Prior Atherosclerotic Cardiovascular Disease Research Articles

Association of Lipoprotein (a) and Standard Modifiable Cardiovascular Risk Factors With Incident Myocardial Infarction: The Mass General Brigham Lp(a) Registry.

Lipoprotein (a) [Lp(a)] is a robust predictor of coronary heart disease outcomes, with targeted therapies currently under investigation. We aimed to evaluate the association of high Lp(a) with standard modifiable risk factors (SMuRFs) for incident first acute myocardial infarction (AMI). This retrospective study used the Mass General Brigham Lp(a) Registry, which included patients aged ≥18 years with an Lp(a) measurement between 2000 and 2019. Exclusion criteria were severe kidney dysfunction, malignant neoplasm, and prior known atherosclerotic cardiovascular disease. Diabetes, dyslipidemia, hypertension, and smoking were considered SMuRFs. High Lp(a) was defined as >90th percentile, and low Lp(a) was defined as <50th percentile. The primary outcome was fatal or nonfatal AMI. A combination of natural language processing algorithms, International Classification of Diseases (ICD) codes, and laboratory data was used to identify the outcome and covariates. A total of 6238 patients met the eligibility criteria. The median age was 54 (interquartile range, 43-65) years, and 45% were women. Overall, 23.7% had no SMuRFs, and 17.8% had ≥3 SMuRFs. Over a median follow-up of 8.8 (interquartile range, 4.2-12.8) years, the incidence of AMI increased gradually, with higher number of SMuRFs among patients with high (log-rank P=0.031) and low Lp(a) (log-rank P<0.001). Across all SMuRF subgroups, the incidence of AMI was significantly higher for patients with high Lp(a) versus low Lp(a). The risk of high Lp(a) was similar to having 2 SMuRFs. Following adjustment for confounders and number of SMuRFs, high Lp(a) remained significantly associated with the primary outcome (hazard ratio, 2.9 [95% CI, 2.0-4.3]; P<0.001). Among patients with no prior atherosclerotic cardiovascular disease, high Lp(a) is associated with significantly higher risk for first AMI regardless of the number of SMuRFs.

Abstract MP22: Age-Varying Implications of Recalibration of Cardiovascular Disease Risk Prediction in a New England-Based Healthcare System

Introduction: Atherosclerotic cardiovascular disease (ASCVD) risk estimation via the 2013 Pooled Cohort Equations (PCE) overestimates risk in population-based cohorts. We evaluated its recalibration performance in a contemporary healthcare cohort. Methods: We identified 160,926 patients in the Mass General Brigham healthcare system aged 40-79 years and without prior ASCVD or lipid-lowering medication use between 2010 and 2012. Recalibration was achieved using sex- and race-specific baseline survival and risk factor distributions of the derivation (80%) set. Internal validation compared Kaplan-Meier-adjusted observed and predicted risk based on original versus recalibrated PCE. Changes in sensitivity and specificity were calculated across various treatment thresholds for each age decile. Results: Of the 160,926 patients (mean [SD] age: 54.6 [8.6] years; 61.4% female; 82.7% non-Hispanic White), 20,373 (12.7%) underwent ASCVD over 10 years. The original PCE underestimated ASCVD risk (observed vs. predicted incidence rate: 0.13 vs. 0.05) globally and across all sex, race, and risk categories. After recalibration (observed vs. predicted incidence rate: 0.13 vs. 0.18), the prediction closely mirrored the actual ASCVD incidence in low-to-borderline risk but overestimated risk in the high risk. At ≥7.5% treatment threshold, patients aged 40-49 years derived the greatest net relative benefit (sensitivity: +42.9%; specificity: -26.6%) whereas the extent of specificity loss surpassed that of sensitivity gain beyond age 50 years with minimal reclassification by seventh decade in life. Treatment threshold yielding the greatest net benefit was incrementally higher with older age from ≥7.4% in age 40-49 years to ≥24.1% in 60-69 years. Conclusion: In healthcare setting, PCE significantly underestimated risk. Recalibration recovered sensitivity at the expense of reduced specificity in age-differential manner, highlighting the need for individualized prediction and clinical decision-making.

