Familial risk of myocardial infarction with non-obstructive and obstructive coronary arteries -A nation-wide cohort study.

BACKGROUND AND AIMS: The familial risk among patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) is unknown. Previous studies of family history in myocardial infarction (MI), have not made a distinction between MINOCA and MI due to coronary artery disease (MI-CAD), based on angiographic findings. We therefore sought to investigate familial risk of MI without and with obstructive coronary arteries. METHODS: Register-based cohort study with a total of 15,462 MINOCA cases, 204,424 MI-CAD cases, 38,220 control subjects without MI and with non-obstructive coronary arteries. First-degree relatives were identified 1995-2020. Cox proportional hazard regression models were used to compare familial risk in MINOCA and MI-CAD with control subjects. RESULTS: During a mean follow-up of 8.1 ± 4.2 years, MINOCA occurred in 1.0% of first-degree relatives with MINOCA whereas MI-CAD occurred in 9.7% of first-degree relatives of MINOCA. The age- and sex-adjusted hazard ratio (HR) for a MINOCA-relative experiencing MINOCA and MI-CAD, compared to control subjects, was 0.99 (95% confidence interval [CI] 0.80-1.23) and 1.10 (95% CI 1.03-1.18), respectively. During a mean follow-up of 8.5 ±4.8 years, MI-CAD occurred in 12.2% of first- degree relatives with MI-CAD with age- and sex-adjusted HR 1.43 (95% CI 1.37-1.49). CONCLUSIONS: No increased familial risk of MINOCA was observed for MINOCA-patients whereas there was an increased familial risk for MI-CAD when compared to control subjects. These results may indicate that genetic factors and shared environmental factors within a family leading to CAD are important also for MINOCA, thus MI-CAD and MINOCA could share underlying mechanisms.

It is unknown whether a familial risk of myocardial infarction is important for developing myocardial infarction without obstructive coronary arteries (MINOCA). In our study we observed an increased familial occurrence for myocardial infarction with obstructive coronary artery disease (MI-CAD) when compared to control subjects whereas no increased familial occurrence of MINOCA was seen among MINOCA patients. These results may indicate that genetic factors and shared environmental factors within a family leading to CAD are important also for MINOCA, thus MI-CAD and MINOCA could share underlying mechanisms.

The impact of the COVID-19 pandemic on blood pressure control in patients with treated hypertension-results of the European Society of Hypertension Study (ESH ABPM COVID-19 Study).

BACKGROUND: We aimed to determine the influence of coronavirus disease 2019 (COVID-19) pandemic on blood pressure (BP) control assessed by ambulatory blood pressure monitoring (ABPM). METHODS: Office BP and ABPM data from two visits conducted within a 9-15 months interval were collected from patients treated for hypertension. In the prepandemic group, both visits took place before, while in the pandemic group, Visit-1 was done before and Visit-2 during the pandemic period. RESULTS: Of 1811 collected patients 191 were excluded because they did not meet the required ABPM time frames. Thus, the study comprised 704 patients from the pandemic and 916 from the prepandemic group. Groups did not differ in sex, age, duration of hypertension, frequency of first line antihypertensive drug use and mean 24 h BP on Visit-1. The prevalence of sustained uncontrolled hypertension was similar in both groups. On Visit-2 mean 24 h BP, daytime and nighttime systolic BP and diastolic BP were higher in the pandemic compared to the prepandemic group ( P  < 0.034). The prevalence of sustained uncontrolled hypertension on Visit-2 was higher in the pandemic than in the prepandemic group [0.29 (95% confidence interval (95% CI): 0.26-0.33) vs. 0.25 (95% CI: 0.22-0.28), P  < 0.037]. In multivariable adjusted analyses a significant difference in BP visit-to-visit change was observed, with a more profound decline in BP between visits in the prepandemic group. CONCLUSIONS: This study using ABPM indicates a negative impact of the COVID-19 pandemic on BP control. It emphasizes the need of developing strategies to maintain BP control during a pandemic such as the one induced by COVID-19.

