Future Myocardial Infarction Research Articles

Exploring protein biomarkers of physical activity and cardiovascular disease

Abstract Background The beneficial effects of physical activity on cardiovascular risk are well documented. Yet, the underlying mechanisms by which physical activity prevents cardiovascular disease remain unclear (1). Advancements of omics technology enables us to explore novel biomarkers of this complex molecular relationship and potentially unravel underlying molecular mechanisms involved in the progression of cardiovascular events. Purpose To investigate associations between long term physical activity and plasma proteins. As a second step investigate associations between identified plasma proteins and future myocardial infarction and mortality. Methods In the population based prospective cohort Uppsala Longitudinal Study of Adult Men (ULSAM), men were repeatedly investigated with a validated questionnaire on physical activity at ages 50, 60 and 70. 720 plasma proteins were analyzed at age 70 (n=782) with follow up on mortality data for 30 years. In the case-cohort MIMI (Markers of Imminent Myocardial Infarction study) the same plasma proteins were measured in disease-free individuals from six European cohorts. Individuals with acute myocardial infarction within 6 months from baseline were defined as cases (n=420) and up tto four cohort representatives per case were defined as controls (n=1598). Results Higher level of physical activity during 20 years was significantly associated with 12 plasma proteins, in a linear regression model adjusted for age, education and smoking after Bonferroni correction for multiple testing (p<0.000069). After additional adjustment for known cardiovascular risk factors (education, smoking status, BMI, blood pressure, low-density lipoprotein, diabetes diagnosis, and hypertensive-, lipid- or diabetes-treatment), all 12 proteins remained negatively associated with higher level of physical activity in the ULSAM cohort (p<0,05). Two proteins of the 12 proteins associated with physical activity were also significantly associated with future myocardial infarction in the MIMI study (FGF21 and IL6, p<0.05 for both) and 10 proteins were associated with increased mortality risk in the ULSAM cohort (p<0.05 for all). Moreover, proteins that were more negatively associated with physical activity were generally more positively associated with the risk of myocardial infarction in MIMI (Figure). Conclusion Multiple novel associations were found between long-term physical activity and plasma proteins. Some proteins were also associated with future myocardial infarction in an independent cohort which could suggest that the cardioprotective effects of physical activity to some degree may be mediated via the circulating proteome. Our findings encourage additional studies in order to understand the underlying causal mechanisms of these associations.

Sex related cardiovascular risk is non-dichotomous: artificial intelligence enhanced electrocardiography reveals continuum of risk in females

Abstract Background Females are typically underserved in cardiovascular medicine and often considered lower risk of cardiovascular disease. The use of sex as a dichotomous variable for risk stratification fails to capture the heterogeneity of risk within each sex. Purpose We aimed to develop an artificial intelligence-enhanced ECG (AI-ECG)-derived continuous sex score that can capture the continuum of risk and sex phenotypes within each sex, with the particular goal of addressing the female disadvantage. Methods We trained a convolution neural network to identify sex using the 12-lead ECG. The derivation cohort was 1,163,401 ECGs from 189,538 subjects from a USA secondary care hospital cohort and validated inthe UK Biobank (UKB). The model outputs a continuous value from 0 to 1 for sex prediction. The AI-ECG sex discordance score is the difference between predicted sex and biological sex. Results AI-ECG accurately identified sex in both the USA cohort (AUROC 0.943 (0.942-0.943)) and UKB datasets (n = 42,386, AUROC 0.971 (0.969-0.972)). In explainability analyses we found QRS duration, T wave morphology, QT interval, heart rate and QRS voltage as the most important factors in contributing to AI-ECG sex identification. In females only but not in males, sex discordance score was associated with a covariate-adjusted increased risk of cardiovascular death in outpatients with normal ECGs from the USA cohort, (Females hazard ratio (HR) 1.64 (1.18-2.29) p = 0.003, Males HR 1.04 (0.66-1.63), p = 0.86). This pattern persisted in the UKB: Females HR 1.39 (1.08-1.78) p = 0.01, Males HR 0.97 (0.77-1.22), p = 0.80, Fig 1). In phenome-wide association studies, we found females with a higher sex score discordance were more likely to have heart failure or myocardial infarction. Covariate-adjusted cox models confirmed the association of sex score discordance with increased future heart failure (HR 1.21 (1.07-1.37) p = 0.002 and future myocardial infarction (HR 1.32 (1.11-1.56) p = 0.001). In age- and body size-adjusted analyses, females with higher sex discordance score had increased left ventricular mass, and chamber volumes as well as increased muscle mass, reduced body fat percentage (Fig 2). In a genome-wide association study of sex discordance score we identified variants adjacent to IGF1R and NDRG4 in females, which have been previously associated with LV mass and sex hormone levels (Fig 2). Conclusion We describe sex discordance score as a novel AI-ECG biomarker capable of identifying females with disproportionately elevated cardiovascular risk. Sex discordance score may help uncover potential underlying mechanisms of cardiovascular disease among females, and future clinical studies are needed to determine its potential utility in identification of females at higher risk of cardiovascular events. Rather than exacerbating biases, AI-ECG has the potential to reduce female cardiovascular health inequalities.

