Recurrent Cardiovascular Events Research Articles

Major Adverse Cardiovascular Event Risk Prediction in Asian Patients After Myocardial Infarction: A Novel, Dynamic, Machine-learning Approach

Background: Cardiovascular disease remains the leading cause of death worldwide. Existing risk scores often focus on primary cardiovascular event prediction among mostly North American and European populations with predictors derived from baseline before and up to index events. Methods: We aim to build machine learning algorithms to model recurrent cardiovascular events among Asian post-MI patients via a retrospective observational cohort study. The study uses multicentre, real-world electronic health records from the Singapore Cardiovascular Longitudinal Outcomes Database (SingCLOUD), integrating nationwide clinical, administrative, laboratory, procedural and medication data from five public hospitals and 18 public outpatient clinics. Data from 4,575 patients admitted between 2011 and 2014 with MI as a primary diagnosis were included in the analysis. Their major adverse cardiovascular events (MACE) risk was modelled using a static approach with baseline and index event information and a dynamic approach which incorporates additional post-discharge data including medication adherence. Results: The static model achieved an area under the receiver operator curve (AUROC) of 0.77 (95% CI [0.72–0.82]) when predicting 1-year MACE risk and 0.80 (95% CI [0.76–0.85]) predicting 2-year MACE risk on a hold-out dataset (n=515); the dynamic model achieved a mean AUROC of 0.75 (95% CI [0.72–0.78]) in estimating 1-year MACE risk from 3, 6, 9 and 12 months post-index. Conclusion: We developed a focused risk model for an Asian population, incorporating post-MI time-variable information via the causal approach. The causal framework enables differentiation of immediate risk components from long-term disease progression, including disease management. The model outperforms existing benchmark risk scores and can be applied to simulate personalised disease trajectory and to inform treatment options.

Economic Burden Associated with the Treatment with a Cardiovascular Polypill in Secondary Prevention in Spain: Cost-Effectiveness Results of the NEPTUNO Study.

The aim of this study was to estimate health-care resources utilization, costs and cost-effectiveness associated with the treatment with CNIC-Polypill as secondary prevention of atherosclerotic cardiovascular disease (ASCVD) compared to other treatments, in clinical practice in Spain. An observational, retrospective study was performed using medical records (economic results [healthcare perspective], NEPTUNO-study; BIG-PAC-database) of patients who initiated secondary prevention between 2015 and 2018. Patients were followed up to 2 years (maximum). Four cohorts were balanced with a propensity-score-matching (PSM): 1) CNIC-Polypill (aspirin+atorvastatin+ramipril), 2) Monocomponents (same separate drugs), 3) Equipotent (equipotent drugs) and 4) Other therapies ([OT], other cardiovascular drugs). Incidence of cardiovascular events, health-care resources utilization and healthcare and non-healthcare costs (2020 Euros) were compared. Incremental cost-effectiveness ratios per cardiovascular event avoided were estimated. After PSM, 1614 patients were recruited in each study cohort. The accumulated incidence of cardiovascular events during the 24-month follow-up was lower in the CNIC-Polypill cohort vs the other cohorts (19.8% vs Monocomponents: 23.3%, Equipotent: 25.5% and OT: 26.8%; p<0.01). During the follow-up period, the CNIC-Polypill cohort also reduced the health-care resources utilization per patient compared to the other cohorts, particularly primary care visits (16.6 vs Monocomponents: 18.7, Equipotent: 18.9 and OT: 21.0; p<0.001) and hospitalization days (2.3 vs Monocomponents: 3.4, Equipotent: 3.7 and OT: 4.0; p<0.001). The treatment cost in the CNIC-Polypill cohort was lower than that in the other cohorts (€4668 vs Monocomponents: €5587; Equipotent: €5682 and OT: €6016; p<0.001) (Difference: -€919, -€1014 and -€1348, respectively). Due to the reduction of cardiovascular events and costs, the CNIC-Polypill is a dominant alternative compared to the other treatments. CNIC-Polypill reduces recurrent major cardiovascular events and costs, being a cost-saving strategy as secondary prevention of ASCVD.

Higher risk of future events, mortality and greater healthcare use among patients with increasingly recurrent atherosclerotic cardiovascular disease events in Taiwan: a retrospective cohort study

ObjectivesTo describe the occurrence of recurrent atherosclerotic cardiovascular disease (ASCVD) events within 3 years after a new-onset event, the associated disease burden and statin prescribing in patients with ASCVD in...

