ASCVD Events Research Articles

The association between breast arterial calcification and atherosclerotic cardiovascular disease in an Australian population-based breast cancer case–control study

PurposeAtherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity and mortality. Breast arterial calcification (BAC) on mammograms is not associated with breast cancer risk. However, there is increasing evidence supporting its association with cardiovascular disease (CVD). This study examines the association between BAC and ASCVD and their risk factors within an Australian population-based breast cancer study.Materials and methodsData from the controls who participated in the breast cancer environment and employment study (BCEES) were linked with the Western Australian Department of Health Hospital Morbidity database and Mortality Registry to obtain ASCVD outcomes and related risk factor data. Mammograms from participants with no prior history of ASCVD were assessed for BAC by a radiologist. Cox proportional hazards regression was used to examine the association between BAC and later occurrence of an ASCVD event. Logistic regression was used to investigate the factors associated with BAC.ResultsA total of 1020 women with a mean age of 60 (sd = 7.0 years) were included and BAC found in 184 (18.0%). Eighty (7.8%) of the 1020 participants developed ASCVD, with an average time to event of 6.2 years (sd = 4.6) from baseline. In univariate analysis, participants with BAC were more likely to have an ASCVD event (HR = 1.96 95% CI 1.29–2.99). However, after adjusting for other risk factors, this association attenuated (HR = 1.37 95% CI 0.88–2.14). Increasing age (OR = 1.15, 95% CI 1.12–1.19) and parity (pLRT < 0.001) were associated with BAC.ConclusionBAC is associated with increased ASCVD risk, but this is not independent of cardiovascular risk factors.

Contemporary patterns of lipoprotein(a) testing and associated clinical care and outcomes

ObjectiveElevated lipoprotein(a) [Lp(a)] is associated with atherosclerotic cardiovascular disease, yet little is known about Lp(a) testing patterns in real-world practice. The objective of this analysis was to determine how Lp(a) testing is used in clinical practice in comparison with low density lipoprotein cholesterol (LDL-C) testing alone, and to determine whether elevated Lp(a) level is associated with subsequent initiation of lipid-lowering therapy (LLT) and incident cardiovascular (CV) events. MethodsThis is an observational cohort study, based on lab tests administered between Jan 1, 2015 and Dec 31, 2019. We used electronic health record (EHR) data from 11 United States health systems participating in the National Patient-Centered Clinical Research Network (PCORnet). We created two cohorts for comparison: 1) the Lp(a) cohort, of adults with an Lp(a) test and 2) the LDL-C cohort, of 4:1 date- and site-matched adults with an LDL-C test, but no Lp(a) test. The primary exposure was the presence of an Lp(a) or LDL-C test result. In the Lp(a) cohort, we used logistic regression to assess the relationship between Lp(a) results in mass units (< 50, 50-100, and > 100mg/dL) and molar units (<125, 125-250, > 250nmol/L) and initiation of LLT within 3 months. We used multivariable adjusted Cox proportional hazards regression to evaluate these Lp(a) levels and time to composite CV hospitalization, including hospitalization for myocardial infarction, revascularization and ischemic stroke. ResultsOverall, 20,551 patients had Lp(a) test results and 2,584,773 patients had LDL-C test results (82,204 included in the matched LDL-C cohort). Compared with the LDL-C cohort, the Lp(a) cohort more frequently had prevalent ASCVD (24.3% vs. 8.5%) and multiple prior CV events (8.6% vs. 2.6%). Elevated Lp(a) was associated with greater odds of subsequent LLT initiation. Elevated Lp(a) reported in mass units was also associated with subsequent composite CV hospitalization [aHR (95% CI): Lp(a) 50-100mg/dL 1.25 (1.02-1.53), p<0.03, Lp(a) > 100mg/dL 1.23 (1.08-1.40), p<0.01]. ConclusionLp(a) testing is relatively infrequent in health systems across the U.S. As new therapies for Lp(a) emerge, improved patient and provider education is needed to increase awareness of the utility of this risk marker.

Cardiovascular disease onset in old people with severe hypercholesterolemia

Background and aimsFamilial hypercholesterolemia (FH) variants are associated with higher atherosclerotic cardiovascular disease risk (ASCVD) even when compared with other forms of severe hypercholesterolemia, especially in young people. Lipid lowering therapies (LLT) may change hypercholesterolemia natural history. This study aimed at evaluating factors associated with occurrence of ASCVD in old severe hypercholesterolemics diagnosed or not with FH and undergoing LLT. MethodsHypercholesterolemic individuals ≥60 years participating on a genetic cascade screening for FH were divided in 4 groups (2 × 2) according to the presence (variant+) or not (variant-) of FH genetic variants and previous ASCVD (ASCVD+ and ASCVD-). Biomarkers associated with new incident ASCVD events were tested using Cox models. Continuous data shown as medians (%25; %75). ResultsFrom 4,111 genotyped individuals, 377 (9.1%) were elderly [age 66 (63; 71) years], 28.9% males, 42.7% variant+, 32.1% with previous ASCVD, LLT duration 9 (5; 16) years, and on treatment LDL-cholesterol 144 (109; 200) mg/dL. After 4.8 (7; 3) years of follow up there were 47 incident events (12.4%, 2.7% patient/year). The annualized event rates were 0.8% (95% CI 0.36%; 1.70%), 2.3% (95% CI 1.3%; 4.1%), 5.2% (95% CI 2.8%; 9.7%) and 6.3% (95% CI 4.0%; 10.0%) respectively for groups variant-/ASCVD-, variant+/ASCVD-, variant-/ASCVD+ and, variant+/ASCVD+ (p log rank p < 0.001). Only presence of previous ASCVD was independently associated with incident ASCVD [hazard ratio 3.236 (95%CI 1.497–6.993, p = 0.003)]. No interaction was found for previous ASCVD and variants. ConclusionsIn old severe hypercholesterolemic individuals undergoing long-term LLT previous ASCVD was associated with incident events while FH causing variants were not.

