Clinical Atherosclerotic Cardiovascular Disease Research Articles

Design and Rationale of Penn Medicine Healthy Heart, a Randomized Trial of Effectiveness of a Centrally Organized Approach to Blood Pressure and Cholesterol Improvement Among Patients at Elevated Risk of Atherosclerotic Cardiovascular Disease

Atherosclerotic Cardiovascular Disease (ASCVD) is the leading cause of morbidity and mortality in the United States. Suboptimal control of hypertension and hyperlipidemia are common factors contributing to ASCVD risk. The Penn Medicine Healthy Heart (PMHH) Study is a randomized clinical trial testing the effectiveness of a system designed to offload work from primary care clinicians and improve patient follow-through with risk reduction strategies by using a centralized team of non-clinical navigators and advanced practice providers, remote monitoring, and bi-directional text messaging, augmented by behavioral science engagement strategies. The intervention builds on prior non-randomized evaluations of these design elements that demonstrated significant improvement in patients' systolic blood pressure and LDL Cholesterol (LDL-C). Penn Medicine Healthy Heart will significantly improve systolic blood pressure and LDL-C compared to usual care over the 6 months of this intervention. Randomized clinical trial of Penn Medicine Healthy Heart in patients aged 35-80 years at elevated risk of ASCVD whose systolic blood pressure and LDL-C are not well controlled. The intervention consists of four modules that address blood pressure management, lipid management, nutrition, and smoking cessation, offered in a phased approach to give the participant time to learn about each topic, adopt any recommendations, and build a relationship with the care team. University of Pennsylvania Health System at primary care practices located in inner-city urban and rural/semi-rural areas PRIMARY OUTCOMES: Improvement in systolic blood pressure and LDL-C SECONDARY OUTCOMES: Cost-effectiveness analyses are planned to evaluate the health care costs and health outcomes of the intervention approach. An implementation evaluation is planned to understand factors influencing success of the intervention. 2,420 active patients of Penn Medicine primary care practices who have clinical ASCVD, or who are at elevated risk for ASCVD, and who are (a) not on statins or have LDL-C > 100 despite being on statins and (b) had systolic blood pressure>140 at two recent ambulatory visits. March 2024-March 2025. The intervention will last 6 months with a 12-month follow-up to determine whether its effects persist. Enrolling (1,240 enrolled as of August 15, 2024) CLINICAL TRIAL REGISTRATION: NCT06062394.

Lipoprotein(a) and Coronary Plaque in Asymptomatic Individuals: The Miami Heart Study at Baptist Health South Florida.

Elevated levels of lipoprotein(a) (Lp(a)) are independently associated with an increased risk of atherosclerotic cardiovascular disease events. However, the mechanisms driving this association are poorly understood. We aimed to evaluate the association between Lp(a) and coronary plaque characteristics in a contemporary US cohort without clinical atherosclerotic cardiovascular disease, undergoing coronary computed tomography angiography, the noninvasive gold standard for the assessment of coronary atherosclerosis. We used baseline data from the Miami Heart Study-a community-based, prospective cohort study-which included asymptomatic adults aged 40 to 65 years evaluated using coronary computed tomography angiography. Those taking any lipid-lowering therapies were excluded. Elevated Lp(a) was defined as ≥125 nmol/L. Outcomes included any plaque, coronary artery calcium score >0, maximal stenosis ≥50%, presence of any high-risk plaque feature (positive remodeling, spotty calcification, low-attenuation plaque, napkin ring), and the presence of ≥2 high-risk plaque features. Among 1795 participants (median age, 52 years; 54.3% women; 49.6% Hispanic), 291 (16.2%) had Lp(a) ≥125 nmol/L. In unadjusted analyses, individuals with Lp(a) ≥125 nmol/L had a higher prevalence of all outcomes compared with Lp(a) <125 nmol/L, although differences were only statistically significant for the presence of any coronary plaque and ≥2 high-risk features. In multivariable models, elevated Lp(a) was independently associated with the presence of any coronary plaque (odds ratio, 1.40, [95% CI, 1.05-1.86]) and with ≥2 high-risk features (odds ratio, 3.94, [95% CI, 1.82-8.52]), although only 35 participants had this finding. Among participants with a coronary artery calcium score of 0 (n=1200), those with Lp(a) ≥125 nmol/L had a significantly higher percentage of any plaque compared with those with Lp(a) <125 nmol/L (24.2% versus 14.2%; P<0.001). In this contemporary analysis, elevated Lp(a) was independently associated with the presence of coronary plaque. Larger studies are needed to confirm the strong association observed with the presence of multiple high-risk coronary plaque features.

