Predictor Of Cardiovascular Events Research Articles

Study protocol and baseline characteristics of Randomized trial for Evaluation in Secondary Prevention Efficacy of Combination Therapy–Statin and Eicosapentaenoic Acid: RESPECT-EPA, the combination of a randomized control trial and an observational biomarker study

Omega-3 polyunsaturated fatty acids (PUFAs) have been a hot topic since the Japan EPA Lipid Intervention Study (JELIS), the first landmark study using a highly purified eicosapentaenoic acid (EPA), indicated that EPA could decrease the incidence of cardiovascular events. Over 20 years have passed since the JELIS was conducted, and the standard treatment for dyslipidemia has altered significantly since then. The JELIS subjects did not undertake the current risk management especially current standard statins and did not exclusively target secondary prevention patients. In addition, the subjects included are relatively high EPA population. Furthermore, the clinical implication of the plasma EPA/arachidonic acid (AA) ratio as a biomarker has not yet been validated. Therefore, the Randomized trial for Evaluation in Secondary Prevention Efficacy of Combination Therapy - Statin and EPA (RESPECT-EPA) was planned and is currently underway in Japan. The RESPECT-EPA comprises two parts: the open-label randomized controlled trial (RCT) and biomarker study (prospective cohort study design). The RCT included patients with a low EPA/AA ratio. These patients were then randomized to highly purified EPA (1800 mg/day) or control groups. The primary endpoint was cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, unstable angina pectoris, and clinically indicated coronary revascularization. The biomarker study assesses the EPA/AA ratio's usefulness as a biomarker for cardiovascular events prediction. In the RCT, a total of 2,460 patients were enrolled in 95 sites in Japan. Patients' baseline characteristics were similar between intervention and control groups in the RCT. The baseline median EPA/AA ratio was 0.243 and 0.235, respectively. A total of 1,314 patients were participated in the observational part, and the baseline median EPA/AA ratio was 0.577. After this study is completed, we will have further evidence on whether a highly purified EPA is effective in reducing cardiovascular events for secondary prevention or not, as well as whether if EPA/AA ratio is a predictor for future cardiovascular events. This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000012069).

O073 Traditional Clinical and Novel Oximetry Measures as Predictors of Cardiovascular Events

Abstract Introduction Intermittent hypoxia is a key mechanism linking Obstructive Sleep Apnoea (OSA) to cardiovascular disease (CVD). Oximetry analysis could enhance understanding of which OSA phenotypes are associated with CVD risk. We investigated if traditional clinical and novel oximetry measures including hypoxic burden (HB) calculated from the polysomnogram SpO2 signal can predict CVD outcomes in all-comers and OSA subsample cohorts from the Sleep Heart Health Study (SHHS). Methods CVD mortality outcome and complete covariate information was used. We implemented 31 oximetry measures and assessed the performance of the parameters in predicting CVD outcomes (CVD death or incident CVD) in the all-comers and sleep apnoea subsamples. The performance of each measure was assessed using an adjusted Cox proportional hazard ratio (HR) analysis. Results In the general subsample, HB successfully predicted CVD death (HR>1.8, p<0.05) but did not predict incident CVD. In the sleep apnoea subsample (AHI>5) with no CVD at baseline, none of the SpO2 measures we considered predicted incident CVD. Discussion The ability of HB to predict CVD outcomes depends on the cohort and the CVD outcome. Our analysis of the selected SpO2 measures in an OSA subsample did not find strong links between any oximetry measures and incident CVD, and therefore no strong candidates for CVD risk phenotyping in the sleep clinic. Further work is needed to understand the complex relationship between OSA-related intermittent hypoxia patterns and development of CVD to further understanding of OSA phenotypes at risk of CVD consequences.

Changes in Arterial Stiffness in Response to Various Types of Exercise Modalities: A Narrative Review on Physiological and Endothelial Senescence Perspectives.

Arterial stiffness is a reliable independent predictor of cardiovascular events. Exercise training might enhance arterial compliance through improved metabolic health status. Different modes of exercise may have different effects on arterial stiffness. However, the interactions among different modes of exercise on endothelial senescence, the development of arterial vascular stiffness, and the associated molecular mechanisms are not completely understood. In this narrative review, we evaluate the current evidence focusing on the effects of various exercise modes on arterial stiffness and vascular health, and the known underlying physiological mechanisms are discussed as well. Here, we discuss the most recent evidence of aerobic exercise, high-intensity interval training (HIIT), and resistance exercise (RE) on arterial stiffness and endothelial senescence in physiological and cellular studies. Indeed, aerobic, HIIT, and progression RE-induced arterial compliance may reduce arterial stiffness by effectively promoting nitric oxide (NO) bioavailability and reducing endothelial senescence. However, the transient increase in inflammation and sympathetic activation may contribute to the temporary elevation in arterial stiffness following whole-body high-intensity acute resistance exercise.

