Ticagrelor vs Clopidogrel in Clopidogrel-Naive Patients With Chronic Coronary Syndrome.

BACKGROUND: Whether ticagrelor may reduce periprocedural myocardial necrosis after elective percutaneous coronary intervention (PCI) in patients with and without chronic clopidogrel therapy is unclear. OBJECTIVES: This study sought to compare ticagrelor vs clopidogrel in patients with and without chronic clopidogrel therapy before undergoing elective PCI. METHODS: In this prespecified analysis of the ALPHEUS (Assessment of Loading With the P2Y12 Inhibitor Ticagrelor or Clopidogrel to Halt Ischemic Events in Patients Undergoing Elective Coronary Stenting) trial, patients were defined as clopidogrel(+) and clopidogrel(-) according to the presence and absence of clopidogrel treatment for ≥7 days before PCI, respectively. The primary endpoint was the composite of PCI-related myocardial infarction and major injury as defined by the third and fourth universal definition 48 hours after PCI. RESULTS: A total of 1,882 patients were included, 805 (42.7%) of whom were clopidogrel(+). These patients were older, had more comorbidities, and had more frequent features of complex PCI. The primary endpoint was less frequently present in clopidogrel(-) compared to clopidogrel(+) patients (32.8% vs 40.0%; OR: 0.73; 95% CI: 0.60-0.88), but no significant differences were reported for the risk of death, myocardial infarction, stroke, or transient ischemic attack at 48 hours or 30 days. Ticagrelor did not reduce periprocedural myocardial necrosis or the risk of adverse outcomes, and there was no significant interaction regarding the presence of chronic clopidogrel treatment. CONCLUSIONS: Clopidogrel-naive patients presented less periprocedural complications compared to clopidogrel(+) patients, a difference related to a lower risk profile and less complex PCI. The absence of clopidogrel at baseline did not affect the absence of a difference between ticagrelor and clopidogrel in terms of PCI-related complications supporting the use of clopidogrel as the standard of care in elective PCI in patients with or without chronic clopidogrel treatment.

Three-Year Outcomes With Fractional Flow Reserve-Guided or Angiography-Guided Multivessel Percutaneous Coronary Intervention for Myocardial Infarction.

BACKGROUND: In patients with multivessel disease with successful primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction, the FLOWER-MI trial (Flow Evaluation to Guide Revascularization in Multivessel ST-Elevation Myocardial Infarction) showed that a fractional flow reserve (FFR)-guided strategy was not superior to an angiography-guided strategy for treatment of noninfarct-related artery lesions regarding the 1-year risk of death from any cause, myocardial infarction, or unplanned hospitalization leading to urgent revascularization. The extension phase of the trial was planned using the same primary outcome to determine whether a difference in outcomes would be observed with a longer follow-up. METHODS: In this multicenter trial, we randomly assigned patients with ST-segment-elevation myocardial infarction and multivessel disease with successful percutaneous coronary intervention of the infarct-related artery to receive complete revascularization guided by either FFR (n=586) or angiography (n=577). RESULTS: After 3 years, a primary outcome event occurred in 52 of 498 patients (9.40%) in the FFR-guided group and in 44 of 502 patients (8.17%) in the angiography-guided group (hazard ratio, 1.19 [95% CI, 0.79-1.77]; P=0.4). Death occurred in 22 patients (4.00%) in the FFR-guided group and in 23 (4.32%) in the angiography-guided group (hazard ratio, 0.96 [95% CI, 0.53-1.71]); nonfatal myocardial infarction in 23 (4.13%) and 14 (2.56%), respectively (hazard ratio, 1.63 [95% CI, 0.84-3.16]); and unplanned hospitalization leading to urgent revascularization in 21 (3.83%) and 18 (3.36%; hazard ratio, 1.15 [95% CI, 0.61-2.16]), respectively. CONCLUSIONS: Although event rates in the trial were lower than expected, in patients with ST-segment-elevation myocardial infarction undergoing complete revascularization, an FFR-guided strategy did not have a significant benefit over an angiography-guided strategy with respect to the risk of death, myocardial infarction, or urgent revascularization up to 3 years. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02943954.

Rationale and design of the FRENch CoHort of myocardial Infarction Evaluation (FRENCHIE) study.

