1mg/dl, and was not different between patients with different forms of ASCVD (p=0.75). Mean LDL concentrations have only started to drop between 2020-2022 as compared to 2019 (p&amp;lt;0.001), but are not different compared to those seen in the years 2010-2018. The mean LDL dropped to 82.3 ± 30.5mg/dl in 2022 as compared to 102.2 ± 38.8mg/dl in 2019. Conclusions: Our study reveals a large care gap in patients with established ASCVD, which did not seem to improve significantly over the past 12 years, despite the excellent availability of aggressive LLT strategies in Greece. Intervention studies are urgently needed to enhance adherence to updated international guidelines and reduce the extremely high ASCVD risk in this fragile population. Presentation: Friday, June 16, 2023

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.

Ambient PM2.5 and its components associated with 10-year atherosclerotic cardiovascular disease risk in Chinese adults

BackgroundExposure to particulate matter with aerodynamic diameters less than 2.5 µm (PM2.5) may increase the risk of 10-year atherosclerotic cardiovascular disease (ASCVD) risk. While PM2.5 is comprised of various components, the evidence on the correlation of its components with 10-year ASCVD risk and which component contributes most remains limited. MethodsData were derived from the baseline assessments of China Multi-Ethnic Cohort (CMEC). In total, 69,722 individuals aged 35–74 years were included into this study. The annual average concentration of PM2.5 and its components (black carbon, ammonium, nitrate, sulfate, organic matter, soil particles, and sea salt) were estimated by satellite remote sensing and chemical transport models. The ASCVD risk of individuals was calculated by the equations from the China-PAR Project (prediction for ASCVD risk in China). The relationship between single exposure to PM2.5 and its components and predicted 10-year ASCVD risk was assessed using the logistic regression model. The effect of joint exposure was estimated, and the most significant contributor was identified using the weighted quantile sum approach. ResultsTotally 69,722 participants were included, of which 95.8 % and 4.2 % had low and high 10-year ASCVD risk, respectively. Per standard deviation increases in the 3-year average concentration of PM2.5 mass (odds ratio [OR] 1.23, 95 % confidence interval [CI]: 1.12–1.35), black carbon (1.21, 1.11–1.33), ammonium (1.21, 1.10–1.32), nitrate (1.25, 1.14–1.38), organic matter (1.29, 1.18–1.42), sulfate (1.17, 1.07–1.28), and soil particles (1.15, 1.04–1.26) were related to high 10-year ASCVD risk. The overall effect (1.19, 1.11–1.28) of the PM2.5 components was positively associated with 10-year ASCVD risk, and organic matter had the most contribution to this relationship. Female participants were more significantly impacted by PM2.5, black carbon, ammonium, nitrate, organic matter, sulfate, and soil particles compared to others. ConclusionLong-term exposure to PM2.5 mass, black carbon, ammonium, nitrate, organic matter, sulfate, and soil particles were positively associated with high 10-year ASCVD risk, while sea salt exhibited a protective effect. Moreover, the organic matter might take primary responsibility for the relationship between PM2.5 and 10-year ASCVD risk. Females were more susceptible to the adverse effect.

Atherosclerotic Cardiovascular Disease (ASCVD) risk assesment among healthy Indonesian Navy Personnel in East Java, Indonesia

Indonesia, as the largest archipelagic country, has a military population of its own. Atherosclerotic Cardiovascular Disease (ASCVD) are common in in Indonesian Navy personnel populations, and recent studies reported an increasing ofits prevalence.However, the data on specific navy military populations are still limited. This study aims to assess ASCVD risk on Indonesian navy personnel. This study use yearly medical check-up data of the Indonesian navy with high rank (fleet commander) aged 25-60 years old in period of January-August 2023. Those who already diagnosed with coronary artery disease were excluded. We use Framingham risk score and EUROS II Score to assess the ASCVD risk among samples. A total of 503 samples were recruited, 474 were male. Mean of age was 45 y.o, predominantly they were active smoker (64,8%) and overweight (44,5%). Among men’s population, the Framingham risk score shows almost half of the samples are at medium risk of ASCVD (40,16%), while a small percentage (17,3%) are at high risk as well as EuroSCORE II show remarkbly 62,21% of high ASCVD risk. The medium to high ASCVD risk among Indonesian Navy personnel need further attention and evaluation. A failure to give a decent preventive intervention may increase the burden of ASCVD in the future.