† Evaluating the Residual Risk of Recurrent Cardiovascular Events in Contemporary Cardiovascular Outcomes Trials

† Evaluating the Residual Risk of Recurrent Cardiovascular Events in Contemporary Cardiovascular Outcomes Trials

Development and validation of a risk prediction algorithm for recurrent cardiovascular events in the Chinese population: P-CARDIAC.

Existing cardiovascular disease (CVD) risk prediction tools may not be applicable to the Chinese populations because of their development based on the mostly Western cohorts and limited list of covariates. To develop and validate a machine learning-based risk prediction model that can be used by primary care physicians in Hong Kong, Personalized CARdiovascular DIsease risk Assessment for Chinese (P-CARDIAC), to predict 10-year CVD risk among the Chinese population. A novel algorithm based on the Hong Kong West Cluster cohort was designed by Cox proportional hazards (CPH) model with LASSO for shortlisting statistically significant risk factors and XGBoost to achieve better performance and interpretability by medical professionals. The internal validation was performed by 100 repeats of 10-fold cross-validation while the external validation was evaluated in two other independent cohorts with the comparison of TIMI risk score and SMART2. A total of 48 799 participants with prior CVD events were included and externally validated by two other Hong Kong cohorts with 119 672 and 140 533 participants. The novel algorithm had better performance than the CPH model with a 0.69 C-statistic. The external validation showed great model calibration and clinical utility with 0.62 and 0.64 C-statistic, respectively, for the two cohorts; while both TIMI and SMART2 were underperforming. Medication treatments also had a strong correlation with recurrent CVD. P-CARDIAC allows a more personalised approach for recurrent CVD prevention with dynamic baseline risk and concurrent medication effect. Such an approach with the potential for being recalibrated for other ethnicities will be used in primary care for managing CVD risk.

A Curious Case of Acute STEMI in a Young Patient; Things are Not Always What They Seem

BACKGROUND: Acute myocardial infarction (MI) is a rare occurrence in patients under 40 years of age without positive family history for coronary artery disease (CAD). Genetic conditions as inherited thrombophilia can lead to a hypercoagulable state, resulting in thromboembolic events and arterial thrombosis. CASE SUMMARY: We present a case of a 35-year-old male patient who presented to the emergency room with an inferior MI after a strenuous cycling exercise. An urgent coronary angiography showed thrombotic formations in the right coronary artery without atherosclerotic plaques. Plain old balloon angioplasty and thrombus aspiration were performed, which was followed by GP IIb/IIIa inhibitor infusion and unfractionated heparin for 24 h. From past medical history, the patient had COVID-19 like symptoms 20 days before the event and had his first dose of anti- COVID vaccine 2 weeks prior. After additional testing, molecular genetic analysis results revealed the patient to be heterozygous for factor V Leiden (FVL) and homozygous for methylenetetrahydrofolate reductase C677T gene mutation. The patient was discharged on direct oral anticoagulant and antiplatelet therapy. After 1-year follow-up, he had no symptoms or recurrent cardiovascular events. CONCLUSION: Inherited thrombophilia is а significant risk factor for CAD and performing genetic testing in younger patients with a cardiovascular event and plays an important role for adequate treatment and prophylaxis from recurrent complications. The use of oral anticoagulation for prophylaxis is shown to be effective in these patients. However, further studies are needed to prove their exact role and duration of treatment.

Coste-efectividad de la polipíldora CNIC frente a los monocomponentes separados en prevención secundaria cardiovascular en España