Abstract 12118: Social Disadvantage, Coronary Artery Calcium, and Their Interplay, in the Prediction of Atherosclerotic Cardiovascular Disease Events: The Multi-Ethnic Study of Atherosclerosis

Introduction: Social determinants of health (SDOH) are key for the identification of populations at increased risk of developing cardiovascular risk factors (RFs) and ASCVD. In contrast, whether at the individual level SDOH improve current ASCVD risk prediction paradigms beyond traditional RFs and CAC, is unknown. Also, while CAC predicts outcomes across a wide range of risk profiles, its performance across groups with increasing levels of social vulnerability has not been evaluated. Methods: MESA is a prospective study of US adults free of clinical ASCVD at baseline. We developed 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; and C-statistics were used to assess improvement in risk discrimination for prediction of all/hard events with CAC, SDOH, and both. Results: We included 6,479 MESA participants (50% with CAC=0, 24% CAC&gt;100). The incidence of hard ASCVD events was higher for increasing CAC scores across all SDOH quartiles ( Figure Panel A ). The lowest incidence was noted in those with CAC=0 and favorable SDOH (2/1000 person-ys) and highest in those with CAC&gt;100 and most unfavorable SDOH (20.6/1000 person-ys). CAC improved the discriminatory ability of prediction models, while improvements with SDOH were smaller and were none on top of CAC ( Panel B ). Results were consistent in analyses that evaluated education and income as SDOH exposures. Conclusion: CAC stratifies ASCVD risk across the spectrum of social vulnerability and can guide personalized risk management also among most socially vulnerable populations. In contrast, SDOH fail to improve risk prediction beyond traditional RFs and CAC. Our results provide further support to current ASCVD risk assessment paradigms in the US, and suggest that SDOH have a limited role in this specific setting.

Abstract 14252: Cumulative Apolipoprotein B Blood Concentrations During Early Adulthood and Incident Atherosclerotic Cardiovascular Disease Risk After Age 40 Years: The Coronary Artery Risk Development in Young Adults Study

Introduction: The associations between cumulative exposure to apolipoprotein B (apoB) containing lipoproteins across early adult life and incident ASCVD in later life have not been quantified. Methods: Of 4945 eligible Coronary Artery Risk Development in Young Adults (CARDIA) cohort participants we used NMR to measure apoB in 3110 participants who had samples available from the years 2, 7, 15, and 30 exams. To mitigate biases from missingness of data we conducted multiple imputation for apoB levels for the residual 1,835 participants without NMR measures of apoB. We estimated the participant-specific apoB throughout the exposure period (ages 19 to 40y) using nonparametric spline models. The area under the apoB/age curve was calculated as cumulative exposure and expressed in mg/dL*years. To quantify the association between cumulative apoB exposure during early life with incident ASCVD after age 40y we used demographic- and risk factor-adjusted* Cox regression models (see table). We used a restricted cubic spline to examine the pattern of association across the range of cumulative apoB exposure. Results: 4945 CARDIA participants were followed for a total of 88664 person*years; 255 incident ASCVD events occurred after age 40y. Participants with higher cumulative apoB levels were more likely to be men; and have higher BMI, BP, glucose, and tobacco use. In demographic and risk factor adjusted models a 100mg/dL*yr difference in cumulative apoB from ages 19 to 40y (representing a mean yearly difference of about +5mg/dL) was associated with HR 1.15 (95% CI:1.10-1.19) and HR 1.10 (95%CI:1.06-1.15) for ASCVD events, respectively. At apoB exposures &gt;1700mg/dL*y (&gt;80mg/dL/y) there was a strong, direct association with incident ASCVD after age 40y. Conclusion: Prevention strategies that reduce apoB exposures in early adult life will likely attenuate ASCVD risks later in life; targeting a usual apoB level &lt; 80mg/dL may provide maximal benefit.