Abstract 12556: Prevalence of Hypertension and Left Ventricular Hypertrophy in Adolescents Following Left Ventricular Outflow Tract Obstruction Repair

Introduction: Left ventricular outflow tract obstructions predispose patients to increased lifetime risk of cardiovascular events even after successful repair (rLVOTO). Left ventricular hypertrophy (LVH) is an adaptive response to elevated afterload and is a predictor of cardiovascular events in adulthood. The prevalence of elevated blood pressure (SBP) and LVH in youths with rLVOTO is limited. Methods: Retrospective analysis of rLVOTO patients between 2012-2019, age 13-17 years with documented body mass index (BMI), SBP, LVOT velocity and left ventricular mass indexed to height (LVMi). Moderate LVOTO was defined as peak velocity ≥ 3 m/s. Patients categorized into normotensive (NT, SBP < 120 mm Hg), elevated (E-BP, 120 ≤ SBP < 130 mm Hg), Stage 1 HTN (HTN-1, 130 ≤ SBP < 140 mm Hg) and Stage 2 HTN (HTN-2, SBP ≥ 140 mm Hg). Prevalence of LVH was reported in each group (pediatric cutoff of LVMi-HT 2.7 ≥ 38.6 g/ht 2.7 ). Results: A total of 193 patients met criteria (age 15.6 ± 1.4 years), 135/193 (70%) male, SBP 120±13 mm Hg, and LVMi-HT 2.7 36.2±9.8 g/ht 2.7 . Half were in the NT group (93/193 (48%)), 55/193 (28%) in E-BP, 32/193 (17%) in HTN-1, and 13/193 (7%) in HTN-2 with no difference in BMI. Prevalence of LVH increased with higher SBP with 24/93 (26%) in NT, 21/55 (38%) in E-BP, 14/32 (43%) in HTN-1, and 4/13 (31%) in HTN-2. 124/193 (64%) had no residual LVOT gradient, 69/193 (36%) with residual LVOT gradient. 52/69 (75%) had LVOT < 3 m/s, of these 12/52 (23%) had ≥ HTN-1. 17/69 (25%) had residual LVOTO ≥ 3 m/s, of these 6/17 (35%) had ≥ HTN-1. No difference in LVMi found between no or mild LVOTO groups (35.9±13 vs 35.6±10 g/ht 2.7 , p = NS). Higher LVMi was found in the LVOTO ≥ 3 m/s group (41.5±13 g/ht 2.7 , p = 0.01 compared to both no or mild LVOTO). Conclusions: Youths with rLVOTO have a high prevalence of elevated BP, HTN, and LVH. When stratified by LVOTO severity, presence of ≥ HTN-1 was common with increased LVMi. No difference in BMI was observed among abnormal SBP groups suggesting BMI is not solely responsible for the increased LVMi. Longitudinal studies are needed to define the impact of rLVOTO and HTN on LVH over time. Our findings support early surveillance and management of hypertension in patients following LVOTO repair to help minimize the risk of future cardiovascular events related to LVH.

Abstract 10068: High Pericoronary Adipose Tissue Attenuation on Coronary Computed Tomography Angiography Predicts Cardiovascular Events in Patients Without Obstructive Coronary Artery Disease

Introduction: Patients without obstructive coronary artery disease (CAD) have an increased risk of major adverse coronary events compared to patients with no coronary artery stenosis. However, risk stratification among patients without obstructive CAD has not been established. Hypothesis: This study was aimed to investigate whether pericoronary adipose tissue attenuation (PCATA) on coronary computed tomography angiography (CCTA), a novel imaging biomarker of pericoronary inflammation, is a useful predictor for cardiovascular events in patients without obstructive CAD. Methods: A total of 1183 patients without obstructive CAD undergoing clinically indicated CCTA in our institute from August 2011 and December 2016 were enrolled. Obstructive CAD was defined as luminal narrowing of ≧50% in any coronary artery. We also examined PCATA and high-risk plaque features on CCTA as well as coronary artery calcium score and pericardial fat volume. PCATA in Hounsfield units (HU) was assessed at proximal 40-mm segments of all 3 major coronary arteries. The outcome was composite cardiovascular events including cardiovascular death, acute coronary syndrome, and late coronary revascularization. Results: During a median follow-up of 23.0 months, 32 cardiovascular events were observed. Left anterior descending artery (LAD)-PCATA in patients with cardiovascular events was significantly higher than that in patients without (-64.0 ± 6.0 HU vs -66.9 ± 7.3 HU, p=0.012), whereas right coronary artery- and left circumflex artery-PCATA were not. High LAD-PCATA was significantly associated with cardiovascular events in a model that included traditional risk factors, coronary artery calcium score and adverse CTA findings, such as degree of stenosis and high-risk plaque (HR; 1.467, 95%CI; 1.03-2.09, p = 0.033). Finally, incremental prognostic value of PCATA was evaluated. After adding LAD-PCATA to a model including traditional risk factors and the adverse CTA findings, global chi-square values increased significantly from 33.0 to 37.5 (p = 0.032). Conclusions: High LAD-PCATA has incremental prognostic value over conventional risk factors and CTA findings in patients without obstructive CAD.