Assessment of aortic stiffness during atrial fibrillation: solutions and considerations.

Background: Methods to assess aortic stiffness are not validated during ongoing atrial fibrillation (AF) We aimed to determine whether aortic stiffness can be assessed reliably in patients during AF. Methods and results: Carotid-to-femoral and aortic pulse wave velocity (cf/aoPWV), central blood pressure (BP), and augmentation index (AIx) were assessed by a two-site applanation method and a one-site cuff-based oscillometric method in 40 patients with persistent AF and repeated after cardioversion to SR. Mean age was 63 ± 8 years, 73% male, 50% hypertensive. For the two-site method, cfPWV values were slightly higher in AF than in SR (9.3 ± 1.8 vs. 8.5 ± 1.6 m/s, p < 0.001), whereas the one-site method provided similar values in AF and SR (10.1 ± 1.5 vs. 10.0 ± 1.8 m/s).The variability indices from the device was higher in AF for the two-site method (SD 2.5 ± 1.7 vs. 1.0 ± 0.5 m/s, p < 0.001) but similar in AF and SR with the one-site method (SD 0.7 ± 0.2 vs. 0.6 ± 0.2 m/s). Both methods yielded higher central BP (+4.8/+6.6 and +4.1/+5.7 mm Hg) and lower Aix (-6.8 and -9.1 mm Hg) in AF. Conclusions: Aortic stiffness can be assessed during AF. Both methods yielded higher central BP and lower AIx in AF, but similar results for PWV in AF and SR, also when adjusted for BP changes. The two-site method showed high variability necessitating repeated measurements. The one-site method showed lower device-calculated variability and needed fewer repeated measurements.

Are medical history data fit for risk stratification of patients with chest pain in emergency care? Comparing data collected from patients using computerized history taking with data documented by physicians in the electronic health record in the CLEOS-CPDS prospective cohort study.

OBJECTIVE: In acute chest pain management, risk stratification tools, including medical history, are recommended. We compared the fraction of patients with sufficient clinical data obtained using computerized history taking software (CHT) versus physician-acquired medical history to calculate established risk scores and assessed the patient-by-patient agreement between these 2 ways of obtaining medical history information. MATERIALS AND METHODS: This was a prospective cohort study of clinically stable patients aged ≥ 18 years presenting to the emergency department (ED) at Danderyd University Hospital (Stockholm, Sweden) in 2017-2019 with acute chest pain and non-diagnostic ECG and serum markers. Medical histories were self-reported using CHT on a tablet. Observations on discrete variables in the risk scores were extracted from electronic health records (EHR) and the CHT database. The patient-by-patient agreement was described by Cohen's kappa statistics. RESULTS: Of the total 1000 patients included (mean age 55.3 ± 17.4 years; 54% women), HEART score, EDACS, and T-MACS could be calculated in 75%, 74%, and 83% by CHT and in 31%, 7%, and 25% by EHR, respectively. The agreement between CHT and EHR was slight to moderate (kappa 0.19-0.70) for chest pain characteristics and moderate to almost perfect (kappa 0.55-0.91) for risk factors. CONCLUSIONS: CHT can acquire and document data for chest pain risk stratification in most ED patients using established risk scores, achieving this goal for a substantially larger number of patients, as compared to EHR data. The agreement between CHT and physician-acquired history taking is high for traditional risk factors and lower for chest pain characteristics. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03439449.

Predictive analytics support for complex chronic medical conditions: An experience-based co-design study of physician managers' needs and preferences.