MiRNA signature related to atherosclerotic lesion induced shear stress modifications in familial hypercholesterolemia patients with subclinical atherosclerosis: a bioinformatics systems biology study

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Institute of Health Carlos III (ISCIII) Background Patients with familial hypercholesterolemia (FH), even when appropriately treated, are at risk of premature clinical atherosclerotic cardiovascular disease (ASCVD) presentation. Although atherosclerosis (AT) is directly related to hemodynamic disturbances affecting the vascular geometry, there is scarce information on whether there is miRNA-mediated/flow-mediated modulation of atherosclerosis in FH. Purpose To identify a differential plasma miRNA signature related to fluid shear stress (FSS) in well controlled FH-patients with asymptomatic atherosclerosis. Methods FH-patients (N=49) with subclinical atherosclerosis, identified by computed tomographic angiography, and a reference cohort of non-FH subjects (N=32), both from a national FH-Registry, were included in the study. Coronary plaque volume and phenotype was analyzed by means of the QAngio CT imaging system. miRNAs associated to FSS were defined in silico by bioinformatics (KEGG, Cytoscape, GTEX portal, miRWalk, miRBase tools) and validated in plasma samples by RT-qPCR using TaqMan technology. Results By in silico analysis, 7 miRNAs targeting genes involved in features of functions (ROS production, oxidative stress, leukocyte transendothelial/migration-inflammation and vasodilation) of shear stress-induced cellular dysfunction and atherosclerosis (KEGG, hsa05418) were identified by miRWalk and miRBase databases. Of the 7 miRNAs, a 6-miRNA signature showed significantly lower plasma levels in FH-patients than in the non-FH group (P&amp;lt;0.01 for: miR-30e-5p, miR-378a-3p, let-7d-3p, and miR-550-5p; P=0.03 for miR-324-3p). In the FH-group, miR-324-3p, miR-30e-5p, miR-378a-3p and let-7d-3p significantly discriminated patients stratified by the plaque volume of non-calcified lesions (fibro-lipidic phenotype), using the median plaque volume as cut-off value. And even further, a high percentage (65-70%) of FH-subjects with low levels of the 4 miRNA had plaque volumes above the median. Interestingly, this miRNA-signature did not differentiate FH-patients stratified by the volume of calcified plaques. Conclusion FH-patients show a significantly lower content of an atherosclerosis/shear stress signature of 4 miRNAs targeting genes involved in subclinical atherosclerosis progression in FH.

Aspirin use for primary prevention among US adults with and without elevated Lipoprotein(a)

ObjectiveLipoprotein(a) [Lp(a)] is an atherogenic and prothrombotic lipoprotein associated with atherosclerotic cardiovascular disease (ASCVD). We assessed the association between regular aspirin use and ASCVD mortality among individuals with versus without elevated Lp(a) in a nationally representative US cohort. MethodsEligible participants were aged 40–70 years without clinical ASCVD, reported on aspirin use, and had Lp(a) measurements from the Third National Health and Nutrition Examination Survey (NHANES III, 1988–1994), the only cycle of this nationally representative US cohort to measure Lp(a). Regular aspirin use was defined as taking aspirin ≥30 times in the previous month. Using NHANES III linked mortality records and weighted Cox proportional hazards regression, the association between regular aspirin use and ASCVD mortality was observed in those with and without elevated Lp(a) (≥50 versus <50 mg/dL) over a median 26-year follow-up. ResultsAmong 2,990 persons meeting inclusion criteria (∼73 million US adults), the mean age was 50 years, 86% were non-Hispanic White, 9% were non-Hispanic Black, 53% were female, and 7% reported regular aspirin use. The median Lp(a) was 14 mg/dL and the proportion with elevated Lp(a) was similar among those with versus without regular aspirin use (15.1% versus 21.9%, p = 0.16). Among individuals with elevated Lp(a), the incidence of ASCVD mortality per 1,000 person-years was lower for those with versus without regular aspirin use (1.2, 95% CI: 0.1–2.3 versus 3.9, 95% CI: 2.8–4.9). In multivariable modeling, regular aspirin use was associated with a 52% lower risk of ASCVD mortality among individuals with elevated Lp(a) (HR=0.48, 95% CI: 0.28–0.83), but not for those without elevated Lp(a) (HR=1.01, 95% CI: 0.81–1.25; p-interaction=0.001). ConclusionRegular aspirin use was associated with significantly lower ASCVD mortality in adults without clinical ASCVD who had elevated Lp(a). These findings may have clinical and public health implications for aspirin utilization in primary prevention.