Factors Associated with Statin Discontinuation Following Metabolic and Bariatric Surgery: A Retrospective Analysis of 2012–2021 Electronic Medical Records Network Data

BackgroundBariatric surgery has been shown to improve hyperlipidemia, decreasing the need for statin medications. Although maintaining statin therapy post-surgery for those with a history of atherosclerotic cardiovascular disease (ASCVD) is advised, it is uncertain if discontinuation risks differ between those with and without ASCVD history.AimThe study aims to analyze the rate and reasons for statin cessation post-bariatric surgery in the US using real-world data.MethodsUsing the TriNetX electronic medical records network from 2012 to 2021, the study involved patients aged 18 or older on statins at the time of bariatric surgery. They were categorized into primary and secondary prevention groups based on prior ASCVD. Statin discontinuation was defined as a 90-day gap post the last statin dosage. The Cox model assessed factors influencing statin cessation.ResultsSeven hundred and thirty-three statin users undergoing bariatric surgery were identified, with 564 (77%) in primary prevention. Six months post-surgery, 48% of primary prevention patients and 34.5% of secondary ones stopped statins. Primary prevention patients had a 30% higher likelihood of cessation compared to secondary prevention (hazard ratio, 1.30; 95% CI, 1.06–1.60) as shown by multivariable analysis.ConclusionsPost-bariatric surgery, primary prevention patients are more likely to discontinue statins than secondary prevention patients.Graphical

Effects of astepwise, structured LDL-C lowering strategy in patients post-acute coronary syndrome.

Low-density lipoprotein cholesterol (LDL-C) lowering constitutes acornerstone of secondary prevention of atherosclerotic cardiovascular disease (ASCVD), yet aconsiderable number of patients do not achieve guideline-recommended LDL‑C targets. The 2016 European guidelines recommended titration of LDL‑C lowering medication in aset number of steps, starting with oral medication. We aimed to investigate the effects of this stepwise approach in post-acute coronary syndrome (ACS) patients. In amulticentre, prospective, non-randomised trial, we evaluated athree-step strategy aiming to reduce LDL‑C to ≤ 1.8 mmol/l in post-ACS patients with prior ASCVD and/or diabetes mellitus. Steps, undertaken every 4-6weeks, included: 1)start high-intensity statin (HIST); 2)addition of ezetimibe; 3)addition of proprotein convertase subtilisin/kexin type9 inhibitors (PCSK9i). The primary outcome was the proportion of patients achieving LDL-C ≤ 1.8 mmol/l after Steps1 and2 (using oral medications alone). Secondary outcomes examined the prevalence of meeting the target throughout all steps ( https://onderzoekmetmensen.nl/nl/trial/21157 ). Out of 999 patients, 84% (95% confidence intervals (CI): 81-86) achieved the LDL‑C target using only statin and/or ezetimibe. In an intention-to-treat analysis, the percentages of patients meeting the LDL‑C target after each step were 69% (95% CI: 67-72), 84% (95% CI: 81-86), and 87% (95% CI: 85-89), respectively. There were protocol deviations for 23,38 and 23patients at each respective step. Through stepwise intensification of lipid-lowering therapy, 84% of very high-risk post-ACS patients achieved an LDL‑C target of ≤ 1.8 mmol/l with oral medications alone. Addition of PCSK9i further increased this rate to 87% (95% CI: 85-89).

Impact of Bempedoic Acid on Total Cardiovascular Events

The ATP citrate lyase (ACL) inhibitor, bempedoic acid, reduces low-density lipoprotein cholesterol (LDL-C) level and major adverse cardiovascular events (MACE) by 13% in patients at high cardiovascular risk with intolerance of statin and high-intensity statin medications. The effects of bempedoic acid on total cardiovascular events remain unknown. To determine the impact of bempedoic acid on the total incidence of MACE. Included in this prespecified analysis of the Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen (CLEAR) Outcomes trial were patients with, or at high risk for, cardiovascular disease, with hypercholesterolemia and inability to take guideline-recommended statins. Study data were analyzed from December 2016 to November 2022. Patients were randomly assigned to treatment with bempedoic acid or placebo daily. The primary end point was the time to first event for a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization (MACE-4). The key secondary end point was time to first event for cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke (MACE-3). This prespecified analysis compared the total number of cardiovascular events in the treatment groups. A total of 13 970 patients (mean [SD] age, 65 [9] years; 7230 male [51.8%]) were included in the study. A total of 9764 participants (69.9%) had prior atherosclerotic cardiovascular disease and a baseline LDL-C level of 139 mg/dL; treatment with bempedoic acid resulted in a 21% reduction in LDL-C level and a 22% reduction in high-sensitivity C-reactive protein (hsCRP) level at 6 months. Median (IQR) follow-up was 3.4 (3.1-3.9) years. A total of 1746 positively adjudicated first MACE-4 events and 915 additional MACE events in 612 patients were recorded, with coronary revascularization representing 32.8% (573 of 1746) of first events and 69.4% (635 of 915) of additional events. For the total incidence of cardiovascular events, treatment with bempedoic acid was associated with a reduction in risk of MACE-4 (hazard ratio [HR], 0.80; 95% CI, 0.72-0.89; P <.001), MACE-3 (HR, 0.83; 95% CI, 0.73-0.93; P = .002), myocardial infarction (HR, 0.69; 95% CI, 0.58-0.83; P < .001), and coronary revascularization (HR, 0.78; 95% CI, 0.68-0.89; P <.001), although no statistically significant difference was observed for stroke (HR, 0.80; 95% CI, 0.63-1.03). A lower HR for protection with bempedoic acid was observed with increasing number of MACE events experienced by patients. Lowering LDL-C level with bempedoic acid reduced the total number of cardiovascular events in patients with high cardiovascular risk, statin therapy intolerance, and elevated LDL-C levels.