Sex differences in coronary atherosclerotic plaque activity using 18F-sodium fluoride positron emission tomography

Abstract Background There are sex differences in the extent, severity, and outcomes of coronary artery disease. Purpose To assess the influence of sex on coronary atherosclerotic plaque activity measured using coronary 18F-sodium fluoride (18F-NaF) positron emission tomography (PET), and to determine whether 18F-NaF PET has prognostic value in both women and men. Methods In a post-hoc analysis of observational cohort studies of patients with coronary atherosclerosis who had undergone 18F-NaF PET CT angiography, we compared the coronary microcalcification activity (CMA) in women and men. Results Baseline 18F-NaF PET CT angiography was available in 999 participants (151 (15%) women) with 4282 patient-years of follow-up. Compared to men, women had lower coronary calcium scores (116 [interquartile range, 27-434] versus 205 [51-571] Agatston units; p=0.002) and CMA values (0.0 [0.0-1.12] versus 0.53 [0.0-2.54], p=0.01). Following matching for plaque burden by coronary calcium scores and clinical comorbidities, there was no sex-related difference in CMA values (0.0 [0.0-1.12] versus 0.0 [0.0-1.23], p=0.21) and similar proportions of women and men had no 18F-NaF uptake (53.0% (n=80) and 48.3% (n=73); p=0.42), or CMA values >1.56 (21.8% (n=33) and 21.8% (n=33); p=1.00). Over a median follow-up of 4.5 [4.0-6.0] years, myocardial infarction occurred in 6.6% of women (n=10) and 7.8% of men (n=66). Coronary microcalcification activity greater than 0 was associated with a similarly increased risk of myocardial infarction in both women (HR: 3.83; 95% CI:1.10-18.49; p=0.04) and men (HR: 5.29; 95% CI:2.28-12.28; p<0.001). Conclusions Although men present with more coronary atherosclerotic plaque than women, increased plaque activity is a strong predictor of future myocardial infarction regardless of sex.Sex differences in CAD activityCase examples

Abstract P333: Predicted Nationwide Health and Economic Impacts of the AMA MAP TM Hypertension Program to Improve Hypertension Control

Introduction: Lack of actionable blood pressure (BP) measurements, therapeutic inertia, and suboptimal patient self-management are three key barriers to better BP control. To help address these barriers, the American Medical Association developed the Measure Accurately, Act Rapidly, and Partner with Patients Hypertension (MAP TM HTN) quality improvement program. Methods: To estimate the 10-year health and economic outcomes achieved when healthcare delivery systems adopt MAP HTN, HealthPartners Institute's ModelHealth™: Cardiovascular disease (CVD) microsimulation model was applied to conduct “what if” analyses for adopting MAP HTN nationwide and in care delivery systems of varying size. MAP HTN targets patients aged 18 to 85 years with diagnosed hypertension. To account for newly diagnosed hypertensive patients over time and outcomes that follow exposure to the program after age 85, the simulation model predicted outcomes for a dynamic cross-section of U.S. adults aged 18 to 100 years. This study was conducted from the health care sector perspective, including that of the payers for medical services and the health care delivery system that provides these services. Risk equations to predict the incidence of CVD events were derived from Framingham Heart Study data and are based upon the following risk factors: age, sex, body mass index, systolic BP (SBP), lipid levels, smoking status, diabetes status, and CVD history. Modeled outcomes over 10 years included prevalence of SBP ≥140 mmHg; incidence of cardiovascular disease (CVD) events and CVD-related mortality; averted medical costs in 2021 U.S. dollars; and net costs. Results: Nationwide adoption of MAP HTN was predicted to improve mean BP control by 4.3% and prevent 601000 CVD events, with 85000 fewer myocardial infarctions, 164000 fewer strokes and 120000 fewer CVD deaths over 10 years as compared to usual care. The majority (93%) of the estimated $17.9 billion in averted costs were among Medicare beneficiaries. Total costs of implementing MAP HTN was $12.6 billion, resulting in a predicted $5.3 billion in net savings to the health care sector over 10 years. Small and large care delivery organizations could economically benefit from implementing MAP HTN at varying levels (5-50%) of shared cost savings from payers. Conclusions: The model demonstrates that AMA’s MAP HTN has the potential to improve population health and provide a positive business case by averting future myocardial infarctions, strokes, and CVD deaths.