BACKGROUND: Despite major advances in prevention and treatment, cardiovascular diseases - particularly acute myocardial infarction - remain a leading cause of death worldwide and in France. Collecting contemporary data about the characteristics, management and outcomes of patients with acute myocardial infarction in France is important. AIMS: The main objectives are to describe baseline characteristics, contemporary management, in-hospital and long-term outcomes of patients with acute myocardial infarction hospitalized in tertiary care centres in France; secondary objectives are to investigate determinants of prognosis (including periodontal disease and sleep-disordered breathing), to identify gaps between evidence-based recommendations and management and to assess medical care costs for the index hospitalization and during the follow-up period. METHODS: FRENCHIE (FRENch CoHort of myocardial Infarction Evaluation) is an ongoing prospective multicentre observational study (ClinicalTrials.gov Identifier: NCT04050956) enrolling more than 19,000 patients hospitalized for acute myocardial infarction with onset of symptoms within 48hours in 35 participating centres in France since March 2019. Main exclusion criteria are age<18 years, lack of health coverage and procedure-related myocardial infarction (types 4a and 5). Detailed information was collected prospectively, starting at admission, including demographic data, risk factors, medical history and treatments, initial management, with prehospital care pathways and medication doses, and outcomes until hospital discharge. The follow-up period (up to 20 years for each patient) is ensured by linking with the French national health database (Système national des données de santé), and includes information on death, hospital admissions, major clinical events, healthcare consumption (including drug reimbursement) and total healthcare costs. FRENCHIE is also used as a platform for cohort-nested studies - currently three randomized trials and two observational studies. CONCLUSIONS: This nationwide large contemporary cohort with very long-term follow-up will improve knowledge about acute myocardial infarction management and outcomes in France, and provide a useful platform for nested studies and trials.

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.

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.

Restrictive vs Liberal Blood Transfusions for Patients with Acute Myocardial Infarction and Anaemia by Heart Failure Status: An RCT Subgroup Analysis.

BACKGROUND: Red blood cell transfusion can cause fluid overload. We evaluated the interaction between heart failure (HF) at baseline and transfusion strategy on outcomes in acute myocardial infarction (AMI). METHODS: We used data from the randomized REALITY trial (https://www. CLINICALTRIALS: gov/study/NCT02648113), comparing restrictive versus liberal transfusion strategies in patients with AMI and anaemia. HF was defined as history of HF or Killip class > 1 at randomization. Primary outcome was major adverse cardiovascular events (MACE: composite of all-cause death, non-recurrent AMI, stroke, or emergency revascularization prompted by ischaemia) at 30 days. RESULTS: Among 658 randomized patients, 311 (47.3%) had HF. HF patients had higher rates of MACE at 30 days and 1 year, and higher rates of non-fatal new-onset HF. There was no interaction between HF and effect of randomized assignment on the primary outcome or non-fatal new-onset HF. A liberal transfusion strategy was associated with increased all-cause death at 30 days and at 1 year in HF patients (Pinteraction = 0.009 and P = 0.049, respectively). The main numerical difference in cause of death between restrictive and liberal strategies was death by HF at 30 days (4 vs 11). CONCLUSIONS: HF is frequent in AMI patients with anaemia and is associated with higher risk of MACE (including all-cause death) and non-fatal new-onset HF. While there was no interaction of HF with effect of transfusion strategy on MACE, a liberal transfusion strategy was associated with higher all-cause death that appears driven by a higher risk of early death due to HF.

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.

Oesophageal-pericardial and atrio-oesophageal fistula complicating a pulmonary vein isolation procedure.

A 66-year-old man with a history of catheter ablation for atrial fibrillation presented with purulent cardiac tamponade, revealing an atrio-oesophageal fistula. He underwent successful endoscopic management. A few days later, the patient fell into a sudden coma due to multiple cerebral air embolisms, resulting from a fistula between the esophagus and the right superior pulmonary vein.

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.

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.

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.

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.

Automatic classification of patients with myocardial infarction or myocarditis based only on clinical data: A quick response.

BACKGROUND: In acute cardiovascular disease management, the delay between the admission in a hospital emergency department and the assessment of the disease from a Delayed Enhancement cardiac MRI (DE-MRI) scan is one of the barriers for an immediate management of patients with suspected myocardial infarction or myocarditis. OBJECTIVES: This work targets patients who arrive at the hospital with chest pain and are suspected of having a myocardial infarction or a myocarditis. The main objective is to classify these patients based solely on clinical data in order to provide an early accurate diagnosis. METHODS: Machine learning (ML) and ensemble approaches have been used to construct a framework to automatically classify the patients according to their clinical conditions. 10-fold cross-validation is used during the model's training to avoid overfitting. Approaches such as Stratified, Over-sampling, Under-sampling, NearMiss, and SMOTE were tested in order to address the imbalance of the data (i.e. proportion of cases per pathology). The ground truth is provided by a DE-MRI exam (normal exam, myocarditis or myocardial infarction). RESULTS: The stacked generalization technique with Over-sampling seems to be the best one providing more than 97% of accuracy corresponding to 11 wrong classifications among 537 cases. Generally speaking, ensemble classifiers such as Stacking provided the best prediction. The five most important features are troponin, age, tobacco, sex and FEVG calculated from echocardiography. CONCLUSION: Our study provides a reliable approach to classify the patients in emergency department between myocarditis, myocardial infarction or other patient condition from only clinical information, considering DE-MRI as ground-truth. Among the different machine learning and ensemble techniques tested, the stacked generalization technique is the best one providing an accuracy of 97.4%. This automatic classification could provide a quick answer before imaging exam such as cardiovascular MRI depending on the patient's condition.

Efficiency and effectiveness of intensive multidisciplinary follow-up of patients with stroke/TIA or myocardial infarction compared to usual monitoring: protocol of a pragmatic randomised clinical trial. DiVa (Dijon vascular) study.

