Sex-specific Prediction of Cardiogenic Shock After Acute Coronary Syndromes: The SEX-SHOCK Score.

BACKGROUND: and aims: Cardiogenic shock (CS) remains the primary cause of in-hospital death after acute coronary syndromes (ACS), with its plateauing mortality rates approaching 50%. To test novel interventions, personalized risk prediction is essential. The ORBI (Observatoire Régional Breton sur l'Infarctus) score represents the first-of-its-kind risk score to predict in-hospital CS in ACS patients undergoing percutaneous coronary intervention (PCI). However, its sex-specific performance remains unknown, and refined risk prediction strategies are warranted. METHODS: This multinational study included a total of 53 537 ACS patients without CS on admission undergoing PCI. Following sex-specific evaluation of ORBI, regression and machine-learning models were used for variable selection and risk prediction. By combining best-performing models with highest-ranked predictors, SEX-SHOCK was developed, and internally and externally validated. RESULTS: The ORBI score showed lower discriminative performance for the prediction of CS in females than males in Swiss (AUC [95% CI]: 0.78 [0.76-0.81] vs. 0.81 [0.79-0.83]; p=0.048) and French ACS patients (0.77 [0.74-0.81] vs. 0.84 [0.81-0.86]; p=0.002). The newly developed SEX-SHOCK score, now incorporating ST-segment elevation, creatinine, C-reactive protein, and left ventricular ejection fraction, outperformed ORBI in both sexes (females: 0.81 [0.78-0.83]; males: 0.83 [0.82-0.85]; p<0.001), which prevailed following internal and external validation in RICO (females: 0.82 [0.79-0.85]; males: 0.88 [0.86-0.89]; p<0.001) and SPUM-ACS (females: 0.83 [0.77-0.90], p=0.004; males: 0.83 [0.80-0.87], p=0.001). CONCLUSIONS: The ORBI score showed modest sex-specific performance. The novel SEX-SHOCK score provides superior performance in females and males across the entire spectrum of ACS, thus providing a basis for future interventional trials and contemporary ACS management.

Postnatally overfed mice display cardiac function alteration following myocardial infarction.

BACKGROUND: Cardiovascular (CV) pathologies remain a leading cause of death worldwide, often associated with common comorbidities such as overweight, obesity, type 2 diabetes or hypertension. An innovative mouse model of metabolic syndrome induced by postnatal overfeeding (PNOF) through litter size reduction after birth was developed experimentally. This study aimed to evaluate the impact of PNOF on cardiac remodelling and the development of heart failure following myocardial infarction. METHODS: C57BL/6 male mice were raised in litter adjusted to 9 or 3 pups for normally-fed (NF) control and PNOF group respectively. After weaning, all mice had free access to standard diet and water. At 4 months, mice were subjected to myocardial infarction (MI). Echocardiographic follows-up were performed up to 6-months post-surgery and biomolecular analyses were carried-out after heart collection. FINDINGS: At 4 months, PNOF mice exhibited a significant increase in body weight, along with a basal reduction in left ventricular ejection fraction (LVEF) and an increase in left ventricular end-systolic area (LVESA), compared to NF mice. Following MI, PNOF mice demonstrated a significant decrease in stroke volume and an increased heart rate compared to their respective initial values, as well as a notable reduction in cardiac output 4-months after MI. After 6-months, left ventricle and lung masses, fibrosis staining, and mRNA expression were all similar in the NF-MI and PNOF-MI groups. INTERPRETATION: After MI, PNOF mice display signs of cardiac function worsening as evidenced by a decrease in cardiac output, which could indicate an early sign of heart failure decompensation.

Sex-specific predictive factors of smoking cessation in subjects at high cardiovascular risk.