Introduction and objectivesDespite advances in treatment, cardiovascular disease is the second leading cause of death in Spain. The objective of this study was to determine the cost-effectiveness of the CNIC-Polypill strategy (acetylsalicylic acid 100mg, atorvastatin 20/40mg, ramipril 2.5/5/10mg) compared with the same separate monocomponents for the secondary prevention of recurrent cardiovascular events in adults in Spain. Materials and methodsA Markov cost-utility model was adapted considering four health states (stable, subsequent major adverse cardiovascular event, subsequent ischemic stroke and death) and the SMART risk equation over a lifetime horizon from the perspective of the Spanish National Healthcare System. The CNIC-Polypill strategy was compared with monocomponents in a hypothetical cohort of 1000 secondary prevention patients. Effectiveness, epidemiological, cost and utilities data were obtained from the NEPTUNO study, official databases and literature. Outcomes were costs (in 2021euros) per life-year (LY) and quality-adjusted LY (QALY) gained. A 3% discount rate was applied. Deterministic one-way and probabilistic sensitivity analyses evaluated the robustness of the model. ResultsThe CNIC-Polypill strategy in secondary prevention results in more LY (13.22) and QALY (11.64) gains at a lower cost than monocomponents. The CNIC-Polypill is dominant and saves €280.68 per patient compared with monocomponents. The probabilistic sensitivity analysis shows that 82.4% of the simulations are below the threshold of €25,000 per QALY gained. ConclusionsThe CNIC-Polypill strategy in secondary cardiovascular prevention is cost-effective compared with the same separate monocomponents, resulting in a cost-saving strategy to the Spanish National Healthcare System.

Contemporary Treatment and Outcome of Patients with Ischaemic Lower Limb Amputation: A Focus on Sex Differences

Chronic limb threatening ischaemia (CLTI) has a devastating prognosis with high rates of lower limb amputation (LLA) and deaths. This is an illustration of contemporary management and the long term fate of patients after ischaemic LLA, particularly with respect to sex, using real world data. This was a multisectoral cross sectional and longitudinal analysis of health claims data from the largest German health insurance database (AOK). Data of 39 796 propensity score matched patients hospitalised for ischaemic LLA between 2010 and 2018 were analysed for cardiovascular comorbidities, treatment, and for subsequent cardiovascular and limb events, with a distinct focus on sex. Matching was performed, to ensure that the rate of major amputations and the age distribution were equal in both groups (in both sexes). An observation period of two years before index and a follow up (FU) period until 2019 were included. Before index amputation, 68% of patients had received any kind of peripheral revascularisation. The use of statins (37.0% vs. 42.6%) and antithrombotic substances (54.9% vs. 61.8%) was lower in women than in men (p < .001). During two year FU, cardiovascular and limb events occurred among women and men as follows: limb re-amputation (26.7% vs. 31.2%), myocardial infarction (10.9% vs. 14.5%), stroke (20.8% vs. 20.7%), and death from any cause (51.0% vs. 53.3%, p < .001 except for stroke). After adjustment for cardiovascular comorbidities and vascular procedures, female sex was associated with a higher probability of death (HR 1.04, 95% CI 1.04 - 1.04). Patients undergoing ischaemic LLA still have a poor prognosis marked by high rates of recurrent cardiovascular and limb events resulting in a > 50% mortality rate within two years. The continuous lack of guideline recommended therapies, particularly in women, may be associated with the persisting poor outcome, necessitating urgent further investigation.

Cost-effectiveness of the CNIC-Polypill versus separate monocomponents in cardiovascular secondary prevention in Spain

Introduction and objectivesDespite advances in treatment, cardiovascular disease is the second leading cause of death in Spain. The objective of this study was to determine the cost-effectiveness of the CNIC-Polypill strategy (acetylsalicylic acid 100 mg, atorvastatin 20/40 mg, ramipril 2.5/5/10 mg) compared with the same separate monocomponents for the secondary prevention of recurrent cardiovascular events in adults in Spain. Materials and methodsA Markov cost-utility model was adapted considering 4 health states (stable, subsequent major adverse cardiovascular event, subsequent ischemic stroke and death) and the SMART risk equation over a lifetime horizon from the perspective of the Spanish National Healthcare System. The CNIC-Polypill strategy was compared with monocomponents in a hypothetical cohort of 1000 secondary prevention patients. Effectiveness, epidemiological, cost and utilities data were obtained from the NEPTUNO study, official databases and literature. Outcomes were costs (in 2021 euros) per life-year (LY) and quality-adjusted LY (QALY) gained. A 3% discount rate was applied. Deterministic one-way and probabilistic sensitivity analyses evaluated the robustness of the model. ResultsThe CNIC-Polypill strategy in secondary prevention results in more LY (13.22) and QALY (11.64) gains at a lower cost than monocomponents. The CNIC-Polypill is dominant and saves є280.68 per patient compared with monocomponents. The probabilistic sensitivity analysis shows that 82.4% of the simulations are below the threshold of є25,000 per QALY gained. ConclusionsThe CNIC-Polypill strategy in secondary cardiovascular prevention is cost-effective compared with the same separate monocomponents, resulting in a cost-saving strategy to the Spanish National Healthcare System.