INTRODUCTION: The ongoing ageing population is associated with an increase in the number of patients suffering a stroke, transient ischaemic attack (TIA) or myocardial infarction (MI). In these patients, implementing secondary prevention is a critical challenge and new strategies need to be developed to close the gap between clinical practice and evidence-based recommendations. We describe the protocol of a randomised clinical trial that aims to evaluate the efficiency and effectiveness of an intensive multidisciplinary follow-up of patients compared with standard care. METHODS AND ANALYSIS: The DiVa study is a randomised, prospective, controlled, multicentre trial including patients >18 years old with a first or recurrent stroke (ischaemic or haemorrhagic) or TIA, or a type I or II MI, managed in one of the participating hospitals of the study area, with a survival expectancy >12 months. Patients will be randomised with an allocation ratio of 1:1 in two parallel groups: one group assigned to a multidisciplinary, nurse-based and pharmacist-based 2-year follow-up in association with general practitioners, neurologists and cardiologists versus one group with usual follow-up. In each group for each disease (stroke/TIA or MI), 430 patients will be enrolled (total of 1720 patients) over 3 years. The primary outcome will be the incremental cost-utility ratio at 24 months between intensive and standard follow-up in a society perspective. Secondary outcomes will include the incremental cost-utility ratio at 6 and 12 months, the incremental cost-effectiveness ratio at 24 months, reduction at 6, 12 and 24 months of the rates of death, unscheduled rehospitalisation and iatrogenic complications, changes in quality of life, net budgetary impact at 5 years of the intensive follow-up on the national health insurance perspective and analysis of factors having positive or negative effects on the implementation of the project in the study area. ETHICS AND DISSEMINATION: Ethical approval was obtained and all patients receive information about the study and give their consent to participate before randomisation. Results of the main trial and each of the secondary analyses will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT04188457. Registered on 6 December 2019.

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.

Time to onset of cardiovascular and cerebrovascular outcomes after hypertensive disorders of pregnancy: a nationwide, population-based retrospective cohort study.

BACKGROUND: The increased maternal cardiocerebrovascular risk after a pregnancy complicated by hypertensive disorders of pregnancy, is well documented in the literature. Recent evidence has suggested a shorter timeframe for the development of these postnatal outcomes, which could have major clinical implications. OBJECTIVE: This study aimed to determine the risk of and time to onset of maternal cardiovascular and cerebrovascular outcomes after a pregnancy complicated by hypertensive disorders of pregnancy. STUDY DESIGN: This study included 2,227,711 women, without preexisting chronic hypertension, who delivered during the period 2008 to 2010: 37,043 (1.66%) were diagnosed with preeclampsia, 34,220 (1.54%) were diagnosed with gestational hypertension, and 2,156,448 had normotensive pregnancies. Hospitalizations for chronic hypertension, heart failure, coronary heart disease, cerebrovascular disease, and peripheral arterial disease were studied. A classical Cox regression was performed to estimate the average effect of hypertensive disorders of pregnancy over 10 years compared with normotensive pregnancy; moreover, an extended Cox regression was performed with a step function model to estimate the effect of the exposure variable in different time intervals: <1, 1 to 3, 3 to 5, and 5 to 10 years of follow-up. RESULTS: The risk of chronic hypertension after a pregnancy complicated by preeclampsia was 18 times higher in the first year (adjusted hazard ratio, 18.531; 95% confidence interval, 16.520-20.787) to only 5 times higher at 5 to 10 years after birth (adjusted hazard ratio, 4.921; 95% confidence interval, 4.640-5.218). The corresponding risks of women with gestational hypertension were 12 times higher (adjusted hazard ratio, 11.727; 95% confidence interval, 10.257-13.409]) and 6 times higher (adjusted hazard ratio, 5.854; 95% confidence interval, 5.550-6.176), respectively. For other cardiovascular and cerebrovascular outcomes, there was also a significant effect with preeclampsia (heart failure: adjusted hazard ratio, 6.662 [95% confidence interval, 4.547-9.762]; coronary heart disease: adjusted hazard ratio, 3.083 [95% confidence interval, 1.626-5.844]; cerebrovascular disease: adjusted hazard ratio, 3.567 [95% confidence interval, 2.600-4.893]; peripheral arterial disease: adjusted hazard ratio, 4.802 [95% confidence interval, 2.072-11.132]) compared with gestational hypertension in the first year of follow-up. A dose-response effect was evident for the severity of preeclampsia with the averaged 10-year adjusted hazard ratios for developing chronic hypertension after early, preterm, and late preeclampsia being 10, 7, and 6 times higher, respectively. CONCLUSION: The risks of cardiovascular and cerebrovascular outcomes were the highest in the first year after a birth complicated by hypertensive disorders of pregnancy. We found a significant relationship with both the severity of hypertensive disorders of pregnancy and the gestational age of onset suggesting a possible dose-response relationship for the development of cardiovascular and cerebrovascular outcomes. These findings call for an urgent focus on research into effective postnatal screening and cardiocerebrovascular risk prevention for women with hypertensive disorders of pregnancy.