PURPOSE: The literature suggests predictive technology applications in health care would benefit from physician and manager input during design and development. The aim was to explore the needs and preferences of physician managers regarding the role of predictive analytics in decision support for patients with the highly complex yet common combination of multiple chronic conditions of cardiovascular (Heart) and kidney (Nephrology) diseases and diabetes (HND). METHODS: This qualitative study employed an experience-based co-design model comprised of three data gathering phases: 1. Patient mapping through non-participant observations informed by process mining of electronic health records data, 2. Semi-structured experience-based interviews, and 3. A co-design workshop. Data collection was conducted with physician managers working at or collaborating with the HND center, Danderyd University Hospital (DSAB), in Stockholm, Sweden. HND center is an integrated practice unit offering comprehensive person-centered multidisciplinary care to stabilize disease progression, reduce visits, and develop treatment strategies that enables a transition to primary care. RESULTS: Interview and workshop data described a complex challenge due to the interaction of underlying pathophysiologies and the subsequent need for multiple care givers that hindered care continuity. The HND center partly met this challenge by coordinating care through multiple interprofessional and interdisciplinary shared decision-making interfaces. The large patient datasets were difficult to operationalize in daily practice due to data entry and retrieval issues. Predictive analytics was seen as a potentially effective approach to support decision-making, calculate risks, and improve resource utilization, especially in the context of complex chronic care, and the HND center a good place for pilot testing and development. Simplicity of visual interfaces, a better understanding of the algorithms by the health care professionals, and the need to address professional concerns, were identified as key factors to increase adoption and facilitate implementation. CONCLUSIONS: The HND center serves as a comprehensive integrated practice unit that integrates different medical disciplinary perspectives in a person-centered care process to address the needs of patients with multiple complex comorbidities. Therefore, piloting predictive technologies at the same time with a high potential for improving care represents an extreme, demanding, and complex case. The study findings show that health care professionals' involvement in the design of predictive technologies right from the outset can facilitate the implementation and adoption of such technologies, as well as enhance their predictive effectiveness and performance. Simplicity in the design of predictive technologies and better understanding of the concept and interpretation of the algorithms may result in implementation of predictive technologies in health care. Institutional efforts are needed to enhance collaboration among the health care professionals and IT professionals for effective development, implementation, and adoption of predictive analytics in health care.

Estimation of aortic stiffness by finger photoplethysmography using enhanced pulse wave analysis and machine learning.

Introduction: Aortic stiffness plays a critical role in the evolution of cardiovascular diseases, but the assessment requires specialized equipment. Photoplethysmography (PPG) and single-lead electrocardiogram (ECG) are readily available in healthcare and wearable devices. We studied whether a brief PPG registration, alone or in combination with single-lead ECG, could be used to reliably estimate aortic stiffness. Methods: A proof-of-concept study with simultaneous high-resolution index finger recordings of infrared PPG, single-lead ECG, and finger blood pressure (Finapres) was performed in 33 participants [median age 44 (range 21-66) years, 19 men] and repeated within 2 weeks. Carotid-femoral pulse wave velocity (cfPWV; two-site tonometry with SphygmoCor) was used as a reference. A brachial single-cuff oscillometric device assessed aortic pulse wave velocity (aoPWV; Arteriograph) for further comparisons. We extracted 136 established PPG waveform features and engineered 13 new with improved coupling to the finger blood pressure curve. Height-normalized pulse arrival time (NPAT) was derived using ECG. Machine learning methods were used to develop prediction models. Results: The best PPG-based models predicted cfPWV and aoPWV well (root-mean-square errors of 0.70 and 0.52 m/s, respectively), with minor improvements by adding NPAT. Repeatability and agreement were on par with the reference equipment. A new PPG feature, an amplitude ratio from the early phase of the waveform, was most important in modelling, showing strong correlations with cfPWV and aoPWV (r = -0.81 and -0.75, respectively, both P < 0.001). Conclusion: Using new features and machine learning methods, a brief finger PPG registration can estimate aortic stiffness without requiring additional information on age, anthropometry, or blood pressure. Repeatability and agreement were comparable to those obtained using non-invasive reference equipment. Provided further validation, this readily available simple method could improve cardiovascular risk evaluation, treatment, and prognosis.

