Rate Of Cardiovascular Events Research Articles

A Repurposing Programme Evaluating Transdermal Oestradiol Patches for the Treatment of Prostate Cancer Within the PATCH and STAMPEDE Trials: Current Results and Adapting Trial Design

AimsAndrogen deprivation therapy (ADT), usually achieved with luteinising hormone releasing hormone analogues (LHRHa), is central to prostate cancer management. LHRHa reduce both testosterone and oestrogen and are associated with significant long-term toxicity. Previous use of oral oestrogens as ADT was curtailed because of cardiovascular toxicity. Transdermal oestrogen (tE2) patches are a potential alternative ADT, supressing testosterone without the associated oestrogen-depletion toxicities (osteoporosis, hot flushes, metabolic abnormalities) and avoiding cardiovascular toxicity, and we here describe their evaluation in men with prostate cancer. Materials and methodsThe PATCH (NCT00303784) adaptive trials programme (incorporating recruitment through the STAMPEDE [NCT00268476] platform) is evaluating the safety and efficacy of tE2 patches as ADT for men with prostate cancer. An initial randomised (LHRHa versus tE2) phase II study (n = 251) with cardiovascular toxicity as the primary outcome measure has expanded into a phase III evaluation. Those with locally advanced (M0) or metastatic (M1) prostate cancer are eligible. To reflect changes in both management and prognosis, the PATCH programme is now evaluating these cohorts separately. ResultsRecruitment is complete, with 1362 and 1128 in the M0 and M1 cohorts, respectively. Rates of androgen suppression with tE2 were equivalent to LHRHa, with improved metabolic parameters, quality of life and bone health indices (mean absolute change in lumbar spine bone mineral density of –3.0% for LHRHa and +7.9% for tE2 with an estimated difference between arms of 9.3% (95% confidence interval 5.3–13.4). Importantly, rates of cardiovascular events were not significantly different between the two arms and the time to first cardiovascular event did not differ between treatment groups (hazard ratio 1.11, 95% confidence interval 0.80–1.53; P = 0.54). Oncological outcomes are awaited. FutureEfficacy results for the M0 cohort (primary outcome measure metastases-free survival) are expected in the final quarter of 2023. For M1 patients (primary outcome measure – overall survival), analysis using restricted mean survival time is being explored. Allied translational work on longitudinal samples is underway.

Abstract 12827: Daylight Savings Time Practice and the Rate of Adverse Cardiovascular Events in the United States: A Probabilistic Assessment in a Large Nationwide Study

Introduction: Previous studies have shown inconsistent changes in the rates of adverse cardiovascular events after daylight savings time (DST) transitions. In this large-scale, U.S.-based nationwide study, we sought to investigate the association of DST transitions with the rates of adverse cardiovascular events. Methods: The study cohort included 36,116,951 unique individuals from de-identified administrative claims data of the OptumLabs Data Warehouse®. There were 74,722 total adverse cardiovascular events during the week of DST transition and the control weeks (two weeks prior and after) in spring and autumn of 2015-2019. We used Bayesian hierarchical Poisson regression models to estimate the event rate ratios (ERR) representing the ratio of composite adverse cardiovascular event rates (acute myocardial infarction, stroke, cardiogenic shock, cardiac arrest, and sudden death) between DST transition weeks and control weeks. Results: Our results showed an average increase of 3% [95% uncertainty interval; -3% to 10%] and 4% [-2% to 12%] in the rate of adverse cardiovascular events during Monday and Friday of the spring DST transition week, respectively. The probability of spring DST transition being associated with a moderate-to-large increase in the event rates (ERR>1.10) was estimated to be <6% for Monday and Friday, and <1% for the remaining days. During autumn DST transition, the probability of any decrease in adverse cardiovascular event rates was estimated to be <46% and a moderate-to-large decrease in the event rates to be <4% across all days of the week. Conclusions: Spring DST transition week had a suggestive association with a minor increase in adverse cardiovascular event rates on Monday and Friday. The probability of this association to be of clinically meaningful magnitude was estimated to be very low. We did not observe any evidence suggestive of a change in adverse cardiovascular event rates immediately following autumn DST transition. Taken together, our findings, based on a large, diverse cohort from across the United States, suggest that DST transitions are unlikely to significantly impact the rate of cardiovascular events.

Abstract 16330: Aspirin Dosing by Body Mass Index: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness

Introduction: Elevated body mass index (BMI) is a risk factor for cardiovascular (CV) events. It remains unclear if the effectiveness and safety of aspirin dose (81mg vs 325mg) is modified by baseline BMI. Research Question: To determine differences in CV event rates and major bleeding between aspirin dose and BMI in patients with coronary artery disease (CAD). Methods: Participants from the ADAPTABLE trial were stratified by BMI categories defined as normal weight (BMI <25 kg/m 2 ), overweight (BMI ≥25 to <30 kg/m 2 ), and obese (≥30 kg/m 2 ). The primary outcome was a composite of all cause death, hospitalization for myocardial infarction (MI), or hospitalization for stroke, assessed in a time-to-event analysis. The event rate represented events per 100 patient years of follow up. The primary safety outcome was hospitalization for major bleeding with blood product transfusion. Cox proportional hazards models were used to evaluate the primary outcome by aspirin dose and BMI category. Results: A total of 12,715 participants (n=1,822 normal weight, n=4,485 overweight, and n=6,408 obese) had data available for BMI and analysis. The event rate for the primary outcome in those at normal weight was similar across aspirin dose (5.38 for 81mg vs 5.43 for 325 mg, adjusted HR 1.06 [95% CI 0.81-1.39]). This relationship was also seen in both overweight (3.53 for 81mg vs. 3.27 for 325mg, 1.10 [0.88-1.36]), and obese (3.50 for 81mg vs 3.45 for 325 mg, 1.04 [0.87-1.25]) BMI (figure). There was no difference in the primary safety outcome by aspirin dose [normal weight 0.92 (0.41-2.08), overweight 1.65 (0.77-3.55), obese 1.17 (0.62-2.20)]. The overall event rate for the primary outcome was lower in overweight (0.68 [0.57-0.81]) and obese (0.65 [0.55-0.78]) groups compared to normal weight. Conclusion: In ADAPTABLE, no difference was seen in CV event rates and major bleeding across BMI by aspirin dose. However, the overall event rates were lower in elevated BMI groups suggesting an obesity paradox.

Abstract 12461: Early Use of Tocilizumab Following Cytokine Release Syndrome During CAR-T Therapy for Multiple Myeloma May Be Associated With Fewer Short and Long Term Adverse Cardiovascular Events

Background: Chimeric antigen receptor-T cell (CAR-T) therapies have recently been approved for multiple myeloma (MM). Patients with MM have a higher burden of cardiovascular (CV) disease compared to other hematologic malignancies due to higher prevalence of CV risk factors, potentially cardiotoxic therapies and older age. Retrospective studies of CAR-T therapy in other hematologic malignancies demonstrated a 20-30% CV event rate following higher grades of cytokine release syndrome (CRS). Early use of the interleukin-6 antagonist, tocilizumab, to reverse CRS has been reported to lower rates of major adverse CV events (MACE). Hypothesis: At our institution, tocilizumab is usually administered as early as grade 1 CRS. We hypothesized that our patients would have lower rates of CV toxicity compared to studies where tocilizumab was administered late or not at all. Methods: We conducted a retrospective chart review of adult patients undergoing CAR-T therapy for MM between 2017 and 2023. The primary outcome was MACE (composite of myocardial injury, new heart failure, stroke, new arrhythmias and CV death) over a median period of 12 months. A Kaplan-Meier curve was used to analyze probability of developing MACE. Results: Of the 145 patients studied, the demographics included median age of 61, male (61%), prior anthracycline use (25%), and carfilzomib use (47%) within 1 year. CV co-morbidities included 57% with hypertension, 35% hyperlipidemia, 23% diabetes mellitus type 2, 17% coronary artery disease, and 14% left ventricular dysfunction. CRS occurred in 121 (83%) patients, of which 99 had grade 1 (82%), 19 (16%) had grade 2 and 3 (2%) had grade 3. Of those with CRS, 108 (89%) received tocilizumab, on average within the first day of CRS. Within 1 year of CAR-T therapy, 14 patients (10%) experienced MACE. The Kaplan-Meier estimates for incidence of MACE were 6% at 30 days, 8% at 6 months and 11% at 12 months. Conclusion: The occurrence of MACE in MM patients following CAR-T therapy with early administration of tocilizumab was lower compared to previously published retrospective studies of CAR-T therapy for other hematologic malignancies despite high CV burden. Further prospective studies are needed to validate these findings.

Abstract 13233: Disparities in Speed of Diagnosis of Hypertrophic Cardiomyopathy in the United States

Background: Hypertrophic cardiomyopathy (HCM) is a cardiac disease that can be genetic in cause. Early diagnosis, risk stratification, and pharmacological management can reduce the disease burden, yet several studies have highlighted disparities in early diagnosis by gender and race. Goals: This study compares age, severity at diagnosis, and time-to-diagnosis, by gender, race, and county-level poverty rate in a nationally representative population of over 65-year-olds. Methods: We used Medicare claims data from 2016-2020 to construct a sample who had at least two HCM claims and continuous enrollment for at least 2 years prior to their first HCM claim. We measured age and severity of heart disease at diagnosis, as well as time from the first observed indication of heart disease to HCM diagnosis. Results: We identified 48,857 patients with an HCM diagnosis in the study period, of which 60% were women and 81% were Non-Hispanic White. Comparing relative rates, Black and Hispanic patients at the time of HCM diagnosis had a 16% higher prior rate of heart failure (HF), and a 11% higher rate of prior major adverse cardiovascular events (MACE). In addition, in Black HCM patients, the share of atrial and non-atrial arrhythmias that were clinically diagnosed before HCM diagnosis was 28% lower than among White patients (p<0.001). Importantly our multi-attribute approach highlighted the composite roles of race and county-level poverty: at the time of HCM diagnosis, Black men in the poorest quartile of counties had a 26% higher rate of HF, 22% higher rate of MACE and a 53% lower rate of clinically diagnosed arrhythmia (all p<0.001) than White men in the wealthiest quartile of counties. Additionally, the median time from the first indication of heart disease until the diagnosis of HCM in Black and Hispanic patients from the poorest quartile of counties was 347 days longer than for Non-Hispanic White patients from the wealthiest quartile of counties (p<0.001). Conclusions: This study shows evidence of disparities in diagnosis of older patients with HCM in the United States, particularly in terms of race and county-level poverty. New approaches are needed to address these disparities and improve access to care for patients in underserved and vulnerable communities.

