Unstable Angina Research Articles

Background: In coronary hemodynamics, laminar flow is a protective mechanism, and turbulent flow is a detrimental factor. In clinical practice, for patients with unstable angina, the necessity of intervention for moderate lesions (50-70% stenosis) is always questioned. In this study, we comprehensively evaluated the risk factors that may lead these plaques to progress to myocardial infarction using angiography, IVUS, and Deep Learning. Hypothesis: Vulnerable lesions are usually associated with plaque eccentricity and stagnant flow, causing chest pain. Methods: Patients with a single lesion admitted with diagnosed of unstable angina underwent the dynamic angiographic technique with IVUS support. First, the coronary artery was fully injected with contrast. After the injection stopped, the blood (white) began streaming in to replace the contrast (black). The flow characteristics and movements will be recorded through the disappearance of the contrast opacity with 15 frames/second. In aditionally, the arterial phase (AP) was calculated as the time from frames with full contrast to frames with washed-out contrast. Moreover, IVUS was performed for evaluate plaque features (eccentricity, calcification and vulnerable). At the same time, deep learning (DL) models were built based on independent datasets (225 angiogram videos). The DL program was constructed using a combination of U-Net and DenseNet-121. The segmentation model and a convolutional neural network were used to detect the starting frame, ending frame of AP. Results: Fifty patients met inclusion criteria (72% males) with a mean age of 66.2 ± 9.5 years. IVUS analysis revealed that 84% (42 patients) had plaque eccentricity without (or minimal) calcification. Contrast stagnation was observed for a longer duration in eccentric coronary regions compared to non-eccentric plaque regions, as quantified by DL analysis of the arterial phase (24.5 +/- 1.6 frames vs 30.1+/- 1.4 frames, p < 0.05). After stenting, the stagnant flow was eliminated, and flow was restored to 25 ± 2.1 frames. Conclusion: Plaque eccentricity along with a prolonged arterial phase (stagnant flow) are causes of chest pain in unstable angina. This is a personalized indication for PCI, even if they are moderate lesions.<div id="gtx-trans" style="position: absolute; left: 393px; top: 368.844px;"><div class="gtx-trans-icon"> </div></div>

Introduction: Ischemic heart disease (IHD) remains a leading global cause of morbidity and mortality despite advances in therapies. Lowering low-density lipoprotein cholesterol (LDL-C) is critical in reducing cardiovascular risk. Statins are usually the first-line agents, but many patients either fail to reach LDL-C targets or remain at residual risk. Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitors effectively lower LDL-C and provide cardiovascular benefits in high-risk patients. This meta-analysis assessed both the efficacy and safety of PCSK9 inhibitors used in conjunction with statins in patients with IHD, with a focus on efficacy and safety endpoints. Methods: We systematically searched PubMed, Cochrane Library, and ClinicalTrials.gov through May 2025 for randomized controlled trials (RCTs) comparing PCSK9 inhibitors plus statins vs. placebo with or without statins in patients with IHD. Three reviewers independently extracted data. Efficacy outcomes included LDL-C at 30 days; ischemic stroke; heart failure hospitalization; unstable angina; neurocognitive events; all-cause mortality; myocardial infarction (MI) and coronary revascularization. Safety outcomes included injection site and allergic reactions. Pooled risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Means and standard deviations were estimated from medians/IQRs by Wan’s method. Study quality was assessed using Cochrane RoB 2.0. Assessment of publication bias was not feasible due to fewer than 10 included studies. Results: In this meta-analysis, five RCTs were included. Combination therapy significantly reduced total cholesterol at 30 days (MD =–49.21 mg/dl; 95% CI; –90.68 to –7.74; p = 0.02) coronary revascularization (RR = 0.84; 95% CI: 0.76–0.93; p = 0.0008), MI (RR 0.76; 95% CI; 0.62-0.93; p= 0.007) and increased the risk of injection site reactions (RR=1.36; 95% CI: 1.16–1.59; p = 0.0001). Sensitivity analyses were conducted to address heterogeneity. No significant differences were observed for all-cause mortality, stroke, heart failure, neurocognitive events, or allergic reactions. Conclusion: In patients with IHD, the addition of PCSK9 inhibitors to statin therapy improved lipid levels and reduced coronary revascularization with a favorable safety profile. These findings support their use in select high-risk populations who remain inadequately managed on statins alone.