Abstract 14083: Prognostic Utility of Neutrophil Gelatinase-Associated Lipocalin in Predicting Cardiovascular Events in Patients With Stable Coronary Artery Disease Treated With Percutaneous Coronary Intervention

Introduction: Neutrophil gelatinase-associated lipocalin (NGAL) modulates matrix metalloproteinase-9 thereby affecting the stability of the atherosclerotic plaque. Accumulating evidence showed that high NGAL levels were independently associated with major adverse cardiac events (MACE) and mortality in patients with acute myocardial infarction (MI). However, only few studies have measured NGAL in stable coronary artery disease (SCAD) patients, and no significant prognostic predicting value between NGAL and SCAD has been established yet. Hypothesis: The aim of this study was to investigate the prognostic role of NGAL in a prospective cohort study of patients with SCAD treated with percutaneous coronary intervention (PCI). Methods: In total, 2296 SCAD patients with previous PCI were enrolled in a multi-center prospective observational study. The primary outcome was the occurrence of MACE (cardiovascular death, nonfatal MI and ischemic stroke). The secondary outcome was the occurrence of combined cardiovascular events (including all-cause death, nonfatal MI, nonfatal stroke, revascularization and hospitalization for heart failure). Results: During the mean follow-up period of 4.6 ±1.7 years, 384 patients reached the primary endpoints and 746 patients reached the secondary endpoints. Kaplan-Meier analysis showed that the event-free survival was significantly different in the first tertile and third tertile groups (log-rank test, p<0.001) in subjects categorized by NGAL levels. In multivariate Cox proportional hazard regression analysis, plasma NGAL was independently associated with MACE (adjusted hazard ratio [aHR] 1.24; 95% confidence interval [CI] 1.03-1.50, p=0.02) and the risk of developing combined cardiovascular events (aHR 1.31; 95% CI 1.14-1.51, p<0.001) during follow-up. Conclusions: High plasma NGAL independently associated with the occurrence of MACE and combined cardiovascular events in SCAD patients treated with PCI.

Abstract 11427: Clot Strength and Platelet Reactivity for Prediction of Major Cardiovascular Events After Percutaneous Coronary Intervention

Introduction: Platelet-fibrin clot strength (PFCS) is associated with the risk of major adverse cardiovascular events (MACE) in patients with coronary artery disease (CAD). Hypothesis: The interaction between PFCS and platelet reactivity, and their prognostic implication remain uncertain. Methods: We enrolled CAD patients undergoing percutaneous coronary intervention (PCI) with available PFCS (measured by thromboelastography) and platelet reactivity (measured by VerifyNow). PFCS High was defined as maximal amplitude (MA)≥68, and high platelet reactivity (HPR) was categorized as P2Y12 reaction unit (PRU) >208. Patients were stratified into 4 groups according to the levels of MA and PRU: (1) normal platelet reactivity (NPR)-PFCS Low (31.9%); (2) HPR-PFCS Low (28.9%); (3) NPR-PFCS High (18.1%); and (4) HPR-PFCS High (21.1%). The primary endpoint was MACE (a composite of all-cause death, myocardial infarction, or stroke) and the risk of major bleeding was also evaluated. Results: At 4-year follow-up, prognostic implication of HPR and PFCS High showed the synergistic effect, and risks of MACE were significantly different across the groups (log-rank test, P < 0.001) (Figure 1). Compared with the NPR-PFCS Low group, the HPR-PFCS High group only showed a significantly higher risk of MACE (adjusted hazard ratio [HR adj ]: 1.87; 95% confidence interval [CI]: 1.22-2.87; p=0.004). In addition, the HPR-PFCS High group had a greater rate of MACE compared with the HPR-PFCS Low group (HR adj : 1.47; 95% CI: 1.04-2.09; p=0.03). Similar results were revealed in the risk of all-cause death. Compared with HPR-PFCS Low , NPR-PFCS Low was associated with a higher major bleeding rate (HR adj : 3.03; 95% CI: 1.27-7.14; p=0.01). Conclusions: In PCI-treated patients, PFCS and HPR phenotypes show important relationships in the occurrence of adverse clinical events. Therefore, a combined assessment of clot strength and platelet reactivity may enhance post-PCI risk stratification.