Using biomaterials to treat myocardial infarction

Myocardial infarction (MI) as a risky disease, raises the awareness of the public. It results in insufficient oxygen supply due to cardiovascular blockage and ultimately leads to extensive cell necrosis. Hence, biomaterial-based therapy, angioplasty, and cardiac patches are exposed for the two stages of MI and indicate a promising direction for future MI treatment. This paper focuses on the biomaterials applicable to them one by one, including (1) The crucial function of angioplasty in treating MI; the discussion of its efficacy, mechanics, and results; analysis of clinical studies, material improvements, procedural advancements, and both the effectiveness and limitations of angioplasty. (2) The application of cardiac patches for post-MI treatment; synthetic or natural patches with different structures; review and highlight how these patches promote tissue repair and functional recovery; and the advantages and disadvantages of each patch.

Exacerbation History and Risk of Myocardial Infarction and Pulmonary Embolism in COPD

Acute exacerbations of COPD (AECOPDs) are increasingly recognized as episodes of heightened risk of cardiovascular events. It is not known whether exacerbation history is differentially associated with future myocardial infarction (MI) or pulmonary embolism (PE). Is the number and severity of AECOPDs associated with increased risk of MI or PE in a real-life cohort of patients with COPD? We identified a cohort of 66,422 patients (≥ 30 years of age) with a primary diagnosis of COPD in the Swedish National Airway Register from January 2014 to June 2022, with complete data on lung function. Patients were classified by moderate (prescription of oral corticosteroids) and severe (hospitalization) exacerbations the year before index date and were followed until December 2022 for hospitalization or death from MI or PE, corresponding to > 265,000 patient-years, with a maximum follow-up time of 9 years. Competing risk regression, according to the Fine-Gray model, was used to calculate subdistribution hazard ratios with 95%CIs. Compared with no AECOPDs in the baseline period, AECOPD number and severity were associated with increased long-term risk of both MI and PE in a gradual fashion, ranging from a subdistribution hazard ratio of 1.10 (95%CI, 0.97-1.24) and 1.33 (95%CI, 1.11-1.60), respectively, for one moderate exacerbation, to 1.82 (95%CI, 1.36-2.44) and 2.62 (95%CI, 1.77-3.89), respectively, for two or more severe exacerbations. In a time-restricted follow-up sensitivity analysis, the associations were stronger during the first year of follow-up and diminished over time. The risk of MI and PE increases with the frequency and severity of AECOPD in this large, real-life cohort of patients with COPD.

Sex differences in coronary atherosclerotic plaque activity using 18F-sodium fluoride positron emission tomography.

There are sex differences in the extent, severity, and outcomes of coronary artery disease. We aimed to assess the influence of sex on coronary atherosclerotic plaque activity measured using coronary 18F-sodium fluoride (18F-NaF) positron emission tomography (PET), and to determine whether 18F-NaF PET has prognostic value in both women and men. In a post-hoc analysis of observational cohort studies of patients with coronary atherosclerosis who had undergone 18F-NaF PET CT angiography, we compared the coronary microcalcification activity (CMA) in women and men. Baseline 18F-NaF PET CT angiography was available in 999 participants (151 (15%) women) with 4282 patient-years of follow-up. Compared to men, women had lower coronary calcium scores (116 [interquartile range, 27-434] versus 205 [51-571] Agatston units; p = 0.002) and CMA values (0.0 [0.0-1.12] versus 0.53 [0.0-2.54], p = 0.01). Following matching for plaque burden by coronary calcium scores and clinical comorbidities, there was no sex-related difference in CMA values (0.0 [0.0-1.12] versus 0.0 [0.0-1.23], p = 0.21) and similar proportions of women and men had no 18F-NaF uptake (53.0% (n = 80) and 48.3% (n = 73); p = 0.42), or CMA values > 1.56 (21.8% (n = 33) and 21.8% (n = 33); p = 1.00). Over a median follow-up of 4.5 [4.0-6.0] years, myocardial infarction occurred in 6.6% of women (n = 10) and 7.8% of men (n = 66). Coronary microcalcification activity greater than 0 was associated with a similarly increased risk of myocardial infarction in both women (HR: 3.83; 95% CI:1.10-18.49; p = 0.04) and men (HR: 5.29; 95% CI:2.28-12.28; p < 0.001). Although men present with more coronary atherosclerotic plaque than women, increased plaque activity is a strong predictor of future myocardial infarction regardless of sex.