A RAND/UCLA-Modified VAS Study on Telemedicine, Telehealth, and Virtual Care in Daily Clinical Practice of Vascular Medicine.

Background: Telemedicine is increasingly used in several fields of healthcare, including vascular medicine. This study aimed to investigate the views of experts and propose clinical practice recommendations on the possible applications of telemedicine in vascular medicine. Methods: A clinical guidance group proposed a set of 67 clinical practice recommendations based on the synthesis of current evidence and expert opinion. The Telemedicine Vascular Medicine Working Group included 32 experts from Europe evaluating the appropriateness of each clinical practice recommendation based on published RAND/UCLA methodology in two rounds. Results: In the first round, 60.9% of clinical practice recommendations were rated as appropriate, 35.9% as uncertain, and 3.1% as inappropriate. The strongest agreement (a median value of 10) was reached on statements regarding the usefulness of telemedicine during the 2019 coronavirus disease (COVID-19) pandemic, its usefulness for geographical areas that are difficult to access, and the superiority of video calls compared to phone calls only. The lowest degree of agreement (a median value of 2) was reported on statements regarding the utility of telemedicine being limited to the COVID-19 pandemic and regarding the applicability of teleconsultation in the diagnosis and management of abdominal aortic aneurysm. In the second round, 11 statements were re-evaluated to reduce variability. Conclusions: This study highlights the levels of agreement and the points that raise concern on the use of telemedicine in vascular medicine. It emphasizes the need for further clarification on various issues, including infrastructure, logistics, and legislation.

Associations between inflammatory and angiogenic proteomic biomarkers, and cardiovascular events and mortality in relation to kidney function.

Background: The links between chronic kidney disease (CKD) and the high burden of cardiovascular disease remain unclear. We aimed to explore the association between selected inflammatory and angiogenic biomarkers, kidney function and long-term outcome in patients with an acute coronary syndrome (ACS) and to test the hypothesis that CKD status modifies this association. Methods: A total of 1293 ACS patients hospitalized between 2008 and 2015 were followed until 31 December 2017. Plasma was collected on days 1-3 after admission. A total of 13 biomarkers were a priori identified and analysed with two proteomic methods, proximity extension assay or multiple reaction monitoring mass spectrometry. Boxplots and multiple linear regression models were used to study associations between biomarkers and kidney function and adjusted standardized Cox regression with an interaction term for CKD was used to assess whether CKD modified the association between biomarkers and major adverse cardiovascular events and death (MACE+). Results: The concentrations of nine biomarkers-endothelial cell-specific molecule-1 (ESM-1), fibroblast growth factor 23 (FGF-23), fractalkine (CX3CL1), interleukin-1 receptor antagonist (IL-1RA), interleukin-18 (IL-18), monocyte chemotactic protein-1 (MCP-1), placenta growth factor (PlGF), transmembrane immunoglobulin 1 (TIM-1) and vascular endothelial growth factor A (VEGFA)-were inversely associated with kidney function. ESM-1, FGF-23 and TIM-1 showed associations with MACE+. Only FGF23 remained independently associated after adjustment for the other biomarkers (hazard ratio per standard deviation increase 1.34; 95% Bonferroni corrected confidence interval 1.19-1.50). None of the biomarkers showed an interaction with CKD. Conclusions: The concentrations of 9 of the 13 prespecified inflammatory and angiogenic proteomic biomarkers increased when kidney function declined. Only FGF-23 demonstrated an independent association with MACE+, and this association was not modified by CKD status. These findings further support FGF-23 as an independent prognostic marker in ACS patients with and without CKD.

Global longitudinal strain in long-term risk prediction after acute coronary syndrome: an investigation of added prognostic value to ejection fraction.

