Adverse Cardiovascular Outcomes Research Articles

A Pharmacist Medication Titration Program for Patients with Cardiac Sarcoidosis and Systolic Heart Failure: A Retrospective Cohort Study

Background A multidisciplinary approach improves guideline‐directed medical therapy (GDMT) in systolic heart failure (HF), but its efficacy in patients with HF due to cardiac sarcoidosis (CS) is unreported. Methods and Results In a retrospective cohort study, we reviewed 848 patients from our institutional CS clinics, identifying those with a CS diagnosis, HF (LVEF < 50%) at index evaluation, and echocardiograms within 90 days and 11‐36 months. Patients were stratified by participation in a pharmacist‐led medication therapy management (MTM) program for GDMT optimization (MTM vs non‐MTM [NMTM]) without randomization. Demographics, LVEF, GDMT (quantified by Kansas City Medical Optimization [KCMO] score), and immunosuppressive therapy were assessed. Primary outcomes included changes in KCMO score, LVEF, and cardiovascular event‐free survival (unplanned HF hospitalization, LVAD/heart transplant, or death). The final cohort included 111 patients (median age 57 years, 34% female, 64% NYHA Class I‐II); 43 (39%) were MTM and 68 (61%) were NMTM. Mean KCMO score was similar at index evaluation (MTM: 23.2; NMTM: 29.6, p=0.83). At follow‐up (median 16 months), the KCMO score increased significantly in both groups (MTM: 23.2 to 74.8, p<0.001; NMTM: 29.6 to 58.7, p<0.001), but was higher in MTM (p=0.001). Mean LVEF trended towards higher values in MTM (44.4% vs 40.0%, p=0.05). The primary clinical outcome occurred in 1 MTM (2.3%) and 16 NMTM (23.5%) patients, with higher risk in NMTM (HR 11.97 [95%CI 1.58 ‐ 90.54], p=0.002). Conclusions In this retrospective cohort study, a pharmacist‐led MTM program was associated with favorable GDMT optimization and lower risk of adverse cardiovascular outcomes in CS patients with HF.

Combined Effect of Air Pollution and Genetic Risk on Incident Cardiovascular Diseases.

Whether genetic susceptibility to cardiovascular diseases (CVDs) enhances the vulnerability to adverse cardiovascular outcomes by air pollution is unknown. We assessed the combined effect of air pollution and genetic predispositions on CVD risk. From the UK Biobank cohort, we selected genetically unrelated White British participants without CVD. Levels of ambient particulate matter with a diameter of <2.5 μm (PM2.5) and <10 μm were estimated using land use regression models. An individual's genetic predisposition to CVDs was determined by polygenic risk scores for coronary artery disease, myocardial infarction, stroke, ischemic stroke, heart failure, and atrial fibrillation. We stratified mortality and CVD risk by PM2.5 exposure across high and low genetic risk groups. A total of 249 082 participants (aged 56.9±8.0 years, 46.8% men) were followed for a median of 10.8 years. The combined effect of PM2.5 exposure and the genetic predisposition of CVD demonstrated the highest risk of cardiovascular death in the high genetic risk group with the greatest PM2.5 exposure (adjusted hazard ratios ranging from 1.73 to 2.12 across the polygenic risk score of each CVD). The combination of higher exposure to ambient PM2.5 and high genetic risk was associated with higher incidence of all CVDs, although no significant interactions were observed between genetic risk and PM2.5 exposure on cardiovascular death or CVD events. A combination of greater PM2.5 exposure and higher genetic predisposition to particular CVDs was modestly associated with elevated risks of cardiovascular death and CVDs. Not only alleviating PM2.5 exposure in the general population but also implementing individualized preventive approach for those at high genetic risk might be beneficial.

Moderately Increased Left Ventricular Filling Pressure Suggesting Early Stage of Heart Failure with Preserved Ejection Fraction in Patients with Invasively Assessed Coronary Microvascular Dysfunction

Background: With modern diagnostic tools, incidence ischemia with no obstructive coronary atherosclerosis (INOCA) and heart failure with preserved ejection fraction (HFpEF) are found to be much higher than previously believed, and—as they lead to adverse cardiovascular outcomes—their causes and development are subjects of ongoing research. There is growing evidence that coronary microvascular dysfunction might be the underlying cause of both INOCA and HFpEF. Methods: In 65 patients with effort angina but no obstructive coronary artery disease, the index of microvascular resistance and coronary flow reserve were measured invasively in the LAD. The echocardiographic parameters, including left atrial strain, left ventricular strain, and indices of left ventricular diastolic dysfunction, were compared between two groups of patients: those with normal coronary microcirculation parameters and those with impaired coronary microvascular function. Results: Patients with coronary microvascular dysfunction had higher a E/E′ index than those with normal microvessel reactivity. This finding was further confirmed by ROC analysis. The groups did not differ significantly in values of other echocardiographic parameters, including the left ventricular and left atrial strain. The prevalence of classical cardiovascular risk factors was similar in both groups. Conclusions: The coexistence of impaired coronary microvascular function with moderately elevated left ventricular filling pressures might correspond to the co-development of early stages of coronary microvascular dysfunction and HFpEF.