Smoking is a major risk factor for cardiovascular diseases (CVD), in particular in women, but smoking cessation (SC) reduces or even cancels the risk for both sexes. Using a nationwide SC services database, we aimed to determine the predictive factors of SC in men and women smokers with CV risk factors (CVRF) or CVD. A retrospective study from the French CDTnet database was conducted. Inclusion criteria were age ≥18years, and≥1 CVRF (Body Mass Index ≥25kg/m2, hypertension, diabetes, hypercholesterolemia) or CVD (myocardial infarction (MI) or angina pectoris, stroke, peripheral arterial disease [PAD]). Self-reported smoking abstinence (≥28 consecutive days) was confirmed by exhaled carbon monoxide<10ppm. Logistic regression analysis assessed the association between SC and sociodemographic, medical characteristics, and smoking profile. Among the 36,864 smokers at high CV risk, abstinence rate was slightly lower in women than in men, (52.6% [n=8,102] vs 55.0% [n=11,848], P<0.001). For both sexes, factors associated with the lowest abstinence rates were diabetes, respiratory and psychiatric diseases, anxiolytic/antidepressant use, and cannabis consumption. In women, the factors associated with smoking abstinence were suffering from MI or angina and taking contraceptive pill and the factors associated with persistent smoking were alcohol disorder and high cigarette consumption. In men, there was a positive relationship between overweight and abstinence while being dual users of cigarettes and electronic cigarettes at first visit, having tobacco-related diseases (cancer and PAD) and taking opioid substitution treatment were associated with persistent smoking. Finally, in both sexes, the factors associated with abstinence were: age≥65years, having a diploma, being employed, self-referred or encouraged by entourage, ≥1 previous quit attempt, ≤20 cigarettes per day consumption, benefiting from SC medication prescription and ≥4 follow-up visits. In conclusion, our results suggest the relevance of SC intensive management in smokers at high CV risk, based on sociodemographic, medical, and smoking behaviour characteristics, as well as a gender-specific SC approach.

Risk factors and prognostic value of endotoxemia in patients with acute myocardial infarction.

Background: There is increasing evidence regarding the association between endotoxemia and the pathogenesis of atherosclerosis and myocardial infarction (MI). During the acute phase of MI, endotoxemia might increase inflammation and drive adverse cardiovascular (CV) outcomes. We aimed to explore the risk factors and prognostic value of endotoxemia in patients admitted for acute MI. Methods: Patients admitted to the coronary care unit of Dijon University Hospital for type 1 acute MI between 2013 and 2015 were included. Endotoxemia, assessed by plasma lipopolysaccharide (LPS) concentration, was measured by mass spectrometry. Major adverse CV events were recorded in the year following hospital admission. Results: Data from 245 consecutive MI patients were analyzed. LPS concentration at admission markedly increased with age and diabetes. High LPS concentration was correlated with metabolic biomarkers (glycemia, triglyceride, and total cholesterol) but not with CV (troponin Ic peak and N-terminal pro-brain natriuretic peptide) or inflammatory biomarkers (C-reactive protein, IL6, IL8, and TNFα). LPS concentration was not associated with in-hospital or 1-year outcomes. Conclusions: In patients admitted for MI, higher levels of endotoxins were related to pre-existing conditions rather than acute clinical severity. Therefore, endotoxins measured on the day of MI could reflect metabolic chronic endotoxemia rather than MI-related acute gut translocation.

Type 2 Myocardial Infarction in a Sub-Saharan Africa Population: Challenging the Current Concepts-Data From REACTIV.

BACKGROUND: From a large observational acute coronary syndrome registry in Côte d'Ivoire, we aimed to assess incidence, clinical presentation, management, and in-hospital outcomes for type 2 myocardial infarction (T2MI) compared with type 1 MI. METHODS AND RESULTS: We conducted a cross-sectional monocentric study using data from REACTIV (Registre des Infarctus de Côte d'Ivoire) at the Abidjan Heart Institute. All patients hospitalized with MI between 2018 and 2022 who underwent coronary angiography were included. For each patient, sociodemographic data, cardiovascular risk factors and history, and clinical and paraclinical presentation were collected at admission. In-hospital outcomes, including major adverse cardiovascular events and mortality, were reported. Among 541 consecutive patients hospitalized with MI, 441 met the definition of type 1 MI or T2MI. T2MI accounted for 14.1% of cases. Patients with T2MI showed a trend toward slightly younger age (54 versus 58 years, P=0.09). Patients with T2MI seemed to have less severe coronary artery disease, with less frequent multivessel disease (P<0.001). Main triggering factors for T2MI were coronary embolism (24.2%), severe hypertension with or without left ventricular hypertrophy (22.6%), and tachyarrhythmia (16.1%). In-hospital event rates were low in both MI types. Although the difference was nonsignificant, death rates for patients with type 1 MI tended to be higher than for patients with T2MI, as well as occurrence of major adverse cardiovascular events. CONCLUSIONS: Our study revealed disparities in clinical characteristics, angiographic features, cause, and in-hospital outcomes in T2MI in our population compared with Western populations. These results suggest the heterogeneity of T2MI and the potential causative and demographic variability depending on geographical area.