Statins, Mortality, and Major Adverse Cardiovascular Events Among US Veterans With Chronic Kidney Disease

There are limited data for the utility of statins for primary prevention of atherosclerotic cardiovascular disease (ASCVD) and death in adults with chronic kidney disease (CKD). To evaluate the association of statin use with all-cause mortality and major adverse cardiovascular events (MACE) among US veterans older than 65 years with CKD stages 3 to 4. This cohort study used a target trial emulation design for statin initiation among veterans with moderate CKD (stages 3 or 4) using nested trials with a propensity weighting approach. Linked Veterans Affairs (VA) Healthcare System, Medicare, and Medicaid data were used. This study considered veterans newly diagnosed with moderate CKD between 2005 and 2015 in the VA, with follow-up through December 31, 2017. Veterans were older than 65 years, within 5 years of CKD diagnosis, had no prior ASCVD or statin use, and had at least 1 clinical visit in the year prior to trial baseline. Eligibility criteria were assessed for each nested trial, and Cox proportional hazards models with bootstrapping were run. Analysis was conducted from July 2021 to October 2023. Statin initiation vs none. Primary outcome was all-cause mortality; secondary outcome was time to first MACE (myocardial infarction, transient ischemic attack, stroke, revascularization, or mortality). Included in the analysis were 14 828 veterans. Mean (SD) age at CKD diagnosis was 76.9 (8.2) years, 14 616 (99%) were men, 10 539 (72%) White, and 2568 (17%) Black. After expanding to person-trials and assessing eligibility at each baseline, there were 151 243 person-trials (14 685 individuals) of nonstatin initiators and 2924 person-trials (2924 individuals) of statin initiators included. Propensity score adjustment via overlap weighting with nonparametric bootstrapping resulted in covariate balance, with mean (SD) follow-up of 3.6 (2.7) years. The hazard ratio for all-cause mortality was 0.91 (95% CI, 0.85-0.97) comparing statin initiators to noninitiators. The hazard ratio for MACE was 0.96 (95% CI, 0.91-1.02). Results remained consistent in prespecified subgroup analyses. In this target trial emulation of statin initiation in US veterans older than 65 years with CKD stages 3 to 4 and no prior ASCVD, statin initiation was significantly associated with a lower risk of all-cause mortality but not MACE. Results should be confirmed in a randomized clinical trial.

Atherosclerotic Cardiovascular Events in Cancer Patients Treated With Immune Checkpoint Inhibitors: A Retrospective Cohort Study

Immune checkpoint inhibitors (ICIs) are effective therapies for numerous cancers, but have been associated with atherosclerotic cardiovascular disease (ASCVD). This study aimed to identify predictors for ASCVD events among cancer patients treated with ICIs and the cardiovascular risk factor (CVRF) control of those who developed ASCVD. A single-centre retrospective study of 366 cancer patients who received ICIs from 2018 to 2020 was performed. Demographic, baseline CVRF, cancer history, and ICI regimen data were obtained from medical records. The primary end point of ASCVD events was defined as myocardial infarction, coronary revascularisation, ischaemic stroke, or acute limb ischaemia. Cox proportional multivariable modelling and competing risks analysis were performed to assess ASCVD predictors. Descriptive analysis was performed to describe CVRF management among those who developed ASCVD events. Over a median follow-up of 3.4 years (2.8-4.3), 26 patients (7.1%) experienced 27 ASCVD events (seven myocardial infarction, one coronary revascularisation, 13 ischaemic stroke, and six acute limb ischaemia events). There were 226 (61.8%) cancer-related deaths and no cardiac deaths. History of ASCVD before ICI initiation was independently associated with ASCVD events on traditional Cox modelling (hazard ratio [HR] 4.00; 95% confidence interval [CI] 1.79-8.91; p<0.01) and competing risks analysis (HR 4.23; 95% CI 1.87-9.60; p<0.01). A total of 17 patients developed ASCVD events after ICI cessation (median 1.4 years). Among those with ASCVD events, 12 had prior ASCVD, 16 had hypertension, nine had hypercholesterolaemia, and four had diabetes, and nine were actively smoking. Variable prescription of cardiovascular preventative therapies was noted. History of ASCVD was associated with subsequent ASCVD events among patients treated with ICIs, which could occur even after active treatment was stopped. Identification and aggressive management of modifiable CVRFs should be considered throughout cancer survivorship in patients who received ICI treatment.