Abstract 13914: Additional ASCVD Risk Factors for Patients With Diabetes: FIB-4 Score and NLR Are Higher in Adults With Diabetes and Current Risk Enhancers vs No Risk Enhancers in Real-World Evidence

Introduction: Obesity, chronic inflammation, and elevated levels of atherogenic lipids have been associated with increased risk of ASCVD events. Current AHA/ACC guidelines identify existing risk enhancers for ASCVD including persistently elevated LDL-C or triglycerides, chronic kidney disease, chronic inflammatory conditions, and elevated inflammatory markers. Hypothesis: We hypothesized that in a population-level study of adults with diabetes mellitus (DM) without a history of prior ASCVD events, the average body mass index (BMI), hepatic fibrosis score (FIB-4), and neutrophil to lymphocyte ratio (NLR) are higher in the cohort of patients with other, AHA-identified ASCVD risk enhancers. Methods: We performed a hypothesis-driven secondary analysis using a cross-sectional dataset of EHR data from 7 health systems participating in PaTH, a Partner Network in PCORnet. Adults over 40 with DM and without ASCVD were included if they had LDL-c assessed in the most recent year of available data and had &gt;6 months of pre-index data available. We describe cohort-level averages and standard deviations of the most recent lab values and clinical measurements for cohorts with and without AHA/ACC defined ASCVD risk enhancers. Results: We identified 50,749 patients in our baseline risk cohort and 67,593 patients in our enhanced risk cohort across the 7 sites. The enhanced risk cohort had a higher mean (SE) BMI 34.1 (0.28) vs 33.7 (0.29) kg/m2, FIB-4 score 1.5 (0.01) vs 1.4 (0.01) and NLR 62.5 (0.24) vs 61.2 (0.23) compared to the baseline risk cohort. NLR and FIB-4 demonstrated consistently higher averages in the enhanced-risk cohorts across sites. Conclusions: FIB-4 score and NLR both have higher population averages in cohorts with other markers of enhanced ASCVD risk in an adult diabetic patient population. The role of these markers in independently predicting ASCVD risk should be further explored with adjusted analyses in longitudinal datasets.

Abstract 12870: Absence of LDL Measurement in Secondary Prevention is Associated With Increased Subsequent Major Adverse Clinical Event (MACE) That is Only Partially Mitigated by Statin Use

Introduction: There has been considerable discussion regarding the value of follow-up LDL-C measurements in secondary prevention of major adverse cardiac events (MACE). We therefore set out to determine in a large healthcare system whether measurement of LDL-C after an ASCVD event was associated with a difference in MACE during follow-up and whether differences in outcomes could be attributed to differences in statin use. Methods: The Intermountain Enterprise Data Warehouse was searched to identify all adults with a first encounter for ASCVD-including coronary artery disease (CAD), cerebrovascular disease (CVD), and peripheral arterial disease (PAD)—between January 1, 1995 and December 31, 2016 who survived the index event and were followed for ≥3 years or until death. Results: Patients (N=68,411) had an average age of 66±14 years; 65% were men; 70.3%, 21.0%, and 8.6% entered with CAD, CVD, and PAD, respectively. A statin was prescribed to 52% of patients during follow-up. A total of 33,698 (49%) did not have and 34,713 (51%) did have a follow-up LDL-C test prior to a subsequent MACE (death, MI, CVA, and revascularization) or end of follow-up. By 3 years, MACE occurred in 14,835 (37.4%) vs. 5,770 (20.1%) of those without vs. with an LDL-C measurement, respectively (Figure top). The multivariable hazard ratio for 3 year MACE based on measuring LDL-C was 0.47. The increased MACE rate associated with not measuring LDL-C was partially mitigated by statin use (Figure bottom). Only 44.7% vs. 58.9% of patients without vs. with LDL-C measurement were taking statins. Conclusion: These data indicate that there is a significant and clinically meaningful difference in MACE based on a follow-up measurement of LDL-C. Statin administration partially, but not completely mitigated the increased MACE rate. While these results are limited in that they are from a retrospective registry, they indicate that LDL-C should be measured, and statin should be administered after an initial ASCVD event.

Abstract 12728: The Addition of Social Determinants of Health Improves the Predictive Accuracy of the Pooled Cohort Equations for 10-year Ascvd Events in African Americans

Introduction: The gold standard risk prediction tool for atherosclerotic cardiovascular disease (ASCVD), the Pooled Cohort Equations (PCE) underestimates risk among the socially disadvantaged, yet social determinants of health are absent from the PCE. This may be contributing to racial inequities in CVD since due to systemic and structural racism, socioeconomic disadvantage is disproportionately concentrated in African American (AA) communities. This analysis aimed to determine whether SDOH variables were important for the prediction of 10-year ASCVD risk in a large cohort of AA and to test whether the addition of these variables improved PCE model performance. Methods: Retrospective observational study of 3,470 Jackson Heart Study (JHS) participants aged 40-79 years old without prior ASCVD at baseline study visit. 10-year ASCVD event was defined as stroke, MI, or death from MI. First, we used competing risk random survival forests to determine variable importance of risk factors, then we used cox-proportional hazards to identify which variables among those found to be important, were independently associated with our outcome. We used time dependent AUC to compare the performance of PCE alone to models with the PCE plus SDOH to assess concordance with the true event rates for prediction of 10-year ASCVD. Results: Our sample was 35% male, 100% AA and 46% of participants had an income of &lt;$35K/year. Of 30 SDOH factors tested, the following 6: BMI, depression, weekly stress, insurance status, family income, and neighborhood violence were determined most important for prediction and were independently associated with 10-year ASCVD risk. In this sample, the PCE only model had an AUC of 0.822; adding a limited panel of SDOH factors - income, insurance status and occupation, increased the AUC to 0.859, but this improvement was only statistically significant at the 0.10 level (p=0.093). The model adding the full 6 SDOH risk panel to the PCE, saw the highest AUC at 0.863 (p=0.029). Conclusions: Adding SDOH risk factors to the PCE improved risk prediction. These findings should be explored in a larger database to determine if adding SDOH to the PCE can improve risk prediction for ASCVD events among vulnerable populations and guide more optimal use of prevention strategies.