Deaths and major cardiovascular events in patients with lymphoma: Analysis from a French nationwide hospitalization database.

BACKGROUND: There are few data assessing the risk of death and cardiovascular events in patients with lymphoma. AIM: Using a nationwide hospitalization database, we aimed to address cardiovascular outcomes in patients with lymphoma. METHODS: From 01 January to 31 December 2013, 3,381,472 adults were hospitalized in French hospitals; 22,544 of these patients had a lymphoma. The outcome analysis (all-cause or cardiovascular death, myocardial infarction, ischaemic stroke, bleedings, new-onset heart failure and new-onset atrial fibrillation) was performed over a 5-year follow-up period. Each patient with lymphoma was matched with a patient without a lymphoma or other cancer (1:1). A competing risk analysis was also performed. RESULTS: After adjustment on all risk factors, cardiovascular and non-cardiovascular co-morbidities, the subdistribution hazard ratios for all-cause death, major bleeding, intracranial bleeding, new-onset heart failure and new-onset atrial fibrillation were higher in patients with lymphoma; conversely, the subdistribution hazard ratios for cardiovascular death, myocardial infarction and ischaemic stroke were lower in patients with lymphoma. In the matched analysis, the risk of all-cause death (subdistribution hazard ratio 1.936, 95% confidence interval 1.881-1.992) and major bleeding (subdistribution hazard ratio 1.117, 95% confidence interval 1.049-1.188) remained higher in patients with lymphoma. CONCLUSION: In this large nationwide cohort study, patients with lymphoma had a higher incidence of all-cause death and major bleeding.

Acute coronary syndrome in patients treated by vitamin K antagonists or non-vitamin K antagonist oral anticoagulants: Proposed management algorithm for the first 48hours.

Around 10% of patients with acute coronary syndrome are treated by vitamin K antagonists or non-vitamin K antagonist oral anticoagulants for various indications. The initial management of these patients is highly complex, and new guidelines specify that, only during percutaneous coronary intervention, a bolus of unfractionated heparin is recommended in one of the following circumstances: (1) if the patient is receiving a non-vitamin K antagonist oral anticoagulant; or (2) if the international normalized ratio is<2.5 in a patient being treated with a vitamin K antagonist. In this review, we report on five key messages essential for the management of these patients. There are no randomized studies to date, and we propose two diagnostic and/or therapeutic decision algorithms. However, randomized studies are needed to validate these strategies.

Glycemic and lipid control in patients with diabetes at time of myocardial infarction.

OBJECTIVE: Cardiovascular risk is increased in patients with diabetes. Little is known about glycemic and lipid control in patients with diabetes. We aimed to assess glycemic and lipid controls in patients with diabetes at time of their myocardial infarction. METHOD: All known patients with type 2 diabetes consecutively admitted for a myocardial infarction in our coronary care unit between March 1st and December 31st, 2021 were included in this retrospective study. Glycemic and lipid control was assessed through individualized target of glycated haemoglobin (HbA1c) and low-density lipoprotein cholesterol (LDL-c), respectively. At admission, the comprehensive list of chronic medications was obtained through medication reconciliation. RESULTS: This study included 112 patients with a median age of 72 years. Most of patients had an individualized target of HbA1c and LDL-c of 7.0% (67%) and 0.55g/L (96%), respectively. The rate of uncontrolled patients for HbA1c and LDL-c and both was 46%, 90%, and 42% respectively. The rate of patients with non-optimal glucose- and lipid-lowering medications in uncontrolled patients was 63% and 87%, respectively. The rate of inappropriate glucose- and lipid-lowering medications was 73% and 91%, respectively. CONCLUSION: We highlighted the poor glycemic and lipid control in high-risk CV patients. There is an urgent need to develop multidisciplinary approaches to optimize CV risk factors control to reduce myocardial infarction and strokes.

Characteristics and prognosis of patients with elevated triglycerides in acute myocardial infarction: observational data from a large database over a 17-year period: High triglycerides in acute myocardial infarction.

From a large regional registry, we aimed to address the characteristics and prognosis of patients with elevated triglycerides (TG) among patients hospitalized for an acute myocardial infarction (MI). From the multicenter database of the RICO survey, all consecutive patients hospitalized for an acute MI (2001-2017) and alive at discharge were included. Among the 10,667 patients included, 17.7% had elevated TG. When compared with patients with TG ≤ 200 mg/dL, patients with high TG (>200 mg/dL) were 10 years younger, had a higher BMI, were more frequently men, diabetic, and smokers. At 1-year follow-up, recurrent ischemic events were more frequent in elevated TG patients. In multivariate logistic regression analysis, high TG (OR (95%CI): 1.356 (1.095-1.679)) remained an independent estimate for recurrent ischemic events, even after adjustment for confounding factors. In our large population-based cohort, elevated TG are common in acute MI, and associated with residual risk of recurrent ischemic events, beyond traditional prognostic markers.