Background: Noise exposure is a risk factor for the development of cardiovascular disease risk factors (CVDRFs, i.e., diabetes, hypertension, and hyperlipidemia) and major adverse cardiovascular events (MACE). Yet, it is not known how the development of CVDRFs contributes to the association between noise and MACE. Objective: We hypothesized that (1) high noise exposure (>45 dBA) increases MACE risk via the accelerated development of CVDRFs, and (2) the findings are similar across categories of MACE [overall MACE, heart failure (HF), peripheral vascular disease (PVD), acute coronary syndrome (ACS, i.e., unstable angina, myocardial infarction), stroke, and coronary MACE (i.e., ACS and coronary revascularization)]. Methods: Individuals with transportation noise exposure data without MACE before study onset were identified in the Mass General Brigham Biobank. Average 24-h transportation noise was estimated at each participant’s residence using a US Department of Transportation tool. Presence and timing of MACE and CVDRFs were determined using ICD-10 codes; air pollution exposure and median neighborhood income were assessed with US government data. Logistic regression and mediation analyses that accounted for temporal relationships were employed. Primary models were adjusted for age, sex, and baseline CVDRFs. Results: Of 25,761 participants (median age 61 years (IQR: 46-71); 51.4% female), 8,397 lived in areas with high noise exposure. Over 10-years of follow-up, high noise exposure associated with incident MACE (OR=1.10, p=0.005) and development of new CVDRFs (1.15, p<0.001). Among individual MACE endpoints, noise associated with HF (1.10, p=0.033), PVD (1.32, p =0.013), ACS (1.13, p=0.020), and stroke (1.12, p=0.018) but not coronary MACE (p=0.136, Fig 1A). Noise also associated with the development of a new CVDRF (Fig 1B). Further, the development of a CVDRF predicted MACE (Fig 1C). Most models remained robust to further separate adjustment for air pollution and neighborhood median income. Moreover, the development of a CVDRF mediated the link between noise and overall MACE (indirect pathway: log odds 0.03, p<0.05) as well as the separate MACE endpoints (Fig 1D). Conclusions: High noise exposure accelerates the development of CVDRFs, which contributes to increased MACE risk. These findings suggest that noise-exposed individuals may benefit from amplified efforts to diagnose and treat CVDRFs to prevent downstream MACE.

Background: Medication non-adherence following acute coronary syndrome (ACS) is a critical implementation gap in socioeconomically disadvantaged patients. The SECURE trial demonstrated benefits of polypill therapy in chronic CAD but excluded P2Y12 inhibitors and did not target socioeconomically disadvantaged populations with recent ACS. Methods: In this open-label, two-center pilot RCT, adults within 30 days of ACS with stent placement were randomized 1:1 to once-daily polypill (aspirin 81mg, rosuvastatin 40mg, plus clopidogrel 75mg or prasugrel 10mg) versus usual care. Key endpoints were follow-up low-density lipoprotein cholesterol (LDL-C) and platelet reactivity, measured by impedance aggregometry (ohms [Ω]; lower = better inhibition), at 30 days. Patient-centered endpoints included treatment satisfaction (TSQM), adherence (MMAS-8), and quality of life (SAQ). Within-group changes from baseline to follow-up were compared, and treatment effects were assessed as differences least square means (LSM) using baseline-adjusted linear regression models. Results: Among 140 randomized participants (median age 58 years, 29% female, 14% Black, 63% Hispanic), 128 (91.4%) completed follow-up. Index ACS events were STEMI (29%), NSTEMI (51%), and unstable angina (19%). In the polypill arm, there was a significant LDL-C reduction (-6.74 mg/dL, p=0.013) with no change in platelet reactivity (+0.55Ω, p=0.21) from baseline to 30-day follow-up. In contrast, the usual care participants had no change in LDL-C and a significant worsening in platelet reactivity (0.76Ω, p=0.028). The between-group (polypill vs. usual care) differences were non-significant for LDL-C (LSM difference: -4.58mg/dL, p=0.27) and platelet reactivity (-0.08Ω, p=0.88). Between-group differences were non-significant for all patient-reported endpoints. In exploratory subgroup in those with poor baseline adherence, between-group LDL-C difference was numerically greater (-9.32 mg/dL, p=0.10). Composite ED/hospitalizations events were similar between polypill vs usual care (0.14 vs 0.19 events/participant, p=0.50). Conclusions: This pilot RCT demonstrates feasibility of a polypill strategy incorporating P2Y12 inhibitors and statins among socioeconomically disadvantaged patients in the post-ACS period. Significant within-group improvements in LDL-C and adherence support the need for adequately powered longer-duration trials to evaluate sustained clinical benefits.

Background: Cardiovascular disease is a leading cause of morbidity and mortality worldwide, but its risk among patients with multiple sclerosis (MS) remains underexplored. This study aimed to evaluate the 10-year risk of acute coronary syndrome (ACS) in patients with MS compared to matched controls without MS. Methods: A retrospective cohort analysis was conducted using de-identified electronic health records from the TriNetX Global Collaborative Network, encompassing over 160 million patients from 143 healthcare organizations. Patients with MS (n=300,268) were matched 1:1 to controls without MS (n=584,256) based on age, sex, race, diabetes, hypertension, obesity, and tobacco use. After exclusions and matching, each cohort included 254,992 patients. Individuals with a prior history of heart failure, cardiomyopathy, chronic ischemic heart disease, or acute myocardial infarction were excluded. The primary outcome was ACS, defined as unstable angina or acute myocardial infarction (ICD-10-CM: I20.0, I21), assessed over a 10-year follow-up. Statistical analyses included risk estimates, Kaplan-Meier survival analysis, and Cox proportional hazards modeling. Results: Over 10 years, MS patients had significantly fewer ACS events (1,014 vs. 3,032) than controls. The risk of ACS was 0.4% in the MS cohort and 1.2% in controls (risk difference -0.008; p<0.001). The hazard ratio for ACS in MS patients was 0.44 (95% CI: 0.41–0.47), indicating a 56% lower risk than controls. Conclusions: Patients with MS had a significantly reduced risk of ACS over 10 years compared to matched controls. These findings suggest a potential cardioprotective effect from immunosuppressive therapies employed in MS and frequent medical monitoring in the MS population. The results of this study warrant further investigation to elucidate the mechanisms underlying the reduced cardiovascular risk observed in individuals with MS.