Abstract 16725: Cost-Effectiveness Analysis of Intensive Treatment of Systolic Hypertension: Results From Sprint Patient-Level Data

Background: The Systolic Blood Pressure Intervention Trial (SPRINT) showed that treating patients at high risk for cardiovascular events but without diabetes or a history of stroke to a systolic blood pressure (SBP) target goal of <120 mm Hg (Intensive Care, IC), compared with <140 mm Hg (Standard Care, SC), resulted in lower rates of fatal and nonfatal major cardiovascular events and death. We examined the cost-effectiveness of IC vs SC over a life-time horizon, based on patient-level data, from a health-sector perspective. Methods: Patient-level data from SPRINT were used to calculate and estimate cost, effectiveness, quality adjusted life years (QALY), and the incremental cost-effectiveness ratio (ICER). For participants who died during the trial, life years and QALYs were estimated from in-trial analysis; for who survived to the end of the trial, pooled, harmonized data from six epidemiologic cohorts included in the National Heart, Lung, and Blood Institute Pooled Cohorts Study was used to estimate risk of lifetime primary fatal and non-fatal events and calculate life-years. Published utilities estimates were used to calculate QALYs. For participants without SPRINT lifetime primary event estimates, we applied multiple imputation method via machine learning to impute the life-years and QALYs. The ICER was expressed as cost per QALY gained. Results: IC participants were estimated to gain an average of 0.51 QALY (95% CI: 0.21, 0.81) relative to SC participants. Estimated total lifetime costs were $17,449 higher with IC (95% CI: $10,697, $24,201) than SC. The ICER for IC vs SC was $34,214 per QALY gained, with 68.5% of bootstrap-derived estimates <$50,000/QALY. The results from multiple imputation chained equations for addressing missing data showed that IC is cost effectiveness at $50,000/QALY. Across various scenario analyses, we consistently found a more than 60% probability that IC is cost-effective over a lifetime when the willingness-to-pay value exceeds $100,000 per QALY. Conclusions: Based on participant-level trial and epidemiologic cohort data, IC is cost-effective, with significant clinical benefit at acceptable higher lifetime cost. Recommending intensive SBP targets in patients at high CVD risk is an effective, high-value therapy.

Abstract 13289: Medicaid Patients in Cardiac Rehabilitation: Underrepresented, High Risk, High Need

Purpose: Patients with lower-socioeconomic status (SES) have higher rates of cardiovascular (CV) events and therefore, have the most to gain from cardiac rehabilitation (CR). Unfortunately, those with lower-SES are much less likely to engage in CR which has made characterization of this population quite difficult. Our CR program specifically increased recruitment of lower-SES patients, allowing for careful comparison of medical, psychosocial, and behavioral risk factors between lower and higher-SES patients eligible for secondary prevention. Methods: Demographic and clinical characteristics were prospectively gathered on consecutive individuals entering Phase 2 CR from 1/2014-12/2022. Patients were classified as lower-SES if they had Medicaid insurance. Statistical methods included chi-square and non-paired t-tests. A p value of <0.01 was used to determine significance. Results: The entire cohort consisted of 3131 individuals. Compared to higher-SES patients, lower-SES individuals (n=405, 13%) were a decade younger, almost 6 times more likely to be current smokers, nearly 3 times more likely to have elevated depressive symptoms, and had significantly higher body mass index, waist circumference, and hemoglobin A1c, with more abnormal lipid profiles (all p<0.001). Despite being a decade younger, lower-SES patients had lower measures of peak VO 2 and self-reported lower levels of physical function (both p<0.001). Conclusion: Lower-SES patients have a remarkably prominent high-risk CV profile resulting in a substantially higher risk for a recurrent coronary event than higher-SES patients. Accordingly, strong efforts must be placed to engage this high-risk population in CR. It is imperative for CR programs to ensure that they are appropriately equipped to intervene on risk factors such as low fitness, depression, and smoking.

Abstract 15254: Temporal Assessment of Clinical Outcomes in Patients With ST-Elevation Myocardial Infarction and Non-ST-Elevation Myocardial Infarction