AIMS: This study aimed to investigate the additional value of global longitudinal strain (GLS) on top of left ventricular ejection fraction (LVEF) in long-term risk prediction of combined death and heart failure (HF) re-hospitalization after acute coronary syndrome (ACS). METHOD AND RESULTS: This retrospective study included patients admitted with ACS between 2008 and 2014 from the three participating university hospitals. LVEF and GLS were assessed at a core lab from images acquired during the index hospital stay. Their prognostic value was studied with the Cox proportional hazards model (median follow-up 6.2 years). A nested model comparison was performed with C-statistics. A total of 941 patients qualified for multivariable analysis after multiple imputation of missing baseline covariables. The combined outcome was reached in 17.7% of the cases. Both GLS and LVEF were independent predictors of the combined outcome, hazard ratio (HR) 1.068 (95% CI 1.017-1.121) and HR 0.980 (95% CI 0.962-0.998), respectively. The C-statistic increased from 0.742 (95% CI 0.702-0.783) to 0.749 (95% CI 0.709-0.789) (P = 0.693) when GLS entered the model with clinical data and LVEF. CONCLUSION: GLS emerged as an independent long-term risk predictor of all-cause death and HF re-hospitalization. However, there was no significant incremental predictive value of GLS when LVEF was already known.

Inter-relationships between cardiovascular, renal and metabolic diseases: Underlying evidence and implications for integrated interdisciplinary care and management.

Cardiovascular, renal and metabolic (CaReMe) diseases are individually among the leading global causes of death, and each is associated with substantial morbidity and mortality. However, as these conditions commonly coexist in the same patient, the individual risk of mortality and morbidity is further compounded, leading to a considerable healthcare burden. A number of pathophysiological pathways are common to diseases of the CaReMe spectrum, including neurohormonal dysfunction, visceral adiposity and insulin resistance, oxidative stress and systemic inflammation. Because of the shared pathology and common co-occurrence of the CaReMe diseases, the value of managing these conditions holistically is increasingly being realized. A number of pharmacological and non-pharmacological approaches have been shown to offer simultaneous metabolic, cardioprotective and renoprotective benefits, leading to improved patient outcomes across the CaReMe spectrum. In addition, increasing value is being placed on interdisciplinary team-based and coordinated care models built on greater integration between specialties to increase the rate of early diagnosis and adherence to practice guidelines, and improve clinical outcomes. This interdisciplinary approach also facilitates integration between primary and specialty care, improving the patient experience, optimizing resources, and leading to efficiencies and cost savings. As the burden of CaReMe diseases continues to increase, implementation of innovative and integrated care delivery models will be essential to achieve effective and efficient chronic disease management and to ensure that patients benefit from the best care available across all three disciplines.

Helicobacter pylori and Pro-Inflammatory Protein Biomarkers in Myocardial Infarction with and without Obstructive Coronary Artery Disease.

Myocardial infarction (MI) with obstructive coronary artery disease (MI-CAD) and MI in the absence of obstructive coronary artery disease (MINOCA) affect different populations and may have separate pathophysiological mechanisms, with greater inflammatory activity in MINOCA compared to MI-CAD. Helicobacter pylori (Hp) can cause systemic inflammation and has been associated with cardiovascular disease (CVD). We aimed to investigate whether Hp infection is associated with concentrations of protein biomarkers of inflammation and CVD. In a case-control study, patients with MINOCA (n = 99) in Sweden were included, complemented by matched subjects with MI-CAD (n = 99) and controls (n = 100). Protein biomarkers were measured with a proximity extension assay in plasma samples collected 3 months after MI. The seroprevalence of Hp and cytotoxin-associated gene A (CagA) was determined using ELISA. The associations between protein levels and Hp status were studied with linear regression. The prevalence of Hp was 20.2%, 19.2%, and 16.0% for MINOCA, MI-CAD, and controls, respectively (p = 0.73). Seven proteins were associated with Hp in an adjusted model: tissue plasminogen activator (tPA), interleukin-6 (IL-6), myeloperoxidase (MPO), TNF-related activation-induced cytokine (TRANCE), pappalysin-1 (PAPPA), soluble urokinase plasminogen activator receptor (suPAR), and P-selectin glycoprotein ligand 1 (PSGL-1). Hp infection was present in one in five patients with MI, irrespective of the presence of obstructive CAD. Inflammatory proteins were elevated in Hp-positive subjects, thus not ruling out that Hp may promote an inflammatory response and potentially contribute to the development of CVD.