Introduction: Coronary heart disease (CHD) remains a leading global health burden. Cine cardiovascular magnetic resonance (CMR), the gold standard for evaluating left ventricular (LV) structure and function, avoids contrast but relies on human-derived clinical measures. Radiomics, a high-throughput image analysis method, offers a quantitative, agnostic approach to LV analysis. We hypothesized that radiomics could classify individuals with prevalent CHD in a large bi-racial cohort. Methods: bSSFP cine CMR was performed in 2,629 participants from the Framingham Heart Offspring Study (n=1277, mean age 64.5 ± 10.0 years, 53.0% female, CHD = 93) and the Jackson Heart Study (n=1352, mean age 59.1 ± 10.3 years, 62.1% female, CHD = 37) using 1.5T scanners (FHS: Philips Achieva and Siemens Espree; JHS: Philips Medical Systems HS). 130 participants had prevalent CHD, 2,499 did not. LV myocardium was segmented from 5 short-axis slices (base to apex), and 939 shape&texture radiomic features were extracted using PyRadiomics. After restricting to previously published reproducible features and principal component analysis, 92 radiomic features were retained. XGBoost with 5-fold cross-validation selected the top 5 based on mean feature importance (average gain across folds), and used in all radiomics-based models. CHD was defined as prior coronary artery disease, myocardial infarction, or unstable angina. Logistic regression models were developed to classify CHD using five configurations: (1) radiomics-only, (2) demographics only (age, sex, race), (3) demographics + LVEF (ejection fraction), and combined models: (4) demographics + radiomics, and (5) demographics + LVEF + radiomics. Model performance was compared using the DeLong test. Results: Radiomics-only models performed similarly to Demographics (AUC = 0.71 [0.66–0.76], p = 0.20) and Demographics + LVEF (AUC = 0.71 [0.67–0.76], p = 0.14), with overlapping confidence intervals and p-values for comparison ≥ 0.14 (Figure, Table), indicating no significant difference. Classification performance improved with combined radiomics, demographics, and LVEF (AUC = 0.78 [0.72–0.82], p = 0.38). Conclusion: Radiomics-only models from routine cine CMR performed comparably to models using key demographic and functional factors(LVEF) for CHD. These findings underscore that cine images alone hold valuable information about underlying disease and may enhance the discriminative ability of agnostic image interrogation in CHD classification.

Introduction: Improving the risk stratification of cardiovascular events based on the analysis of structural changes in the coronary arteries in patients (pts) with ACS is relevant and significant. Purpose: Development of a "Risk Score Scale" ("RSS") of MACE based on computed tomographic angiography (CTA) data for pts with ACS. Methods: The study included 249 pts with ACS (77.5% men, age 58.2 ±10.7 years). Unstable angina occurred in 26.5% of pts, MI – in 73.5%. PCI for culprit lesions was performed in 90% of pts. On the 3rd-7th day of hospitalization CTA was performed by 64 - row CT scanner in 16% of pts and 320 - row CT scanner in others. The characteristics of 785 plaques were determined in pts, including 609 uncalcified ones. We assessed coronary obstruction, morphology and signs of uncalcified plaques instability, such as the presence of low-attenuation area <30 HU, napkin-ring sign, positive remodeling, spotty calcifications, rough contour. The total number of plaques and the number of plaques with certain characteristics were also evaluated. Results: During 39.1 [18.0;57.4] months of follow-up, 71 (28.5%) pts had MACE (at least one of the following events: nonfatal MI, unstable angina, cardiac death, unplanned PCI, ischemic stroke). In the univariate Cox analysis a significant association with the MACE was found in 14 out of 30 CTA characteristics. Multifactorial Cox analysis showed that 11 of the 14 predictors are independent of known clinical risk factors. ROC analysis of significant univariate CT predictors was used to develop the “RSS”. The uncensored period was 305 days. 26 MACE emerged during this period. For each of the significant predictors, the cut-off values were calculated using the Yuden method, as well as corresponding AUC, Sn, Sp, PPV and NPV. The "RSS" includes 8 most optimal predictors. Their values of the points awarded are proportional to the values of their AUCs (Table). For the resulting "RSS" the threshold value calculated by the Yuden method was 3 points. A score of >3 points indicates a high risk of MACE: odds ratio = 7.2, 95% CI: 2.6-19.7, p<0.0001. The AUC of the scale was 0.77 (Figure), Sn = 0.81, Sp = 0.63, PPV = 0.21, NPV = 0.97. Conclusion: The use of “RSS” based on CTA characteristics is a new and practically significant technique that makes it possible to improve the risk stratification of adverse outcomes in the first year after ACS.