Abstract 4137695: Bundle Branch Block(BBB) is Independently Associated With Adverse Cardiovascular Outcomes in Patients With Heart Failure With Preserved Ejectionfraction(HFPEF): A Propensity Score Matched Analysis

Background: Ventricular dyssynchrony due to BBB can cause adverse cardiovascular(CV) outcomes in HF with reduced EF and is known to occur in HFpEF but its independent impact on is unclear. Objective: To determine if BBB is an independent risk factor for adverse HF outcomes in HFpEF and the impact of atrial fibrillation (AF).. Methods: We studied the impact of BBB in HFpEF utilizing propensity score(PS) matched cohorts without and with BBB from the TOPCAT Americas trial to account for confounding by other co-morbidities. Outcomes analyzed included the TOPCAT primary outcome, CV death&amp;hospitalization (CVH), sudden death, pump failure death (PFD), HF hospitalizations(H), and progression of HF. The impact of concomitant AF ( defined as any AF or AF on ECG) on these outcomes with and without BBB was analyzed. Results: 329 pts with HFpEF&amp;BBB were PS matched for 24 demographic&amp;disease state variables, BNP strata and AF status with a cohort of 329 pts with HFpEF without BBB. BBB was associated with increased risk of the TOPCAT primary outcome (Hazard ratio{HR} 1.44, 95% confidence intervals {CI} 1.10-1.89, p=0.008), increased risk of HF hospitalizations by 41%(HR 1.41 95% CI 1.04-1.91 p=0.0248) but not CVH (HR 1.18, 95% CI 0.93-1.49, p=..169), but not sudden death (HR 1.40, 95% CI 0.70-2.82, p=0.342) or CV death (HR 1.26, 95% CI 0.84-1.89, p=0.257). Risk of pump failure death (PFD) with BBB was significantly higher in HFpEF subjects without a history of AF (Figure left panel .Kaplan Meier Log rank p=0.0478, HR: 4.22, 95% CI: 0.89 to 19.87, p=0.0689) but not in AF (p=0.138). PFD risk was markedly higher in AF subjects without BBB ( Figure right, Kaplan Meier Log rank p=.0012, HR:7.99, 95% CI:1.80 to 35.41,p = 0.0063) than those with BBB (p=0.91) Conclusion: Ventricular dysynchrony induced by BBB independently worsens HFH risk in HFpEF. Its adverse impact on PFD iis seen in the absence of AF. Increase in PFD risk with AF in HFpEF subjects is most prominent in those with normal intraventricular conduction. Mechanical dyssynchrony induced by BBB may have a role in HFpEF subgroups with preserved atrioventricular filling, leading to these adverse HF outcomes

Abstract 4120332: RISING TRENDS IN ISCHEMIC HEART DISEASE RELATED MORTALITY AMONG OLDER ADULTS WITH SLEEP APNEA IN THE UNITED STATES FROM 1999 TO 2021

Introduction: Sleep apnea (SA) is often underrecognized and undertreated despite its high prevalence in the adult population and its association with adverse cardiovascular outcomes. There are limited estimates of national trends on cardiovascular mortality in older patients with sleep apnea. We aimed to assess the sex and race-related trends of ischemic heart disease (IHD) mortality in the older adults with SA using a large population-based database. Methods: We utilized the Centers for Disease Control and Prevention Wide-Ranging, Online Data for Epidemiologic Research (CDC WONDER) database which provides information from death certificates of all US residents according to the International Classification of Diseases, Tenth Revision (ICD-10). The demographic and mortality data were obtained for the United States population &gt;65 years from 1999 to 2021. Ischemic heart disease (ICD-10 codes I20-I25) was listed as the underlying cause of death, and SA (G47.3) as a contributing cause of death. Age adjusted mortality rates (AAMRs) per 1,000,000 population were calculated by standardizing deaths to the year 2000 US population. We used Jointpoint Regression Program to analyze temporal trends in mortality from 2000 to 2021. Average annual percentage change (AAPC) with 95% CI were calculated to examine trends in AAMR over time. Results: Overall, AAMR of IHD mortality for patients with SA increased from 7.9 per 1,000,000 (95% CI, 6.9-8.8) in 1999 to 53.4 per 1,000,000 (95% CI, 51.4-55.4) in 2021 with an AAPC of 9.1% per year (95% CI, 8.8-9.5). Men had consistently higher AAMR than women throughout the study period (overall AAMR men: 45.51 (95% CI, 44.8-46.2); women: 12.5 (95% CI, 12.2-12.8). Both the groups had a similar increasing trend in AAMR, with men having a steeper increase. [AAPC men: 9.3% (95% CI, 8.5-10.8) versus AAPC women: 8.6%, 95% CI, 8.1-9.7]. Non Hispanic (NH) White population had the greatest AAMR throughout the study period, followed by NH Black and Hispanic or Latino. The NH White population had the largest increase in AAMR from 1999 to 2021 (AAPC 9.4%, 95% CI:8.9-10.1). Conclusion: In the United States, there has been a general increase in IHD mortality related to sleep apnea over the last two decades. This rising trend as noted in our analysis is concerning and underscores the need for more robust cardiovascular surveillance in these patients.