Association of the trimethylamine N-oxide with cardiovascular risk and vascular alterations in middle-aged patients with risk factors for cardiovascular diseases.

Trimethylamine N-oxide (TMAO) is synthesized by the intestinal microbiota and is an independent predictor of cardiovascular disease (CVD). However, its underlying mechanisms remain unclear. We investigated TMAO levels across different CVD-risk patient groups, and evaluated associations between TMAO and vascular alterations (e.g., arterial stiffness, intima-media thickness [IMT], and the presence and grade of carotid artery plaques [CAPs]). We examined 95 patients (58.5 ± 7.3 years): 40 with clinical atherosclerotic cardiovascular disease (ASCVD), 40 with atherosclerosis risk factors (RF), and 15 controls. Arterial stiffness was measured by Carotid-Femoral Pulse Wave Velocity (C-F PWV). B-mode ultrasound was used to evaluate the presence and grade of CAPs and carotid IMT (CIMT). TMAO was measured by high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) and results were presented as the median (interquartile range). TMAO levels were higher in patients with ASCVD (251.5 [164.5] µg/l) when compared with patients with RFs (194.0 [174] µg/l, P=0.04) and controls (122.0 (77) µg/l, P<0.001). A significant correlation was observed between TMAO and PWV (r = 0.31, P=0.003), which was not confirmed after adjustment for RFs. TMAO levels were significantly correlated with plaque score (r = 0.46, P<0.001) and plaque height (r=0.41, P=0.003), and were independent predictors for grade III plaques (odds ratio [OR] = 1.002, confidence interval (CI) 95%: 1.000047-1.003, P=0.044). TMAO levels are increased with expanded CVD risk. Across different types of vascular damage, TMAO is associated with atherosclerotic changes.

Lipid-lowering therapies in patients undergoing percutaneous coronary intervention

Cardiovascular disease is the leading cause of death worldwide. Over past decades, multiple clinical trials have provided substantial evidence supporting the advantages of managing plasma lipids in individuals with coronary artery disease (CAD). A primary focus in reducing clinical atherosclerotic cardiovascular disease (ASCVD) in patients who have undergone percutaneous coronary intervention (PCI) is the regulation of blood lipids, with an emphasis on low-density lipoprotein (LDL) cholesterol. Statins represent the cornerstone of lipid-lowering therapy (LLT), with high-intensity statins consistently associated with beneficial outcomes in patients at high risk of ASCVD. Nevertheless, a notable portion of patients do not achieve their target cholesterol levels through statin monotherapy, necessitating the inclusion of complementary LLT strategies. Among these therapies are ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors, which have also demonstrated clinical advantages by further reducing cholesterol levels. Existing guidelines recommend using these agents when maximally tolerated statin doses fall short of achieving target LDL levels. Additionally, recently introduced ATP-citrate lyase inhibitors, such as bempedoic acid, have gained approval as adjunctive treatments. Furthermore, icosapent ethyl, a purified derivative of eicosapentaenoic acid, targets hypertriglyceridemia and has shown cardiovascular benefits compared to placebo. In this article, we delve into the mechanisms of blood lipids and molecular targets in connection with CAD undergoing PCI. We also explore the current landscape of available LLT options, guidelines in practice, and the subtleties of therapy.

Lipid-lowering therapies in patients undergoing percutaneous coronary intervention

Cardiovascular disease is the leading cause of death worldwide. Over past decades, multiple clinical trials have provided substantial evidence supporting the advantages of managing plasma lipids in individuals with coronary artery disease (CAD). A primary focus in reducing clinical atherosclerotic cardiovascular disease (ASCVD) in patients who have undergone percutaneous coronary intervention (PCI) is the regulation of blood lipids, with an emphasis on low-density lipoprotein (LDL) cholesterol. Statins represent the cornerstone of lipid-lowering therapy (LLT), with high-intensity statins consistently associated with beneficial outcomes in patients at high risk of ASCVD. Nevertheless, a notable portion of patients do not achieve their target cholesterol levels through statin monotherapy, necessitating the inclusion of complementary LLT strategies. Among these therapies are ezetimibe and proprotein convertase subtilisin/kexin type 9 inhibitors, which have also demonstrated clinical advantages by further reducing cholesterol levels. Existing guidelines recommend using these agents when maximally tolerated statin doses fall short of achieving target LDL levels. Additionally, recently introduced ATP-citrate lyase inhibitors, such as bempedoic acid, have gained approval as adjunctive treatments. Furthermore, icosapent ethyl, a purified derivative of eicosapentaenoic acid, targets hypertriglyceridemia and has shown cardiovascular benefits compared to placebo. In this article, we delve into the mechanisms of blood lipids and molecular targets in connection with CAD undergoing PCI. We also explore the current landscape of available LLT options, guidelines in practice, and the subtleties of therapy.