Coronary microvascular dysfunction in Takotsubo syndrome and associations with left ventricular function.

AIMS: Coronary microvascular dysfunction (CMD) has been proposed as an important pathophysiological mechanism in Takotsubo syndrome (TTS). Our aims were (i) to evaluate and compare levels of CMD in patients with TTS and patients with ischaemia and no obstructive coronary arteries (INOCA) and (ii) to investigate associations between CMD and clinical parameters, left ventricular function, and coronary atherosclerosis in TTS. METHODS AND RESULTS: We conducted a prospective study of 27 female TTS patients and an equally sized, age- and gender-matched, cohort of INOCA patients. Coronary microvascular function was quantified invasively using the index of microcirculatory resistance (IMR), coronary flow reserve (CFR), and resistive reserve ratio (RRR). CMD was defined as IMR ≥ 25 and/or CFR ≤ 2. In the TTS patients, left ventricular function was assessed with echocardiography and cardiovascular magnetic resonance (CMR) imaging, and coronary atherosclerosis was visualized with intravascular ultrasound with near-infrared spectroscopy (IVUS-NIRS). The incidence of CMD was higher in the TTS patients than in the INOCA cohort (78% vs. 44%, P = 0.01), with higher IMR (30 vs. 14, P = 0.002), lower CFR (1.8 vs. 2.8, P = 0.009), and lower RRR (2.1 vs. 3.5, P = 0.003). In apical compared with midventricular TTS, IMR was numerically higher (50 vs. 28, P = 0.20), whereas CFR and RRR were lower (1.5 vs. 2.5, P = 0.003 and 1.6 vs. 2.7, P = 0.01, respectively). Global longitudinal strain and global circumferential strain, assessed with CMR imaging, were more impaired in apical than in midventricular TTS (-11 vs. -14, P < 0.001 and -12 vs. -15, P = 0.049, respectively). In the TTS patients, CFR and RRR correlated with echocardiography-derived (R2  = 0.15, P = 0.002 and R2  = 0.18, P = 0.007, respectively) and CMR-derived (R2  = 0.09, P = 0.025 and R2  = 0.10, P = 0.038, respectively) ejection fraction. CFR and RRR correlated inversely with CMR-derived end-diastolic volume index, end-systolic volume index, and left ventricular mass index. IMR, CFR, and RRR were not associated with measures of coronary atherosclerosis derived by IVUS-NIRS. CONCLUSIONS: Coronary microvascular dysfunction is common in patients with TTS and more frequent than in patients with INOCA. CMD in TTS is more severe in the apical compared with the midventricular phenotype of the syndrome, is associated with left ventricular function, but is unrelated to coronary atherosclerosis. Our results support the notion of CMD as a key mediator in TTS.

National Knowledge-Driven Management of Obstructive Sleep Apnea-The Swedish Approach.

INTRODUCTION: This paper describes the development of "Swedish Guidelines for OSA treatment" and the underlying managed care process. The Apnea Hypopnea Index (AHI) is traditionally used as a single parameter for obstructive sleep apnea (OSA) severity classification, although poorly associated with symptomatology and outcome. We instead implement a novel matrix for shared treatment decisions based on available evidence. METHODS: A national expert group including medical and dental specialists, nurses, and patient representatives developed the knowledge-driven management model. A Delphi round was performed amongst experts from all Swedish regions (N = 24). Evidence reflecting treatment effects was extracted from systematic reviews, meta-analyses, and randomized clinical trials. RESULTS: The treatment decision in the process includes a matrix with five categories from a "very weak"" to "very strong" indication to treat, and it includes factors with potential influence on outcome, including (A) OSA-related symptoms, (B) cardiometabolic comorbidities, (C) frequency of respiratory events, and (D) age. OSA-related symptoms indicate a strong incitement to treat, whereas the absence of symptoms, age above 65 years, and no or well-controlled comorbidities indicate a weak treatment indication, irrespective of AHI. CONCLUSIONS: The novel treatment matrix is based on the effects of treatments rather than the actual frequency of respiratory events during sleep. A nationwide implementation of this matrix is ongoing, and the outcome is monitored in a prospective evaluation by means of the Swedish Sleep Apnea Registry (SESAR).