Abstract 4119992: 12-lead electrocardiograms predict adverse cardiovascular outcomes of emergency department patients

Introduction: Chest pain is a common cause for presentation to the emergency department (ED). Identifying patients at increased risk of adverse cardiovascular outcomes may help guide testing. Aims: We sought to determine if deep learning enabled 12-lead electrocardiogram (ECG) analysis may improve prediction of adverse cardiovascular outcomes of ED patients presenting with chest pain compared to conventional approaches. Methods: A pretrained convolutional neural network was applied to derive numerical representations of the index ECG waveforms from patients presenting to the Brigham and Women’s Hospital (BWH) ED with chest pain. We trained a neural network model (‘CP-AI’) to predict 30-day major adverse cardiovascular events (MACE) defined as myocardial infarction (MI), pulmonary embolism (PE), aortic dissection (AD), or mortality using age, sex, cardiac biomarkers (troponin and d-dimer), and the numerical ECG representations as inputs ( Figure 1 ). In a holdout sample of Massachusetts General Hospital (MGH) ED patients, we compared the performance of the CP-AI model to alternative models fit on (1) demographics (‘Age and Sex’) (2) demographics + cardiac biomarkers (‘Biomarker Model’), and (3) demographics + numerical ECG representations (‘ECG Model’). Results: The BWH derivation sample included 18,811 individuals (51% female, mean age 65 ± 16 years). The MGH validation sample included 14,476 individuals (45% female, mean age 65 ± 15 years). The CP-AI model significantly outperformed the comparison models for prediction of 30-day MACE with an area under the receiver operating characteristic curve (AUROC) of 0.82 [95% CI 0.81-0.83] ( Figure 1 ). CP-AI also significantly outperformed the comparison models for classification of the 30-day MACE components including MI (AUROC 0.91 [95% CI 0.90-0.92]), PE (AUROC 0.74 [95% CI 0.72-0.76]), and mortality (AUROC 0.86 [95% CI 0.85-0.87]), but not aortic dissection (0.71 [95% CI 0.68-0.75]). Conclusions: The integration of deep learning ECG analysis with conventional assessment improved prediction of adverse cardiovascular of ED patients presenting with chest pain.

Abstract 4113885: Impact of Sodium-glucose Cotransporter 2 Inhibitor on Recurrence and Cardiovascular Outcomes after Catheter Ablation for Atrial Fibrillation in Patients with Heart Failure

Background: Catheter ablation for Atrial fibrillation (AF) has been proven to improve the prognosis in patients with heart failure (HF), while it remains a high risk for AF recurrence and adverse cardiovascular outcomes. The impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on these outcomes in HF patients after AF ablation is unknown. Method: HF patients with AF undergoing catheter ablation between January 2017 and December 2022 from the China-AF Registry were included. Patients were stratified into 2 groups based on the use of SGLT2i at discharge and were 1:1 matched by propensity score, with SGLT2i using (n=368) and non-SGLT2i using (n=368) in each group. The primary outcome was AF recurrence after a 3-month blanking period. Results: During a total of 1315 person-year follow-ups, AF recurrence occurred in 83 patients (22.6%) in the SGLT2i group and 132 patients (35.8%) in the non-SGLT2i group. SGLT2i was associated with a lower risk of AF recurrence (adjusted HR = 0.56, 95% CI: 0.43-0.74, P&lt;0.001). The composite risk of cardiovascular death, thrombotic events, or cardiovascular hospitalization was significantly lower in the SGLT2i group compared with those without SGLT2i (adjusted HR = 0.58, 95%CI: 0.41-0.80, p = 0.001). Although there was a tendency towards benefits, significant differences in all-cause mortality (adjusted HR = 0.76, 95%CI: 0.35-1.63, p = 0.480), cardiovascular mortality (adjusted HR = 0.62, 95%CI: 0.24-1.57, p = 0.312) and thrombotic events (adjusted HR = 0.40, 95%CI: 0.16-1.03, p = 0.056) were not noted between groups. Conclusion: The use of SGLT2i was associated with a lower risk of AF recurrence and the composite outcome of cardiovascular death, thrombotic events, or cardiovascular hospitalization after catheter ablation for AF in patients with HF.