Introduction: The PREVENT risk prediction equations for primary prevention of atherosclerotic cardiovascular disease (ASCVD) was developed to overcome limitations of prior ACVD equations. Despite the inclusion of additional risk factors, there has been criticism that PREVENT underestimates risk. We explored the impact of adding a polygenic risk score (PRS) to improve clinical utility of PREVENT. Methods: We used Genetic Epidemiology Resource in Adult Health and Aging (GERA) cohort of 60,544 members of Kaiser Permanente of Northern California between the ages of 30-74 years at baseline in 2007-08 (68% female, 81.2% European, 3.4% African-American, 7.0% Hispanic, 7.6% Asian) . There were 3,026 CHD (stable/ unstable angina, myocardial infarction, coronary revascularization, CHD death) incident events during 14 years of follow-up. A validated 12-SNP polygenic risk score (PRS) optimized for CHD (CARDIO inCode-Score) was used to capture genetic predisposition to CHD (Low=quintile 1; Intermediate=quintiles 2-4; High=quintile 5). We implemented time-to-event survival analysis and clinical utility evaluation of adding PRS to a model containing PREVENT. Results: Mean (SD) age of cohort was 59 (9) years. Mean (SD) 10-year PREVENT risk was 4.8% (3.8%). Distribution of PREVENT risk groups was: 61% low (<5%), 18% borderline (5≤7.5%), 11% intermediate (7.5-10%) and 10% high (≥10%). Absolute CHD rates (per 100 persons) according to joint categories of PREVENT and polygenic risk are shown in the Figure. Among subjects with high PRS (n=10,865), 29% were at borderline/intermediate PREVENT risk and, of those, 50.2% were not taking statins at baseline. Notably, individuals with borderline PREVENT/high PRS had significantly higher rate than intermediate PREVENT/low PRS and similar for intermediate PREVENT/high PRS versus high PREVENT/low PRS. In a Cox model with simultaneous entry of categories of PREVENT and polygenic risk adjusting for 10 principal components of genetic ancestry, adding PRS to model containing PREVENT increased Harrell’s C statistic by 0.01 (0.747 to 0.757; p<0.0001). The category based Net Reclassification Improvement was 10.7 (7.6-13.9) in borderline/intermediate PREVENT risk. Conclusion: A polygenic risk score added significant and clinically meaningful predictive information to the PREVENT equation and may help refine risk assessment, particularly among PREVENT borderline/intermediate individuals where decisions to initiate/intensify therapy is critical.

Background: We investigated the impact of genetic risk factors for coronary heart disease (CHD) -polygenic risk score (PRS), familial hypercholesterolemia (FH), and family history (FamHx)- on CHD risk estimates, across the age spectrum, in two diverse cohorts of US adults -eMERGE IV (eIV) and All of Us (AoU). Methods: CHD was defined as myocardial infarction, unstable angina, and coronary revascularization. Self-identified race/ethnicity (SIRE) was used as a population descriptor. We calculated a PRS for CHD (PRS CHD , PGS004698), ascertained FH as the presence of pathogenic/likely pathogenic variants in FH genes, and defined FamHx as early-onset CHD in first-degree relatives. We employed Pooled Cohort Equations (PCE) to estimate the 10y risk of CHD for adults ≥40y and modeled the association of conventional risk factors with CHD in adults <40y. AoU served as the training set, and eIV as the testing set. We analyzed the impact of PRS CHD and FamHx on CHD risk estimates by a) using multivariable logistic regression and Cox proportional hazard models, assessing discrimination and the extent of risk reclassification; and b) net benefit analysis and decision curves to assess the performance of prediction models across actionable thresholds. Results: We analyzed data for 19348 participants from eIV (age 50±15, 68% female, 41% non-White) and 239645 participants from AoU (age 55±17, 61% female, 48% non-White). Genetic risk factors were significantly associated with CHD. PRS CHD performance varied by SIRE groups, while FamHx was consistent. The effects of PRS CHD and FamHx on CHD were independent and additive (Figure 1). In adults ≥40y, incorporating PRS CHD and FamHx into PCE improved discrimination (C-statistic increased from 0.719 to 0.753; P -diff=9.1×10 -3 , Figure 2) and reclassified risk in 19% and 20% of participants at the 7.5% and 10% 10y CHD risk thresholds, respectively. Between the 7.5% and 10% 10y CHD risk thresholds, incorporating PRS CHD and FamHx into the PCE improved the net benefit of the risk prediction models across White, Black, and Hispanic/Latino groups (Figure 3). Conclusion: PRS CHD and FamHx were independently and additively associated with CHD in two large diverse cohorts in the US. Incorporating PRS CHD and FamHx into PCE improved risk discrimination, reclassified risk in a significant portion of participants, and improved net benefit of the PCE across all three major SIRE groups, motivating the addition of these factors to clinical risk calculators.

Background: Acute coronary syndrome (ACS) requires immediate medical attention to reduce morbidity and mortality. However, prehospital delay remains a global challenge, leading to increased complications and reduced survival rates. We investigated predictors of delay in seeking treatment among Taiwanese ACS patients. Methods: A total of 163 Taiwanese ACS patients (diagnosed with STEMI, NSTEMI, or unstable angina) were recruited. Data were collected through structured questionnaires covering demographics, clinical characteristics, and symptom response based on the self-regulation model. Delay time was defined as the period from symptom onset to hospital registration. Descriptive statistics, t-tests, ANOVA, and multiple linear regression were performed using SPSS 29.0. Results: The mean delay time was 86.85 hours (SD = 187.38), ranging from 0.22 to 600 hours. Most patients (76.1%) did not experience typical chest pain as they expected. Common symptoms included chest tightness (38.7%), dyspnea (19.6%), and fatigue (6.1%). Significant predictors of longer delay included lack of recognition of symptoms as cardiac-related (β = .62, p = .04), intermittent symptom presentation (β = .22, p = .03), presence of heart failure (β = –.31, p = .01), and chronic obstructive pulmonary disease (COPD) (β = –.25, p = .01). The model explained 41% of the variance in delay time (R 2 = .41). Conclusion: There are critical cognitive and clinical predictors of treatment delay in Taiwanese ACS patients. Health education emphasizing early symptom recognition, especially atypical presentations, and targeted intervention for patients with comorbidities like heart failure and COPD, may reduce prehospital delays and improve outcomes.