Epidemiology and Prognostic Implications of Coronary Artery Calcium in Asymptomatic Individuals With Prediabetes: A Multicohort Study.

To describe the epidemiology and prognostic value of coronary artery calcium (CAC) in individuals with prediabetes. We pooled participants free of clinical atherosclerotic cardiovascular disease (ASCVD) from four prospective cohorts: the Multi-Ethnic Study of Atherosclerosis, Heinz Nixdorf Recall Study, Framingham Heart Study, and Jackson Heart Study. Two definitions were used for prediabetes: inclusive (fasting plasma glucose [FPG] ≥100 to <126 mg/dL and hemoglobin A1c [HbA1c] ≥5.7% to <6.5%, if available, and no glucose-lowering medications) and restrictive (FPG ≥110 to <126 mg/dL and HbA1c ≥5.7% to <6.5%, if available, among participants not taking glucose-lowering medications). The study included 13,376 participants (mean age 58 years; 54% women; 57% White; 27% Black). The proportions with CAC ≥100 were 17%, 22%, and 37% in those with euglycemia, prediabetes, and diabetes, respectively. Over a median (25th-75th percentile) follow-up time of 14.6 (interquartile range 7.8-16.4) years, individuals with prediabetes and CAC ≥100 had a higher unadjusted 10-year incidence of ASCVD (13.4%) than the overall group of those with diabetes (10.6%). In adjusted analyses, using the inclusive definition of prediabetes, compared with euglycemia, the hazard ratios (HRs) for ASCVD were 0.79 (95% CI 0.62, 1.01) for prediabetes and CAC 0, 0.70 (0.54, 0.89) for prediabetes and CAC 1-99, 1.54 (1.27, 1.88) for prediabetes and CAC ≥100, and 1.64 (1.39, 1.93) for diabetes. Using the restrictive definition, the HR for ASCVD was 1.63 (1.29, 2.06) for prediabetes and CAC ≥100. CAC ≥100 is frequent among individuals with prediabetes and identifies a high ASCVD risk subgroup in which the adjusted ASCVD risk is similar to that in individuals with diabetes.

Impact of Race on Classification of Atherosclerotic Risk Using a National Cardiovascular Risk Prediction Tool

The use of race in clinical risk prediction tools may exacerbate racial disparities in healthcare access and outcomes. This study quantified the number of individuals reclassified for primary prevention of cardiovascular disease owing to a change in their race alone on the basis of a commonly used risk prediction tool. This is a cross-sectional analysis of individuals aged 40-75 years without a history of cardiovascular events, diabetes, or other high-risk features using the 2005-2018 National Health and Nutritional Examination Survey. Authors compared atherosclerotic cardiovascular disease risk scores using the American Heart Association/American College of Cardiology equation recommended for White individuals or individuals of other races with that recommended for Black individuals. A total of 2,946 White individuals; 1,361 Black individuals; and 2,495 individuals of other races were included in the analysis. Using the American Heart Association/American College of Cardiology equation, the mean 10-year atherosclerotic cardiovascular disease risk was 5.80% (95% CI=5.54, 6.06) for White individuals, 7.04% (956% CI=6.69, 7.39) for Black individuals, and 4.93% (95% CI=4.61, 5.24) for individuals of other races. When using the American Heart Association/American College of Cardiology equation designated for the opposite race (White/other race versus Black), the mean atherosclerotic cardiovascular disease risk score increased by 1.02% (95% CI=0.90, 1.13) for White individuals, decreased by 1.82% (95% CI= -1.67, -1.96) for Black individuals, and increased by 0.98% (95% CI=0.85, 1.10) for individuals of other races. When using clinical atherosclerotic cardiovascular disease categories of <7.5%, 7.5%-10%, and >10%, 16.93% of all individuals were reclassified when using the American Heart Association/American College of Cardiology's equation designated for the opposite race. Changing race within a commonly used cardiovascular risk prediction tool results in significant changes in risk classification among eligible White and Black individuals in the U.S.