Tackling dynamic prediction of death in patients with recurrent cardiovascular events.

In the field of cardiovascular disease, recurrent events such as stroke or myocardial infarction (MI) are often encountered, leading to an increase in the risk of death. Accurately evaluating the prognosis of patients and dynamically predicting the risk of death by considering the historical recurrent events can improve medical decisions and lead to better health care outcomes. Recently proposed joint modeling approaches within the Bayesian framework have inspired the development of a dynamic prediction tool, which can be applied for subject-level prediction of death with implementation in software packages. The prediction model incorporates subject heterogeneity with subject-level random effects that account for unobserved time-invariant factors and an extra copula function capturing the part caused by unmeasured time-dependent factors. Thereafter, given the prespecified landmark time , the survival probability for a prediction horizon time of interest can be estimated for each individual. The prediction accuracy is assessed by time-dependent receiving operating characteristic curve and the area under the curve and the Brier score with calibration plots is compared to traditional joint frailty models. Finally, the tool is applied to patients with multiple attacks of stroke or MI in the Cardiovascular Health study and the Atherosclerosis Risk in Communities study for illustration.

Factors associated with diet quality among Brazilian individuals with cardiovascular diseases.

An individual's dietary pattern contributes in different ways to the prevention and control of recurrent cardiovascular events. However, the quality of the diet is influenced by several factors. The present study aimed to evaluate the quality of the diet of individuals with cardiovascular diseases and determine whether there is an association between sociodemographic and lifestyle factors. This is a cross-sectional study carried out with individuals with atherosclerosis (coronary artery disease, cerebrovascular disease or peripheral arterial disease) recruited from 35 reference centres for the treatment of cardiovascular disease in Brazil. Diet quality was assessed according to the Modified Alternative Healthy Eating Index (mAHEI) and stratified into tertiles. For comparing two groups, the Mann-Whitney or Pearson's chi-squared tests were used. However, for comparing three or more groups, analysis of variance or Kruskal-Wallis was used. For the confounding analysis, a multinomial regression model was used. p < 0.05 was considered statistically significant. In total, 2360 individuals were evaluated: 58.5% male and 64.2% elderly. The median (interquartile range [IQR]) of the mAHEI was 24.0 (20.0-30.0), ranging from 0.4 to 56.0 points. When comparing the odds ratios (ORs) for the low (first tertile) and medium (second tertile) diet quality groups with the high-quality group (third tertile), it was observed that there was an association between diet quality with a family income of 1.885 (95% confidence intervals [CI] = 1.302-2.729) and 1.566 (95% CI = 1.097-2.235), as well as physical activity of 1.391 (95% CI = 1.107-1.749) and 1.346 (95% CI = 1.086-1.667), respectively. In addition, associations were observed between diet quality and region of residence. A low-quality diet was associated with family income, sedentarism and geographical area. These data are extremely relevant to assist in coping with cardiovascular disease because they enable an assessment of the distribution of these factors in different regions of the country.

Associations of Serum 25(OH)D With Risk of Recurrent Cardiovascular Events in Individuals With Coronary Heart Disease.

Few studies have examined the relationship between vitamin D and the risk of recurrent cardiovascular (CV) events in people with coronary heart disease (CHD). This study aimed to investigate the associations of serum 25-hydroxyvitamin D (25(OH)D) concentration and the vitamin D receptor (VDR) polymorphisms with the risk of recurrent CV events in individuals with established CHD. A total of 22 571 participants with CHD were included from the UK Biobank. Recurrent CV events, including myocardial infarction (MI), heart failure (HF), stroke, and CV disease mortality, were identified from electronic health records. Cox proportional-hazard models were used to calculate hazard ratios (HRs) and 95% CIs. The median (interquartile range) of serum 25(OH)D concentration was 44.8 nmol/L (range, 30.3-61.4 nmol/L), and 58.6% of participants had 25(OH)D below 50 nmol/L. During a median follow-up of 11.2 years, a total of 3998 recurrent CV events were documented. After multivariable adjustment, there was a nonlinear inverse relationship between serum 25(OH)D and recurrent CV events (P nonlinearity <.01), and the decreasing risk gradually leveled off at around 50 nmol/L. Compared with participants with serum 25(OH)D less than 25.0 nmol/L, the HRs (95% CIs) for participants with serum 25(OH)D of 50.0 to 74.9 nmol/L were 0.64 (0.58-0.71) for recurrent CV events, 0.78 (0.65-0.94) for MI, 0.66 (0.57-0.76) for HF, and 0.66 (0.52-0.84) for stroke. In addition, these associations were not modified by genetic variants in the VDR. In people with established CHD, higher serum 25(OH)D concentrations were nonlinearly associated with a lower risk of recurrent CV events, with a potential threshold around 50 nmol/L. These findings highlight the importance of maintaining adequate vitamin D status in the prevention of recurrent CV events among individuals with CHD.