Introduction/Background: Acute coronary syndrome (ACS) is potentially a life-threatening emergency, and prompt diagnosis and reperfusion are essential to prevent adverse outcomes. Individuals with ACS can experience an array of symptoms which may be non-specific. The emergence of new technology for home-based monitoring of cardiac electrical activity (rhythm and ischemia) may supplement individuals’ symptom appraisal, improve diagnostic accuracy, and reduce prehospital delay. The feasibility of individuals with ACS to acquire their own electrocardiogram (ECG) using remote cardiac monitoring is unknown. The purpose of this pilot study was to evaluate if hospitalized patients could acquire a derived 12-lead ECG using a KardiaMobile 6L remote cardiac monitoring device. Methods/Approach: Hospitalized patients > 21 years of age at high risk for ischemic events (e.g., ACS diagnosis, HEART score >3) who owned a smart phone were included. After consent, research assistants trained participants, using apps on their own smart phones, to 1) acquire an ECG with KardiaMobile 6L, at least once daily, for the duration of their hospitalization, and 2) document symptoms with the validated 13-item ACS Symptom Checklist following ECG acquisition. Results/Data: Between November 2024 - June 2025, we enrolled 27 participants (mean age 64.8 years; ± 11.4). The sample was 29.6% female, 74.1% White, 40.7% transported by ambulance, and 44.4% admitted to ICU. Mean length of stay was 5.26 ± 4.42 days. Most (88.9%) were diagnosed with an ACS condition: STEMI (33.3%), NSTEMI (44.4%), or unstable angina (11.1%). Of 26 patients with complete KardiaMobile data, 25 (96.2%) acquired at least one ECG, 9 (39%) completed an ECG on every day of hospitalization, and 13 (50%) completed an ECG on at least half of the days. A blinded cardiologist classified a majority of KardiaMobile ECGs as clean and interpretable (90.4%). All 27 participants submitted at least one ACS Symptom Checklist, with patients submitting an average of 2.6 ±1.9 checklists. Conclusions: In this ongoing study, preliminary results suggest hospitalized patients can successfully use a KardiaMobile 6L device to capture derived 12-lead ECGs. KardiaMobile 6L demonstrates potential for detecting critical ECG changes relevant to ACS. Future studies are needed to examine ECG acquisition and transmission from home and remote evaluation (e.g., telehealth) for early ischemia detection and response (i.e., call 911) among community dwelling adults.

Background: Current AHA/ACC guidelines recommend high-intensity statin (HIS) therapy plus adjuvant therapies including ezetimibe and PCSK-9 inhibitors for the secondary prevention of major adverse cardiac events (MACE) with a goal low-density lipoprotein cholesterol (LDL-C) level <70 mg/dL. ESC guidelines recommend a goal LDL-C <55 mg/dL for this population. Attention to guideline-recommended 12-week LDL-C levels in high-risk patients provides an opportunity to escalate lipid-lowering therapies (LLT) in high-risk patients to achieve an LDL <55 mg/dL. Here, we describe a multidisciplinary virtual care protocol for the escalation of LLTs in the outpatient setting at an urban safety net hospital. Methods: All patients ≥ 18 years of age who underwent a Left Heart Catheterization (LHC) for Acute Coronary Syndrome (STEMI, NSTEMI and Unstable Angina) were referred to a virtual lipid clinic at discharge. The virtual lipid clinic was staffed by a cardiology PharmD, and patients completed virtual visits at 6, 12, 24 and 36 weeks after discharge. Medication adherence was also evaluated by the PharmD during these visits. LLT with HIS were escalated to include ezetimibe, PCSK9i, and bempedoic acid as appropriate until LDL-C <55 mg/dL. Results: Between June 1, 2024 and April 7, 2025 196 patients underwent LHC for ACS and were subsequently referred to the virtual lipid clinic. A total of 68 patients were excluded. Of the remaining 128 patients, 50 patients (39%) met LDL-C goal and were discharged from the program. Of the 50 patients who met goal, 19 (88%) achieved LDL-C goal with HIS +/- ezetimibe, only 5 required evolocumab and 1 required bempedoic acid. A total of 39 patients (30%) were either lost to follow-up or transferred care to another facility, and 38 patients (30%) remain enrolled in our protocol. Discussion: In a safety-net system serving the urban poor, a virtual care model effectively improved LDL-C in high-risk patients with nearly half of 128 enrolled patients achieving LDL-C ≤55 - most within 12 weeks. Notably 88% reached this goal using only stantins and ezetimibe, highlighting the value of adherence education in delivering cost-effective care. Our experience supports using RNs, PharmDs, and titration protocols to provide high-quality care for underserved populations.