Coronary Artery Disease: A Key Issue in Type 2 Myocardial Infarction: Systematic Review and Recent Findings.

Underlying coronary artery disease (CAD) is increasingly considered to be a key issue in the pathophysiology of type 2 myocardial infarction (T2MI). In T2MI, which is attributable to a mismatch between oxygen supply/demand, CAD is common and appears to be more severe than in type 1 myocardial infarction (T1MI). Little is known about the heterogeneous mechanisms that cause supply/demand imbalance and non-coronary triggers leading to myocardial ischemia or about how they are potentially modulated by the presence and severity of CAD. CAD seems to be underrecognized and undertreated in T2MI, even though previous studies have demonstrated both the short and long-term prognostic value of CAD in T2MI. In this literature review, we attempt to address the prevalence and severity of CAD, challenges in the discrimination between T2MI and T1MI in the presence of CAD, and the prognostic value of CAD among patients with T2MI.

Interplay between efferocytosis and atherosclerosis.

In an adult human, billions of cells die and turn over daily. During this process, many apoptotic cells are produced and subsequently cleared by phagocytes - a process termed efferocytosis, which plays a critical role in tissue homeostasis. Efferocytosis is an important mechanism in the control of inflammatory processes. Efficient efferocytosis inhibits accumulation of apoptotic cells/debris and maintains homeostasis before the onset of necrosis (secondary necrosis), which promotes inflammation or injury. During efferocytosis, mitochondrial fission and the oxidative stress process are linked through reactive oxygen species production and oxidative stress control. Autophagy plays an important role in inhibiting inflammation and apoptosis, and in promoting efferocytosis by activated inflammatory cells, particularly neutrophils and macrophages. Autophagy in neutrophils is activated by phagocytosis of pathogens or activation of pattern recognition receptors. Autophagy is essential for major neutrophil functions, including degranulation, reactive oxygen species production, oxidative stress and release of neutrophil extracellular cytokines. Failed efferocytosis is a key mechanism driving the development and progression of chronic inflammatory diseases, including atherosclerosis, cardiometabolic pathology, neurodegenerative disease and cancer. Impairment of efferocytosis in apoptotic macrophages is a determinant of atherosclerosis severity and the vulnerability of plaques to rupture. Recent results suggest that inhibition of efferocytosis in the protection of the myocardium results in reduced infiltration of reparatory macrophages into the tissue, in association with oxidative stress reduction. Activated macrophages play a central role in the development and resolution of inflammation. The resolution of inflammation through efferocytosis is an endogenous process that protects host tissues from prolonged or excessive inflammation. Accordingly, therapeutic strategies that ameliorate efferocytosis control would be predicted to dampen inflammation and improve resolution. Thus, therapies targeting efferocytosis will provide a new means of treating and preventing cardiovascular and metabolic diseases involving the chronic inflammatory state.

Outcomes in Patients with Acute Myocardial Infarction and Known Sleep Apnea: A Nationwide Analysis.

Background. Sleep apnea (SA) is a common breathing disorder characterized by repetitive upper airway narrowing and closure. Although SA has been demonstrated to be an independent risk factor for all-cause mortality, the direct contribution of SA to worse cardiovascular prognosis may be difficult to evaluate, and its independent association with the different types of cardiovascular outcomes may be debated, particularly in the context of patients with acute myocardial infarction (AMI). The aim of this study was to assess the impact of known SA on the outcomes of hospitalized patients who have had an AMI by analyzing 10-year data collected from a national registry. Methods. This longitudinal cohort study was based on the national hospitalization database that covers hospital care for the entire French population, including all patients admitted with AMI from January 2010 to June 2019. The clinical outcomes for the analysis were as follows: all-cause death, cardiovascular death, ischemic stroke, new-onset atrial fibrillation (FA), and re-hospitalization for heart failure (HF). Results. Among the 797,212 patients who presented with an AMI (528,351 men and 268,861 women), 37,075 (4.7%) had documented SA. During follow-up (mean [SD] 1.8 [2.4] years, median [interquartile range] 0.7 [0.1-3.1] years), 163,845 deaths (of which 85,649 were cardiovascular deaths), 20,168 ischemic strokes, 58,498 new-onset AF, and 92,381 rehospitalizations due to HF were recorded. Patients with known SA had a worse prognosis in the short and medium term, but after adjusting for all covariables, SA was only independently associated with a higher risk of rehospitalization for HF and new-onset AF in men and women. Conclusion. Data from our large nationwide analysis confirm that known SA is associated with poor cardiovascular outcomes in patients who have had an AMI. However, this impact is tem-pered when the model is adjusted for age, cardiovascular risk, or other covariables. Further studies need to be conducted to assess the independent impact of SA on the prognosis of patients with AMI.