Background: Limited data exist regarding the temporal progression of outcomes in patients with ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI). Research Questions: Are there any significant differences in the occurrence of cardiovascular events over time between patients with STEMI and NSTEMI in the modern era of percutaneous coronary intervention? Aims: We aimed to compare the incidence rates of major cardiovascular events over time between patients with STEMI and NSTEMI using the Korea Acute Myocardial Infarction Registry-National Institutes of Health database. Methods: We analysed the data of 13,056 patients diagnosed with STEMI or NSTEMI between 2011 and 2015 (median age, 65 years [interquartile range {IQR}, 54-74]). We calculated yearly, monthly, weekly, and daily time-point event rates after admission, considering the number of events during the specific periods divided by the number of event-free patients just before those periods. The primary outcome measure was all-cause mortality. Results: During the 3-year follow-up (median, 1095 [IQR, 1044-1095] days), 12.4% of patients (1589/12,836) died from any cause. Patients with STEMI had a significantly higher mortality rate in the first week of admission than that of patients with NSTEMI (4.54% [283/6235] vs 1.76% [120/6823], P < 0.001), but this difference was not observed in the second week (0.59% [35/5952] vs 0.67% [45/6703], P = 0.635). Subsequently, higher mortality rates were observed in patients with NSTEMI than in those with STEMI for all time points. Daily outcome analysis revealed a gradual decrease in the difference in mortality rates in patients with STEMI versus NSTEMI from the first to the ninth day, followed by an inversion on the tenth day: STEMI: 2.39% (149/6235) vs NSTEMI: 0.59% (40/6823) on the first day; 0.13% (8/5942) vs 0.10% (7/6694) on the ninth day; and 0.03% (2/5934) vs 0.13% (9/6687) on the tenth day. Conclusions: This analysis of temporal outcomes from a nationwide Korean registry demonstrated that patients with STEMI initially had higher mortality than patients with NSTEMI, but this difference gradually decreased and subsequently inverted during the second week, specifically after the ninth day.

Abstract 16478: Effect of Sodium Glucose Cotransporter 2 Inhibitors on Major Adverse Cardiovascular Events in Cancer Patients Treated With Immune Checkpoint Inhibitors

Introduction: The cardiac adverse events (irAEs) secondary to immune checkpoint inhibitors (ICI) are associated with a high rate of morbidity and mortality. There are no data on the effect of concomitant sodium glucose cotransporter 2 inhibitors (SGLT2i) on the rates of major adverse cardiovascular events (MACE) among patients treated with an ICI. Hypothesis: Whether, the use of SGLT2i among ICI-treated patients may reduce MACE. Methods: This was a population-based cohort study between 2014 and 2023 including cancer patients treated with ICI aged over 18 years across the United States. SGLT2i use while on an ICI was defined as the initiation of SGLT2i therapy after the first record of ICI treatment among patients currently undergoing ICI therapy. The risk of incident MACE in patients on an ICI who were also prescribed an SGLT2i therapy was compared with 1:1 propensity score-matched patients on ICI who were never prescribed an SGLT2i. Hazard ratios (HRs) and 95% confidence intervals (CIs) for MACE were estimated using Cox proportional hazards regression. MACE was defined as a composite of myocardial infarction, heart failure (HF), and ischemic stroke. Results: There were 216 cancer patients undergoing ICI therapy who were newly treated with SGLT2i. These were compared to 216 controls. Over a mean follow-up period of six years, there were 107 MACE events. There were 44 events (20.4%) among those on an SGLT2i and 63 among controls (HR=0.61, 95% CI: 0.41-0.90; log-rank test p=0.011). Of the individual components of MACE, rates of HF were lower where there were 22 HF events (20.4%) among those on an SGLT2i and 37 among controls (HR=0.51, 95% CI: 0.30-0.86; log-rank test p=0.010). There were no differences in the rates of stroke (HR: 0.55, 95% CI: 0.29-1.04) and myocardial infarction (HR: 0.97, 95% CI: 0.38-2.43). Conclusions: In an observational, retrospective study, SGLT2i therapy was associated with a reduced risk for cardiac events compared to those who never treated with SGLT2i. These findings underscore the potential therapeutic value of SGLT2i in the prevention of MACE in cancer patients receiving immunotherapy and warrant further research.

Abstract 13238: Persistence of High Rates of Major Adverse Cardiovascular Events at 1 Year Post-Myocardial Infarction in Patients With Multivessel Disease: A Systematic Literature Review

Background: Multivessel disease (MVD) heightens the risk of major adverse cardiovascular events (MACE) in post-myocardial infarction (MI) patients. The risk of MACE is elevated in the early period after an MI, a period unaddressed by current secondary preventative therapies. Research aims: To better understand the impact of MVD on clinical and patient-centered outcomes post-MI in the current treatment landscape. Methods: A systematic literature review was conducted to identify relevant articles published between March 2019 and July 2022 from MEDLINE, Embase, Cochrane databases, and cardiovascular (CV) and health outcomes conferences. Articles reporting on pre-specified clinical or patient-centered outcomes in post-MI patients with MVD at timepoints within 1 year were included. Studies that included patients with cardiogenic shock were excluded from this review. Results: Clinical and patient-centered outcomes were reported in five randomized-controlled trials (RCTs) and 24 observational studies across 30 articles; and one RCT across two articles, respectively. Although the definition of MVD varied, it was generally characterized by ≥50% stenosis in ≥1 noninfarct-related coronary artery. Rates of individual MACE endpoints (all-cause mortality, CV mortality, MI, stroke) were variable (Table), likely due to heterogeneity in study populations and interventions. Nevertheless, a key trend was identified; MACE rates at 1-year post-MI were typically not substantially higher than those at earlier timepoints. EQ-5D scores, reflective of quality of life (QoL), increased following treatment; however, increases were marginal, indicating minimal improvements in QoL. Conclusions: MVD is associated with high rates of MACE early after MI that persist at 1 year. Novel therapies that address CV risk in the early period post-MI may support improved CV outcomes among patients with MVD. Further data on patient-centered outcomes are warranted.