Familial Hypercholesterolemia in the Elderly: An Analysis of Clinical Profile and Atherosclerotic Cardiovascular Disease Burden from the Hellas-FH Registry.

Familial hypercholesterolemia (FH) carries a high risk of atherosclerotic cardiovascular disease (ASCVD). As the population ages, the age-related influence on clinical characteristics and outcomes becomes increasingly pertinent. This cross-sectional analysis from the HELLAS-FH registry aims to explore potential differences in clinical characteristics, treatment, ASCVD, and goal achievement between those younger and older than 65 years with FH. A total of 2273 adults with heterozygous FH (51.4% males) were studied. Elderly FH patients (n = 349) had a higher prevalence of ASCVD risk factors, such as hypertension (52.1% vs. 20.9%, p < 0.05) and type 2 diabetes (16.9% vs. 6.0%, p < 0.05), compared to younger patients (n = 1924). They also had a higher prevalence of established ASCVD (38.4% vs. 23.1%, p < 0.001), particularly CAD (33.0% vs. 20.2%, p < 0.001), even after adjusting for major ASCVD risk factors. Elderly patients were more frequently and intensively receiving lipid-lowering treatment than younger ones. Although post-treatment LDL-C levels were lower in elderly than younger patients (125 vs. 146 mg/dL, p < 0.05), both groups had similar attainment of the LDL-C target (3.7% vs. 3.0%). Elderly FH patients have a higher prevalence of ASCVD, particularly CAD. Despite more aggressive treatment, the achievement of LDL-C targets remains very poor. These results emphasize the importance of early FH diagnosis and treatment in reducing ASCVD.

First Report of Inclisiran Utilization for Hypercholesterolemia Treatment in Real-world Clinical Settings in a Middle East Population

Inclisiran is the first small interfering RNA-based treatment approved for reducing pro-atherogenic lipoproteins in patients with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease, who require additional lowering of low-density lipoprotein cholesterol (LDL-C). We report the first evaluation of the effects of inclisiran in a Middle East population. We conducted a retrospective review of patients initiating inclisiran treatment at an outpatient diabetology, endocrinology, and cardiology center between May 2021 and December 2022. All patients followed up for 90 days or more, or with at least 1 lipid determination post initiation were included. Participants were categorized into primary prevention (n = 57) and secondary prevention (n = 89) groups according to previous atherosclerotic cardiovascular disease. Inclisiran was initiated in 146 patients; mean (SD) age was 54.8 (12.12) years, 82 patients (56.2%) were male, 28 patients (19.2%) had received a diagnosis of familial hypercholesterolemia, 89 patients (61%) had received a diagnosis of diabetes mellitus, and 35 patients (23.9%) had a statin intolerance. Median (interquartile range) follow-up was 137 (90 to 193) days. At 90 days, median (interquartile range) reductions in serum LDL-C and triglycerides were -37.9% (-9.5% to -51.2%) and -12.0% (-9.8% to -40.5%), respectively, in primary prevention and -54.1% (-17.1% to -71.4%) and -15.3% (-14% to -38.8%), respectively, in secondary prevention (all, P < 0.001). LDL-C goals were attained in 110 patients (75.3%). Nonattainment of LDL-C goal was attributed to system effect in 26 patients (72.2%), biological effect in 5 patients (13.9%), and discontinuation of treatment in 5 patients (13.9%). Therapy was well tolerated. This study is the first from the Middle East and North Africa region that reported the real-world efficacy and safety profile of inclisiran in a mixed-risk population of patients with heterozygous familial hypercholesterolemia and other non-familial hypercholesterolemia indications. Clinically meaningful and sustained reductions in pro-atherogenic lipids with good tolerability were observed after inclisiran initiation. Fewer AEs were reported in this predominantly Arabic population, consistent with previous safety reports for inclisiran. It is important to note that no patient stopped inclisiran treatment due to AEs. Strengths of our study included an optimal cohort, patient heterogeneity, and high retention. In addition, we were able to report mean robust effects of inclisiran and good medication tolerability, quite like randomized studies and open-label extension periods. Despite this, our study had some limitations, including selection bias due to the retrospective design and the absence of a comparative group.

Pharmacist impact on evidence-based prescribing of diabetes medications in patients with clinical atherosclerotic cardiovascular disease.