Abstract 12563: Creation of an Artificial Intelligence Model For Prediction of Major Adverse Cardiovascular Events Late After Tetralogy of Fallot Repair

Introduction and Hypothesis: Despite successful tetralogy of Fallot repair (rTOF) in childhood, advancing age is associated with escalating risk of morbidity and mortality. Published risk scores for prediction of major adverse cardiovascular events (MACE) typically incorporate invasive and/or specialized measures. We hypothesized that an artificial intelligence (AI) model using an array of parameters available in routine clinical practice could successfully predict MACE in rTOF. Methods: Adults with rTOF were identified using institutional databases (the prospective observational Comprehensive Outcomes Registry Late After Tetralogy of Fallot Repair [CORRELATE] and the retrospective Toronto Outcomes Registry of Congenital Heart disease [TORCH]). A random forest AI model for prediction of MACE was trained on CORRELATE using repeated random sub-sampling validation. External validation was achieved using non-overlapping retrospective data from TORCH. The MACE composite outcome included all-cause mortality, resuscitated sudden death, sustained ventricular tachycardia (>30 seconds) or heart failure (hospital admission>24 hours). Results: In total, 804 subjects were studied and MACE was observed in 73 (9%) subjects. Patients were either included in the training dataset (n=312, 59% male, median age 32 years [IQR 23-43], median follow-up 6 years [IQR 4-7]) or the testing dataset (n=492, 58% male, median age 26 years [IQR 20-37], median follow up 10 years [IQR 6-10]). Variables incorporated into the AI model are shown (Figure 1). Predictive capacity of the AI models were similar in testing (AUC 0.81, CI 0.75-0.86) and training (AUC 0.88, CI 0.71-0.99) datasets with excellent receiver operating characteristics (Figure 1). Conclusions: An AI model based on routinely used and widely available clinical and imaging variables could successfully predict MACE in rTOF. Further study is required to determine the value of AI for risk management in rTOF.

Abstract 13415: Coronary Calcium Score on Standard of Care Oncologic CT Scans for the Prediction of Adverse Cardiovascular Events in Patients With Non-Small Cell Lung Cancer Treated With Concurrent Chemoradiotherapy

Introduction: Chemoradiotherapy (CRT) has been associated with increased incidence of cardiovascular (CV) adverse events (CAE) including coronary events. Coronary calcium scoring (CAC) has shown to predict coronary events beyond the traditional CV risk factors. This study examines whether CAC, measured on standard, non-gated, non-contrast chest CT (NCCT) imaging, predicts the development of CAE in patients with non-small cell lung cancer (NSCLC) treated with CRT. Methods: Patients with NSCLC who were treated with CRT at MD Anderson Cancer Center from 7/2009 until 4/2014 and who had at least one NCCT scan within 6 months from their first CRT were identified. CAC scoring was performed on NCCT scans by an expert cardiologist and a cardiac radiologist following the 2016 SCCT/STR guidelines (software: Syngo.Via, Siemens Healthcare). CAE were graded based on the most recent Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. CAE were also grouped into i. coronary/vascular events ii. arrhythmias iii. heart failure or iv. pericardial disease. All CAE were adjudicated by a board-certified cardiologist. Results: Out of a total of 193 patients, 45% were female and 91% were white. Median age was 65 years (IQR: 58-72) and median BMI was 27 kg/m 2 (24-32). Of 193 patients, 142 (74%) had CAC > 0 Agatston units (AU), 93 (48%) had CAC > 100 AU and 36 (49%) CAC > 300 AU. Twenty-nine patients (15%) developed a grade > 2 CAE during a median follow up of 26.2 months (12.7-53.5). Of those, 11 (38%) were coronary/vascular events. In the multivariate cox regression analysis, controlling for mean heart dose and pre-existing heart disease, higher CAC was independently associated with development of a grade > 2 CAE (HR: 1.04, 95% CI: 1.01-1.08, p=0.022) and with worse OS (CAC > 100 AU, HR: 1.64, 95% CI: 1.11-2.44, p=0.013). In a sub-analysis evaluating the type of the CAE, it was the coronary/vascular events that were significantly associated with higher baseline CAC (median: 676 AU vs 73 AU, p=0.035). Conclusions: CAEs are frequent in patients with NSCLC treated with CRT. CAC calculated on “standard of care” NCCT can predict the development of CAEs and specifically coronary/vascular events, as well as OS, independently from other traditional risk factors and radiation mean heart dose.