Time for Routine Helicobacter pylori Screening in Coronary Artery Disease?

Time for Routine Helicobacter pylori Screening in Coronary Artery Disease?

EXTREME CARDIOVASCULAR RISK IN CARDIOLOGICAL REHABILITATION: PREVALENCE AND IMPACT ON PATIENT'S FUNCTIONAL IMPROVEMENT

Objective: Among patients at very high cardiovascular risk, some are more likely to experience recurrent cardiovascular events. In may 2022, an article was published in the European Heart Journal proposing different definitions of patients at extreme cardiovascular risk. However, the process of defining the patient at extreme cardiovascular risk is still ongoing and more data also on its prevalence are needed. To assess the prevalence of patients at extreme cardiovascular risk in cardiological rehabilitation, to evaluate the clinical features of these patients. Furthermore, we want to establish how the extreme cardiovascular risk condition correlates with the functional improvement obtained during cardiac rehabilitation. Design and method: The study included 938 patients suffering from atherosclerosis who attended the cardiological rehabilitation of Niguarda Hospital in Milan. Patients diagnosed with non-ischemic heart failure or congenital heart disease have been excluded. Patients classified as at extreme cardiovascular risk were compared with the remaining patients and a multivariate linear regression was performed with absolute functional improvement as the dependent variable. Results: Among 938 patients, 26.9% belong to the category of extreme cardiovascular risk. Patients at extreme cardiovascular risk showed a higher average age (67.8 ± 10.4 vs 64.1 ± 11.1 years; p &lt;0.001), a higher prevalence of significant comorbidities (peripheral arterial disease, cerebrovascular disease, chronic kidney disease, dyslipidemia, diabetes, hypertension) and a lower functional improvement during cardiac rehabilitation (102.9 ± 68.6 vs 138.1 ± 86.5 m; p &lt; 0.001). At multivariate analysis extreme cardiovascular risk remains a significant determinant of the absolute functional improvement at Six-Minute Walking Test obtained during cardiac rehabilitation with b = -0.137 and p = 0.035, together with female sex (b = -0.136; p = 0.035). Conclusions: Extreme cardiovascular risk is a widespread condition among patients with chronic coronary syndrome and adversely affects the patient's functional improvement during cardiac rehabilitation. The identification of patients at extreme cardiovascular risk is a goal to be pursued in order to intensify secondary prevention strategies.

FACTORS ASSOCIATED WITH PROGRESSION OF ARTERIAL STIFFNESS IN ISCHEMIC STROKE SURVIVORS: THE NORWEGIAN STROKE IN THE YOUNG STUDY

Objective: Progressive arterial stiffening may contribute to risk for recurrent cardiovascular events in ischemic stroke survivors. Few studies have investigated sex differences in prospective change in arterial stiffness in this patient group. Design and method: Arterial stiffness by carotid-femoral pulse wave velocity (PWV) and ambulatory 24-hours blood pressure (BP) were assessed in 81 women and 190 men included in the Norwegian Stroke in the Young (NOR-SYS) study at 3 months and 5.5 years after the incident ischemic stroke. Results: At baseline patients were 49.5 ± 9.9 years old. Women had less prevalent hypertension (48 % vs. 62 %, p&lt;0.05) than men, while age, obesity and smoking prevalence did not differ significantly. During follow-up, BP increased from 129/79 mmHg to 133/83 mmHg in women (p&lt;0.05) and remained statistically unchanged in men (136/83 vs 139/84 mmHg, p = 0.10). Among patients with hypertension, 79% of women were treated at baseline and 77% at follow-up (p = ns), while antihypertensive treatment increased from 82% to 87% in men (p&lt;0.05). Daily smoking was reduced from 47% to 21% in women and from 51% to 21% in men (both p&lt;0.001). Fewer women than men were treated with statins at follow-up (63% vs. 76%, p&lt;0.05). PWV was lower in women than in men both at baseline (7.3 m/s vs. 8.1 m/s) and at follow-up (7.3 m/s vs. 8.0 m/s, both p&lt;0.001), but the average change during follow-up did not differ between genders. In linear regression analysis, increase in PWV was associated with higher 24-hour systolic BP, and lack of antihypertensive treatment at follow-up (both with p&lt;0.05); while no association was found with sex, smoking at follow-up or statin treatment (Table1). Conclusions: In ischemic stroke survivors, 5-year increase in PWV did not differ between the sexes and was associated with higher 24-hour systolic BP and lack of antihypertensive treatment, pointing to the importance of antihypertensive treatment in this patient group.