Long-term prognosis of low high-sensitivity cardiac troponin T in the emergency department compared with the general population

BackgroundLong-term prognosis associated with low–high-sensitivity cardiac troponin T (hs-cTnT) concentrations in patients with chest pain is unknown. We investigated these prognostic implications compared with the general population.MethodsAll first visits to...

Coronary Artery Bypass Grafting versus Percutaneous Coronary Intervention in Patients with Chronic Total Occlusion.

Mechanisms of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) differ as CABG provides surgical collateralization and may prolong life by preventing future myocardial infarctions (MIs). However, evidence for CABG in patients with chronic total occlusion (CTO) has not been fully elucidated and the impact of PCI is discussed controversially. We performed a meta-analysis of studies comparing outcomes in patients with/without multivessel disease undergoing CABG or PCI for CTO. The primary outcome was long-term all-cause mortality (≥5 years). Secondary outcomes were MIs, repeat revascularization, cardiac mortality, major adverse cardiovascular events, and stroke, as well as short-term mortality (30 days/in-hospital) and stroke. A pooled Kaplan-Meier survival curve after reconstruction analysis was generated. Random-effects models were used. Six studies totaling 12,504 patients were included. In the pooled Kaplan-Meier analysis, PCI showed a significantly higher risk of death in the follow-up compared with CABG (hazard ratio [HR]: 2.12, 95% confidence interval [CI]: 1.88-2.38, p < 0.01). During the observation period, PCI was also associated with higher rates of MI (odds ratio [OR]: 2.86, 95% CI: 1.82-4.48, p < 0.01) and more repeat revascularization (OR: 4.88, 95% CI: 1.99-11.91, p = 0.0005). The other outcomes did not show significant differences. CABG is associated with superior survival to PCI over time in patients with CTO who are eligible for both PCI and CABG. This survival advantage is associated with fewer events of MI and repeat revascularization.

Association of Lipoprotein(a) Levels With Myocardial Infarction in Patients With Low-Attenuation Plaque

BackgroundLipoprotein(a) (Lp[a]) is associated with an increased risk of myocardial infarction (MI). However, the mechanism underlying this association has yet to be fully elucidated. ObjectivesThis multicenter study aimed to investigate whether association between Lp(a) and MI risk is reinforced by the presence of low-attenuation plaque (LAP) identified by coronary computed tomography angiography (CCTA). MethodsIn a derivation cohort, a total of 5,607 patients with stable chest pain suspected of coronary artery disease who underwent CCTA and Lp(a) measurement were prospectively enrolled. In validation cohort, 1,122 patients were retrospectively collected during the same period. High Lp(a) was defined as Lp(a) ≥50 mg/dL. The primary endpoint was a composite of time to fatal or nonfatal MI. Associations were estimated using multivariable Cox proportional hazard models. ResultsDuring a median follow-up of 8.2 years (Q1-Q3: 7.2-9.3 years), the elevated Lp(a) levels were associated with MI risk (adjusted HR [aHR]: 1.91; 95% CI: 1.46-2.49; P < 0.001). There was a significant interaction between Lp(a) and LAP (Pinteraction <0.001) in relation to MI risk. When stratified by the presence or absence of LAP, Lp(a) was associated with MI in patients with LAP (aHR: 3.03; 95% CI: 1.92-4.76; P < 0.001). Mediation analysis revealed that LAP mediated 73.3% (P < 0.001) for the relationship between Lp(a) and MI. The principal findings remained unchanged in the validation cohort. ConclusionsElevated Lp(a) augmented the risk of MI during 8 years of follow-up, especially in patients with LAP identified by CCTA. The presence of LAP could reinforce the relationship between Lp(a) and future MI occurrence.

Why selective screening for asymptomatic carotid stenosis is currently appropriate: a special report.