Abstract 15238: Impact of Statins on All-Cause Mortality in Subjects With Severe Coronary Artery Calcium Score: Results Form the Confirm (Coronary Ct Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry) Registry

Introduction: Coronary artery calcium (CAC) score improves prognostic accuracy of atherosclerotic cardiovascular disease outcomes. However, the relative impact of statins on outcomes stratified by CAC score is limited. Methods: The open-label, 12-center, 6-country prospective longitudinal CONFIRM registry was queried. Individuals with severe CAC (≥300), with long term follow up were selected. Subjects with prior ASCVD events were excluded. The primary study end point was all-cause mortality (ACM) which was compared in individuals on stain versus those not on statin. Kaplan-Meier cumulative incidence curves were performed and compared with log rank test. Multivariate Cox proportional hazard regression analysis was used to calculate hazard ratio (HR) with 95% confidence interval (CI). Results: Of 21,863 participants from the CONFRIM registry, 5,928 had no prior ASCVD events and had information on CAC and statin use. Of these, 972 had a CAC score of ≥300. The mean age of statin users and non-users with CAC≥300 was similar at 67.7± 9.0 vs. 66.9±10.5; p=0.166, and both groups were predominantly male (70% vs 69%, p=0.736). Statin users were more likely to have high cholesterol (93% vs 43%), hypertension (74% vs. 67%), diabetes mellitus (27% vs 20%), family history of cardiovascular disease (41% vs. 34%) and less likely to be a current smoker (22% vs 34%); all p&lt;0.05. There were 42 (9%) deaths over a mean follow-up of 4.2 years among statin users and 86 (18%) deaths over 3.9 years in non-users. In multivariable proportional hazard Cox modeling with a reference group of non-statin users, statin participants with CAC of ≥300 had significantly reduced risk for ACM, HR 0.52- (95% CI, 0.33-0.82, p=0.005). Conclusions: In this large prospective registry, in the primary prevention cohort of patients without prior ASCVD events, severe CAC ≥ 300 identified patients most likely to benefit from statin use. Statins lowered ACM in patients with CAC≥ 300 by 48%.

Abstract 13909: Use of Advanced Lipoprotein Testing in Real-World Data: A Cross Sectional Study Across Multiple Health Systems

Introduction: Per AHA guidelines, adults between 40-75 with borderline (5-7.5%) 10-year ASCVD risk (approximately 2.5% of this population in prior studies) should have the decision to start statin therapy personalized. Per AHA guidelines, elevated apolipoprotein B-100 (apoB) and elevated lipoprotein(a) (Lp(a)) are risk enhancing factors that may be considered in this decision. Hypothesis: We hypothesize that &lt;10% of the estimated borderline 10-year ASCVD risk population between 40-75 years of age are tested for apo(B) or Lp(a). Methods: We performed a hypothesis-driven secondary analysis of a cross-sectional dataset of adults with LDL-c assessed in the most recent year of available data from 7 health systems participating in PaTH, a Partner Network in PCORnet. Participating sites reported summaries of demographics, diagnoses and lab testing for their health system populations as well as sub-cohorts of patients with prior ASCVD events, diabetes (DM), and a history of LDL &gt; 190mg/dl. We evaluated the lifetime testing for apo(B) and Lp(a) in the whole population and subtracted out the testing in the high-risk cohorts. Results: From a population of 784,406 adults, we identified a cohort of 301,235 aged 40-75 without prior ASCVD event, DM, or LDL &gt; 190. We estimated that 2.5% of this population (7,531) had borderline 10-year ASCVD risk. A total of 730 individuals were tested for apoB and 892 for Lp(a) across the entire non-high-risk cohort (0.2% and 0.3%). Assuming only the borderline risk group was tested, this represents testing rates of 9.7% for apoB and 11.8% for Lp(a), ranging across healthcare systems from 0-27% for apoB and 0-42% for Lp(a). Conclusions: Within the constraints of our population-based cross-sectional study, we found it plausible that &gt;10% of the borderline-risk population utilized either apoB or Lp(a) testing for further risk stratification. Future work should be done to directly evaluate the use of these parameters in the borderline-risk population.