Acute Kidney Injury: Clinical Characteristics and Short-Term Outcomes in 1,519 Patients.

Introduction: Complex integrated information on disease mechanisms and in-hospital outcomes in mild to moderate acute kidney injury (AKI) is scarce. Methods: The Stockholm Prospective AKI Cohort Study (SAKIS) included all patients (≥18 years, n = 1,519) with community-acquired AKI (KDIGO criteria) admitted to the nephrology ward at Danderyd University Hospital, Stockholm, Sweden, between 2009 and 2018. Detailed laboratory measures were registered. Odds ratio for hypo- and hyperkalemia, recovery of kidney function by 30% and 50%, and in-hospital mortality were assessed by logistic regression analysis. Results: Factors independently associated with the presence of hyperkalemia at admission were high age, high serum creatinine (sCr), and low C-reactive protein (CRP). Signs of malnutrition, inflammation, and acidosis were seen in 31% of patients. Kidney recovery, defined as a reduction of sCr by 30% in-hospital (63% of all patients), was associated with higher age, female sex, lower body mass index (BMI), higher hemoglobin, and higher CRP. Factors independently associated with mortality (4.4% of patients) were high age, high BMI, and low albumin. Conclusion: This study provides a detailed description of community-acquired AKI and comprehensive analyses of integrated clinical and laboratory data associated with kidney recovery. Features related to anemia, albuminuria, malnutrition, inflammation, and acidosis associate with partial or moderate short-term recovery of kidney function, with disturbances in potassium homeostasis, and with in-hospital mortality. Future studies are warranted to analyze the long-term consequences of AKI in terms of risk of kidney failure, cardiovascular morbidity, and mortality.

Statin Treatment Intensity, Discontinuation, and Long-Term Outcome in Patients With Acute Myocardial Infarction and Impaired Kidney Function.

ABSTRACT: Statin dosage in patients with acute myocardial infarction (AMI) and concomitant kidney dysfunction is a clinical dilemma. We studied discontinuation during the first year after an AMI and long-term outcome in patients receiving high versus low-moderate intensity statin treatment, in relation to kidney function. For the intention-to-treat analysis (ITT-A), we included all patients admitted to Swedish coronary care units for a first AMI between 2005 and 2016 that survived in-hospital, had known creatinine, and initiated statin therapy (N = 112,727). High intensity was initiated in 38.7% and low-moderate in 61.3%. In patients with estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m 2 , 25% discontinued treatment the first year; however, the discontinuation rate was similar regardless of the statin intensity. After excluding patients who died, changed therapy, or were nonadherent during the first year, 84,705 remained for the on-treatment analysis (OT-A). Patients were followed for 12.6 (median 5.6) years. In patients with eGFR 30-59 mL/min, high-intensity statin was associated with lower risk for the composite death, reinfarction, or stroke both in ITT-A (hazard ratio [HR] 0.93; 95% confidence interval, 0.87-0.99) and OT-A (HR 0.90; 0.83-0.99); the interaction test for OT-A indicated no heterogeneity for the eGFR < 60 mL/min group ( P = 0.46). Similar associations were seen for all-cause mortality. We confirm that high-intensity statin treatment is associated with improved long-term outcome after AMI in patients with reduced kidney function. Most patients with reduced kidney function initiated on high-intensity statins are persistent after 1 year and equally persistent as patients initiated on low-moderate intensity.

Reliability of estimating left ventricular ejection fraction in clinical routine: a validation study of the SWEDEHEART registry.