Ups and downs in PCSK9 inhibition in the cardiovascular arena: a review.

This article reviews PCSK9 inhibitors (PCSK9i) with a focus on clinically relevant studies published in the last 18 months. Prespecified subgroup evaluations, secondary analyses, and open-label extension studies from the two landmark trials, FOURIER and ODYSSEY Outcomes, have provided new data on the safety and efficacy of the monoclonal PCSK9 antibodies evolocumab and alirocumab. Recent studies of PCSK9i early in ACS and post percutaneous coronary intervention have explored early effects on biomarkers and plaque morphology with various imaging modalities. Two large outcome trials with PCSK9i in lower risk patients without prior myocardial infarction or stroke are ongoing and could expand the eligible population for these potent therapies. Additionally, novel methods to inhibit PCSK9 using oral administration, vaccination, and gene therapy are in various stages of clinical development. PCSK9i represent a potent class of lipid-lowering therapies that are well tolerated and effective in a wide group of patients with high-risk atherosclerotic cardiovascular disease. Ongoing studies of PCSK9i in patients at lower risk and with acute myocardial infarction have the potential to broaden their indication. Alternative methods of PCSK9i are being evaluated and could provide easier and less expensive options for this important class of medication.

Concordance between Dash Diet and Hypertension: Results from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study.

High blood pressure is an important predictor of atherosclerotic cardiovascular disease (ASCVD), particularly among South Asians, who are at higher risk for ASCVD when compared to other population groups. The Dietary Approaches to Stop Hypertension (DASH) dietary pattern is established as the best proven nonpharmacological approach to preventing hypertension in adults. Using data from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort, we calculated a DASH dietary score to examine the association between adherence to the DASH diet and its components, and prevalent and incident hypertension and systolic and diastolic blood pressure, after five years of follow-up. We found that the relative risk ratio (RRR) of incident hypertension was 67% lower among participants in the highest DASH diet score category (aRRR: 0.33; 95% CI: 0.13, 0.82; ptrend = 0.02) compared with those in the lowest DASH diet score category in fully adjusted models. These findings are consistent with previous clinical trials and large prospective cohort studies, adding to evidence that supports the diet-disease relationship established between DASH diet and hypertension. This study is the first to examine DASH diet adherence and hypertension among South Asian adults in the U.S.

Assessing Adherence to Statin Prescription Guidelines at a Student-Run Free Clinic: A Retrospective Review.

The goals of this quality improvement project are to assess the BRIDGE Student-Run Free Clinic's adherence to the 2019 American College of Cardiology (ACC)/American Heart Association (AHA)Guideline on the Primary Prevention of Cardiovascular Disease and to compare our rate of statin prescription to the national average and to uninsured groups. A quality improvement project of 205 patients qualified by initial inclusion criteria at a student-run free healthcare clinic. Socio-demographic information, clinical measures associated with cardiovascular risk, and documentation regarding statin prescription at the follow-up visit after a patient's first lipid panel were abstracted from medical records. Descriptive statistics were calculated on the sample (proportions, means), and the proportion of patients eligible for statin treatment was determined. Of 58 patients eligible by guidelines to receive statins, 29 received a statin (50%) at their follow-up visit. Patients with clinical atherosclerotic cardiovascular disease (ASCVD) were more likely to receive statin therapy (83.3%) compared to other groups. Patients who were prescribed a statin were older, had higher total cholesterol, higher low-density lipoprotein (LDL), higher systolic blood pressure, and had higher ASCVD risk. Patients receiving statins were also more likely to be male or have a history of either hypertension, diabetes, or clinical ASCVD. Patients with established ASCVD had high rates of statin prescription.Following the first lipid panel, clinicians prescribed statins to approximately 50% of eligible patients.Although this proportion is below the national average for insured patients, it is higher than the national average for uninsured patients and represents a relatively high proportion of eligible patients within the examined time frame.