Osteoprotegerin is associated with subclinical left ventricular systolic dysfunction in non-dipper hypertensive patients: a 2D speckle tracking echocardiographic study.

Past studies have shown that non-dipper hypertensive patients have more frequent subclinical left ventricular (LV) systolic dysfunction compared to dippers. Many different parameters have been examined to predict subclinical LV dysfunction. The role of osteoprotegerin (OPG) in the pathogenesis of heart failure and LV systolic dysfunction through different mechanisms had well described. In the present study, we hypothesized that increased OPG levels could predict subclinical LV systolic dysfunction in non-dipper hypertensive patients. Hypertensive patients were divided into two groups according to the results of ambulatory blood pressure (BP) monitoring. Non-dipper patients were subsequently divided into two further groups (normal LV function and impaired LV function) according to LV global longitudinal strain (GLS). A total of 103 hypertensive patients (51 dippers, 52 non-dippers) were included in the study. In the non-dipper group, LV GLS was normal in 21 patients and impaired in 31 patients. Based on the results of the multivariate logistic regression test, it was determined that OPG levels (OR: 2.413, 95% CI: 1.284-4.535, P = 0.006) and LVMI (OR: 1.086, 95% CI: 1.013-1.165, P = 0.021) were independently associated with impaired GLS. Higher OPG values were associated with subclinical LV systolic dysfunction in non-dipper hypertensive patients. It could be used for the early diagnosis of subclinical LV systolic dysfunction, which would allow for strategies to be designed to reduce the cardiovascular event rate in this patient population.

Short duration of dual antiplatelet therapy following complex percutaneous coronary intervention: A systematic review and meta-analysis

Introduction and aimThe optimal composition and duration of antiplatelet therapy after complex percutaneous coronary intervention (PCI) remains unclear. We conducted a meta-analysis to compare 1–3 months of dual antiplatelet therapy (DAPT) followed by monotherapy vs. 12 months of DAPT. MethodMEDLINE/PubMed, EMBASE, and Cochrane Central Register of Controlled Trials were queried for studies comparing 1–3 months of DAPT followed by monotherapy vs. 12 months of DAPT in the outcomes of complex PCI from inception through January 2023. Outcomes of interest included major bleeding, all-cause mortality, cardiovascular mortality, myocardial infarction (MI), stent thrombosis, target vessel revascularization, and stroke. ResultsCompared to 12 months, 1–3 months of dual antiplatelet therapy had a weak association with less major bleeding (OR 0.67; 95 % CI, 0.44–1.00; p = 0.05; I2 = 28 %). There were no significant differences between the shorter and longer antiplatelet therapy in terms of all-cause mortality (OR 0.83; 95 % CI, 0.59–1.16; p = 0.21; I2 = 17 %), cardiovascular mortality (OR 0.87; 95 % CI, 0.53–0.42; p = 0.50; I2 = 0), MI (OR 0.97; 95 % CI, 0.69–1.35; p = 0.82; I2 = 32 %), stent thrombosis (OR 1.17, 95 % CI, 0.77–1.76; p = 0.38; I2 = 0 %), target vessel revascularization (OR 1.05, 95 % CI, 0.58–1.89; p = 0.82; I2 = 64 %), or stroke (OR 1.10, 95 % CI, 0.55–2.17; p = 0.37; I2 = 7 %);. ConclusionAmong patients undergoing complex PCI, DAPT for 1–3 months may be associated with less major bleeding but similar rates of cardiovascular events (death, MI, stroke, stent thrombosis, and revascularization) compared to DAPT for 12 months.

Urinary cortisol and cardiovascular events in women vs. men: The multi-ethnic study of atherosclerosis

Research suggests that women experience greater cardiovascular ischemic effects from stress than men. Visceral adiposity is an endocrine tissue that differs by sex and interacts with stress hormones. We hypothesized that urinary cortisol would be associated with increased cardiovascular events and change in coronary artery calcium score (CAC) in women, and these relationships would vary by central obesity. In the Multi-Ethnic Study of Atherosclerosis Stress Ancillary study, cortisol was quantified by 12-h overnight urine collection. Central obesity was estimated by waist-hip ratio (WHR). Multivariable Cox models estimated the relationship between cortisol and cardiovascular events and assessed for moderation by WHR. The relationship between cortisol and change in CAC Agatston score was assessed by Tobit regression models. 918 patients were analyzed with median follow up of 11 years. There was no association between urinary cortisol and cardiovascular events in the cohort. However, in individuals with below median WHR, higher urinary cortisol levels (upper tertile) were associated with higher cardiovascular event rates in the full cohort, women, and men, but not in groups with above median WHR. There was significant moderation by WHR in women, but not men, whereby the association between elevated cortisol and increased cardiovascular events diminished as WHR increased. Urinary cortisol was associated with increased change in CAC in women (P = 0.003) but not men, without moderation by WHR. Our study highlights associations between cortisol and subclinical atherosclerosis in women, and moderation of the relationship between cortisol and cardiovascular events by central obesity in both genders.