Cross-sectional analysis of demographic and clinical characteristics of patients using icosapent ethyl

Abstract Background/Introduction Icosapent ethyl (IPE) is an ethyl ester of eicosapentaenoic acid first approved in 2012 in the United States for the treatment of severe hypertriglyceridemia (triglyceride [TG] levels ≥500 mg/dL).1 Following results from the global REDUCE-IT trial in 2019 in which IPE substantially reduced the risk of cardiovascular (CV) events,2 IPE was approved in European countries and the United States to reduce the risk of CV events in adults treated with statins who have elevated TG levels (≥150 mg/dL) and established CV disease (CVD) or diabetes mellitus (DM) with additional risk factors for CVD.1,3 An estimated 3 million American adults are eligible to receive IPE for primary and secondary CVD prevention.4 Purpose Provide the first descriptive study of demographic and clinical characteristics of US patients taking IPE. Methods A database with electronic medical records of &amp;gt;89 million patients from 56 US health care organizations was used to identify those taking IPE, defined as those for whom at least 2 IPE prescriptions were documented (ie, on 2 separate dates). No specific date range or exclusion criteria were applied. Patient demographic information, prior/existing conditions, prior/concomitant medications, and laboratory data were retrieved. Results As of January 19, 2023, a total of 40,408 patients taking IPE were identified; they had a mean (SD) age of 60.3 years (12.9) and a body mass index of 31.9 kg/m2 (6.07). Most patients started taking IPE after January 1, 2019 (72.8%), were men (60.5%), White (75.2%), non-Hispanic or Latino (73.1%), and from the southern (46.0%) or northeastern (34.0%) United States (Table). In line with the indication of IPE, 65.3% had prior atherosclerotic CVD or DM and at least 1 risk factor. Common prior or existing conditions associated with those indicated for IPE treatment were DM (41.0%), coronary artery disease (30.2%), prior myocardial infarction (11.0%), prior stroke (7.4%), and severe hypertriglyceridemia (8.1%); hypertension (68.4%) and obesity (40.9%) were common comorbidities. Mean (SD; median) TG level in the 3 months before IPE initiation was 422 mg/dL (506; 300). Treatment with statins was very high (71.8%), and common other concomitant medications included anticoagulants (53.3%), antidiabetic agents (52.3%), and antiplatelets (46.0%; Table). Fibrates were used by 26.0% of patients taking IPE any time on or before IPE initiation. Conclusion(s) Patients using IPE commonly had a history of CVD, DM, or both, took statins, and had elevated levels of TG, thereby meeting the indication for IPE treatment. The high baseline TG levels in this population suggest that IPE is underutilized.

Abstract 16133: Lipoprotein(a) Screening Practices in a Large US Healthcare Dataset

Introduction/Background: Elevated Lipoprotein(a) [Lp(a)] is an independent, genetically determined, causal risk factor for atherosclerotic cardiovascular disease (ASCVD). European and Canadian guidelines recommend Lp(a) screening in all adults, while US guidelines recognize elevated Lp(a) as a risk enhancer. Research Hypothesis: Although elevated Lp(a) is an important ASCVD risk factor with a high prevalence, testing is infrequent. Aims: To characterize adults screened for Lp(a) and their clinicians using real-world data from the Family Heart Database of &gt;324M US individuals with medical and/or lab data from 2012-2021. Methods: In this retrospective cohort study of &gt; 44 million adults with lab data and medical claims one year before and after initial Lp(a) measurement, screening rates, demographics, ASCVD status, comorbidities, Lp(a) level (median; IQR) and ordering clinician are described. Results: Lp(a) screening rates were 1.1% (n=500,899 of 44,857,734) and 2.0% (n=218,331 of 10,658,820) in all and in those with ASCVD respectively. Among those with any Lp(a) test, median age was 60 (IQR 50-69) years, 55.0% were female,43.6%, 33.0%, 33.9%, and 13.9% had prior ASCVD, hypertension, hyperlipidemia and diabetes respectively. 20% had an Lp(a) level &gt; 139 nmol/L. Lp(a) level was higher in females than males 36 (IQR 11-118) versus 28 (IQR 10-95) nmol/L, and in Blacks versus White and Hispanic populations 73 (IQR 24-170), 29 (IQR 10-102) and 28 (IQR 10-85) nmol/L. A small number of clinicians (n=687 of 41,976; 1.6%) ordered 50% of Lp(a) tests. Conclusions: Measurement of Lp(a) in US adults with and without ASCVD was rare but increased substantially after 2018. Individuals who had Lp(a) assessed were older and frequently had ASCVD and comorbidities. A small number of clinicians were responsible for most Lp(a) orders. Additional research into barriers and facilitators of Lp(a) screening is needed.