Background: In the SCORED trial that included 10,584 participants with type 2 diabetes (T2D) and chronic kidney disease (CKD), sotagliflozin significantly reduced the incidence of major adverse cardiovascular events (MACE) demonstrating a significantly lower total 3-point MACE with a hazard ratio of 0.77. To further evaluate the cardiovascular effects of sotagliflozin, prespecified MACE-focused meta-analyses were performed using data from 9 additional Phase 3 trials conducted in persons with T2D. Methods: These patient level meta-analyses pooled data from 9 Phase 3 trials assessing glycemic control and other cardiometabolic parameters in a total of 5,100 participants with T2D. Of these, 2,904 participants were treated with sotagliflozin (200 or 400 mg QD), while 2,196 were in an All-Comparators group (pooling placebo, empagliflozin, and glimepiride). The median duration of follow up was 1 year in both groups. Both sotagliflozin doses were pooled for the MACE analyses. Time to first event for 4-point MACE [CV death, nonfatal myocardial infarction (MI), nonfatal stroke, and hospitalization for unstable angina) was the prespecified primary analysis. Secondary outcomes included 3-point MACE (omitting unstable angina) and analyses of each MACE component outcome. Time-to-event analyses were conducted using Cox proportional hazards models for the first occurrence of any adjudication-confirmed event. Results: There were 98 4-point MACE events and 96 3-point MACE events across the dataset. The event rate of 4-point MACE was 1.6 events per 100 patient-years (PY) in the sotagliflozin group compared with 2.2 events per 100 PY in the All-Comparators group. Sotagliflozin was associated with a 39% relative risk reduction in 4-point MACE (hazard ratio (HR) [95% CI]: 0.61 [0.41, 0.90]; p = 0.013). All four component outcomes positively contributed to the overall treatment effect (Figure). For 3-point MACE, sotagliflozin demonstrated a 37% relative risk reduction compared with All-Comparators (HR [95% CI]: 0.63 {0.42, 0.94]). Similar results were observed in analyses using only placebo as the comparator. Conclusion: Two independent data sources (9 cardiometabolic Phase 3 studies and the SCORED CV outcomes trial), including approximately 15,000 participants, support a reduction in MACE with sotagliflozin in a broad group of persons with T2D, and reinforce the role of sotagliflozin in reducing atherosclerotic cardiovascular risk.

Background: Icosapent ethyl, a purified eicosapentaenoic acid, has demonstrated CV risk reduction. Emerging evidence suggests that the antiplatelet effects of icosapent ethyl may contribute to this CV benefit. Hypothesis: Clinical outcomes with icosapent ethyl among patients with or without aspirin use have not been reported. This is an important evidence gap given the potential overlapping antiplatelet effects. Methods: REDUCE-IT was a double-blind clinical trial randomizing patients to icosapent ethyl (2g twice per day) or placebo. Statin-treated patients with elevated triglycerides (135-499 mg/dL), controlled LDL-C (41-100 mg/dL), and increased CV risk were included. In this analysis, patients with or without aspirin use were included and evaluated by randomization group. Patients were assessed overall as well as among the primary and secondary (prior CV disease) prevention cohort. The primary composite endpoint included events of nonfatal MI, nonfatal stroke, coronary revascularization, hospitalization for unstable angina, or CV death. The key secondary endpoint included events of nonfatal MI, nonfatal stroke, or CV death. Results: Among 8179 patients, 6179 (75.5%) were with aspirin use. Icosapent ethyl significantly reduced the primary endpoint events compared with placebo (67.3 vs 99.1 events/1000 patient-years [p-y]; Rate Ratio (RR): 0.69 [95% CI: 0.61, 0.77]; P<0.0001), with consistent effects among those with aspirin use (70.2 vs 109.4 events/1000 p-y; RR: 0.64 [95% CI: 0.56, 0.74]) or without (57.9 vs 67.2 events/1000 p-y; RR: 0.85 [95% CI: 0.65, 1.11]) (Pinteraction[int]=0.15) ( Figure ). Similar benefits were observed with icosapent ethyl for key secondary composite endpoint events (Pint=0.20). Findings were numerically similar in the primary prevention cohort, though not statistically significant. Among 5785 patients in the secondary prevention cohort, icosapent ethyl similarly reduced primary endpoint events (78.8 vs 120.8 events/1000 p-y; RR: 0.65 [95% CI: 0.57, 0.74]; P<0.0001), with consistency among those with aspirin use (75.9 vs 123.7 events/1000 p-y; RR: 0.61 [95% CI: 0.53, 0.70]) or without (95.6 vs 104.8 events/1000 p-y; RR: 0.89 [95% CI: 0.64, 1.23]) (Pint=0.12). Conclusion: Among patients with elevated triglycerides, controlled LDL, and high CV risk, icosapent ethyl reduced CV outcomes irrespective of aspirin use. These findings suggest icosapent ethyl has CV benefit incremental to concomitant background therapy with statins plus aspirin.

Background: Smoking is related to systemic inflammation and is a major modifiable risk factor for coronary artery disease (CAD) and adverse cardiovascular (CV) outcomes. However, these associations have not been studied in low-to-intermediate risk symptomatic patients with suspected CAD. Aim: To examine the role of smoking in promoting inflammation, and to assess its possible contribution to unfavorable CV test outcomes and adverse events in outpatients with stable chest pain. Methods: Patients from the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) with known smoking status and analyzable diagnostic testing were included. Noninvasive testing (coronary CT angiography or functional stress test) was used to evaluate for presence of a coronary stenosis ≥70% or inducible ischemia, respectively. Inflammatory biomarkers hsCRP, IL-6, and MMP-9 were compared between ever-smokers and nonsmokers. Multivariable logistic and Cox regressions were used to evaluate the associations of smoking with positive noninvasive (NI) testing and adverse events, adjusting for demographics and traditional CV risk factors. The primary end point was death, myocardial infarction, or unstable angina hospitalizations over a median follow-up of 24.4 months. Results: A total of 9,100 patients (mean age 61±8 years; 52.6% female, 51.2% ever-smokers) were analyzed. Compared to non-smokers, smokers were slightly younger (60±8 vs 61±8 years, p<0.001), more often male (53% vs 42%, p<0.001), with higher median ASCVD risk (14% [IQR: 9-23] vs 8% [IQR: 4-15], p<0.001) and higher event rates (3.8% vs. 2.0%, p<0.001). Inflammatory biomarkers were higher among smokers (hsCRP +9%, p=0.008, IL-6 +12%, p<0.001, MMP-9 +22%, p<0.001). Smoking was independently related to positive NI test results (aOR 1.24, 95% CI 1.09-1.42) and events (aHR 1.75, 95% CI 1.35-2.26). Smoking was a strong event predictor in patients without significant test abnormality (aHR 2.05, 95% CI 1.49-2.84), but not in those with positive test results (aHR 1.32, 95% CI 0.87-2.02). Conclusions: Among patients with stable chest pain, smoking was linked to greater inflammation, more frequent abnormal NI test results, and higher CV risk. This was particularly true in those with negative noninvasive testing, highlighting the need for early smoking cessation, even in patients with negative NI testing.