Abstract 4133257: Circulating Ketone Bodies, Lipoprotein(a) and Incident Cardiovascular Outcomes and Mortality: Insights from The UK Biobank

Background: Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD). Recent epidemiological studies have revealed an association between ketone bodies (KB) and adverse cardiovascular outcomes, offering a unique insight into metabolic health and its impact on mortality risk. Elevated levels of both Lp(a) and KB may synergistically amplify pathological processes, including endothelial dysfunction, inflammation, and oxidative stress, through their involvement in shared pathophysiological pathways, thereby exacerbating disease progression beyond the impact of each biomarker individually. Methods: Utilizing data from the UK Biobank, KB were measured by nuclear magnetic resonance spectroscopy and serum Lp(a) concentrations were measured using an immunoturbidimetric assay. Four groups were created as follows: Group 1: Lp(a)&lt;125 nmol/L and Total KB&lt;75 th percentile (&lt;94 μmol/L); Group 2: Lp(a)≥125 nmol/L and Total KB&lt;75 th percentile; Group 3: Lp(a)&lt;125 nmol/L and Total KB≥75 th percentile; and Group 4: Lp(a)≥125 nmol/L and Total KB≥75th percentile. Multivariable-adjusted Cox proportional hazard models were used to examine the association of Lp(a) and total KB with incident cardiovascular outcomes and mortality. Results: A total of 72,704 UK Biobank participants (mean age 56 y, SD=8, 55% women) without prevalent CVD or HF with a median follow up of 13.4 years were included. In the fully adjusted model, compared with those in the reference group (Group 1), participants in Group 2, Group 3, and Group 4 demonstrated a 14%, 17%, and 38%, increased risk of incident ASCVD events, respectively (p&lt;0.01 for all). However, those with Lp(a) ≥ 125 nmol/L and total KB &lt; 75th percentile demonstrated no increased risk of HF, all-cause mortality, stroke, or CVD mortality. Participants with elevated levels of both Lp(a) and KB had significantly increased risk of all outcomes (Table). There was no evidence for a statistically significant interaction between Lp(a) and KB on any outcome. Conclusion: Consistent with prior literature, Lp(a) was associated with atherosclerotic outcomes. However, elevated KB was associated with all outcomes, irrespective of Lp(a) levels.

Abstract 4143281: The Influence of Personal and Family Support on Maternal Cardiovascular Health: Insights from a TriNetX Study

Background: Maternal cardiovascular health during and after pregnancy is influenced by various factors, including personal and family support. However, the specific impact of abnormal personal and family support on maternal outcomes remains understudied. Methods: Utilizing the TriNetX global health research network within the US Collaborative Network, we investigated the influence of abnormal personal and family support (ICD10CM:Z63) on maternal cardiovascular outcomes within one year post-pregnancy. Cohort 1 comprised women aged 15 to 60 with documented problems relating to primary and family support during or after childbirth between 2008 and 2023. Cohort 2 included a similar demographic with good primary and family support. Data were extracted from electronic health records, and the cohorts were matched based on diverse sociodemographic traits and medical comorbidities. Results: Our analysis revealed significant associations between problems relating to primary and family support during and after pregnancy and adverse maternal cardiovascular outcomes. Specifically, the presence of such challenges significantly increased the risk of major adverse cardiac and cerebrovascular events (MACCE) (OR: 4.823, 95% CI: 3.361 to 6.919, p&lt;0.001) and all-cause mortality (OR: 8.461, 95% CI: 5.184 to 13.812, p&lt;0.001). Interestingly, it was associated with a reduced risk of peripartum or postpartum preeclampsia (OR: 0.603, 95% CI: 0.403 to 0.903, p&lt;0.001). However, no significant association was observed between these personal and family support challenges and acute MI (OR: 1.092, 95% CI: 0.482 to 2.747, p=NS), ischemic stroke (OR: 1.403, 95% CI: 0.623 to 3.160, p=NS), hemorrhagic stroke (OR: 1.000, 95% CI: 0.416 to 2.404, p=NS), heart failure (OR: 1.075, 95% CI: 0.636 to 1.817, p=NS), or peripartum cardiomyopathy (OR: 0.586, 95% CI: 0.322 to 1.068, p=NS). Conclusion: Our findings highlight the significant impact of abnormal personal and family support on maternal cardiovascular health outcomes during and one year after pregnancy. Addressing challenges related to primary and family support during and after pregnancy may be crucial for reducing adverse outcomes and enhancing overall maternal well-being.

Abstract 4136600: Hypertensive disorders of pregnancy and the risk of Dementia, Alzheimer’s disease, and Vascular Dementia. A Systematic review and Meta-analysis of 25,03,538 women participants.