Targeting PCSK9 and Beyond for the Management of Low-Density Lipoprotein Cholesterol.

Reducing low-density lipoprotein cholesterol (LDL-C) levels is crucial to the prevention of atherosclerotic cardiovascular disease (ASCVD). However, many patients, especially those at very high ASCVD risk or with familial hypercholesterolemia (FH), do not achieve target LDL-C levels with statin monotherapy. The underutilization of novel lipid-lowering therapies (LLT) globally may be due to cost concerns or therapeutic inertia. Emerging approaches have the potential to lower LDL-C and reduce ASCVD risk further, in addition to offering alternatives for statin-intolerant patients. Shifting the treatment paradigm towards initial combination therapy and utilizing novel LLT strategies can complement existing treatments. This review discusses innovative approaches including combination therapies involving statins and agents like ezetimibe, bempedoic acid, cholesterol ester transfer protein (CETP) inhibitors as well as strategies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) and angiopoietin-like protein 3 (ANGPTL3) inhibition. Advances in nucleic acid-based therapies and gene editing are innovative approaches that will improve patient compliance and adherence. These strategies demonstrate significant LDL-C reductions and improved cardiovascular outcomes, offering potential for optimal LDL-C control and reduced ASCVD risk. By addressing the limitations of statin monotherapy, these approaches provide new management options for elevated LDL-C levels.

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.

Glycemic and metabolic sub-classification of prediabetes and risk factors for cardiovascular disease in the D2d cohort

ObjectivesPrediabetes represents a spectrum of metabolic abnormalities, including insulin resistance and secretory impairment, that carries increased cardiovascular disease (CVD) risk. It is unclear whether specific glycemic and metabolic sub-classifications are associated with CVD risk. This cross-sectional analysis of 3946 participants from the Vitamin D and Type 2 Diabetes (D2d) study cohort aimed to determine the associations between various baseline CVD risk factors, glycemic sub-classifications of prediabetes (FPG, 2hPG, and HbA1c), and measures of insulin sensitivity and secretion from an OGTT. MethodsThe metabolic syndrome and atherosclerotic cardiovascular disease (ASCVD) risk scores were determined for tertiles of insulin sensitivity (HOMA2S) and insulinogenic index (IGI). Unadjusted analyses showed elevated CVD risk factors in the lowest tertile for both IGI and HOMA2S. ResultsAfter adjustment for age, gender, race, obesity, and smoking status, the association remained between HOMA2S and ASCVD score (r = -0.11, p< 0.001) but not for IGI. Those who met at least 2 diagnosic criteria for prediabetes had the largest proportion (> 40%) of participants with high ASCVD risk score >20. A higher percentage of individuals that met all 3 criteria for prediabetes had metabolic syndrome and ASCVD risk score >20 (87.2% and 15.3%, respectively) than those who only met 1 prediabetes criterion (51.6% and 7.1%, respectively). ConclusionsIn conclusion, multiple metabolic (HOMA2S, IGI) and glycemic criteria of prediabetes (FPG, 2hPG, & HbA1c) are needed to fully recognize the elevated CVD risk profile that can manifest in prediabetes.

A machine learning based approach to identify carotid subclinical atherosclerosis endotypes.