Effect of obstructive sleep apnea on prognosis in patients with acute coronary syndromes with varying numbers of standard modifiable risk factors: insight from the OSA-ACS study

BackgroundStandard modifiable risk factors (SMuRFs) increase the risk of cardiovascular events in patients with acute coronary syndrome (ACS) and are also strongly associated with obstructive sleep apnea (OSA) in a bidirectional relationship. However, the association of OSA with recurrent cardiovascular events in ACS patients based on the number of SMuRFs remains unclear. Hence, we aimed to elucidate the prognostic implication of OSA in ACS patients stratified by the number of SMuRFs.MethodsThis was a post hoc analysis of the OSA-ACS study (NCT03362385), including 1927 patients admitted for ACS and undergoing portable sleep monitoring. OSA was defined as an apnea hypopnea index ≥ 15 events/h. The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE) including cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina or heart failure, and ischemia-driven revascularization. Cox proportional hazards model and Kaplan-Meier analysis were used to investigated the relationship between OSA and subsequent cardiovascular events after patients were stratified by the number of SMuRFs.ResultsAmong 1927 patients enrolled, 130 (6.7%) had no SMuRF, 1264 (65.6%) exhibited 1–2 SMuRFs and 533 (27.7%) presented 3–4 SMuRFs. With the increase of the number of SMuRFs, the proportion of OSA in ACS patients tended to increase (47.7% vs. 51.5% vs. 56.6%), but there was no significant difference between them (P = 0.08). After the stratification of ACS patients via SMuRF numbers and adjustment for confounding factors, fully adjusted Cox regression indicated that OSA increased the risk of MACCE (adjusted HR, 1.65; 95%CI, 1.06–2.57; P = 0.026) and ischemia-driven revascularization (adjusted HR, 2.18; 95%CI, 1.03–4.65; P = 0.042) in ACS patients with 3–4 SMuRFs.ConclusionsIn hospitalized ACS patients, OSA is associated with an increased risk of MACCE and ischemia-driven revascularization among patients with 3–4 SMuRFs. Therefore, screening for OSA should be emphasized in ACS patients with 3–4 SMuRFs, and intervention trials should be prioritized in these high-risk patients.

Gender difference in the association between prediabetes and post-myocardial infarction prognosis

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Higher incident coronary heart disease in females with prediabetes compared to males is seen in the general population. This interaction in post-MI patients for recurrent events is largely unexplored. Purpose Explore the interaction between sex and newly diagnosed glycaemic abnormalities in terms of its association with recurrent cardiovascular events. Methods Retrospective analysis of a cohort of MI-survivors without known diabetes who had pre-discharge OGTT. MACE (death and non-fatal MI) had fasting (FPG) and 2-hour post-load plasma glucose (2h-PG), were recorded. Cox regression models adjusted for confounders were used. The modifying effect of sex on the association between MACE and, glycaemic groups or fasting or post-load glucose levels was tested by adding an interaction term combining gender and glycaemic category prediabetes (pDM) and new diabetes (NDM) (pDM*sex and NDM*sex) or glucose levels (FPG*sex and 2h-PG*sex) to the base model to additionally adjust for sex-specific confounding. Results Crude MACE was higher in women with pDM (35.8% v 16.7%, p=0.001) and men with NDM (29.6% v 17.3%, p=0.003) compared to normal glucose tolerance (NGT). Adjusted MACE was higher only in women with pDM (HR 2.15, 95% CI 1.24 to 3.72, p=0.007) and only in men with NDM (HR 1.57, 95% CI 1.01 to 2.42, p=0.044) compared to NGT. In pDM group, risk of MACE was higher in women compared to men (HR 1.72, 95% CI 1.13 to 2.60, p=0.011), (p for interaction=0.040) but not NDM (HR 0.83, 95% CI 0.43 to 1.60, p=0.575), (p for interaction=0.378). Increasing 2h-PG, but not FPG, was associated with MACE in both sexes with no sex interaction. Compared to NGT, IGT, not IFG, predicted MACE in women, (HR 2.08, 95% CI 1.21 to 3.57, p=0.008) but not in men, (p for interaction=0.043). 2h-PG determined NDM predicted MACE in men (HR 1.59, 95% CI 1.04 to 2.44, p=0.034) but not in women without sex interaction, (p for interaction=0.365) (Fig 2). Conclusion Female sex adversely modifies the association between 2h-PG determined pDM and post-MI MACE.