Background: Hypertensive disorders of pregnancy (HDP) are associated with maternal adverse cardiovascular outcomes. However, their association with maternal Dementia and Alzheimer’s disease is not well established with limited and conflicting results to date. Objective: We sought to evaluate the association between HDP and risk of incidence of Dementia, and Alzheimer’s disease. Methods: We performed a systematic review and meta-analysis of available literature that enrolled women with HDP and women without HDP groups. PubMed, Embase and ClinicalTrials.gov were systematically searched from inspection till May 2024 without any language restrictions. Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) were pooled using a random-effect model. Results: A total of 8 studies with 2503538 patients (1,51,905 in women with HDP and 23,51,633 in the women without HDP group) were included. Pooled analysis shows that HDP women were having 37% higher risk of dementia (aHR, 1.37(95%CI: 1.27-1.46), P&lt;0.001, I2=0%) when compared with women without HDP. Further pooled analysis showed that women with HDP were having 28% higher risk of Alzheimer’s disease (aHR, 1.28(95%CI: 1.56), P&lt;0.001, I2=53.98%), and 2-fold higher risk of vascular dementia (aHR, 2.49(95%CI: 1.29-3.68), P&lt;0.001, I2=71.51%) when compared with women without HDP. Conclusion: Women with HDP were at higher risk of developing Dementia, and Alzheimer's disease in future.

Abstract 4134345: Diastolic Dysfunction And The Risk Of Stroke And Major Bleeding

Background: Diastolic dysfunction (DD) is associated with adverse cardiovascular outcomes including atrial fibrillation. Whether DD is independently associated with incident ischemic stroke/transient ischemic attack (TIA) and with bleeding events is not well established. Aims: To examine the association of presence and severity of DD with the risk of incident ischemic stroke/TIA and major bleeding. Methods: A total of 219,667 patients who underwent at least one echocardiogram between 2010 and 2022 at a large academic institution and were followed for at least 3 months were included. Patients with prior history of stroke or TIA (n=21,505, 10%) were excluded. Smart key-phrase search was applied to echocardiographic reports to classify patients into 4 groups, based on the most severe DD assessment: Normal (n=113,265), grade I (n=21,981), grade II (n=7,215), and grade III (n=1,627). Patients in whom the presence of DD could not be determined (n=54,074) were excluded. The final study cohort (n=144,088) was followed to the endpoint of hospital admission for ischemic stroke/TIA or for major bleeding. Results: Over a median follow-up of 3.4 years, 3482 (2.4%) patients were hospitalized for stroke/TIA and 6994 (4.9%) for major bleeding. After adjusting for several confounding variables (Table), DD remained a strong predictor of incident stroke/TIA (hazard ratio (HR)=1.34 per grade increase in DD, p&lt;0.001, Figure) and of major bleeding (HR=1.32 per grade increase in DD, p&lt;0.001, Figure). These results were similar in patients with (n=11,508, 8%) or without prior history of atrial fibrillation. Conclusions: Patients with DD have a heightened risk of ischemic cerebrovascular accidents and major bleeding independent of the presence of atrial fibrillation. These risks escalate with the severity of DD. DD should be considered when counseling patients regarding their risk profile and management options.

Abstract 4138633: Infusion of human apolipoprotein A-I (CSL112) promotes several aspects of reverse cholesterol transport

Background: High-density lipoprotein (HDL)-cholesterol is inversely correlated with cardiovascular risk, but increasing its circulating concentration is insufficient to prevent adverse cardiovascular outcomes. Instead, the emerging paradigm is on increasing the function of HDL and its major protein constituent apolipoprotein A-I (apoA-I), to increase reverse cholesterol transport. Objective: To investigate the effect of apoA-I [human] (CSL112) infusion on HDL protein composition, and provide further insights into the mechanism of action of CSL112 administered post-acute myocardial infarction (AMI). Methods: A mass spectrometry (MS)-based proteomic approach was used to evaluate changes in HDL protein composition in patients (n=50) from the AEGIS-I (ApoA-I Event Reducing in Ischemic Syndromes I) study who received either placebo or CSL112 post AMI. HDL was immuno-isolated from patient plasma using anti-apoA-I antibodies. Cholesterol esterification rate (CER) was measured to determine lecithin-cholesterol acyl transferase (LCAT) activity. Cholesterol efflux capacity (CEC) and hepatocyte uptake were assessed using patient serum in ex vivo cell-based assays. Results: CSL112 induced extensive rearrangement of HDL proteins at 4 hours post-infusion. Levels of apolipoproteins A2, B, C, and E as well as the acute phase proteins serum amyloid A1 and A4 were significantly reduced. By contrast, apoA-I, apoM, and LCAT significantly increased. Elevated apoA-I and LCAT levels on HDL were associated with an increase in CEC, plasma HDL-C levels, and CER in CSL112-treated patients. Furthermore, enhanced CEC strongly correlated with cholesterol uptake by hepatic cells (r=0.95 p&lt;0.001). Conclusion: CSL112 altered HDL composition and increased HDL functionality by promoting multiple steps of the reverse cholesterol transport pathway.