To define endotypes of carotid subclinical atherosclerosis. We integrated demographic, clinical, and molecular data (n = 124) with ultrasonographic carotid measurements from study participants in the IMPROVE cohort (n = 3340). We applied a neural network algorithm and hierarchical clustering to identify carotid atherosclerosis endotypes. A measure of carotid subclinical atherosclerosis, the c-IMTmean-max, was used to extract atherosclerosis-related features and SHapley Additive exPlanations (SHAP) to reveal endotypes. The association of endotypes with carotid ultrasonographic measurements at baseline, after 30 months, and with the 3-year atherosclerotic cardiovascular disease (ASCVD) risk was estimated by linear (β, SE) and Cox [hazard ratio (HR), 95% confidence interval (CI)] regression models. Crude estimates were adjusted by common cardiovascular risk factors, and baseline ultrasonographic measures. Improvement in ASCVD risk prediction was evaluated by C-statistic and by net reclassification improvement with reference to SCORE2, c-IMTmean-max, and presence of carotid plaques. An ensemble stacking model was used to predict endotypes in an independent validation cohort, the PIVUS (n = 1061). We identified four endotypes able to differentiate carotid atherosclerosis risk profiles from mild (endotype 1) to severe (endotype 4). SHAP identified endotype-shared variables (age, biological sex, and systolic blood pressure) and endotype-specific biomarkers. In the IMPROVE, as compared to endotype 1, endotype 4 associated with the thickest c-IMT at baseline (β, SE) 0.36 (0.014), the highest number of plaques 1.65 (0.075), the fastest c-IMT progression 0.06 (0.013), and the highest ASCVD risk (HR, 95% CI) (1.95, 1.18-3.23). Baseline and progression measures of carotid subclinical atherosclerosis and ASCVD risk were associated with the predicted endotypes in the PIVUS. Endotypes consistently improved measures of ASCVD risk discrimination and reclassification in both study populations. We report four replicable subclinical carotid atherosclerosis-endotypes associated with progression of atherosclerosis and ASCVD risk in two independent populations. Our approach based on endotypes can be applied for precision medicine in ASCVD prevention.

Evaluating Plasma Galectin-3 Levels in Patients With an Increased Risk of Atherosclerotic Cardiovascular Disease Who Underwent Coronary Artery Revascularization

Coronary artery disease (CAD) is a common atherosclerotic cardiovascular disease (ASCVD) associated with significant mortality. Galectin-3 is a novel inflammatory factor implicated in the initiation and progression of atherosclerosis. We aimed to evaluate the association of plasma galectin-3 with the risk of ASCVD and the need for coronary artery revascularization. Patients with angina who underwent coronary angiography were divided into groups per their risk of ASCVD. Patients (n=385) were stratified into having low (n=21), moderate (n=40), high (n=41), and very high risk (n=283) for ASCVD. The mean age ± standard error of the mean was 53.9 ± 0.5years and 73% of patients were men. Plasma galectin-3 levels were higher in patients with CAD than non-CAD primarily in patients with stable and unstable angina. Patients with stable CAD had higher levels of galectin-3 relative to acute coronary syndrome patients. Increased plasma galectin-3 level was associated with increased risk of ASCVD and degree of coronary stenosis. By multivariate analysis, the plasma galectin-3 level was independently associated with increased ASCVD risk and body mass index. Plasma galectin-3 levels were independently higher in patients who underwent percutaneous coronary intervention (PCI) than medically treated patients. In addition, age, male gender, smoking, and diabetes mellitus were associated with PCI. In conclusion, plasma galectin-3 levels are elevated in patients with CAD and associated with increased risk of ASCVD and the need for PCI. Plasma galectin-3 could be used as a potential improving predictor of ASCVD risk and when making therapeutic guidance or selecting patients who underwent PCI when the decision is difficult.

Prevalence, awareness, treatment, and risk factor control of high atherosclerotic cardiovascular disease risk in Guangzhou, China.