Including pharmacists on care teams of patients with type 2 diabetes (T2D) has been shown to promote guideline-based prescribing and improve glycemic control, lowering risks of adverse cardiovascular outcomes. Evidence is lacking regarding whether including pharmacists on the care team is associated with the prescribing of GLP-1 receptor agonists (GLP-1 RA) and SGLT-2 inhibitors (SGLT-2i) recommended for use in patients with T2D and atherosclerotic cardiovascular disease (ASCVD). To assess the association between having a pharmacist on the primary care team of patients with T2D and ASCVD and being prescribed a guideline-recommended GLP-1 RA or SGLT-2i. A cross-sectional analysis of patients with T2D and ASCVD seen by primary care providers at an academic medical center between June 2019 and May 2020 was completed. Patients with prescriptions for GLP-1 RA or SGLT-2i with evidence of cardiovascular benefit were identified and compared between those with pharmacist care vs usual care using multivariable log-binominal regression analyses. Of 1,497 included patients, 1,283 (85.7%) were in the usual care group (mean age 68.9 years, hemoglobin A1c 7.6%) and 214 (14.3%) in the pharmacist care group (mean age 64.5 years, A1c 9.0%). Of the pharmacist care group, 50.5% were prescribed a GLP-1 RA or SGLT-2i with cardiovascular benefit vs 17.9% in the usual care group (P < 0.001). In multivariable analyses controlling for A1c and other potential confounders, those in the pharmacist care group were 2.15 times as likely to have been prescribed a GLP-1 RA or SGLT-2i than those in the usual care group (adjusted risk ratio 2.15, 95% CI = 1.83-2.52; P < 0.001). These data provide preliminary evidence that integrating pharmacists into patient care teams is associated with increased prescribing of guideline-recommended treatment with GLP-1 RA and SGLT-2i in patients with T2D and ASCVD, yet there is room for improvement in prescribing these agents to patients with T2D and ASCVD.

Severe hypertriglyceridemia and its correlation with clinical atherosclerosis and pancreatitis investigated in beta-quantification

Abstract Background Severe hypertriglyceridemia is commonly associated with pancreatitis and questionably atherosclerotic cardiovascular disease (ASCVD). However, while some patients develop those sequelae at relatively low levels, others with extreme levels remain spared from it. Purpose This study serves to validate, whether the distribution of triglycerides (TG), either in very-low-density lipoprotein (VLDL) particles or chylomicrons (CM) can be decisive for the development of clinical disease. Methods Patients with TG levels above 500 mg/dL, who routinely visited our lipid outpatient clinic between 2016 and 2021 with their lipid panel done via beta-quantification were retrospectively investigated for the presence of clinical pancreatitis and ASCVD via electronic chart-review. Results In total, 221 patients met eligibility criteria, with a mean age of 48 years, BMI of 29.7, with 72.4% males. Median TG and low-density lipoprotein cholesterol levels were 827 mg/dL and 62 mg/dL, respectively. A history of pancreatitis was present in 13.7% of patients, while ASCVD was present in 20.7%. TG distribution, described as the ratio of TG in VLDL per TG in CM showed no significant differences with regards to pancreatitis incidence (p=0.393). For ASCVD, the ratio was significantly higher in those with ASCVD vs those without (3.54 vs 2.25) (p=0.008). CM-dominant TG distribution was present in 19.5% of patients and was associated with higher total TG levels (2122 mg/dL vs 825 mg/dL), compared to VLDL-dominant TG distribution. Conclusion A higher relative amount of TGs in VLDL compared to CM, as most prevalent pattern, was associated with ASCVD, while very high levels of TG frequently relate to hyperchylomicronemia.

Abstract 16180: The Adherence and LDL-C Lowering Effect of Inclisiran Among Patients Who Received Treatment at Outpatient Clinics