Abstract 14786: Disparities in Composite Cardiovascular Risk Factor Control in US Adults With Diabetes in the NIH Precision Medicine Initiative All of Us Research Program

Background/Objective: There are limited contemporary data in real-world populations on composite cardiovascular risk factor (RF) control in adults with diabetes mellitus (DM). We studied the proportions of patients with DM at target for individual and multiple cardiovascular RFs including HbA1c, LDL-C, BMI, blood pressure, and smoking status. Methods: We included adults ≥18 years of age with DM from the NIH Precision Medicine Initiative All of Us Research Program 2018-2022. RFs and target values were defined as 1) HbA1c (&lt;7% w/ atherosclerotic cardiovascular disease (ASCVD) or &lt;8% w/o ASCVD), 2) LDL-C (&lt;55mg/dL w/ ASCVD or &lt;70mg/dL w/o ASCVD), 3) blood pressure (&lt;130/80 mmHg), 4) BMI (&lt;25 kg/m 2 ), and 5) smoking status (never or former smoker). We investigated the proportion (%) of patients at target for individual RFs, ≥3 RFs, ≥4 RFs, and mean number at target by sex, race/ethnicity, and ASCVD status. Results: Individual and composite cardiovascular RF control was found to be low among the 83,093 participants with DM. Control of &gt; 3 RFs and ≥ 4 RFs was only 25% and 5% overall, respectively, with fewer than 1% at target for all 5 RFs; female sex, Asian race/ethnicity, and those with prior ASCVD were more likely to have multiple RFs at target. Non-Hispanic black participants had the lowest proportion of RFs at target. In a multiple logistic regression, higher income, higher education level, employment, female sex, and Non-Hispanic White &amp; Asian race/ethnicity positively predicted control of ≥ 4 RFs with p-value &lt; 0.001. Conclusions: Individual and composite RF control remains suboptimal in many patients with DM, with disparities across certain demographic subsets. Further efforts are required to address social determinants that may be responsible for continuing gaps in adequate RF control and to educate clinicians and patients on the importance of controlling key RFs that impact ASCVD and other outcomes in those with DM.

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

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

Abstract 16773: The Association of Lp(a) and Standard Modifiable Cardiovascular Risk Factors (SMuRFs) With Incident Myocardial Infarction: The Mass General Brigham Lp(a) Registry

Introduction: Lp(a) is a robust predictor of coronary heart disease outcomes, with targeted therapies currently under investigation. However, there is a paucity of data regarding the risk of elevated Lp(a) in relation to other cardiovascular risk factors. Objective: To evaluate the association of high Lp(a) with standard modifiable risk factors (SMuRFs) for incident first acute myocardial infarction (AMI). Methods: This retrospective study utilized the MGB Lp(a) Registry which included patients ≥18 years with an Lp(a) measurement between 2000-2019. Exclusion criteria were severe kidney dysfunction, malignant neoplasm, and prior known atherosclerotic cardiovascular disease (ASCVD). Diabetes mellitus, hyperlipidemia, hypertension, and smoking were considered SMuRFs. High Lp(a) was defined as &gt;90 th percentile and low Lp(a) as &lt;50 th . The primary outcome was fatal or non-fatal AMI. A combination of natural language processing algorithms, ICD codes, and laboratory data were employed to identify the outcome and covariates. Results: A total of 6,238 patients met the eligibility criteria. The median age was 54 (IQR: 43-65) years and 45% were women. Overall, 23.7% had no SMuRFs and 17.8% had ≥3 SMuRFs. Over a median follow-up of 8.8 (IQR: 4.2-12.8) years, the incidence of AMI increased in a stepwise manner with higher number of SMuRFs among patients with high (logrank p=0.031) and low Lp(a) (logrank p&lt;0.001). Across all SMuRFs subgroups, the incidence of AMI was significantly higher for patients with high Lp(a) vs. low Lp(a) (Figure 1). The risk of high Lp(a) was higher than the risk imposed by any of the SMuRFs and was similar to having two SMuRFs. Following adjustment for confounders and number of SMuRFs, high Lp(a) remained independently associated with the primary outcome (HR=2.9 (95%CI=2.0-4.3), p&lt;0.001). Conclusions: Among patients with no prior ASCVD, high Lp(a) is independently associated with increased risk for first AMI regardless of the number of SMuRFs.