Diagnostic and prognostic impact of new pathophysiology-based categorization of type 1 and type 2 myocardial infarction: data from the French RICO survey.

BACKGROUND: A new classification of type 1 and 2 myocardial infarction (MI) derived from the fourth universal definition of MI (UDMI) has been recently proposed, based on pathophysiology of coronary artery disease (CAD). We assessed the impact of this new MI categorization on epidemiology and outcomes, considering type 1 MI (T1MI) and type 2 MI (T2MI), with and without CAD. METHODS: Retrospective study including all consecutive patients hospitalized for an acute MI in a multicenter database (RICO). MI was defined according to current UDMI. Rates and outcomes of T1MI and T2MI were addressed according to the new classification. RESULTS: Among the 4,573 patients included in our study, 3,710 patients (81.1%) were initially diagnosed with T1M1 and 863 (18.9%) with T2MI. After reclassification, 96 T2MI patients were moved into the T1MI category. Out of the remaining 767 patients with T2MI, 567 underwent coronary angiography, and were adjudicated as type 2A MI (68.6%) with obstructive CAD, and type 2B MI (31.4%) without obstructive CAD. When compared with T1MI and T2BMI, T2AMI patients had worse in-hospital outcomes, including severe heart failure (P < .001), atrial fibrillation or flutter (P < .001) and severe bleeding (P < .001). Kaplan-Meier 1-year survival curves showed higher all-cause and CV causes mortality in T2AMI patients compared to T1MI and T2BMI (P < .001). In multivariate Cox regression analysis, type of MI was independent predictor of death. CONCLUSION: Our large observational multicenter study shows major disparities in mortality according to type of MI and support the relevance of the new MI classification to improve risk classification, taking into account CAD in T2MI. Our findings may help identifying specific phenotypes and considering personalized diagnostic and management strategies.

Antitumoral Activity of Molecular Hydrogen and Proton in the Treatment of Glioblastoma: An Atypical Pharmacology?

Antioxidants in cancer therapy have been a hot topic in the medical field for 20 years. Antioxidants are able to reduce the risk of cancer formation by neutralizing free radicals. Protons (H+) and molecular hydrogen (H2) interact in the cell and are essential in a wide variety of processes. The antioxidant, anti-inflammatory, and antiapoptotic effects of H2 have been studied in numerous experimental and clinical studies. Experimental data indicate that H2 is an antitumor agent in the treatment of glioblastoma (GBM). In vivo H2 inhalation could suppress the growth of GBM tumors, thereby extending the survival of mice with GBM. The sphere-forming ability of glioma cells was suppressed by hydrogen treatment. In addition, H2 treatment also suppressed the migration, invasion, and colony-forming ability of glioma cells. Proton therapy and proton beam radiotherapy offer some advantages over other modern conformal photon-based therapies when used in the treatment of central nervous system malignancies.

Noise Exposure and Cardiovascular Health.

Noise is considered an environmental stressor adversely affecting well-being and quality of life, inter-individual communications, and attention and cognitive function and inducing emotional responses, corresponding to noise annoyance. In addition, noise exposure is associated with nonauditory effects including worsening mental health, cognitive impairments, and adverse birth outcomes, sleep disorders, and increased annoyance. An accumulating body of evidence has indicated that traffic noise is also associated with CVD, through multiple pathways. It has been shown that psychological stress and mental health disorders such as depression and anxiety have a negative impact on the development of cardiovascular diseases and outcomes. Likewise, reduced sleep quality and/or duration has been reported to increase sympathetic nervous system activity, which can predispose to conditions like hypertension and diabetes mellitus, known risk factors for CVD. Finally, there seems to be a disruption in the hypothalamic-pituitary-axis secondary to noise pollution that also results in an increased risk of CVD. The World Health Organization has estimated that the number of DALYs (disability-adjusted life-years) lost resulting from environmental noise in Western Europe ranges from 1 to 1.6 million, making noise the second major contributor to the burden of disease in Europe, only after air pollution. Thus, we sought to explore the relationship between noise pollution and risk of CVD.