Left ventricular myocardial tissue characteristics and function among healthy subjects with varying atherosclerotic cardiovascular disease risk

Abstract The Atherosclerotic Cardiovascular Disease Risk (ASCVD) score by pooled cohort equation is a reliable predictor for future ASCVD events and is used to guide primary prevention in asymptomatic aging subjects. ASCVD risk is associated with burden of coronary artery disease as measured from computed tomography angiography. Purpose We aim to investigate the association between ASCVD risk and cardiac magnetic resonance (CMR) derived left ventricular (LV) myocardial tissue characteristics (T1 values) and LV systolic and diastolic ventricular function in a large cohort of healthy subjects. Methods We selected all healthy subjects who underwent CMR from the UK-Biobank cohort study. We collected patient characteristics, cardiovascular risk factors, blood pressure at CMR, medication use and cholesterol levels. We used AI-CMRQC, our quality-controlled tool for analysis of cardiovascular function metrics from CMR using artificial intelligence [1,2], to automatically extract septal T1 values from native T1 maps and LV ejection fraction (EF), peak ejection and early filling rates (PER, PEFR), peak systolic longitudinal strain and diastolic strain-rate, mitral valve annular plane systolic excursion and diastolic peak velocity from cine long and short axis acquisitions. Subjects were stratified for low (&amp;lt;7.5%), intermediate (7.5–21%) and high (&amp;gt;21%) ASCVD risk. One-way repeated measures ANOVA was used to examine the association between cardiovascular metrics and ASCVD risk groups. Results 12,493 healthy subjects were included (females n=6,000). Mean age was 62.7±7.5 years, 3.2% had diabetes, 12.5% received treatment for hypertension and 23% smoked. ASCVD risk score could be calculated in 9,487 subjects. Mean ASCVD risk was 12.7±9%. 38% of subjects had low, 43% intermediate and 19% high ASCVD risk. T1 values fell across the incremental ASCVD groups (low: 943±51 ms, intermediate: 921±47 ms, high: 918±50 ms, P&amp;lt;0.001). Indexed LV PEFR (low: 188±45 ml/ms·m2, intermediate: 170±48 ml/ms·m2, high: 147±45 ml/ms·m2, P&amp;lt;0.001), diastolic longitudinal strain rate (low: 1.25±0.36, intermediate: 1.20±0.37, high: 1.17±0.36, P&amp;lt;0.001) also fell consistently with incremental risk. A statistically significant, but clinically less relevant decrease was seen for LVEF (low: 59±6%, intermediate 58±6%, high: 57±6% p&amp;lt;0.001) and longitudinal systolic strain (low: 21±3.5%, intermediate: 21±3.4%, high: 21±3.5%). Conclusion Increasing ASCVD risk was associated with lower native T1 values and decreasing metrics of diastolic and systolic LV function. The fall in T1 might suggest fibrofatty replacement in the LV myocardium in patients with incremental ASCVD risk that could contribute to the observed deterioration of LV function. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): NIHR MedTech cooperation awarded to Guy's and ST Thomas NHS Foundation Trust

Performance of SCORE2 and SCORE2-OP risk algorithms in a Cypriot cohort.

SCORE2 and SCORE2-OP algorithms and associated online calculators provide a new and easy method of estimating the 10-year cardiovascular risk in apparently healthy Europeans. The aim of the study was to determine the performance of these algorithms in terms of discrimination and calibration in the cohort of the Cyprus Epidemiological Study on Atherosclerosis (CESA), not only for the 10-year risk for myocardial infarction (MI), stroke and cardiovascular death, but also for all types of atherosclerotic cardiovascular events (ASCVE). SCORE2 and SCORE2-OP for low-risk regions were calculated in a non-diabetic subset of CESA consisting of 908 people (mean age±SD: 57.8±10.5; range 40-89; 58.8% female) using baseline risk factors. Mean follow-up was 13.2±3.7 years (range 1-17) with 89 primary endpoints (MI, stroke and cardiovascular death) and 136 secondary endpoints (primary endpoints, angina, cardiac failure, coronary revascularization, transient ischemic attack, claudication and critical limb ischemia). The C-statistic for the prediction of the primary endpoint for all ages was 0.76 (95% CI 0.70 to 0.81) and the observed 10-year event rate was similar to the predicted one. However, the observed 10-year rate for secondary events was similar to the estimated one only when the algorithm for high-risk regions was used. SCORE2 and SCORE2-OP moderate risk algorithms perform well in the Cypriot population for predicting the 10-year risk for MI, stroke and fatal cardiovascular disease. However, an estimate of the 10-year risk for all ASCVD events is best calculated from the high-risk algorithm.

Clinical implications of central blood pressure measured by radial tonometry and automated office blood pressure measured using automatic devices in cardiovascular diseases.

ObjectiveCentral aortic systolic blood pressure (CBP) measured by carotid-femoral pulse wave analysis (cfPWA) is a gold standard method to estimate true arterial pressure. However, the impact of the CBP level measured by radial PWA on cardiovascular (CV) risk assessment is unclear. This study aimed to determine the impact on CV outcome assessment and the association between the optimal levels of non-invasively measured CBP and automated office blood pressure (OBP) in clinical practice.Materials and methodsA total of 2,115 patients underwent non-invasive semiautomated radial artery applanation tonometry (Omron HEM-9000AI) in the Department of Internal Medicine, St. Vincent’s Hospital, from July 2011 to December 2015. The patients were followed for at least 5 years, and atherosclerotic cardiovascular (ASCVD) outcomes were collected.ResultsAmong 2,115 patients (mean age 58 ± 14 years, 50.4% men) who were followed up, the median follow-up period was 52 months (range: 1–104 months). The total number of patients with ASCVD events was 163 (7.70%). In multivariate Cox regression analysis, a CBP of more than 125 mmHg and an automated OBP of more than 131 mmHg were independently associated with a significant increase in ASCVD outcomes. After adjusting for confounding factors, the hazard ratio for ASCVD events increased by 12.5, 11.7, and 12.7%, for every 10 mmHg increase in automated OBP, CBP, and central pulse pressure (PP), respectively.ConclusionThis study demonstrated that the automated OBP measured using the method used in real clinical practice and CBP measured by radial tonometry were associated with an increased risk for adverse ASCVD outcomes.