Two of the main reasons recent guidelines do not recommend routine population-wide screening programs for asymptomatic carotid artery stenosis (AsxCS) is that screening could lead to an increase of carotid revascularization procedures and that such mass screening programs may not be cost-effective. Nevertheless, selective screening for AsxCS could have several benefits. This article presents the rationale for such a program. The benefits of selective screening for AsxCS include early recognition of AsxCS allowing timely initiation of preventive measures to reduce future myocardial infarction (MI), stroke, cardiac death and cardiovascular (CV) event rates. Mass screening programs for AsxCS are neither clinically effective nor cost-effective. Nevertheless, targeted screening of populations at high risk for AsxCS provides an opportunity to identify these individuals earlier rather than later and to initiate a number of lifestyle measures, risk factor modifications, and intensive medical therapy in order to prevent future strokes and CV events. For patients at 'higher risk of stroke' on best medical treatment, a prophylactic carotid intervention may be considered.

Association Between Automated 3D Measurement of Coronary Luminal Narrowing and Risk of Future Myocardial Infarction

This study focuses on identifying anatomical markers with predictive capacity for long-term myocardial infarction (MI) in focal coronary artery disease (CAD). Eighty future culprit lesions (FCL) and 108 non-culprit lesions (NCL) from 80 patients underwent 3D quantitative coronary angiography. The minimum lumen area (MLA), minimum lumen ratio (MLR), and vessel fractional flow reserve (vFFR) were evaluated. MLR was defined as the ratio between MLA and the cross-sectional area at the proximal lesion edge, with lower values indicating more abrupt luminal narrowing. Significant differences were observed between FCL and NCL in MLR (0.41 vs. 0.53, p < 0.001). MLR correlated inversely with translesional vFFR (r = − 0.26, p = 0.0004) and was the strongest predictor of MI at 5 years (AUC = 0.75). Lesions with MLR < 0.40 had a fourfold increased MI incidence at 5 years. MLR is a robust predictor of future adverse coronary events.Graphical The minimum lumen ratio (MLR) is defined as the ratio between the minimum lumen area (MLA) and the cross-sectional area at the proximal edge of the lesion (PROXA). A lower MLR suggests a more pronounced luminal narrowing upstream of the MLA. This specific anatomical lesion characteristic correlates with higher translesional pressure gradients and has been found to be highly predictive of lesion destabilization over a 5-year period. Notably, lesions exhibiting MLR values below 0.399 were associated with a fourfold increase in the incidence of myocardial infarction (MI) within the same timeframe.

Females Display Lower Risk of Myocardial Infarction From Higher Estimated Cardiorespiratory Fitness Than Males: The Tromsø Study 1994-2014

ObjectiveTo examine the dose-response association between estimated cardiorespiratory fitness (eCRF) and risk of myocardial infarction (MI). Patients and MethodsAdults who attended Tromsø Study surveys 4-6 (Janurary 1,1994-December 20, 2008) with no previous cardiovascular disease were followed up through December 31, 2014 for incident MI. Associations were examined using restricted cubic splines Fine and Gray regressions, adjusted for education, smoking, alcohol, diet, sex, adiposity, physical activity, study survey, and age (timescale) in the total cohort and subsamples with hyperlipidemia (n=2956), hypertension (n=8290), obesity (n=5784), metabolic syndrome (n=1410), smokers (n=3823), and poor diet (n=3463) and in those who were physically inactive (n=6255). ResultsOf 14,285 participants (mean age ± SD, 53.7±11.4 years), 979 (6.9%) experienced MI during follow-up (median, 7.2 years; 25th-75th, 5.3-14.6 years). Females with median eCRF (32 mL/kg/min) had 43% lower MI risk (subdistributed hazard ratio [SHR], 0.57; 95% CI, 0.48-0.68) than those at the 10th percentile (25 mL/kg/min) as reference. The lowest MI risk was observed at 47 mL/kg/min (SHR, 0.02; 95% CI, 0.01-0.11). Males had 26% lower MI risk at median eCRF (40 mL/kg/min; SHR, 0.74; 95% CI, 0.63-0.86) than those at the 10th percentile (32 mL/kg/min), and the lowest risk was 69% (SHR, 0.31; 95% CI, 0.14-0.71) at 60 mL/kg/min. The associations were similar in subsamples with cardiovascular disease risk factors. ConclusionHigher eCRF associated with lower MI risk in females and males, but associations were more pronounced among females than those in males. This suggest eCRF as a vital estimate to implement in medical care to identify individuals at high risk of future MI, especially for females.

Selecting the appropriate patients for coronary artery bypass grafting in ischemic cardiomyopathy-importance of myocardial viability.