Abstract 16212: Sex-Based Statin Utilization and Cardiovascular Disease Outcomes: A Real World Secondary Prevention Cohort

Introduction: Current guidelines recommend using high-intensity statins in patients with clinical ASCVD.However, real world adherence to GDSI use and recurrent events remains less known. Sex difference in statin use have been previously reported. We evaluated sex-based disparities in GDSI use and recurrent ASCVD outcomes in a large healthcare network. Methods: Using EMR, we assessed statin use and intensity amongst patients with established prior ASCVD events (MI, ischemic stroke/TIA) and PAD from 2010-2022. Statins were categorized into GDSI (high intensity), &lt;gdsi (moderate="" or="" low="" intensity)="" or no statin use. Outcomes of interest included repeat MI, stroke/TIA and all-cause mortality. Incident rates (IR) and Cox regression hazard ratios (HR) of ASCVD outcomes were calculated across statin categories stratified by sex. Results: Amongst 45,949 patients,31% were women. Women had more diabetes (29% vs 24%) and higher LDL-C (94.9 ± 40.8 vs 87.6 ± 37.1 mg/dL) than men. During a follow-up period of 5 years, women were less likely to be started on GDSI (61.6% vs 65.8%, p&lt;0.01) and achieve LDL-C&lt;70mg/dL (41% vs and 49%, p&lt;0.01) as compared to men. GDSI use lowered IRs for all outcomes in both sexes (Table 1). Women on GDSI had higher risk of MI (HR 1.21 [1.12-1.31)],stroke (1.21 [1.08-1.34] and mortality (1.12 [1.05-1.20]), all p&lt;0.01) than men. Conclusions: In a contemporary cohort of secondary prevention patients, women were less likely to be prescribed GDSI than men and less likely to achieve guideline concordant LDL-C&lt;70mg/dL. This was associated with a higher risk of recurrent ASCVD events in women as compared to men. More sex specific interventions are needed to ensure adequate preventive treatment for both sexes. Abbreviations: Atherosclerotic cardiovascular disease (ASCVD), guideline directed statin intensity (GDSI), Electronic medical records (EMR),Myocardial Infarction (MI), Peripheral arterial disease (PAD), Transient Ischemic attack (TIA)

Novel Size-Based High-Density Lipoprotein Subspecies and Incident Vascular Events.

Background High-density lipoprotein (HDL) particle concentration likely outperforms HDL cholesterol in predicting atherosclerotic cardiovascular events. Whether size-based HDL subspecies explain the atheroprotective associations of HDL particle concentration remains unknown. Our objective was to assess whether levels of specific size-based HDL subspecies associate with atherosclerotic cardiovascular disease in a multiethnic pooled cohort and improve risk prediction beyond traditional atherosclerotic cardiovascular disease risk factors. Methods and Results Seven HDL size-based subspecies were quantified by nuclear magnetic resonance (LP4 algorithm; H1=smallest; H7=largest) among participants without prior atherosclerotic cardiovascular disease in ARIC (Atherosclerosis Risk in Communities), MESA (Multi-Ethnic Study of Atherosclerosis), PREVEND (Prevention of Renal and Vascular Endstage Disease), and DHS (Dallas Heart Study) cohorts (n=15 371 people). Multivariable Cox proportional hazards models were used to evaluate the association between HDL subspecies and incident myocardial infarction (MI) or ischemic stroke at follow-up (average 8-10 years) adjusting for HDL cholesterol and risk factors. Improvement in risk prediction was assessed via discrimination and reclassification analysis. Within the pooled cohort (median age 57 years; female 54%; Black 22%) higher H1 (small) and H4 (medium) concentrations were inversely associated with incident MI (hazard ratio [HR]/SD, H1 0.88 [95% CI, 0.81-0.94]; H4 0.89 [95% CI, 0.82-0.97]). H4 but not H1 improved risk prediction indices for incident MI. Increasing H2 and H4 were inversely associated with improved risk prediction indices for composite end point of stroke, MI, and cardiovascular death (HR/SD, H2 0.94 [95% CI, 0.88-0.99]; H4 0.91 [95% CI, 0.85-0.98]). Levels of the large subspecies (H6 and H7) were not associated with any vascular end point. Conclusions Two of 7 HDL size-based subspecies modestly improved risk prediction for MI and composite vascular end points in a large multiethnic pooled cohort. These findings support assessment of precise HDL subspecies for future studies regarding clinical utility.