Treatment patterns and use of healthcare resources of patients with atherosclerotic cardiovascular disease and hypercholesterolemia and patients with familial hypercholesterolemia in Spain: Protocol of the Reality study.

BackgroundAtherosclerotic cardiovascular diseases (ASCVD) and dyslipidemia are associated to a higher risk of cardiovascular events, mortality, use of healthcare resources and costs. In Spain, the evidence about the administration of lipid-lowering treatments in clinical practice, and their clinical effectiveness in patients with ASCVD and hypercholesterolemia and patients with FH is scarce. Therefore, a multidisciplinary working group of cardiologists, family physicians, internal medicine specialists and neurologists was gathered for the Reality study. The aim of this study is to describe the demographic and clinical characteristics, comorbidities, and concomitant medication of patients with ASCVD and hypercholesterolemia and of patients with familial hypercholesterolemia (FH). The use of healthcare resources and costs associated to the management of these diseases after their diagnosis were also considered.MethodsThis is an observational and retrospective study, based on the BIG-PAC® database, which includes the electronic medical registries (EMRs) of 1.8 million people from 7 Autonomous Communities in Spain (including public primary care centers and hospitals). The study includes patients who had a new or recurrent episode of ASCVD during the recruitment period (from 01/01/2017 to 31/12/2018). The index date will be defined as the date of the ASCVD event, and the follow-up period will be 24 months. According to their first diagnosis in the database, patients will be classified as ASCVD (5 groups: stable/unstable angina, acute myocardial infarction, ischemic stroke, transient ischemic attack, and peripheral arterial disease) or FH.DiscussionThis study aims to analyze the treatment patterns and use of healthcare resources of ASCVD and FH in Spain. The prevalence of these disorders will also be estimated. Due to the high morbidity and mortality associated with these diseases, it is expected that our study will provide useful information for healthcare systems and decision makers to improve the management of these disabling diseases.

The Prediction of Cardiac Events Using Contemporary Risk Prediction Models after Radiation Therapy for Head and Neck Cancer.

Simple SummaryRadiation therapy is associated with an increased risk for atherosclerotic cardiovascular disease (ASCVD). Contemporary risk prediction models accurately predict ASCVD in general populations. Whether these models adequately capture ASCVD risk after radiation therapy (RT) is unknown. Our data show that these standard risk scores do not reliably differentiate between those who will and those who will not have an ASCVD event after RT and underestimate the risk for ASCVD among patients receiving RT for HNCA.This study aims to evaluate the efficacy of the Pooled Cohort Equation (PCE), U.S. Preventative Services Task Force (USPSTF), and Framingham Risk Score (FRS) models in predicting ASCVD events among patients receiving radiation therapy (RT) for head and neck cancer (HNCA). From a large cohort of HNCA patients treated with RT, ASCVD events were adjudicated. Observed vs. predicted ASCVD events were compared. We compared rates by statin eligibility status. Regression models and survival analysis were used to identify the relationship between predicted risk and post-RT outcomes. Among the 723 identified patients, 274 (38%) were statin-eligible based on USPSTF criteria, 359 (49%) based on PCE, and 234 (32%) based on FRS. During follow-up, 17% developed an ASCVD, with an event rate of 27 per 1000 person-years, 68% higher than predicted (RR 1.68 (95% CI: 1.02, 2.12), p < 0.001). In multivariable regression, there was no difference in event rates by statin eligibility status (p > 0.05). Post-RT, the observed event rate was higher than the predicted ASCVD risk across all grades of predicted risk (p < 0.05) and the observed risk of an ASCVD event was high even among patients predicted to have a low risk of ASCVD. In conclusion, current ASCVD risk calculators significantly underestimate the risk for ASCVD among patients receiving RT for HNCA.

469 LDL Particle Number Association With Plaque Burden In Patients With Normal LDL-C

Introduction: In primary prevention, the identification of risk factors that enhance atherogenesis and inflammation are key to reducing the risk of an ASCVD event. LDL cholesterol has been known to underestimate risk in certain patient populations. Advanced lipid testing can obtain LDL particle number (LDL-P) which has been shown to be associated with an increased risk of having an event when elevated and discrepant with LDL-C. Coronary computed tomography angiography (CCTA) is a tool that is validated to assess plaque burden using the semi-quantitative segment involvement score (SIS) and coronary calcium score (CAC).