Introduction: Inclisiran is a novel small interfering RNA (siRNA) indicated as an adjunct to diet and maximally tolerated statin to lower LDL-C among adults with clinical atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) in the US. It is administered subcutaneously initially, again at 3 months, and then every six months by an HCP. Subsequent doses may be administered within three months after the scheduled dose without restarting a new dose schedule. Metro Infusion Center (MIC) is one of the largest infusion centers across the US with over 200 centers in 38 states and has clinician oversight over each administration. Hypothesis: To describe the real-world adherence to inclisiran and changes in low-density lipoprotein cholesterol (LDL-C) levels associated with inclisiran use at MICs. Methods: Patient charts for those who initiated inclisiran from March 1, 2022 to November 31, 2022 were reviewed retrospectively. Demographics and clinical characteristics at initiation were collected and patients were followed until May 2023 for the current analysis. The study outcomes included the proportion of eligible patients who received the 2 nd or 3 rd dose and the percent change in LDL-C levels from baseline to the latest available data. Results: A total of 562 patients were included in the analysis from 107 different MICs in over 21 states. Mean (SD) age was 70.6 (9.6) years; 51% were female. The majority of patients (80%) were covered by Medicare. 492 (88%) had a history of ASCVD and 60 (11%) had HeFH. Mean (SD) baseline LDL-C was 147.6 (59.9) mg/dl. Of the 562 patients initiated inclisiran, 531 (95%) received their 2 nd dose, and 91% received the 2 nd dose within ±7 days of the schedule. There were 233 patients eligible to receive a 3 rd dose, 196 (84%) of them had received the 3 rd dose. Among 274 patients who had the LDL-C measured after inclisiran initiation, the average LDL-C reduction from baseline was 46.3%. On average, the first LDL-C measurement was taken at 3 months after receiving at least one dose of Inclisiran. Conclusions: These real-world data demonstrate high adherence to inclisiran with LDL-C reductions of 46.3% at 3 months. This finding was consistent with the ORION clinical development program.

Abstract 14460: Impact of Carotid Artery Plaque Detection on Cardiovascular Disease Risk and the Importance of Age in the Multi-Ethnic Study of Atherosclerosis

Background Carotid artery plaque (CAP) predicts future atherosclerotic cardiovascular disease (ASCVD) events; however, its prevalence increases with age and differs by sex and race/ethnicity, so how its presence influences ASCVD risk in clinical settings is uncertain. Hypothesis: We hypothesized that the impact of CAP detection on relative ASCVD risk declines with age. Methods: CAP was detected and quantified by ultrasound in adults free of clinical ASCVD at Exam 1 of the Multi-Ethnic Study of Atherosclerosis who were followed longitudinally for coronary death, myocardial infarction, angina, stroke, and ASCVD death. Cox proportional hazards models investigated associations of CAP and incident ASCVD events in subsets defined by age categories. These models were adjusted for confounders and an age*CAP interaction. Results: The 5198 participants were a mean (standard deviation) 61.8 (10.1) years old (53% female, 27% Black, 22% Hispanic, 12% Chinese) and experienced 880 ASCVD events over 14.3 (5.7) years. Prevalence of CAP and the age at which 50% of participants had detectable CAP differed by age, sex, and race/ethnicity, ranging from 13% in Chinese women &lt;50 years old to 97% in Non-Hispanic White men 80-84 years old (Figure). CAP presence independently predicted ASCVD events (hazard ratio, 1.35, [95% confidence interval 1.17-1.57], p&lt;0.001), however the strength of this association declined with increasing age (p interaction =0.029, Figure). CAP detection in younger individuals conferred higher relative ASCVD risk than in older participants who had higher absolute risk, regardless of CAP. Conclusions: Prevalence of CAP varies by sex and race/ethnicity. CAP becomes very common with increasing age and its relative association with future ASCVD events declines. These data can assist in guiding ASCVD risk assessment in younger adults and provide perspective for incidentally detected CAP on clinical imaging studies in older adults who have higher absolute ASCVD risk.

Abstract 12485: Cardiovascular Disease Risk, Cognitive Function, and Serum Biomarkers in Older Women Participating in a Lifestyle Intervention

Background: Cardiovascular disease (CVD), including atherosclerotic CVD (ASCVD) and stroke, increase risk of cognitive dysfunction. Serum biomarkers, including brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and insulin-like growth factor 1 (IGF-1) may be associated with elevated CVD risk and are also emerging as early indicators of cognitive dysfunction. Yet, few studies have investigated associations among all three: CVD risk, cognitive function, and serum biomarkers. Aims: We examined associations between CVD risk, cognitive function, and serum biomarkers in older women with CVD. Methods: Baseline data from an ongoing lifestyle intervention trial for the prevention of cognitive decline in older women with CVD (NCT04556305) were analyzed. Women ( N =253) aged ≥65 years were recruited from ambulatory cardiology clinics. At baseline, CVD risk factors, including blood pressure, body mass index (BMI), waist circumference, and step test (cardiorespiratory fitness) were assessed. ASCVD and CHA 2 DS 2 -VASc scores were calculated to estimate clinical ASCVD and stroke risk, respectively. Serum biomarkers included BDNF, VEGF, and IGF-1. Neurocognitive tests for global cognition, including episodic memory, executive function, semantic memory, and working memory domains, were administered. Linear regression models adjusted for age, education, and race or ethnicity were used to evaluate associations of individual CVD risk factors, ASCVD and CHA 2 DS 2 -VASc scores with cognitive function and serum biomarkers, separately. Results: Of CVD risk factors, waist circumference and BMI were associated with cognition: waist circumference with global cognition, episodic memory, and executive function ( β = -.14 - -.20); BMI with executive function ( β = -.13). ASCVD and CHA2DS2-VASc scores were associated with semantic memory ( β = -.23 and -.16, respectively). Only the ASCVD risk score was associated with BDNF ( β = .18) and VEGF ( β = .24) levels. Conclusion: In older women with CVD, body composition and CVD risk scores appear to be correlated with cognitive function. Future studies should explore associations prospectively and consider serum biomarkers as mediators of the relation of CVD risk to cognitive dysfunction.