Percentiles of predicted 10-year cardiovascular disease risk by sex and age in Brazil and their association with estimated risk of long-term atherosclerotic events

ObjectiveExpressing the cardiovascular disease (CVD) risk in relation to peers may complement the estimation of absolute CVD risk. We aimed to determine 10-year CVD risk percentiles by sex and age in the Brazilian population and evaluate their association with estimated long-term atherosclerotic CVD (ASCVD) risk. MethodsA cross-sectional analysis of baseline data from the ELSA-Brasil study was conducted in individuals aged 40–74 years without prior ASCVD. Ten-year CVD risk and long-term ASCVD risk were estimated by the WHO risk score and the Multinational Cardiovascular Risk Consortium tool, respectively. Ten-year risk percentiles were determined by ranking the calculated risks within each sex and age group. ResultsTen-year CVD risk versus percentile plots were constructed for each sex and age group using data from 13,364 participants (55% females; median age, 52 [IQR, 46–59] years). Long-term ASCVD risk was calculated in 12,973 (97.1%) participants. Compared to individuals at the <25th risk percentile, those at the ≥75th percentile had a greater risk of being in the highest quartile of long-term risk (ORs [95% CIs] 6.57 [5.18–8.30] in females and 11.59 [8.42–15.96] in males) in regression models adjusted for age, race, education, and 10-year CVD risk. In both sexes, the association between risk percentile and long-term risk weakened after age 50. A tool for calculating 10-year CVD risk and the corresponding percentile is available at https://bit.ly/3CzPUi6. ConclusionsWe established percentiles of predicted 10-year CVD risk by sex and age in the Brazilian population, which independently reflect the estimated long-term ASCVD risk in younger individuals.

Identification and risk stratification of coronary disease by artificial intelligence-enabled ECG

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death worldwide, driven primarily by coronary artery disease (CAD). ASCVD risk estimators such as the pooled cohort equations (PCE) facilitate risk stratification and primary prevention of ASCVD but their accuracy is still suboptimal. Using deep electronic health record data from 7,116,209 patients seen at 70+ hospitals and clinics across 5 states in the USA, we developed an artificial intelligence-based electrocardiogram analysis tool (ECG-AI) to detect CAD and assessed the additive value of ECG-AI-based ASCVD risk stratification to the PCE. We created independent ECG-AI models using separate neural networks including subjects without known history of ASCVD, to identify coronary artery calcium (CAC) score ≥300 Agatston units by computed tomography, obstructive CAD by angiography or procedural intervention, and regional left ventricular akinesis in ≥1 segment by echocardiogram, as a reflection of possible prior myocardial infarction (MI). These were used to assess the utility of ECG-AI-based ASCVD risk stratification in a retrospective observational study consisting of patients with PCE scores and no prior ASCVD. The study period covered all available digitized EHR data, with the first available ECG in 1987 and the last in February2023. ECG-AI for identifying CAC ≥300, obstructive CAD, and regional akinesis achieved area under the receiver operating characteristic (AUROC) values of 0.88, 0.85, and 0.94, respectively. An ensembled ECG-AI identified 3, 5, and 10-year risk for acute coronary events and mortality independently and additively to PCE. Hazard ratios for acute coronary events over 3-years in patients without ASCVD that tested positive on 1, 2, or 3 versus 0 disease-specific ECG-AI models at cohort entry were 2.41 (2.14-2.71), 4.23 (3.74-4.78), and 11.75 (10.2-13.52), respectively. Similar stratification was observed in cohorts stratified by PCE or age. ECG-AI has potential to address unmet need for accessible risk stratification in patients in whom PCE under, over, or insufficiently estimates ASCVD risk, and in whom risk assessment over time periods shorter than 10 years is desired. Anumana.