Novel Use of Therapeutic Plasma Exchange and Evinacumab in a Patient with Homozygous Familial Hypercholesterolemia

<h3>Lead Author's Financial Disclosures</h3> Nothing to disclose. <h3>Study Funding</h3> None. <h3>Background/Synopsis</h3> We present a 47-year-old woman with homozygous familial hypercholesterolemia (HoFH), recurrent ASCVD events, and multiple intolerances to therapy (including lipoprotein apheresis) who was treated successfully with a unique combination of therapeutic plasma exchange (TPE) and pharmacotherapy, including evinacumab. Her treatment with TPE required 1) pre-medication to prevent allergic reactions, 2) use of a specific TPE system selected to reduce risk of allergic reactions, and 3) medical flights bi-monthly across California to perform TPE at our institution. Following initiation of evinacumab, the patient achieved persistent low levels of LDL-C and subsequently discontinued TPE. <h3>Objective/Purpose</h3> To describe the novel use of TPE and evinacumab in HoFH when treatment options are limited. <h3>Methods</h3> Patient consent was obtained. A review of the electronic health records for the patient was completed. <h3>Results</h3> A 47-year-old woman was referred to our Advanced Lipid Disorders Treatment Center for management of HoFH. Genetic testing revealed a heterozygous pathogenic variant in LDLR; however, phenotypically her presentation was consistent with HoFH (initial LDL-C 356 mg/dL, recurrent myocardial infarction, and repeated revascularization starting at age 39 years, and extensive family history of dyslipidemia and early myocardial infarction). The following treatments were attempted: statin therapy (caused intense, intolerable myalgia), lomitapide (caused intractable vomiting and diarrhea), and lipoprotein apheresis (anaphylactoid-like reaction ultimately thought due to ethylene oxide sterilant in the apheresis column and tubing). She tolerated ezetimibe, bempedoic acid, and PCSK9 inhibitor monoclonal antibodies; however, atherogeniclipid-loweringg was insufficient with this regimen (mean+/-SD LDL-C over 1 year: 234.33+/-13.47 mg/dL). Therefore, TPE was initiated with a system that utilizes tubing sterilized via gamma irradiation, however patient still received empiric pretreatment with antihistamines and steroids. This was successful but required the patient to travel by medical flight to receive TPE every 2 weeks. After initiating evinacumab, the patient achieved persistently low LDL-C levels and TPE was successfully discontinued (Figure). <h3>Conclusions</h3> HoFH is a rare genetic disorder that portends high morbidity and early mortality. Patients with HoFH who are intolerant of treatments due to side-effects and allergies represent a unique challenge to the clinical lipid specialist. We present a patient with limited therapeutic options who was responsive to bi-monthly TPE. Similar to what has been observed in clinical trials with lipoprotein apheresis, our patient with HoFH was able to discontinue TPE following initiation of evinacumab. Our patient is tolerating her current therapy, no longer makes bi-monthly medical flights to our center for TPE, and has maintained low levels of atherogenic lipids.

PCSK-9 Inhibitors

Hyperlipidemia (elevated levels of LDL-C) is a well-known risk factor of cardiovascular diseases (CVD). Statins are well known and proven drugs for the lipid management of those who are at elevated risk for developing CVD events1. However, the patients who do not tolerate statin therapy, develop any cardiovascular disease despite maximal tolerated statins, or with severe hypercholesterolemia i.e familial hypercholesterolemia had limited options. Recently the Food and Drug Administration (FDA) approved medications (PCSK-9 inhibitors) which act on a novel pathway to reduce LDL-C levels in blood.&#x0D; HOW DO PCSK9 INHIBITORS WORK?&#x0D; PCSK-9 inhibitors (monoclonal antibodies) act on proprotein convertase subtilsin-kexin type 9 (PCSK9) and inactivate it. The PCSK9 protein has strongly inhibit recycling of the LDL receptor (LDLR). It is predominantly produced by hepatocytes, with other sites being kidneys and intestines.2,3 On the surface of liver cell, LDL binds to its receptor called LDLR. This LDL-LDLR complex is then internalized, after which the LDLR is recycled back to the cell surface up to 150 times.4 The role of PCSK9 protein is to bind the LDLR on the surface of the hepatocyte, causing internalization and degradation of the LDL receptors in the lysosomes, this process in turn reduces the number of LDL receptors on the cell surface. So, by Inhibition of PCSK9, number of available LDL receptors on the cell surface is increased and uptake of LDL?C into the cell is augmented. PCSK9 inhibition thus offers a novel therapeutic approach for the lowering of LDL-C levels.5 Currently, the only FDA?approved PCSK9 inhibitors are two human monoclonal antibodies which bind extracellular PCSK9: alirocumab6 and evolocumab.7&#x0D; FDA APPROVAL OF PCSK9 INHIBITORS AND REDUCTION IN LDL-C:&#x0D; Alirocumab (Praluent) was approved by FDA in 2015 for adult patients with heterozygous familial hypercholesterolemia or for patients with clinically significant atherosclerotic CVD requiring additional LDL lowering despite being on diet control and maximal tolerated statin therapy. Alirocumab’s long-term safety and efficacy was evaluated in ODYSSEY trials which include CHOICE I, CHOICE II, OLE, LONG TERM, COMBO I, COMBO II, FH I, FH II, HIGH FH, MONO, ALTERNATIVE, OPTIONS I and OPTIONS II. There was a 65% LDL-C levels reduction in a dose dependent fashion at maximal doses.8&#x0D; FDA also approved Evolocumab (Repatha) in 2015 for use in adult patients with homozygous familial hypercholesterolemia, heterozygous familial hypercholesterolemia, or clinical atherosclerotic CVD requiring additional lowering of LDL cholesterol despite being on a controlled diet and maximally-tolerated statin therapy. PROFICIO (Program to reduce LDL-C and cardiovascular outcomes following inhibition of PCSK9 in different populations) phase III 14 trials were designed to evaluate efficacy and long-term safety of evolocumab. Every two-week regimen reduced LDL-C levels by up to 65% as compared to approximately 50% with every 4-wk regimen.&#x0D; DOSAGE:&#x0D; Alirocumab (Praluent) is given in dosage of 75-150 mg every two weeks while Evolocumab (Repatha) is given in dosage of 140 mg every two weeks or 420 mg monthly&#x0D; ADVERSE EFFECTS AND LIMITATIONS&#x0D; The most common adverse effects observed with Alirocumab include nasopharyngitis, erythema, itchiness, swelling, pain or tenderness, influenza, urinary tract infection, diarrhea, bronchitis, myalgia, muscle spasms, sinusitis and cough. The most common adverse effects of Evolocumab include nasopharyngitis, upper respiratory tract infection, back pain and nausea. A small percentage (2.4%) of some serious cardiac adverse events were also noted which include palpitations, angina pectoris, and ventricular premature contractions.&#x0D; Some common limitations of PCSK9 inhibitors are that they are very expensive, not readily available in our country and are required in injection form.&#x0D; CONCLUSION:&#x0D; PCSK9 inhibitors are exciting and very welcome new treatment option for patients who require treatment for their elevated LDL-C levels. They have proven to be very effective in reducing LDL-C levels and in-turn reducing ASCVD events