For suspected acute myocardial infarction (AMI) and unstable angina patients, prehospital aspirin (ASA) administration has been the standard of care by Emergency Medical Services (EMS) field providers. Recently, Emergency Medical Dispatchers (EMDs), using Medical Priority Dispatch System (MPDS), provide telephone instructions to qualifying suspected AMI patients to take ASA, prior to EMS field provider arrival. No formal studies exist that measure time saved from earlier Dispatcher-Directed Aspirin Administration (DDAA). The primary objectives of the study were: (1) to determine the amount of time saved, if any, using DDAA; and (2) to describe the frequency of DDAA and Field Provider-Directed Aspirin Administration (FPAA). The retrospective study analyzed EMD and EMS data collected during a six-month period at three dispatch services and three EMS agencies in the United States. The frequency and mean (plus 95% confidence interval [CI]) time of DDAA and FPAA were calculated. Reasons why patients who qualified to take ASA per dispatch protocol but did not take it were also assessed. A total of 108,459 EMS cases were analyzed; EMD/EMS delivered ASA to 4.0% (n = 4,113) of these patients. The most frequent primary impressions were: cardiac chest pain (angina), cardiovascular (CV)-chest pain (presumed cardiac), ST-segment elevation myocardial infarction (STEMI), and CV-chest pain - acute coronary syndrome (ACS; 50.0%). Overall, DDAA saved 13 minutes mean time (95% CI, 11.4-14.6; P < .001) (median: 12.3 minutes) from the case creation time. It was found that DDAA provides measurable time savings in ASA delivery to patients. Further studies will need to assess if the reduction of ASA delivery time by EMDs has the potential to improve overall care and survival for patients. The study identified beneficial new knowledge for possible future enhancements to medical dispatch protocols and for EMS providers.

BACKGROUND: Patients with prior ischemic stroke are at high risk for recurrent stroke and other major adverse cardiovascular events (MACE). The incremental benefit of achieving very low LDL-C in such patients remains undefined. HYPOTHESIS: In stable ASCVD patients with prior ischemic stroke, achieving very low LDL-C is associated with a lower risk of MACE without an excess in hemorrhagic stroke. METHODS: Participants with history of ischemic stroke were selected for the current analysis from the FOURIER trial, a randomized placebo-controlled trial studying evolocumab in patients with stable ASCVD (median follow-up 2.2 years) and the open-label extension study (median follow-up extended by 5 years) at participating sites. Using a modified-Poisson regression models, we examined the relationship between achieved LDL-C with the incidences of the composite primary endpoint (CV death, myocardial infarction, stroke, and hospitalization for unstable angina or coronary revascularization) and stroke-related endpoints (all type, ischemic, and hemorrhagic) adjusted for clinical covariates. RESULTS: A total of 5,291 patients with history of ischemic stroke, occurring at a median of 3.3 years prior to enrollment, were followed for a total of 14,418 patient years (max follow-up 8.6 years). Median achieved LDL-C with evolocumab was 31.5 mg/dl (IQR 21.5-47.0 mg/dL). Patients with lower achieved LDL-C (modeled continuously) exhibited significantly lower annualized incidence rates (IR) of the primary composite endpoint (P trend &lt;0.001, panel A). When LDL-C was modeled categorically, the lowest IRs for the primary endpoint and for stroke were observed in patients whose achieved LDL-C was below 40 mg/dl, whereas there was no difference in hemorrhagic stroke (panel B). CONCLUSION: In patients with prior ischemic stroke, achieving very low LDL-C (&lt;40 mg/dl) was associated with a lower long-term risk of MACE, including recurrent stroke, without an increase in hemorrhagic stroke. These findings suggest to lower LDL-C target in patients with prior ischemic stroke further than current guidelines.

Background: Peripheral arterial disease (PAD) is a leading cause of atherosclerotic disease mortality, with prevalence estimated to be 11% in the US. Studies have found that major adverse cardiovascular events (MACE) are increased in PAD patients, particularly in the presence of atherosclerotic cardiac diseases. However, whether cardiac arrhythmic diseases such as atrial fibrillation (AF) also increase this risk is unknown. We sought to determine, in a PAD population, whether the presence of AF, compared to its absence, increases the risk of MACE (all-cause death, myocardial infarction, hospitalization for heart failure [HF], stroke, and hospitalization for unstable angina). Methods: The Intermountain Health data from Jan 2006 to Dec 2021 was used to identify adult patients with a first-time PAD diagnosis and having a second visit within 18-months (n=7613; 98.8% with symptomatic PAD). Outcomes were examined using multivariable Cox proportional hazard regressions. Results: A total of 1723 (22.6%) PAD patients had prior AF. The table shows differences in demographic and clinical PAD patients with and without AF. Approximately 25% of PAD patients with AF had a MACE within 1-year and 46% within 3-years compared to 12% and 25%, respectively, for those without AF. Death and HF hospitalization were the two greatest contributors to MACE. After adjustment for baseline differences and guideline-directed medical therapy (GDMT), those with AF were 21% more likely to have MACE and were 1.4-1.5 times more likely to be hospitalized for HF compared to those without AF. Conclusions: AF was prevalent, found in a quarter of patients with PAD. The rate of MACE events was double when AF was present. After adjustment for other factors, AF patients had a 21% increased risk of MACE. HF hospitalization was a major contributor to this risk. AF should be assessed for in PAD patients and aggressive preventative treatment for MACE implemented.