Abstract 13582: Biomarkers of Adverse Cardiovascular Events in Chronic Coronary Disease: Data From the ISCHEMIA Trial

Introduction: Circulating biomarkers may improve prediction of cardiovascular (CV) events in chronic coronary disease (CCD). The incremental value of biomarkers in CCD after adjustment for clinical factors, inducible ischemia and coronary artery disease (CAD) severity is uncertain. Methods: 756 ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) participants with site-determined moderate-severe ischemia and 9 assayed biomarkers (Figure) were included. Among participants with interpretable stress tests for ischemia and CAD by computed coronary tomography angiography (CCTA) (N=507), associations of biomarkers with the primary (CV death, myocardial infarction (MI), or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest) or secondary endpoints (CV death or MI) were evaluated using sequentially adjusted multivariable Cox proportional hazards models (Model 1=unadjusted, Model 2=clinical features, Model 3=Model 2 + multivessel CAD by CCTA, and Model 4=Model 3 + severe ischemia). Results: Median (IQR) participant age was 64 (57-70) years, 19% were female, 81% white, and 5% Hispanic. Hypertension (85%), diabetes (46%) and obesity (45%) were common, 28% had an estimated glomerular filtration rate <60 ml/min/1.73m 2 . Severe ischemia was present in 44%, and 39% had multivessel CAD (≥70% stenosis) by CCTA. Over 3.5 (2.4-4.7) years of follow-up there were 146 (19%) primary and 128 (17%) secondary endpoints. Soluble CD40L, GDF-15, NT-proBNP, hsTnT were associated with the primary and secondary endpoints in univariable and multivariable (adjusting for clinical features, multivessel CAD and severe ischemia) models. Conclusion: Biomarkers of inflammation (GDF-15), thrombosis (sCD40L), myocardial stretch (NT-proBNP) and injury (hs-troponin) were associated with CV endpoints in the ISCHEMIA trial independent of clinical features, multivessel CAD and severe ischemia.

Development and Validation of a Cardiovascular Disease Risk Prediction Model for Patients with Non-Dialysis-Dependent Chronic Kidney Diseases Based on the Nomogram

Introduction: Most chronic kidney disease (CKD) patients experience cardiovascular issues before commencing renal replacement therapy. An accuracy prediction model is helpful for physicians to assess cardiovascular prognoses in each individual and to provide insights on how to outline individualized lines of therapy. Method: This study enrolled 1,138 participants with non-dialysis-dependent chronic kidney disease (NDD-CKD). Following a proportion of 7:3, patients were randomly assigned to training and validation cohorts. The relevant predictors of cardiovascular events were screened using the least absolute shrinkage and selection operator (Lasso) regression. The area under the receiver operating characteristic curve (AUC) and the calibration curve with 1,000 bootstrap resamples were used to assess the nomogram’s performance. Tests on the discrimination of the prediction model used Kaplan-Meier (KM) curve. Results: After screening all the predictors by lasso regression, the five remaining ones (albumin, estimated glomerular filtration rate, etiology of CKD, cardiovascular disease history, and age) were used to construct the prediction model. The AUCs of 1 year, 2 years, and 3 years were 0.81 (95% CI = 0.75–0.87), 0.80 (95% CI = 0.75–0.86), and 0.80 (95% CI = 0.73–0.86), respectively. The calibration curve and the KM curve showed good prediction features, and the external validation also had a good prediction performance (AUCs of 1, 2, and 3 years were 0.77, 0.84, and 0.82, respectively). Conclusion: We successfully developed a novel nomogram that has decent prediction performance and can be used for assessing the probability of cardiovascular events in patients with NDD-CKD, displaying valuable potential for clinical application.

Abstract 13368: Effect of Peripheral Endothelial Function Assessment in Improving the Risk Stratification of Major Cardiovascular Events Beyond CHA2DS2-Vasc

Introduction: Peripheral microvascular endothelial dysfunction (PMED) is a marker and precursor of atherosclerosis and is associated with an increased risk of cardiovascular events. The present study aims to identify the best cut-off value of PMED, assessed by the reactive hyperemia index, in predicting major adverse cardiovascular events (MACE). Additionally, we investigate whether integrating PMED to CHA2DS2-Vasc score improves the predicting accuracy of cardiovascular disease. Methods: this is a retrospective study of patients who underwent reactive hyperemia peripheral arterial tonometry (PAT). The optimal cut-off value of reactive hyperemia index associated with MACE was calculated using the area under the receiver-operating curve and the maximum Youden index. Traditional cardiovascular risk factors such as age, sex, congestive heart failure, hypertension, diabetes, stroke, vascular disease were determined to calculate the CHA2DS2-VASc score. MACE was defined as myocardial infarction, heart failure hospitalization, and cerebrovascular events. Results: 1,690 patients were enrolled (average age 51.1±13.9, 64.1% female). The optimal cut-off value of the reactive hyperemia index was 2.0 in the overall population and females and 2.17 in males. The risk of MACE during 10 (Interquartile range: 4,16) years of follow-up was 15.3%. Multivariable logistic regression revealed that PMED as an independent predictor of MACE (PMED: OR, 3.6, 95% CI, 2.6-4.9, p<0.001) (Table1). Furthermore, integrating PMED to CHA2DS2-VASc significantly improved the predictive accuracy (area under the curve, 0.747 vs. 0.708, p<0.001). Conclusion: PMED is a strong predictor of cardiovascular events. Non-invasive assessment of peripheral endothelial function may be useful in early detection and improving the stratification of high-risk patients for cardiovascular events.