Abstract 244: The Potential Population Health Impact Of Treating US Adults With Icosapent Ethyl.

Background: To estimate the population health impact of treating all US adults eligible for the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) with icosapent ethyl (IPE), we estimated (1) the number of ASCVD events and healthcare costs that could be prevented; and (2) medication costs. Methods: We derived REDUCE-IT eligible cohorts in (1) the National Health and Nutrition Examination Surveys (NHANES) 2009-2014 and (2) the Optum Research Database (ORD). Population sizes were obtained from NHANES and observed first event rates at five years (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, unstable angina requiring hospitalization, or coronary revascularization) were estimated from ORD. Hazard ratios from REDUCE-IT USA estimated events prevented with IPE. Total (i.e., first and recurrent) event rates were estimated from the REDUCE-IT USA subgroup, applying the treatment effect on total events observed in the entire REDUCE-IT trial. The National Inpatient Sample estimated facility and professional event costs and daily IPE treatment cost was approximated at $4.16. Results: We estimate 3.6 million US adults to be REDUCE-IT eligible, and an observed first event rate of 19.0% could be lowered to 13.1% with five years of IPE treatment, preventing 212,000 events (Table). We projected the annual IPE treatment cost for all eligible persons to be $5.5 billion, but saving $1.7 billion annually due to first events prevented (net annual cost $3.8 billion). The total five-year event rate (first and recurrent) could be reduced from 42.5% to 28.9% with five years of IPE therapy, preventing 490,000 events (net annual cost $2.3 billion). Conclusions: Treating all REDUCE-IT eligible US adults has substantial medication costs but could prevent a substantial number of ASCVD events and associated direct costs. Indirect cost savings by preventing events could outweigh much of the incurred direct costs.

The potential population health impact of treating REDUCE-IT eligible US adults with Icosapent Ethyl

ObjectiveTo explore the population health impact of treating all US adults eligible for the Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT) with icosapent ethyl (IPE), we estimated (1) the number of ASCVD events and healthcare costs that could be prevented; and (2) medication costs. MethodsWe derived REDUCE-IT eligible cohorts in (1) the National Health and Nutrition Examination Surveys (NHANES) 2009-2014 and (2) the Optum Research Database (ORD). Population sizes were obtained from NHANES and observed first event rates (composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, unstable angina requiring hospitalization, or coronary revascularization) were estimated from the ORD. Hazard ratios from REDUCE-IT USA estimated events prevented with IPE therapy. The National Inpatient Sample estimated event costs (facility and professional) and daily IPE treatment cost was approximated at $4.59. ResultsWe estimate 3.6 million US adults to be REDUCE-IT eligible, and the observed five-year first event rate without IPE of 19.0% (95% confidence interval [CI] 16.6%-19.5%) could be lowered to 13.1% (95% CI 12.8%-13.5%) with five years of IPE treatment, preventing 212,000 (uncertainty range 163,000-262,000) events. We projected the annual IPE treatment cost for all eligible persons to be $6.0 billion (95% CI $4.7-$7.5 billion), but saving $1.8 billion annually due to first events prevented (net annual cost $4.3 billion). The total five-year event rate (first and recurrent) could be reduced from 42.5% (95% CI 39.6%-45.4%) to 28.9% (95% CI 26.9-30.9%) with five years of IPE therapy, preventing 490,000 (uncertainty range 370,000-609,000) events (net annual cost $2.6 billion). ConclusionsTreating all REDUCE-IT eligible US adults has substantial medication costs but could prevent a substantial number of ASCVD events and associated direct costs. Indirect cost savings by preventing events could outweigh much of the incurred direct costs.