Abstract 4136930: Plasminogen Activator Urokinase Receptor (PLAUR) Levels are a Predictor of Adverse Cardiovascular Outcomes in the General Population, Independent of High-Sensitive CRP (hs-CRP)

Background: The gene Plasminogen Activator Urokinase Receptor (PLAUR) encodes the urokinase plasminogen activator surface receptor (uPAR), which upon cleavage releases Soluble Urokinase Plasminogen Activator Receptor (suPAR). SuPAR has emerged as a novel biomarker of inflammation and immunity and is associated with adverse cardiovascular events, particularly coronary artery disease (CAD), regardless of hs-CRP levels, a well-established inflammatory biomarker. However, whether the PLAUR gene predicts adverse cardiovascular events remains uncertain. Methods: We investigated the relationship between PLAUR levels, measured via Olink Immunoassay, in 40,790 individuals from the UK Biobank, and the occurrence of adverse cardiovascular events such as myocardial infarction (MI), as well as all-cause and cardiovascular mortality. Our analysis involved the use of Cox and Fine and Gray proportional hazards models, adjusting for age, sex, race, HDL, LDL, triglyceride levels, BMI, prevalence of hypertension (HTN), prevalence of type 2 diabetes (T2D), smoking history, and use of blood pressure and cholesterol medications. Main Outcomes: The primary outcome was a composite outcome of cardiovascular mortality and MI and the secondary outcome was all-cause mortality. Results: The mean (SD) age was 58 (8) years, 45% men and 94% white. During a median follow-up of 14 (interquartile range 12.3 – 15) years, 7.9% of the population had an MI, 2.7% suffered cardiovascular death, 9.5% all-cause mortality. After adjusting for aforementioned demographic and clinical factors, as well as medication usage, each standard deviation increase in PLAUR levels was associated with a heightened risk of incident non-fatal MI and cardiovascular (CV) death, with a hazard ratio (HR) of 2.31 (95% CI 2.00-2.45), and all-cause mortality, with an HR of 3.81 (95% CI 3.48-4.18). Even after further adjustment for hs-CRP levels, PLAUR levels remained predictive of non-fatal MI and CV death (HR 2.03, 95% CI 1.83-2.26) and all-cause mortality (HR 3.43, 95% CI 3.12-3.77). Furthermore, in a fully adjusted Cox regression model, a significant interaction between PLAUR levels and sex (p = 0.0003) was observed in predicting the primary outcome. The interaction was found to have a stronger predictive value in females compared to males. Conclusion: PLAUR levels are a strong predictor of adverse cardiovascular outcomes in the general population, independent of traditional risk factors and inflammation.

Incidental Coronary Artery Calcification and the Risk of Major Adverse Cardiovascular Outcomes

Incidental Coronary Artery Calcification and the Risk of Major Adverse Cardiovascular Outcomes

Abstract 4144548: High Morbidity and Mortality in Adults With Turner Syndrome and Aortic Dilation: A Retrospective Cohort Study from the Healthy Heart Project

Introduction: Turner syndrome (TS) is caused by the partial or complete absence of one sex chromosome and affects 1 in 2500 liveborn infants. Hypertension, bicuspid aortic valve (BAV), and thoracic aortic aneurysms (TAAs) are more prevalent in TS compared to the general population and predispose to aortic dissections, which may occur in young adults with TS. We hypothesize that adults with TS who have TAAs experience a high rate of adverse cardiovascular outcomes. Methods: Adults with TS who had Healthy Heart Project (HHP) echocardiograms at national conferences between 2003 and 2023 were contacted for enrollment in descending order of the aortic size index (ASI, cm/m 2 ), defined as the ratio of the maximum ascending aortic diameter to body surface area. After informed consent, clinical characteristics and outcomes (as numbers of participants or median and interquartile range) were abstracted from questionnaires and medical records. Results: Sixty-four of 704 total HHP participants were contacted and 19 (with 10 of the 20 highest ASI values) were enrolled with complete data. The baseline ASI was 2.19 (0.48), compared to 1.51 (0.36) for all other HHP participants. The median age was 59 (13) years. The most prevalent characteristics were 45,X (10) or 45,X/46,XX (6) karyotypes; BAV (9), coarctation (4), or no congenital lesions (6); and hypertension (12). A mean of 10 serial aortic images were available for each participant over a follow up period of 14 (9.8) years. The median increase in aortic diameter was 0.09 (0.29) mm/yr at the sinuses of Valsalva and 0.26 (0.44) mm/yr at the ascending aorta. Seven participants underwent aortic operations due to enlarging TAAs when the median ascending diameter was 3.83 (0.67) cm (ASI 2.58 (0.11) cm/m 2 ). In 3 cases, operations were urgent due to cardiovascular symptoms or rapid aortic dilation, but there were no acute aortic dissections. The median time between the index image and subsequent repair was 3.5 (7.0) years. Three HHP participants with the 8th, 15th, and 42nd largest ASI values died prior to follow up. One death was caused by complications after surgical aortic valve replacement at age 20. Conclusions: In a cohort of adults with TS and TAAs, 40% (7/19) developed progressive aortic enlargement requiring aortic repairs and there were 3 deaths. These observations underscore the importance of lifelong surveillance and timely intervention to prevent deaths due to cardiovascular disease in TS.