Patients with acute myocardial infarction and aortic valve sclerosis have an increased risk of recurrent myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Gigi e Pupa Ferrari ONLUS. Background It has been shown that atherosclerosis risk factors have been associated with aortic valve sclerosis (AVSc) and that AVSc is associated with both all-cause and cardiovascular mortality. Thus, it is not surprising that atherosclerotic disorders (e.g., carotid or coronary atherosclerosis) and AVSc often coexist in the same subject, eventually leading to acute myocardial infarction (AMI). Patients with AMI are at increased risk of recurrent cardiovascular events with an average all-cause mortality rate at 5 years of 25%. Therefore, it is crucial to identify the precise phenotype(s) that characterize(s) patients who will experience adverse events after AMI and AVSc may serve as a marker of risk. Purpose To evaluate whether AVSc can be an independent prognostic predictor in patients with AMI or a biomarker reflecting their comorbidity burden. Methods We analysed 2388 AMI patients who were admitted at our cardiology center (2010-2019). All patients underwent echocardiographic evaluation for AVSc assessment. Long-term all-cause mortality was retrieved from a regional database system and medical records of cardiovascular hospitalizations were collected for composite events. We employed unsupervised topological data analysis (TDA) to stratify sub-groups of AMI patients with specific probabilities of recurrent AMI and evaluate the importance of AVSc in this setting. Results AVSc was detected in 1151 (48%) patients. We found a significant association of AVSc with adverse cardiovascular events even after full adjustment (HR 1.29, 95%CI 1.02-1.63; p=0.037). Since the composite outcome included cardiovascular conditions with different aetiologies, we performed a sub-analysis looking closely at each outcome. We found that recurrent AMI was associated with AVSc presence in AMI patients (HR 1.54, 95%CI: 1.16-2.05; p=0.003). Of note, in the fully adjusted model, AVSc was significantly associated with recurrent AMI in patients younger than 75 years of age (HR 1.59, 95%CI: 01.04-2.45; p=0.034). Finally, the TDA highlighted the presence of 8 clusters of patients and these clusters exhibit specific risks of recurrent AMI within 2 years after discharge. The evaluation of time-to-event curves allowed us to combine these clusters into three super-clusters (i.e., mild-, moderate-, and high-risk patients) with the average risk of event-free rate after 2 years from discharge close to 98%, 92%, and 83%, respectively. Of note, the random forest procedure showed that AVSc was the most relevant variable to discriminate the three classes of risk (i.e., super-clusters). Conclusions AVSc is frequently detected in AMI patients and it is strongly associated with long-term cardiovascular events, especially in those younger than 75 years old. AVSc has been identified to be the most relevant variable to identify patients at high risk of recurrent AMI.

Lipid-lowering therapy and LDL-cholesterol in patients after acute coronary syndromes