48-Month Clinical Outcomes and Prognostic Factors in an All-Comers Population with Acute Coronary Syndrome and Chronic Coronary Syndrome Undergoing Percutaneous Coronary Intervention with a Sirolimus-Eluting Stent.

We characterized the performance as well as safety of a second-generation thin-strut sirolimus-eluting stent with a biodegradable polymer, Alex Plus (Balton, Poland), deployed in the acute coronary syndrome (ACS) setting. We enrolled patients who were subjected to percutaneous coronary intervention (PCI) between July 2015 and March 2016 and took into consideration demographics, clinical and laboratory data, and clinical outcomes. We defined the primary endpoint as the 48-month rate of major cardiovascular adverse events (MACE), including cardiac death, myocardial infarction (MI), or target lesion revascularization (TLR). The secondary endpoints were all-cause death, cardiac death, MI, and TLR rates at 12-, 24-, 36-, and 48 months. We enrolled 232 patients in whom 282 stents were implanted, including 88 ACS and 144 chronic coronary syndrome (CCS) patients. The mean age of the ACS population was 67 ± 13 years old, and 32% of it consisted of females. Patients with ACS were characterized by lower rates of arterial hypertension (85.2% vs. 95.8%, p = 0.004), dyslipidemia (67% vs. 81.9%, p = 0.01), prior MI (34.1% vs. 57.6%, p < 0.001), and prior PCI (35.2% vs. 68.8%, p < 0.001). At 48 months, among the ACS patients, the rates of MACE, death, cardiac death, MI, and TLR were 23.9%, 11.4%, 7.9%, 9.1%, and 10.2%, respectively. No stent thrombosis cases were reported. Multivariable Cox regression revealed that the statistically significant MACE predictors were massive calcifications in coronary arteries (HR 9.0, 95% CI 1.75-46.3, p = 0.009), post-dilatation (HR 3.78, 95% CI 1.28-11.2, p = 0.016), prior CABG (HR 6.64, 95% CI 1.62-27.1, p = 0.008), vitamin K antagonist use (HR 5.99, 95% CI 1.29-27.8, p = 0.022), and rivaroxaban use (HR 51.7, 95% CI 4.48-596, p = 0.002). The study findings show that Alex Plus was effective and safe in a contemporary cohort of real-world ACS patients undergoing primary PCI. The outcomes were comparable between the ACS and chronic coronary syndrome patients, with a trend of lower TLR in ACS patients at 4 years.

Impact of Pemafibrate Therapy on Reducing Small Dense Low-Density-Lipoprotein-Cholesterol Levels in Patients with Hypertriglyceridemia.

Small dense LDL-cholesterol is a recently discovered cardiovascular risk factor beyond LDL-cholesterol. Pemafibrate is a novel selective peroxisome proliferator-activated receptor-α modulator that reduces triglyceride levels. Given the significant association between triglycerides and small dense LDL-cholesterol levels, pemafibrate may reduce the levels of small dense LDL-cholesterol. Patients with hypertriglyceridemia who started pemafibrate therapy and continued it for >3 months between 2018 and 2022 were included in this retrospective study. The levels of small dense LDL-cholesterol, which was estimated using Sampson's equation, consisting of the LDL-cholesterol and triglyceride levels, were compared between baseline and 3-month follow-up. A total of 98 patients receiving pemafibrate therapy (median age: 63 years, 69 male) were eligible, including 33 patients (34%) who received concomitant statins. Small dense LDL-cholesterol levels decreased significantly during the course of 3-month pemafibrate therapy from 48.9 (IQR: 35.7, 57.9) mg/dL to 38.8 (IQR: 30.0, 45.1) mg/dL, regardless of the concomitant administration of statins (p < 0.001). The rate of cardiovascular events decreased significantly from the pre-treatment 1-year period to the treatment 1-year period (from 13 to 2 events, from 0.133 to 0.021 events per year, incidence rate ratio: 0.16, 95% confidence interval: 0.14-0.17, p < 0.001). Pemafibrate therapy may mitigate the concentrations of small dense LDL-cholesterol autonomously in patients manifesting hypertriglyceridemia within the authentic clinical milieu. The clinical importance of the diminishment in small dense LDL-cholesterol instigated via pemafibrate merits further scrutiny.

Real-World Effectiveness and Safety Outcomes of Acalabrutinib Treatment By Line of Therapy in Patients with Chronic Lymphocytic Leukemia and/or Small Lymphocytic Lymphoma