Nephrotic syndrome and acute coronary syndrome in children, teenagers and young adults: Systematic literature review.

Myocardial infarction is rare in children, teenagers and young adults (aged<20 years). The most common aetiologies identified include Kawasaki disease, familial hypercholesterolaemia, collagen vascular disease-induced coronary arteritis, substance abuse (cocaine, glue sniffing), trauma, complications of congenital heart disease surgery, genetic disorders (such as progeria), coronary artery embolism, occult malignancy and several other rare conditions. Nephrotic syndrome is a very rare cause of myocardial infarction, but it is probably underestimated. The purpose of this review was to determine the current state of knowledge on acute coronary syndrome related to nephrotic syndrome. We thus performed a comprehensive structured literature search of the Medline database for articles published between January 1st, 1969 and December 31st, 2021. Myocardial infarction in young adults can be broadly divided into two groups: cases of angiographically normal coronary arteries; and cases of coronary artery disease of varying aetiology. There are several possible mechanisms underlying the association between acute coronary syndrome and nephrotic syndrome: (1) coronary thrombosis related to hypercoagulability and/or platelet hyperactivity; (2) atherosclerosis related to hyperlipidaemia; and (3) drug treatment. All of these mechanisms must be evaluated systematically in the acute phase of disease because they evolve rapidly with the treatment of nephrotic syndrome. In this review, we propose a decision algorithm for the management of acute coronary syndrome in the context of nephrotic syndrome. The final part of the review presents the short- and medium-term therapeutic strategies available. Thromboembolism related to nephrotic syndrome is a rare non-atherosclerotic cause of acute coronary syndrome, and prospective studies are needed to evaluate a systematic approach with personalized therapeutic strategies.

Incidence of clinical atrial fibrillation and related complications using a screening algorithm at a nationwide level.

AIMS: In a recent position paper, the European Heart Rhythm Association (EHRA) proposed an algorithm for the screening and management of arrhythmias using digital devices. In patients with prior stroke, a systematic screening approach for atrial fibrillation (AF) should always be implemented, preferably immediately after the event. Patients with increasing age and with specific cardiovascular or non-cardiovascular comorbidities are also deemed to be at higher risk. From a large nationwide database, the aim was to analyse AF incidence rates derived from this new EHRA algorithm. METHODS AND RESULTS: Using the French administrative hospital discharge database, all patients hospitalized in 2012 without a history of AF, and with at least a 5-year follow-up (FU) (or if they died earlier), were included. The yearly incidence of AF was calculated in each subgroup defined by the algorithm proposed by EHRA based on a history of previous stroke, increasing age, and eight comorbidities identified via International Classification of Diseases 10th Revision codes. Out of the 4526 104 patients included (mean age 58.9 ± 18.9 years, 64.5% women), 1% had a history of stroke. Among those with no history of stroke, 18% were aged 65-74 years and 21% were ≥75 years. During FU, 327 012 patients had an incidence of AF (yearly incidence 1.86% in the overall population). Implementation of the EHRA algorithm divided the population into six risk groups: patients with a history of stroke (group 1); patients > 75 years (group 2); patients aged 65-74 years with or without comorbidity (groups 3a and 3b); and patients < 65 years with or without comorbidity (groups 4a and 4b). The yearly incidences of AF were 4.58% per year (group 2), 6.21% per year (group 2), 3.50% per year (group 3a), 2.01% per year (group 3b), 1.23% per year (group 4a), and 0.35% per year (group 4b). In patients aged < 65 years, the annual incidence of AF increased progressively according to the number of comorbidities from 0.35% (no comorbidities) to 9.08% (eight comorbidities). For those aged 65-75 years, the same trend was observed, i.e. increasing from 2.01% (no comorbidities) to 11.47% (eight comorbidities). CONCLUSION: These findings at a nationwide scale confirm the relevance of the subgroups in the EHRA algorithm for identifying a higher risk of AF incidence, showing that older patients (>75 years, regardless of comorbidities) have a higher incidence of AF than those with prior ischaemic stroke. Further studies are needed to evaluate the usefulness of algorithm-based risk stratification strategies for AF screening and the impact of screening on major cardiovascular event rates.