Introduction: Small, dense low-density lipoprotein (sdLDL) particles are believed to be a highly atherogenic subfraction of LDL due to prolonged residence time in circulation, greater adherence to and penetration of vascular endothelium, and higher susceptibility to oxidation. Automated biochemical measurement of sdLDL cholesterol (sdLDL-C) has demonstrated good fidelity to gold standard gradient ultracentrifugation or NMR spectroscopy. We evaluated the relationship of sdLDL-C and conventional LDL-C to risk of major adverse cardiovascular events (MACE) and treatment benefit of alirocumab in patients with recent acute coronary syndrome (ACS) receiving high-intensity or maximum-tolerated statin treatment. Methods: The analysis included 11,837 participants in the ODYSSEY OUTCOMES trial (NCT01663402) with recent ACS and LDL-C ≥70 mg/dL despite optimized statin treatment. At baseline prior to randomized treatment with the PCSK9 monoclonal antibody alirocumab (N=5917) or placebo (N=5920), sdLDL-C was measured using the Denka (Nigata, Japan) method on a Roche cobas autoanalyzer and LDL-C was calculated with the Friedewald formula. In the placebo group, natural cubic splines depicted the relationships of sdLDL-C, LDL-C, and their ratio to the risk of MACE (CV death, non-fatal myocardial infarction or ischemic stroke, hospitalization for unstable angina, and ischemia-driven coronary revascularization) and treatment hazard ratio (HR: alirocumab/placebo) as a function of sdLDL-C and LDL-C. Results: In Figure Panel A, the risk of MACE in the placebo group increased with concentrations of baseline sdLDL-C and LDL-C, with nearly superimposable splines. In Panel B, the relationship of sdLDL-C/LDL-C to risk of MACE in the placebo group (adjusted for LDL-C) showed no evidence of greater risk with greater sdLDL-C fraction. Overall, alirocumab reduced the risk of MACE (HR 0.87, 95% CI 0.79, 0.95). Panel C shows that the treatment HR did not vary significantly across the range of either LDL-C or sdLDL-C. Conclusion: In patients with recent ACS and LDL-C ≥70 mg/dL on optimized statin treatment, sdLDL-C and conventional LDL-C similarly predict risk of MACE and benefit of treatment with alirocumab. Measurement of sdLDL-C does not appear to provide additional prognostic or predictive information.

Background: While the burden and morphological features of coronary atherosclerosis are both important drivers of major adverse cardiovascular events (MACE), there remains uncertainty about which plaque type is more likely to predispose to MACE i.e. noncalcified plaque (NCP) or calcified plaque (CP). Research question: Does NCP:CP ratio or NCP volume influence MACE in patients from the CONFIRM2 registry, an international, observational cohort study? Methods: Symptomatic patients without prior MI/revascularization referred to coronary CTA for clinical indications were included. CP and NCP volumes were determined using artificial intelligence-facilitated coronary CT (AI-QCT). The primary endpoint (MACE) was a composite of all-cause death, myocardial infarction, stroke, heart failure, late revascularization, and hospitalization for unstable angina. Results: Of the 3,551 patients (median age 59 years; 49.5% women), data were available for 3,301. A total of 250 patients with no identifiable plaque were excluded from the analysis. MACE occurred in 4.7% of patients (median f/u 51 months). Hypertension, hyperlipidemia, and smoking were present in 54.3%, 48.1%, and 14%. Statin use in 67.3%, CACS = 0 in 41.7%. 91% had NCP &lt;250 mm 3 , 8.4% 250-750 mm 3 and 0.7% &gt;750 mm 3 . MACE rates for tertiles of NCP:CP ratio were statistically significant (Panel A; p=0.0003): 1 st tertile (Mean NCP:CP ratio of 46%; n=1100 patients; median NCP volume = 85.6 mm 3 ; MACE rate of 5.6%); 2 nd tertile (NCP:CP 81%; n=1101; NCPvol. = 67.6 mm 3 ; 6.6%); 3 rd tertile (NCP:CP 99%; n=1100; NCPvol. = 22.3 mm 3 ; 2.9%). However, in a multivariable Cox proportional hazards model adjusted for sex and age, when adjusting also for NCP volume, the NCP:CP tertile ratio did not remain a significant predictor of MACE, p=0.115 (Model#3, Panel B). Only 9 patients had predominant CP (NCP:CP ratio&lt;10%) while the majority had predominant NCP. Conclusions: The main driver of incident MACE was the noncalcified plaque volume (NCP) rather than the NCP:CP ratio. More data with a larger cohort of patients with relatively more CP is needed to evaluate the role of individual features of partially calcified plaques such as spotty calcification to assess if they are better predictors of MACE or whether NCP volume alone is sufficient.