Concordance of a High Lipoprotein(a) Concentration Among Relatives

Lipoprotein(a) (Lp[a]) concentrations are a highly heritable and potential causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Recent consensus statements by the European Atherosclerosis Society and American Heart Association recommend screening of relatives of individuals with high Lp(a) concentrations, but the expected yield of this approach has not been quantified in large populations. To measure the prevalence of high Lp(a) concentrations among first- and second-degree relatives of individuals with high Lp(a) concentrations compared with unrelated participants. In this cross-sectional analysis, pairs of first-degree (n = 19 899) and second-degree (n = 9715) relatives with measured Lp(a) levels from the UK Biobank study and random pairs of unrelated individuals (n = 184 764) were compared. Data for this study were collected from March 2006 to August 2010 and analyzed from December 2021 to August 2023. Serum Lp(a) levels, with a high Lp(a) level defined as at least 125 nmol/L. Concordance of clinically relevant high Lp(a) levels in first- and second-degree relatives of index participants with high Lp(a) levels. A total of 52 418 participants were included in the analysis (mean [SD] age, 57.3 [8.0] years; 29 825 [56.9%] women). Levels of Lp(a) were correlated among pairs of first-degree (Spearman ρ = 0.45; P < .001) and second-degree (Spearman ρ = 0.22; P < .001) relatives. A total of 1607 of 3420 (47.0% [95% CI, 45.3%-48.7%]) first-degree and 514 of 1614 (31.8% [95% CI, 29.6%-34.2%]) second-degree relatives of index participants with high Lp(a) levels also had elevated concentrations compared with 4974 of 30 258 (16.4% [95% CI, 16.0%-16.9%]) pairs of unrelated individuals. The concordance in high Lp(a) levels was generally consistent among subgroups (eg, those with prior ASCVD, postmenopausal women, and statin users). The odds ratios for relatives to have high Lp(a) levels if their index relative had a high Lp(a) level compared with those whose index relatives did not have high Lp(a) levels were 7.4 (95% CI, 6.8-8.1) for first-degree relatives and 3.0 (95% CI, 2.7-3.4) for second-degree relatives. The findings of this cross-sectional study suggest that the yield of cascade screening of first-degree relatives of individuals with high Lp(a) levels is over 40%. These findings support recent recommendations to use this approach to identify additional individuals at ASCVD risk based on Lp(a) concentrations.

10-Year Cardiovascular Risk in Patients With Newly Diagnosed Type 2 Diabetes Mellitus

BackgroundContemporary data on cardiovascular disease (CVD) risk in patients with newly diagnosed type 2 diabetes mellitus (T2DM) is needed to guide appropriate preventive management. ObjectivesThe authors sought to investigate sex- and age-specific 10-year CVD risk in patients with newly diagnosed T2DM compared with the general population. MethodsA cohort study was conducted of all Danish patients with T2DM diagnosed between 2006 and 2013 (n = 142,587) and sex- and age-matched individuals from the general population (n = 388,410), all without prior atherosclerotic CVD. Ten-year CVD risk (myocardial infarction, stroke, and fatal CVD) was estimated. ResultsA total of 52,471 CVD events were recorded. Compared with the general population, the 10-year CVD risks were higher in patients with T2DM in both sexes and across all age groups, especially among younger individuals. For example, patients aged 40 to 49 years had the largest 10-year CVD risk difference (T2DM 6.1% vs general population 3.3%; risk difference: 2.8%, subdistribution HR: 1.91; 95% CI: 1.76-2.07). The age when a given CVD risk was reached differed substantially between the cohorts. Thus, a 10-year CVD risk of 5% was reached at age 43 in men with T2DM compared with 12 years later, at age 55, in men without T2DM. A 10-year CVD risk of 5% was reached at age 51 in women with T2DM and 10 years later, at age 61, in women without T2DM. ConclusionsNewly diagnosed T2DM increased 10-year CVD risk across both sexes and all age groups, especially among younger patients, with CVD occurring ≤12 years earlier than in general population individuals.

Race and Ethnicity With Atherosclerotic Cardiovascular Disease Outcomes Within a Universal Health Care System: Insights From the CARTaGENE Study.

It remains unclear whether racial and ethnic disparities for atherosclerotic cardiovascular disease (ASCVD) persist within universal health care systems. We aimed to explore long-term ASCVD outcomes within a single-payer health care system with extensive drug coverage in Québec, Canada. CARTaGENE (CaG) is a population-based prospective cohort study of individuals aged 40 to 69 years. We included only participants without previous ASCVD. The primary composite endpoint was time to the first ASCVD event (cardiovascular death, acute coronary syndrome, ischemic stroke-transient ischemic attack, or peripheral arterial vascular event). The study cohort included 18,880 participants followed for a median of 6.6 years (2009 to 2016). The mean age was 52 years, and 52.4% were female. After further adjustment for socioeconomic and cardiovascular factors, the increase in ASCVD risk for South Asians (SAs) was attenuated (hazard ratio [HR], 1.41; 95% confidence interval [CI], 0.75, 2.67), whereas Black participants' risk was lower (HR, 0.52; 95% CI, 0.29, 0.95) compared with White participants. After similar adjustments, there were no significant differences in ASCVD outcomes among the Middle Eastern, Hispanic, East-Southeast Asian, Indigenous, and mixed race-ethnicities participants and the White participants. After adjustment for CV risk factors, the risk of ASCVD was attenuated in the SA CaG participants. Intensive risk-factor modification may mitigate the ASCVD risk of the SAs. Within a universal health care context and comprehensive drug coverage, the ASCVD risk was lower among Black compared with White CaG participants. Future studies are needed to confirm whether universal and liberal access to health care and medications can reduce the rates of ASCVD among the Black population.

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

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