Social disadvantage, coronary artery calcium, and their interplay in the prediction of atherosclerotic cardiovascular disease events

Background and aimsSocial determinants of health (SDOH) are key for the identification of populations at increased risk of atherosclerotic cardiovascular disease (ASCVD). However, whether at the individual level SDOH improve current ASCVD risk prediction paradigms beyond traditional risk factors and the coronary artery calcium (CAC) score, is unknown. We evaluated the interplay between CAC and SDOH in ASCVD risk prediction. MethodsMESA is a prospective study of US adults free of clinical ASCVD at baseline. We used an SDOH index inclusive of 14 determinants from 5 domains. The index ranged 0–1 and was divided into quartiles, with higher ones representing worse SDOH. Cox regression was used to evaluate the adjusted associations between CAC, SDOH, their interplay, and ASCVD events. The C-statistic was computed to assess improvement in risk discrimination for prediction of ASCVD events. ResultsWe included 6479 MESA participants (50% with CAC = 0, 24% CAC>100). ASCVD incidence increased with increasing CAC scores across SDOH quartiles. The lowest incidence was noted in those with CAC = 0 and favourable SDOH (2/1000 person-years) and highest in those with CAC>100 and most unfavourable SDOH (20.6/1000 person-years). While CAC was strongly associated with ASCVD across SDOH quartiles, SDOH was weakly associated with ASCVD across CAC strata. CAC improved the discriminatory ability of all prediction models beyond traditional risk factors, the improvement in C-statistic ranging +0.02 - +0.05. Improvements with SDOH were smaller, and were none on top of CAC. ConclusionsCAC improves ASCVD risk stratification across the spectrum of social vulnerability, while SDOH fail to improve risk prediction beyond traditional RFs and CAC.

Incidental Coronary Artery Calcium on Chest CT in Persons Without Known Atherosclerotic Cardiovascular Disease

This cross-sectional study examines the expected prevalence of coronary artery calcium (CAC) on chest computed tomography (CT) in people without clinical atherosclerotic cardiovascular disease (ASCVD) by age, sex, and race and ethnicity.

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.

Does Elevated High-Density Lipoprotein Cholesterol Protect Against Cardiovascular Disease?

High-density lipoprotein (HDL) contributes to reverse cholesterol transport, which is 1 of the main explanations for the described inverse association between HDL-cholesterol (HDL-C) and atherosclerotic cardiovascular disease (ASCVD) risk. However, efforts to therapeutically raise HDL-C levels with niacin, fibrates, or cholesteryl ester transfer protein inhibitors have not demonstrated a reduction in ASCVD events when compared with placebo among individuals treated with statins. Furthermore, mendelian randomization studies suggest that HDL-C is unlikely to be a direct biologic variable impacting ASCVD risk. More recently, observations from well-conducted epidemiologic studies have indicated a nonlinear U-shaped relationship between HDL-C and subclinical atherosclerosis, and that very high HDL-C (≥80 mg/dL in men, ≥100 mg/dL in women) is paradoxically associated with higher all-cause and ASCVD-related mortality. These observations suggest that HDL-C is not a universal protective factor for atherosclerosis. Thus, there are several opportunities for reframing the contribution of HDL-C to ASCVD risk and related clinical calculators. Here, we examine our growing understanding of HDL-C and its role in ASCVD risk assessment, treatment, and prevention. We discuss the biological functions of HDL-C and its normative values in relation to demographics and lifestyle markers. We then summarize original studies that observed a protective association between HDL-C and ASCVD risk and more recent evidence indicating an elevated ASCVD risk at very high HDL-C levels. Through this process, we advance the discussion regarding the future role of HDL-C in ASCVD risk assessment and identify knowledge gaps pertaining to the precise role of HDL-C in atherosclerosis and clinical ASCVD.