Abstract 4124709: Accelerometer-Measured Sedentary Behavior and Future Cardiovascular Disease

Background: Current consensus guidelines emphasize the importance of achieving 150 minutes or more of moderate to vigorous physical activity (MVPA) per week to promote cardiovascular health but give little guidance about sedentary behavior. Research Question: Is sedentary behavior associated with cardiovascular (CV) disease in a manner distinct from insufficient physical activity? Aims: Examine associations between accelerometer-measured sedentary behavior with risk of specific CV outcomes, including potential interactions with MVPA. Methods: Using 89,530 individuals providing one week of accelerometer-based physical activity data from the UK Biobank, we fit Cox models adjusted for demographic and lifestyle factors to assess associations between sedentary time (as a spline term) and incident atrial fibrillation (AF), myocardial infarction (MI), heart failure (HF), and CV mortality. We assessed the potential effect of MVPA on these associations by including MVPA as an adjustment variable, as well as performing subgroup analyses stratified at the guideline-recommended MVPA threshold. Results: Among 89,530 individuals (age 62±8 years, 56.4% women) undergoing accelerometry, median sedentary time was 9.4 hours/day (quartile-1: 8.2, quartile-3: 10.6). In multivariable models, using the second quartile (8.2-9.4 hours/day) as a referent, sedentary time in the top quartile (&gt;10.6 hours/day) was associated with greater risk of HF (hazard ratio [HR] 1.45, 95% CI 1.28-1.65), and CV mortality (HR 1.62, 95% CI 1.34-1.96), with evidence of a threshold effect at 10.6 hours/day. Higher sedentary time was also associated with greater risk of incident AF (HR 1.11, 95% CI 1.01-1.21) and MI (HR 1.15, 95% CI 1.00-1.32), with an approximately linear relation. Associations with HF and CV mortality persisted after adjustment for MVPA, as well as among individuals both above and below the guideline-based activity threshold of ≥150 minutes MVPA/week. Conclusions and Relevance: Sedentary behavior is broadly associated with future adverse CV outcomes. For HF and CV mortality, associations appear distinct from insufficient MVPA, and sedentary time in excess of 10.6 hours/day conferred an increased risk.

Associations of SGLT2i with Cardiorenal Outcomes Among Diabetics with Prostate Cancer on Hormone Therapy.

Studies have reported associations between prostate cancer, type II diabetes mellitus (T2DM), and cardiovascular disease in the context of treatment with hormone therapy (HT). This study aimed to assess the role of Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i) in preventing adverse cardiovascular and renal outcomes in diabetics with prostate cancer. Patients ≥ 18years of age with T2DM and prostate cancer who received HT between August 1, 2013, and August 31, 2021, were identified using the TriNetX research network. Patients were divided into two cohorts based on treatment with SGLT2i or alternative antidiabetic therapies. The primary outcome was the composite of all-cause mortality, new-onset heart failure (HF), acute myocardial infarction (MI), and peripheral artery disease over 2years from HT initiation. After propensity score matching, 2155 patients remained in each cohort. The primary composite outcome occurred in 218 patients (16.1%) in the SGLT2i cohort versus 355 patients (26.3%) in the non-SGLT2i cohort (OR 0.539, 95% CI 0.446-0.651; p < 0.001). Furthermore, SGLT2i were associated with significantly lower odds of HF, HF exacerbation, peripheral artery disease, atrial fibrillation/flutter, cardiac arrest, need for renal replacement therapy, overall emergency room visits/hospitalizations, and all-cause mortality. Use of SGLT2i for the treatment of T2DM among patients with prostate cancer on HT is associated with favorable cardiovascular, renal, and all-cause mortality outcomes. This observation supports the hypothesis that a therapeutically relevant link exists between HT and cardiovascular disease in the context of prostate cancer.