Patients who undergo coronary artery bypass graft (CABG) surgery in ischemic cardiomyopathy have a survival advantage over medical therapy at 10years. The survival advantage of CABG over medical therapy is due to its ability to reduce future myocardial infarction, and by conferring electrical stability. The presence of myocardial viability does not provide a differential survival advantage for CABG over medical therapy. Presence of angina and inducible ischemia are also less predictive of outcome. Moreover, CABG is associated with significant early mortality. Hence, careful patient selection is more important for reducing the early mortality and improving the long-term outcome than relying on results of myocardial viability. Younger patients with good exercise tolerance benefit the most, while patients who are frail and patients with renal dysfunction and dysfunctional right ventricle seem to have very high operative mortality. Elderly patients, because of poor life expectancy, do not benefit from CABG, but the age cutoff is not clear. Patients also need to have revascularizable targets, but this decision is often based on experience of the surgical team and heart team discussion. These recommendations are irrespective of the myocardial viability tests. Optimal medical treatment remains the cornerstone for management of ischemic cardiomyopathy.

Comparing outcomes between coronary artery bypass grafting and percutaneous coronary intervention in octogenarians with left main or multivessel disease

Mechanisms of coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) differ as CABG provides surgical collateralization and may prolong life by preventing future myocardial infarctions (MI). However, CABG benefits are unclear in octogenarians, where surgical risk is often perceived as higher and PCI is chosen more liberally. We performed a meta-analysis of studies comparing outcomes in octogenarians with left main or multivessel disease who underwent CABG or PCI. Primary outcome was late mortality (> 5 years). Secondary outcomes were perioperative mortality, MI, re-revascularization (R-R), acute renal failure (ARF), and stroke. Fourteen studies with 17,942 patients were included. CABG was associated with lower late mortality (hazard ratio, HR: 1.23, 95% confidence interval: CI 1.05–1.44, p < 0.01). In the pooled Kaplan–Meier analysis CABG showed significantly lower risk of death in the follow-up compared to PCI (HR: 1.08, 95%CI 1.02–1.41, p = 0.005). Landmark analyses confirmed the survival advantage of CABG over PCI after 21.5 months of follow-up (HR: 1.31, 1.19–1.44, p < 0.0001), but suggested advantage of PCI over CABG in the first 30-days (HR: 0.72, 0.64–0.82, p < 0.0001) and comparable survival from 1 to 21.5 months (HR: 0.98, 0.92–1.05, p = 0.652). We found lower risk for MI and R-R after CABG but higher perioperative mortality and no differences in ARF and stroke. CABG appears superior to PCI over time in octogenarians with complex CAD. This survival advantage is associated with fewer events of MI and R-R; however, it comes with an increased risk in perioperative mortality.

Prediabetes and Associated Risk of Cardiovascular Events and Chronic Kidney Disease Among Adult Survivors of Childhood Cancer in the St Jude Lifetime Cohort.

Little is known about the prevalence of prediabetes and associated risk of cardiovascular events and chronic kidney disease (CKD) with this reversable condition in survivors. Prevalence of prediabetes (fasting plasma glucose 100-125 mg/dL or hemoglobin A1c 5.7%-6.4%) and diabetes was clinically assessed in 3,529 adults ≥5 years from childhood cancer diagnosis and 448 controls stratified by age. Cox proportional hazards regression estimated progression from prediabetes to diabetes, and risk of future cardiac events, stroke, CKD, and death. Among survivors, median age 30 years (IQR, 18-65), and the prevalence of prediabetes was 29.2% (95% CI, 27.7 to 30.7) versus 18.1% (14.5 to 21.6) in controls and of diabetes was 6.5% (5.7 to 7.3) versus 4.7% (2.7 to 6.6). By age 40-49 years, more than half of the survivors had prediabetes (45.5%) or diabetes (14.0%). Among 695 survivors with prediabetes and longitudinal follow-up, 68 (10%; median follow-up, 5.1 years) progressed to diabetes. After adjustment for demographic factors and body composition, risk of progression was associated with radiation exposure to the pancreatic tail ≥10 Gy (hazard ratio [HR], 2.7 [95% CI, 1.1 to 6.8]) and total-body irradiation (4.4 [1.5 to 13.1]). Compared with survivors with normal glucose control, adjusting for relevant treatment exposures, those with prediabetes were at increased risk of future myocardial infarction (HR, 2.4 [95% CI, 1.2 to 4.8]) and CKD (2.9 [1.04 to 8.15]), while those with diabetes were also at increased risk of future cardiomyopathy (3.8 [1.4 to 10.5]) or stroke (3.4 [1.3 to 8.9]). Prediabetes is highly prevalent in adult survivors of childhood cancer and independently associated with an increased risk of future cardiovascular and kidney complications. Prediabetes, a modifiable risk factor among childhood cancer survivors, represents a new target for intervention that may prevent subsequent morbidity and mortality.