Identifying individuals at high risk of atherosclerotic cardiovascular disease (ASCVD) and implementing targeted prevention strategies might be the key to reducing the heavy disease burden in China. This study aimed to evaluate the prevalence, awareness, treatment, and risk factor control among individuals with high 10-year ASCVD risk in Guangzhou, China. This study included 15,165 adults (aged 18 years and older) from 138 urban and rural communities in the 2018 survey of China Chronic Disease and Risk Factors Surveillance in Guangzhou. 10-year ASCVD risk was estimated using the risk assessment models recommended in the Chinese Guideline for the Prevention of Cardiovascular Disease 2017. The prevalence, awareness, treatment, and risk factor control of high ASCVD risk (defined as 10-year risk ≥10%) were examined. Among the study population, the weighted proportion of men was 51.9%, and the mean age was 41.27 ± 0.52 years. The overall standardized prevalence of high 10-year ASCVD risk was 13.8% (95% CI, 12.4%-15.3%). The awareness rates for hypertension, diabetes, and hyperlipidemia were 48.0% (95% CI, 42.8%-53.4%), 48.3% (95% CI, 43.0%-53.7%), and 17.9% (95% CI, 14.4%-22.1%) among those with corresponding risk factors. The proportions of drug use in prevention were relatively low in primary prevention, with the rates of using BP-lowering, glucose-lowering, lipid-lowering, and aspirin being 37.7% (95% CI, 32.8%-42.8%), 41.4% (95% CI, 35.8%-47.3%), 6.7% (95% CI, 4.5%-10.0%), and 1.0% (95% CI, 0.6%-1.8%), respectively. As for risk factor control, only 29.3% (95% CI, 25.7%-33.2%), 16.8% (95% CI, 15.0%-18.6%), and 36.0% (95% CI, 31.1%-41.2%) of individuals with high ASCVD risk had ideal levels of blood pressure, LDL-C, and body weight. The estimated prevalence of 10-year high ASCVD risk was high in Guangzhou, while the rates of treatment and risk factor control in primary prevention were still far from optimal, especially for lipid management. These findings suggested that substantial improvement in ASCVD prevention is needed in this population.

The Association of Lipoprotein(a) and Neutrophil-to-Lymphocyte Ratio Combination with Atherosclerotic Cardiovascular Disease in Chinese Patients.

The association of lipoprotein(a) [Lp(a)] with atherosclerotic cardiovascular disease (ASCVD) risk can be modified by chronic systemic inflammation. The neutrophil-to-lymphocyte ratio (NLR) is a reliable and easily available marker of immune response to various infectious and non-infectious stimuli. The purpose of this study was to assess the combined effects of Lp(a) and NLR in predicting the ASCVD risk and coronary artery plaque traits. This study included 1618 patients who had coronary computed tomography angiography (CTA) with risk assessment of ASCVD. CTA was used to evaluate the traits of coronary atherosclerotic plaques, and the association of ASCVD with Lp(a) and NLR was assessed by multivariate logistic regression models. Plasma Lp(a) and NLR were significantly increased in patients having plaques. High Lp(a) was defined as the plasma Lp(a) level > 75 nmol/L and high NLR as NLR > 1.686. The patients were grouped into four categories according to normal or high NLR and plasma Lp(a) as nLp(a)/NLR-, hLp(a)/NLR-, nLp(a)/NLR+ and hLp(a)/NLR+. The patients in the latter three groups had higher risk of ASCVD compared to the reference group nLp(a)/NLR-, with the highest ASCVD risk in the hLp(a)/NLR+ group (OR = 2.39, 95% CI = 1.49-3.83, P = 0.000). The occurrence of unstable plaques was 29.94% in the hLp(a)/NLR+ group, which was significantly higher than groups nLp(a)/NLR+, hLp(a)/NLR- and nLp(a)/NLR- with 20.83%, 26.54% and 22.58%, respectively, and there was a significantly increased risk of unstable plaque in the hLp(a)/NLR+ group compared to the nLp(a)/NLR- group (OR = 1.67, 95% CI = 1.04-2.68, P = 0.035). The risk of stable plaque was not significantly increased in the hLp(a)/NLR+ group compared to the nLp(a)/NLR- group (OR = 1.73, 95% CI = 0.96-3.10, P = 0.066). The concomitant presence of elevated Lp(a) and higher NLR is associated with increased unstable coronary artery plaques in patients with ASCVD.