Abstract 10747: Left Atrial Volume Index is Associated With New-Onset Heart Failure Admission and Cardiovascular Death in Patients With Asymptomatic Moderate Aortic Stenosis

Background: Left atrium enlargement is the marker of increased left ventricular (LV) filling pressure and morphological indicator of chronically increased hemodynamic burden. However, the potential utility and clinical significance of left atrial volume (LAV) index in asymptomatic moderate aortic stenosis (AS) patients have been unknown. Therefore, we assessed the impact of LAV index on cardiovascular events in asymptomatic moderate AS patients. Methods: We retrospectively analyzed 549 patients (mean age 79±13 years) with asymptomatic moderate AS (mean transaortic pressure gradient 20 to 39 mmHg) and LVEF ≥50 %. Cardiovascular events were defined as cardiovascular death or admission for heart failure (HF). Results: During a follow-up period (median, 1301 days; range, 296 to 2179 days), 216 patients underwent aortic valve replacement (AVR) or balloon aortic valvuloplasty (BAV), and 132 HF admission and 37 cardiovascular deaths occurred. In the multivariable analysis, LAV index, lateral E/e′, and peak tricuspid regurgitation velocity were independent predictors of cardiovascular events (Hazard ratio (HR) 1.07 [1.05 to 1.09]; HR 1.04 [1.00 to 1,08]; HR 1.04 [1.00 to 1.07], respectively) after adjusting for age, female, body mass index, previous myocardial infarction, atrial fibrillation, chronic kidney disease, chronic obstructive pulmonary disease, moderate mitral regurgitation, E velocity, LV hypertrophy, and surgical or transcatheter AVR or BAV. LAV index of 27 mL/m 2 was the optimal cutoff value for predicting cardiovascular events with sensitivity of 89% and specificity of 60% and C-statistics for LAV index demonstrated superiority to lateral E/e′ and peak tricuspid regurgitation velocity ( P <0.001) (Figure). Conclusion: LAV index is an important predictor for cardiovascular events in asymptomatic moderate AS patients.

Abstract 10409: Performance of the Hart Cve Panel for Prediction of Cardiovascular Events in Patients With Chronic Kidney Disease

Background: Patients with chronic kidney disease (CKD) are at increased risk for cardiovascular events (CVE: incident myocardial infarction [MI], stroke, or cardiovascular death) following an angiographic procedure. Methods: Among 446 patients undergoing coronary or peripheral angiography, we applied a previously-developed biomarker panel to predict incident cardiovascular events (HART CVE, Prevencio, Kirkland WA); the panel consists of 4 biomarkers (N-terminal pro-B type natriuretic peptide, kidney injury molecule-1, osteopontin, and tissue inhibitor of matrix metalloproteinase-1) with results expressed in 2 risk levels (CVE high risk and low risk). Patients were followed for 2 years for incident cardiovascular events. Results: During the 2-year follow-up, 74 CVE occurred. Participants were categorized into four groups based on CKD stages (Stage 1-2 vs Stage 3-5) and CVE risk level (high risk and low risk). In our multivariable model, considering patients at CKD stage 1-2/CVE low-risk as a reference, the hazard ratio (95 % confidence interval) of cardiovascular events was 2.28 (1.53-5.22) for CKD stage 1-2/CVE high-risk, 0.50 (0.07-3.73) for CKD stage 3-5/CVE low-risk and 4.56 (2.54-8.18) for CKD stage 3-5/CVE high-risk ( Table ). The C-statistic for predicting 2-years cardiovascular events in all 446 patients was 0.77 (0.72, 0.82). Conclusion: Patients with CKD are at high risk for incident MI, stroke, and CV death. Utilizing a multiple-protein biomarker panel can assist clinicians in identifying patients at higher risk of CVE, particularly among those at high stages of CKD.