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Medical University of Vienna. Background Intensive lipid lowering after acute coronary syndromes (ACS) reduces recurrent cardiovascular events, however recent studies have shown that LDL-cholesterol goal achievement is low in patients after myocardial infarction. We compared LDL-C goal achievement in patients after ACS that were discharged with statin monotherapy or with a combination lipid lowering therapy (LLT). Methods and Results We included 227 consecutive patients with a median age of 62 (IQR 52-72) years of which 67.8% of patients were male. 59.5% of patients underwent PCI because of ST-elevation myocardial infarction (STEMI) and 40.5% because of NSTEMI. 30.4% were on LLT at time of the ACS. Median LDL-C decreased from 104.8 (IQR 75.3-139.2) mg/dL before the acute event to 52.2 (IQR 37.8-74.6) mg/dL three to six months after the myocardial infarction, resulting in 55.1% of patients on LDL-C goal of 55 mg/dL. Only 5 (2.2 %) patients were discharged without LLT and 5 (2.2 %) patients were treated with PCSK9-inhibitors. 89.4% of patients were treated with high dose and 7.5% of patients with moderate or low dose statins. Patients that were discharged on statin monotherapy (n=160, 70.5%) reached a median LDL-C of 55.0 (IQR 41.0 to 78.8) mg/dL that was significantly higher as compared to patients on combination therapy with ezetimibe (n=62, 27.3%) that was 43.0 (IQR 32.3 to 62.5) mg/dL (p&amp;lt;0.002). The proportion of patients with statin monotherapy that reached the LDL-C goal was only 50.6% as compared to 71.0% of patients with combination therapy (p&amp;lt;0.001). Logistic regression analysis revealed that out of age, gender, type of myocardial infarction and statin-pretreatment only baseline LDL-C (p&amp;lt;0.005) and combination therapy (HR 4.6; p&amp;lt;0.001) were predictors for LDL-C goal achievement. Conclusions After acute myocardial infarction, only 50.6% of patients on statin monotherapy reach the recommended LDL-C goal of 55mg/dL. LLT combination therapy with ezetimibe significantly increased the proportion of patients reaching the treatment target and should be mandatory in most of the patients after acute myocardial infarction.

Sustained inflammation and high cortisol reactivity following an coronary event

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Heart and lung foundation Sweden. Background Over the last decades, significant improvements have been made in medical and lifestyle managements of patients with coronary artery disease (CAD). Nonetheless, "residual inflammatory risk" for recurrent cardiovascular events is high in this patient group and remains a diagnostic and therapeutic challenge. Activation of the NLRP3 inflammasome, involving release of interleukin (IL)-1β and IL-18 followed by their downstream target IL-6, is considered a major component of the inflammatory process in atherosclerosis. One major immunomodulator is the hypothalamic–pituitary–adrenal (HPA) axis. Interestingly, there is increasing evidence that cortisol exerts proinflammatory effects through the induction of NLRP3 expression. Purpose We investigated whether sustained inflammation was associated with altered HPA stress reactivity in patients with CAD. From 4 weeks up to 6 months after a coronary event, we measured systemic inflammation, with focus on inflammasome-related cytokines, and HPA axis hormones (ACTH and cortisol) before and after acute physical stress. Method We included 81 patients (mean age 62 years, 77 % males) and 30 controls (mean age 69 years, 67 % males). Patients underwent a standardized submaximal exercise stress test at 4 weeks (visit A) and 3-6 months after the coronary event (visit B) while controls performed one test only. Free cortisol was measured in saliva before, directly and 30 min after exercise. IL-18, IL-Ra (as a surrogate for IL-1 β), IL-6, ACTH and total cortisol were measured in plasma before and 30 min after exercise. Results At visit A, plasma levels of CRP (baseline only) and IL-6 did not differ between patients and controls while IL-18 and IL-1Ra were significantly higher in patients both before and after exercise, 500 (391-632) vs 386 (295-493), p=0.002; and 179 (141-267) vs 147 (117- 182), p=0.005, respectively(table 1). At visit B, CRP decreased while IL-18 and IL-1Ra levels remained at higher levels than controls. At both visits, patients showed a heightened cortisol reactivity (i.e. significant increase directly after exercise) while this did not occur in controls (Figure 1). At visit B, the relative increase in cortisol directly after exercise was even higher than at visit A (p=0.024). At both visits, ACTH decreased significantly after exercise in patients (p&amp;lt;0.01), probably due to negative feedback, while no change in ACTH was observed in controls. Conclusion Sustained elevations in IL-18 and IL-1Ra in CAD patients following a coronary event may indicate enhanced activity of NLRP3 inflammasome. Furthermore, patients exhibited a heightened cortisol stress reactivity, a phenomenon which has been associated with atherosclerosis progression and sedentary lifestyle in the population. It may be speculated that HPA axis alteration is directly associated with NLRP3 inflammasome activation in CAD, thus opening doors to new insights in prevention. However, this remains to be further investigated.