Cardiac Rehabilitation After Hospitalization for Acute Coronary Syndrome.

Acute coronary syndrome (ACS) carries a high burden of morbidity and mortality. Cardiac rehabilitation over the past century has developed as an important tool in treating and preventing future myocardial infarction events in this critical group. We summarize the rationale and literature evidence supporting the use of cardiac rehabilitation and its role in ACS patients, with an emphasis on its impact on outcomes following hospitalization. Current literature and large-scale reviews and registry analyses provide conflicting data on the benefits of cardiac rehabilitation after ACS, including its impact on mortality, readmission, and quality of life. Cardiac rehabilitation is an important tool in the management ACS patients. It encompasses not only a graduated exercise regimen but also a holistic approach and is therefore best implemented as a comprehensive cardiac rehabilitation strategy including, in addition to exercise regimen, psychosocial counseling, smoking cessation education, medication adherence, nutrition guidance, and other tools for risk modification. Further trials on the role of cardiac rehabilitation after ACS are needed, especially trials examining different cardiac rehabilitation protocols, time period for its implementation after ACS, and optimal program duration.

Varying Definitions of Carotid Intima-Media Thickness and Future Cardiovascular Disease: A Systematic Review and Meta-Analysis.

Carotid intima-media thickness (cIMT) has been widely used as a predictor of future cardiovascular disease (CVD); however, various definitions of cIMT exist. This study provides a systematic review and meta-analysis of the associations between different cIMT definitions and CVD. A systematic review of the different cIMT definitions used in prospective cohort studies was performed. The relationships between cIMT of different definitions (common carotid artery IMT [CCA-IMT], internal carotid artery IMT [ICA-IMT], combined segments [combined-IMT], mean CCA-IMT, and maximum CCA-IMT) with future stroke, myocardial infarction (MI), and CVD events were analyzed using random effects models. Among 2287 articles, 18 articles (14 studies) with >10 different cIMT definitions were identified and included in our meta-analysis. After adjusting for age and sex, a 1-SD increase in CCA-IMT was associated with future stroke (hazard ratio [HR], 1.32 [95% CI, 1.27-1.38]), MI (HR, 1.27 [95% CI, 1.22-1.33]), and CVD events (HR, 1.28 [95% CI, 1.19-1.37]). A 1-SD increase in ICA-IMT was related to future stroke (HR, 1.25 [95% CI, 1.11-1.42]) and CVD events (HR, 1.25 [95% CI, 1.04-1.50]) but not MI (HR, 1.26 [95% CI, 0.98-1.61]). A 1-SD increase in combined-IMT was associated with future stroke (HR, 1.30 [95% CI, 1.08-1.57]) and CVD events (HR, 1.36 [95% CI, 1.23-1.49]). Maximum CCA-IMT was more strongly related than mean CCA-IMT with risk of MI, and both measures were similarly associated with stroke and CVD events. Combined-IMT is more strongly associated with CVD events compared with single-segment cIMT definitions. Maximum CCA-IMT shows a stronger association with MI than mean CCA-IMT. Further research is warranted to validate our findings and to standardize the cIMT measurement protocol, as well as to explore underlying mechanisms.

Long-term prognosis associated with undetectable high-sensitivity cardiac troponin T concentrations in the emergency department