Background: Acalabrutinib is a second-generation Bruton tyrosine kinase inhibitor (BTKi) approved by the Food and Drug Administration for the treatment of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Data from phase 3, randomized, controlled trials of acalabrutinib, as monotherapy or in combination with obinutuzumab, in patients with treatment-naive (TN) and relapsed/refractory (R/R) CLL with long-term follow-up, including ELEVATE-TN, ELEVATE-RR, and ASCEND, have demonstrated sustained improvement vs comparators in progression-free survival and overall survival (OS) with cardiovascular (CV) and bleeding events consistent with previous reports (Sharman et al. J Clin Oncol. 2021; Byrd et al. J Clin Oncol. 2021; Ghia et al. Blood. 2022). As real-world evidence of the acalabrutinib effectiveness and safety profile is limited in CLL/SLL patients, this study aimed to describe time to next treatment (TTNT), OS, and CV and bleeding events in patients receiving first-line (1L) and later-line (2L+) acalabrutinib for the treatment of CLL/SLL in the real-world setting. Methods: A retrospective, observational analysis was conducted utilizing the Optum Clinformatics © Data Mart claims and electronic medical record database to identify patients aged ≥18 years with TN or R/R CLL/SLL who initiated acalabrutinib in any line of therapy (LoT) on or after November 21, 2019 (FDA approval date for acalabrutinib). Patients with CLL/SLL were required to have ≥6 months of continuous enrollment in the Optum database system prior to acalabrutinib treatment initiation. Patients were followed until the earliest of last day of data availability, death, or end of study period (September 30, 2022). Treatment effectiveness was described as TTNT (time from acalabrutinib initiation to next LoT or death of any cause) and OS (time from acalabrutinib initiation to date of death from any cause or end of study period). The Kaplan-Meier (KM) method was used to estimate TTNT and OS. Patients who continued treatment at the last follow-up were censored. CV and bleeding events were assessed in all patients who initiated acalabrutinib. All outcomes were evaluated in patients who received 1L or 2L+ acalabrutinib therapy. Results: A total of 530 patients were identified and included in the analysis. Of these patients, 63% (n=334) received 1L acalabrutinib and 37% (n=196) received 2L+ acalabrutinib. At acalabrutinib initiation, the mean age was 72.8 years in the 1L cohort and 74.2 years in the 2L+ cohort; 61.7% (121/196) of patients treated with 2L+ acalabrutinib had prior BTKi therapy prior to acalabrutinib initiation (ibrutinib, n=120; zanubrutinib, n=1). Distributions of gender and race were similar between the cohorts. At baseline, 18.1%, 75.3%, and 16.0% of patients had atrial fibrillation/flutter, hypertension, and bleeding episodes, respectively. With a median follow-up of 8.9 months in the 1L cohort and 12.4 months in the 2L+ cohort, the median TTNT and OS were not reached in either cohort. At 18 months, the proportion of patients remaining on treatment was 82% in the 1L cohort and 78% in the 2L+ cohort ( Figure 1). Of the patients that progressed, the median TTNT was 4.0 months in the 1L cohort (n=33) and 4.2 months in the 2L cohort (n=31). The 18-month OS rate was 90% and 85% for the 1L and 2L+ cohorts, respectively ( Figure 2). After initiation of acalabrutinib treatment, the incidence rates of atrial fibrillation/flutter, hypertension, and bleeding events were 2.7%, 8.9%, and 2.7% of patients in the 1L cohort and 7.4%, 2.4%, and 3.3% of patients in the 2L+ cohort, respectively, who had no history of these events prior to treatment with acalabrutinib. Conclusions: This is the first study demonstrating real-world effectiveness (OS and TTNT) and safety data of acalabrutinib treatment in first-line and later-line therapy. While clinical trial and clinical practice settings may differ, overall, the survival findings in this study were similar to those of acalabrutinib trials. The observed incidence rates of CV and bleeding events were not inconsistent with those observed in published acalabrutinib trials.

Utility of coronary artery calcium in refining 10-year ASCVD risk prediction using a Thai CV risk score.

Coronary artery calcium (CAC) scanning is a valuable additional tool for calculating the risk of cardiovascular (CV) events. We aimed to determine if a CAC score could improve performance of a Thai CV risk score in prediction of 10-year atherosclerotic cardiovascular disease (ASCVD) risk for asymptomatic patients with CV risk factors. This was a retrospective cohort study that enrolled asymptomatic patients with CV risk factors who underwent CAC scans between 2005 and 2013. The patients were classified as low-, intermediate-, or high-risk (<10%, 10%-<20%, and ≥20%, respectively) of having ASCVD within 10-years based on a Thai CV risk score. In each patient, CAC score was considered as a categorical variable (0, 1-99, and ≥100) and natural-log variable to assess the risk of developing CV events (CV death, non-fatal MI, or non-fatal stroke). The C statistic and the net reclassification improvement (NRI) index were applied to assess whether CAC improved ASCVD risk prediction. A total of 6,964 patients were analyzed (mean age: 59.0 ± 8.4 years; 63.3% women). The majority of patients were classified as low- or intermediate-risk (75.3% and 20.5%, respectively), whereas only 4.2% were classified as high-risk. Nearly half (49.7%) of patients had a CAC score of zero (no calcifications detected), while 32.0% had scores of 1-99, and 18.3% of ≥100. In the low- and intermediate-risk groups, patients with a CAC ≥100 experienced higher rates of CV events, with hazard ratios (95% CI) of 1.95 (1.35, 2.81) and 3.04 (2.26, 4.10), respectively. Incorporation of ln(CAC + 1) into their Thai CV risk scores improved the C statistic from 0.703 (0.68, 0.72) to 0.716 (0.69, 0.74), and resulted in an NRI index of 0.06 (0.02, 0.10). To enhance the performance of the Thai CV risk score, a revision of the CV risk model was performed, incorporating ln(CAC + 1), which further increased the C statistic to 0.771 (0.755, 0.788). The addition of CAC to traditional risk factors improved CV risk stratification and ASCVD prediction. Whether this adjustment leads to a reduction in CV events and is cost-effective will require further assessment.