Abstract 11074: A Model for Predicting Cardiovascular Events in Acute Decompensated Heart Failure Patients With Decreased Renal Function

Background: The models for predicting cardiovascular events, including medication data such as dosage and the number of medications, have not been well studied. This study aimed to develop a model, including medication data, for predicting cardiovascular events within one year after discharge in acute decompensated heart failure (ADHF) patients with decreased renal function. Methods This study included 443 first-time admitted ADHF patients with decreased renal function in the Showa University Fujigaoka Hospital between January 2015 and December 2019. Decreased renal function was defined as an eGFR < 60 mL/min/1.73 m 2 at discharge. The primary outcome was cardiovascular events (cardiovascular death and first heart failure rehospitalization) within one year after discharge. The model for predicting events was developed using predictive factors extracted by multivariate analysis. The cardiovascular events curves were visualized using the Kaplan-Meier method and estimated using a log-rank test. Results The incidence of cardiovascular events was 20.1%. By multivariate analysis, atrial fibrillation (AF), weight loss < 5% during admission, brain natriuretic peptide (BNP) ≥ 200 pg/mL at discharge, polypharmacy (≥ 10 drugs), and beta-blockers use below the maintenance dosage were significantly associated with an increased risk of cardiovascular events. The hazard ratios of the five factors for the cardiovascular events were scored (AF, weight loss, polypharmacy, and beta-blockers dosage = 1 point; BNP = 2 points) and patients divided into three groups. The cardiovascular events rate in the high-risk (≥ 4 points) group was four times as high as the rate in the low-risk (≤ 2 point) group (one-year events rate: 41.0% vs 9.2%, p < 0.001, Figure). Conclusions The developed model for cardiovascular events, including polypharmacy and beta-blockers dosage, will be useful for planning more aggressive and earlier management in ADHF patients with decreased renal function.

Prediction of major adverse cardiovascular events in patients with acute coronary syndrome: Development and validation of a non-invasive nomogram model based on autonomic nervous system assessment.

Disruption of the autonomic nervous system (ANS) can lead to acute coronary syndrome (ACS). We developed a nomogram model using heart rate variability (HRV) and other data to predict major adverse cardiovascular events (MACEs) following emergency coronary angiography in patients with ACS. ACS patients admitted from January 2018 to June 2020 were examined. Holter monitors were used to collect HRV data for 24 h. Coronary angiograms, clinical data, and MACEs were recorded. A nomogram was developed using the results of Cox regression analysis. There were 439 patients in a development cohort and 241 in a validation cohort, and the mean follow-up time was 22.80 months. The nomogram considered low-frequency/high-frequency ratio, age, diabetes, previous myocardial infarction, and current smoking. The area-under-the-curve (AUC) values for 1-year MACE-free survival were 0.790 (95% CI: 0.702-0.877) in the development cohort and 0.894 (95% CI: 0.820-0.967) in the external validation cohort. The AUCs for 2-year MACE-free survival were 0.802 (95% CI: 0.739-0.866) in the development cohort and 0.798 (95% CI: 0.693-0.902) in the external validation cohort. Development and validation were adequately calibrated and their predictions correlated with the observed outcome. Decision curve analysis (DCA) showed the model had good discriminative ability in predicting MACEs. Our validated nomogram was based on non-invasive ANS assessment and traditional risk factors, and indicated reliable prediction of MACEs in patients with ACS. This approach has potential for use as a method for non-invasive monitoring of health that enables provision of individualized treatment strategies.

Diabetic retinopathy predicts cardiovascular disease independently of subclinical atherosclerosis in individuals with type 2 diabetes: A prospective cohort study

Diabetic retinopathy (DR) and preclinical atherosclerosis are associated with higher cardiovascular risk. However, no studies have investigated the predictive role of DR and preclinical atherosclerosis jointly on cardiovascular events in subjects with type 2 diabetes (T2D). We aimed to assess the contribution of DR and subclinical atherosclerosis on the risk of adverse cardiovascular events in subjects with T2D without previous cardiovascular disease (CVD). We included two prospective cohorts of subjects with T2D from the same geographical area. Assessment of subclinical atherosclerosis was performed by carotid ultrasound. An ophthalmologist classified DR according to standard criteria. Cardiovascular outcomes considered for analysis were the following: ischemic heart disease, stroke, heart failure, peripheral artery disease, revascularization procedures, and cardiovascular mortality. Bivariable and multivariable predictive models were performed. From a total of 374 subjects with T2D 44 developed cardiovascular events during the 7.1 years of follow-up. Diabetes duration, total cholesterol, and glycated hemoglobin (HbA1c) at baseline were higher in subjects who developed cardiovascular outcomes (p < 0.001, p = 0.026, and p = 0.040, respectively). Compared with subjects without events, those developing cardiovascular events had higher prevalence of retinopathy (65.9% vs. 38.8%, p = 0.001; respectively) and more than mild retinopathy (43.2% vs. 31.8%, p = 0.002; respectively). Furthermore, all-cause mortality was higher in subjects with MACE than those without events (13.6% vs. 3.3%, p = 0.009; respectively). The multivariable analyses showed that HbA1c and the presence of DR at baseline were predictive of cardiovascular outcomes (p = 0.045 and p = 0.023, respectively). However, the burden of subclinical atherosclerosis was not (p = 0.783 and p = 0.071, respectively). DR is a strong predictor of cardiovascular events in T2D individuals at primary CVD prevention, even after accounting for the presence of preclinical carotid atherosclerosis. These results may help to individualize CVD prevention strategies in T2D.