Abstract Background The long-term prognostic implications of low or undetectable high-sensitivity cardiac troponin T (hs-cTnT) levels in patients presenting with chest pain in the emergency department (ED) have not been thoroughly studied. Furthermore, the prognosis has not been compared to the general population. Purpose This study aimed to investigate the long-term risk of all-cause mortality and cardiovascular outcomes in patients with chest pain but no myocardial injury, compared with the general population in Sweden. Methods Among all visits to 7 major EDs in Sweden from December 9, 2010 to August 31, 2017, we included the first visit by patients ≥18 years of age with chest pain and ≥1 hs-cTnT measurement. Visits in patients with myocardial injury (any hs-cTnT &amp;gt;14 ng/l), including those associated with a diagnosis of myocardial infarction (MI) were excluded. Standardized mortality ratios (SMRs) and incidence ratios (SIRs) were estimated to compare risks of death and future MI with the general population. Hazard ratios (HRs) with 95% CIs were calculated for comparisons of mortality and major adverse cardiovascular events (MACE) between visits with undetectable (&amp;lt;5 ng/l) and low (5-14 ng/l) hs-cTnT concentrations. Results A total of 112,694 visits were included, of which 69,571 (62%) and 43,123 (38%) occurred in patients with hs-cTnT &amp;lt;5 ng/l and 5-14 ng/l, respectively. All-cause mortality was overall lower compared to the standardized Swedish population (SMR 0.51, 95% CI: 0.49-0.54, and 0.88, 95% CI: 0.85-0.90), while risks of a future MI were higher (SIR 1.33, 95% CI: 1.25-1.42, and 1.53, 95% CI: 1.46-1.59). Hs-cTnT concentrations &amp;lt;5 ng/l were associated with a lower all-cause mortality in men ≥55 years and in women ≥65 years of age, respectively (figures 1 and 2). During a median follow-up of 6.4 years (IQR 4.8-8.0), 1769 (2.5%) and 5535 (13%) deaths occurred in patients with hs-cTnT &amp;lt;5 and 5-14 ng/l, respectively. The adjusted risks of death and MACE were 1.7- (HR 1.70, 95% CI: 1.60-1.80) and 1.6-fold (HR 1.63, 95% CI: 1.54-1.73) higher in patients with hs-cTnT 5-14 ng/l compared to patients with hs-cTnT &amp;lt;5 ng/l. Conclusions Patients with chest pain and low or undetectable hs-cTnT concentrations have an overall lower risk of death, but a higher risk of future MIs, compared with the age-standardized general population. In addition, detectable Hs-cTnT concentrations below the 99th percentile cutoff value are associated with long-term risks of death and MACE.Crude mortality rateStandardized mortality ratio

Improving risk stratification of recurrent myocardial infarction in a large real-world dataset using machine learning

Abstract Background Patient (pt) risk stratification for cardiovascular (CV) events is key to determine the appropriate approach to secondary prevention. Several risk scores have been developed (SCORE2, EUROASPIRE, Thrombolysis in Myocardial Infarction [TIMI] risk score for secondary prevention [TRS 2°P]); these are based on few predictors and have low discriminatory power. Machine learning methods using real-word data (RWD) from electronic health records (EHR) databases and capable of handling a multitude of commonly available variables can serve as powerful tools to improve the discriminatory power and generate efficient and clinically relevant risk scores. Purpose This study used a non-linear machine learning model to build an improved risk score for secondary CV events from a large Israeli EHR database. Methods Records of pts with a first record of atherosclerotic CV disease (ASCVD) admission or coronary procedure and available follow-up data (mean: 1052 days) from the period of 01/2005–11/2020 were considered (n=77432 [67% coronary artery disease, 21% carotid artery disease, 12% peripheral artery disease], a stratified 1:1 randomization by cause of admission yielding in training set [n=38716] and test set [n=38716]). The model’s performance was assessed by comparison with TRS 2°P score on the test set independent of the training set. Twenty-six covariates commonly used in clinical routine and widely available in EHR have been selected and a gradient boosting trees algorithm was applied to the pt data at baseline after the original event to predict recurrent myocardial infarction (MI). The ability of the model to discriminate pts was evaluated using the concordance index (c-index), which expresses how well a predicted risk score describes the observed events (1 implies perfect concordance, 0.5 implies random concordance). Results Prediction accuracy of our model showed a c-index for a future MI of 0.74 (95% confidence interval [CI]: 0.72, 0.76) which is significantly higher than 0.57 (95% CI: 0.56, 0.58) obtained with TRS 2°P. Our 2-tier risk score has successfully discriminated a low-risk group (74% of cohort) with a 3-year MI prevalence of 5% from a high-risk group (26% of cohort) that had a 5-fold higher prevalence (26.6%) (Figure 1). In comparison, the 3-tier TRS 2°P yielded an unbalanced distribution of group sizes with a disproportionate intermediate risk group (22% low, 67% intermediate, 11% of high-risk) with a limited clinical discriminatory power (7.1%, 10,2% and 15.6% of observed events, respectively) (Figure 2). Conclusions Our machine learning based risk score model created on a large set of RWD with a long follow-up seems to offer substantial gain of performance compared to the TRS 2°P. The present 2-tier model shows significant gain of accuracy and clinical discriminatory power paving the way for more individualized prevention strategies.Figure 1Figure 2