Impact of Active vs Passive Statin Selection for Primary Prevention: The CorCal Vanguard Trial

BackgroundStatins can improve outcomes in high-risk primary prevention populations. However, application in clinical practice has lagged. ObjectivesThe objective of this study was to compare an active vs a passive strategy (ie, usual care) to statin prescription for primary prevention of atherosclerotic cardiovascular disease (ASCVD). MethodsA total of 3,770 patients ≥50 years of age without a history of ASCVD or statin use were invited to enroll in CorCal, with 601 consenting to participate. These patients were randomized 1:1 to statin initiation guided by the pooled cohort equation or by coronary artery calcium scoring (CACS). Outcomes (2.8-year follow-up) compared patients managed actively vs passively (randomly invited but declined or did not respond). ResultsPatient demographics were well matched. Statin recommendation was common among enrolled patients (41.7%). During follow-up, 25.3% of active patients were taking a statin vs 9.8% managed passively (P < 0.0001). Active patients had more lipid panels (median 2.0 vs 1.0), lower low-density lipoprotein cholesterol (109 vs 117 mg/dL) (both P < 0.0001), and a low rate of major adverse cardiovascular events during follow-up (0.6% vs 1.0%, P = 0.47). Statistical comparisons included t-tests, chi-squared tests, nonparametric tests, and time-to-event tests as appropriate. ConclusionsAn active approach to statin selection for primary ASCVD prevention identified a large treatment opportunity and led to over twice as many patients on statins compared to passive (usual care) management. A large CorCal Outcomes Trial is underway to more definitively assess the impact on outcomes of active management of statins for primary prevention.

Effects of cardiac rehabilitation on inflammatory biomarkers in unstable ischemic heart disease patients following percutaneous coronary intervention: a randomized controlled study.

Several blood inflammatory markers, such as high-sensitivity C-reactive protein (hs-CRP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), are linked to increased risk for cardiovascular diseases. This study aimed to evaluate these inflammatory markers after cardiac rehabilitation (CR) in patients with unstable ischemic heart disease (UIHD) who underwent successful percutaneous coronary intervention (PCI). A cohort of 115 patients with successful PCI due to UIHD enrolled in the study from January 2018 to March 2021. We used a permuted block stratified randomization technique (2 : 1 ratio). Seventy-seven patients were randomized to the CR group and 38 patients to the control group. The CR group underwent a 12-week pre-specified CR regimen. Blood samples were taken at baseline and follow-up at 12 weeks for both groups. Among the 115 patients, 33 patients were female. The mean age was (53 ± 5.55 years) in the control and (53 ± 6.09 years) in the CR group. The two groups were comparable regarding their baseline characteristics and the values of the inflammatory markers. By contrast, at 12 weeks, the inflammatory marker values were significantly lower in the CR group compared to the control group; hs-CRP: 0.11 [0.08-0.14] vs. 0.21 [0.19-0.21], P-value <0.001; NLR: 2.17 [1.42-2.43] vs. 2.26 [2.07-2.6], P-value: 0.016; PLR: 91.2821 [63.3333-103.2000] vs. 92.600 [84.6154-110.0000], P-value: 0.027. CR after PCI in UIHD patients may attenuate some inflammatory markers, which might benefit cardiovascular health. Further studies are required to evaluate these findings with longer follow-up and the powered to measure major cardiovascular event rates.

Gender-affirming hormone treatment: friend or foe? Long-term follow-up of 755 transgender people.

Gender-affirming hormone treatment (GAHT) is one of the main demands of transgender and gender diverse (TGD) people, who are usually categorised as transgender assigned-male-at birth (AMAB) and assigned-female-at birth (AFAB). The aim of the study is to investigate the long-term therapeutic management of GAHT, considering hormonal targets, treatment adjustments and GAHT safety. A retrospective, longitudinal, observational, multicentre clinical study was carried out. Transgender people, both AMAB and AFAB, were recruited from two Endocrinology Units in Italy (Turin and Modena) between 2005 and 2022. Each subject was managed with specific and personalized follow-up depending on the clinical practice of the Centre. All clinical data routinely collected were extracted, including anthropometric and biochemical parameters, lifestyle habits, GAHT regime, and cardiovascular events. Three-hundred and two transgender AFAB and 453 transgender AMAB were included. Similar follow-up duration (p = 0.974) and visits' number (p = 0.384) were detected between groups. The transgender AFAB group reached therapeutic goals in less time (p = 0.002), fewer visits (p = 0.006) and fewer adjustments of GAHT scheme (p = 0.024). Accordingly, transgender AFAB showed a higher adherence to medical prescriptions compared to transgender AMAB people (p < 0.001). No significantly increased rate of cardiovascular events was detected in both groups. Our real-world clinical study shows that transgender AFAB achieve hormone target earlier and more frequently in comparison to transgender AMAB individuals. Therefore, transgender AMAB people may require more frequent check-ups in order to tailor feminizing GAHT and increase therapeutic adherence.