Predictive significance of a complex approach in determining the vascular wall stiffness parameters in patients with arterial hypertension and in patients with arterial hypertension after ischemic stroke

The article presents the information about the predictive significance of a complex approach in determining vascular wall stiffness parameters. A total of 159 people with arterial hypertension (AH) and AH after a previous ischemic stroke were examined. A model with a conditional linear predictor (LP) was constructed, using a binary regression equation with a probit-link function for prediction of cardiovascular events. LP is a combination of indicators such as age (А), glomerular filtration rate (CKD-EPI), pulse wave velocity (PWV), intima- media thickness (IMT), cardio-ankle vascular index (CAVI) and augmentation index (AI). The equation has the following form: LP = –6.6139 – 0.0978A + 0.031CKDEPI + 0.0758PWV + 3.2086IMT + 0.4421CAVI + 1.2429AI. The cut-off threshold for LP = 0.0238, sensitivity (Se) 85.71 %, specificity (Sp) 77 % and accuracy (Acc) 78.07 %.

Cardiovascular Risk Reduction After Renal Denervation According to Time in Therapeutic Systolic Blood Pressure Range

BackgroundRenal denervation (RDN) has been shown to lower blood pressure (BP), but its effects on cardiovascular events have only been preliminarily evaluated. Time in therapeutic range (TTR) of BP is associated with cardiovascular events. ObjectivesThis study sought to assess the impact of catheter-based RDN on TTR and its association with cardiovascular outcomes in the GSR (Global SYMPLICITY Registry). MethodsPatients with uncontrolled hypertension were enrolled and treated with radiofrequency RDN. Office and ambulatory systolic blood pressure (OSBP and ASBP) were measured at 3, 6, 12, 24, and 36 months postprocedure and used to derive TTR. TTR through 6 months was assessed as a predictor of cardiovascular events from 6 to 36 months using a Cox proportional hazard regression model. ResultsAs of March 1, 2022, 3,077 patients were enrolled: 42.2% were female; mean age was 60.5 ± 12.2 years; baseline OSBP was 165.6 ± 24.8 mm Hg; and baseline ASBP was 154.3 ± 18.7 mm Hg. Patients were prescribed 4.9 ± 1.7 antihypertensive medications at baseline and 4.8 ± 1.9 at 36 months. At 36 months, mean changes were −16.7 ± 28.4 and −9.0 ± 20.2 mm Hg for OSBP and ASBP, respectively. TTR through 6 months was 30.6%. A 10% increase in TTR after RDN through 6 months was associated with significant risk reductions from 6 to 36 months of 15% for major adverse cardiovascular events (P < 0.001), 11% cardiovascular death (P = 0.010), 15% myocardial infarction (P = 0.023), and 23% stroke (P < 0.001). ConclusionsThere were sustained BP reductions and higher TTR through 36 months after RDN. A 10% increase in TTR through 6 months was associated with significant risk reductions in major cardiovascular events from 6 to 36 months. (Global SYMPLICITY Registry [GSR] DEFINE; NCT01534299)

Discovery of four plasmatic biomarkers potentially predicting cardiovascular outcome in peripheral artery disease

Peripheral artery disease (PAD) patients have an increased cardiovascular risk despite pharmacological treatment strategies. Biomarker research improving risk stratification only focused on known atherothrombotic pathways, but unexplored pathways might play more important roles. To explore the association between a broad cardiovascular biomarker set and cardiovascular risk in PAD. 120 PAD outpatients were enrolled in this observational cohort study. Patients were followed for one year in which the composite endpoint (myocardial infarction, coronary revascularization, stroke, acute limb ischemia and mortality) was assessed. Patient data and blood samples were collected upon inclusion, and citrated platelet-poor plasma was used to analyze 184 biomarkers in Olink Cardiovascular panel II and III using a proximity extension assay. Fifteen patients reached the composite endpoint. These patients had more prior strokes and higher serum creatinine levels. Multivariate analysis revealed increased plasma levels of protease-activated receptor 1 (PAR1), galectin-9 (Gal-9), tumor necrosis factor receptor superfamily member 11A (TNFRSF11A) and interleukin 6 (IL-6) to be most predictive for cardiovascular events and mortality. Positive regulation of acute inflammatory responses and leukocyte chemotaxis were identified as involved biological processes. This study identified IL-6, PAR1, Gal-9, TNFRSF11A as potent predictors for cardiovascular events and mortality in PAD, and potential drug development targets.