Safety and Efficacy of Aspiration Thrombectomy With Intracoronary Tirofiban in Patients Undergoing Primary Percutaneous Coronary Intervention: A Systematic Review and Meta-analysis

BACKGROUND: Primary percutaneous coronary intervention (PPCI) may be complicated by heavy intracoronary thrombus burden leading to decrease in myocardial perfusion and increase in infarct size. The current meta-analysis aims to investigate the clinical outcomes of aspiration thrombectomy (AT) with intracoronary tirofiban during PPCI. METHODS: A systematic search for randomized controlled trials that evaluate the safety and efficacy of AT with intracoronary tirofiban in ST-elevation myocardial infarction (STEMI) patients who underwent PPCI was done using PubMed, MEDLINE, EMBASE, Cochrane, ClinicalTrials.gov., and Herdin PH. Studies included those published between 2010 and 2023 and involved human subjects. Search terms included “aspiration thrombectomy,” “intracoronary tirofiban,” “primary percutaneous coronary intervention,” and “STEMI patients.” RESULTS: Four randomized controlled trials (n = 490 participants) were included in this metaanalysis comparing AT with intracoronary tirofiban versus AT alone in STEMI patients undergoing PPCI. The results revealed no statistically significant difference in ST-segment resolution (risk ratio [RR], 1.02; 95% confidence interval [CI], 0.97–1.08; P = 0.41, I2 = 0%), myocardial blush grade 2–3, (RR, 1.04; 95% CI, 0.97–1.12; P = 0.22, I2 = 62%), and Thrombolysis In Myocardial Infarction 3 flow (RR, &lt;1.0; 95% CI, 0.95–1.04; P = 0.87). The occurrence of major adverse cardiovascular events did not significantly differ between the two groups (RR, 0.46; 95% CI, 0.19–1.09; P = 0.08, I2 = 0%). There was no statistically significant difference in terms of bleeding when combining intracoronary tirofiban to standard medical therapy (RR, 1.35; 95% CI, 0.64–2.84; P = 0.78, four trials [490 patients]). CONCLUSION: In PPCI, major adverse cardiovascular event outcomes of AT with intracoronary tirofiban were similar to those for AT alone in terms of improving myocardial perfusion in STEMI patients without increasing the risk for bleeding. Our meta-analysis suggests that AT alone may be the more acceptable standard during PPCI when encountering heavy thrombus burden. Future validated studies may help further investigate the strategy of adding tirofiban during AT.

Oral Health and Systemic Disease: A Systematic Review of the Impact of Dental Care on Overall Health

Oral health is increasingly recognized as a critical component of overall health, with research highlighting its potential impact on various systemic diseases. This systematic review examines the current evidence on the association between oral health, particularly dental care, and systemic conditions such as cardiovascular disease, diabetes, respiratory illnesses, and adverse pregnancy outcomes. A comprehensive literature search was conducted across multiple databases, focusing on studies published from 2016 onward. Studies indicate that periodontal disease and other oral health issues may contribute to systemic inflammation, a common factor in many chronic conditions. Specifically, findings suggest that managing oral health can have beneficial effects on cardiovascular health, glycemic control in diabetic patients, and respiratory function, as well as reduce risks for adverse pregnancy outcomes. However, while associations are evident, causality remains difficult to establish, and further longitudinal research is needed to clarify these relationships. This review underscores the importance of incorporating dental care into holistic health approaches, advocating for greater collaboration between dental and medical professionals. Public health initiatives promoting regular dental check-ups and preventive care may play a crucial role in improving overall health outcomes.

Diastolic Dysfunction and the Risk of Stroke and Major Bleeding.

Left ventricular diastolic dysfunction (DD) is associated with adverse cardiovascular outcomes including atrial fibrillation. Whether DD is independently associated with incident stroke and transient ischemic attack (TIA) and with bleeding events is not known. We performed this observational cohort analysis to examine the impact of DD on the risk of stroke/TIA and major bleeding. Patients who underwent at least 1 cardiac echocardiogram and were followed for at least 3 months were included in this study. Patients with a prior history of stroke, TIA, or major bleeding, as determined by International Classifications of Diseases codes, were excluded. Smart key-phrase search was applied to echocardiographic reports to classify patients into 4 groups based on the most severe DD assessment. Patients in whom the presence of DD could not be determined were excluded. The final study cohort was followed to the end point of hospital admission for stroke/TIA and major bleeding, and independent predictors of these events were evaluated using the multivariable Cox proportional hazards method. The final study cohort (age, 56±18 years; 56% women) had 96 702 patients with no DD and 18 164, 5881, and 1340 patients with DD grades I, II, and III, respectively. Over a median follow-up of 3.4 years, 2938 (2.4%) patients were hospitalized for stroke/TIA and 5567 (4.6%) for major bleeding. After adjusting for age, the CHA2DS2-VASc score, chronic kidney disease, use of antiplatelet agents, use of anticoagulation agents, the year of echocardiographic testing, household income, and history of atrial fibrillation, DD remained a strong predictor of incident stroke/TIA (hazard ratio, 1.22 per grade increase in DD [95% CI, 1.16-1.29]; P<0.001) and major bleeding (hazard ratio, 1.20 per grade increase in DD [95% CI, 1.16-1.25]; P<0.001). DD is independently associated with a higher risk of cerebrovascular accidents and major bleeding. DD should be considered when counseling patients regarding their risk profile and management options.