OBJECTIVE: Patients hospitalized with acute coronary syndrome (ACS) in Sweden routinely undergo an echocardiographic examination with assessment of left ventricular ejection fraction (LVEF). LVEF is a measurement widely used for outcome prediction and treatment guidance. The obtained LVEF is categorized as normal (> 50%) or mildly, moderately, or severely impaired (40-49, 30-39, and < 30%, respectively) and reported to the nationwide registry for ACS (SWEDEHEART). The purpose of this study was to determine the reliability of the reported LVEF values by validating them against an independent re-evaluation of LVEF. METHODS: A random sample of 130 patients from three hospitals were included. LVEF re-evaluation was performed by two independent reviewers using the modified biplane Simpson method and their mean LVEF was compared to the LVEF reported to SWEDEHEART. Agreement between reported and re-evaluated LVEF was assessed using Gwet's AC2 statistics. RESULTS: Analysis showed good agreement between reported and re-evaluated LVEF (AC2: 0.76 [95% CI 0.69-0.84]). The LVEF re-evaluations were in agreement with the registry reported LVEF categorization in 86 (66.0%) of the cases. In 33 (25.4%) of the cases the SWEDEHEART-reported LVEF was lower than re-evaluated LVEF. The opposite relation was found in 11 (8.5%) of the cases (p < 0.005). CONCLUSION: Independent validation of SWEDEHEART-reported LVEF shows an overall good agreement with the re-evaluated LVEF. However, a tendency towards underestimation of LVEF was observed, with the largest discrepancy between re-evaluated LVEF and registry LVEF in subjects with subnormal LV-function in whom the reported assessment of LVEF should be interpreted more cautiously.

Health-related quality-of-life up to one year after myocardial infarction with non-obstructive coronary arteries.

AIMS: Patients with Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) are a heterogenous group and previous studies indicate a decreased Health-related quality-of-life (HRQoL) compared with patients with myocardial infarction with obstructive coronary artery disease and healthy individuals. However, longitudinal data are scarce. Therefore, the aim was to explore HRQoL among patients with MINOCA during a one-year period after the acute event in comparison with a group of healthy individuals and to describe HRQoL in patients with Takotsubo Syndrome (TTS). METHODS AND RESULTS: Patients with MINOCA were recruited from five hospitals in the Stockholm region (SMINC-2 study, clinical trials: NCT2318498). Patients responded to the HRQoL questionnaire RAND-36 between days 2-4, after 6 and 12 months respectively. A sample of population-based individuals was used as a comparison group. A total of 142 MINOCA patients, (70% women) mean age of 56 years, responded. A population-based sample of 317 volunteers (66% women) mean age of 57 years. Patients with MINOCA scored lower than the comparison group in the domains role functioning physical, social functioning, and role functioning emotional (P = 0.01-0.02) at 12 months. In these domains of HRQoL there was no improvement in MINOCA patients during 12 months follow-up. In the domains of energy/fatigue vitality and emotional well-being the scores improved and were similar to the comparison group at 12 months. Patients with TTS scored generally lower on RAND-36 than MINOCA patients without TTS. CONCLUSION: Physical, social, and emotional functioning did not improve during the first year after MINOCA, indicating a need for increased follow-up including psychological support.

Prognostic importance of biomarkers associated with haemostatic, vascular and endothelial disturbances in acute coronary syndrome patients in relation to kidney function.

BACKGROUND: Patients with kidney failure have a high risk for cardiovascular events. We aimed to evaluate the prognostic importance of selected biomarkers related to haemostasis, endothelial function, and vascular regulation in patients with acute coronary syndrome (ACS), and to study whether this association differed in patients with renal dysfunction. METHODS: Plasma was collected in 1370 ACS patients included between 2008 and 2015. Biomarkers were analysed using a Proximity Extension Assay and a Multiple Reaction Monitoring mass spectrometry assay. To reduce multiplicity, biomarkers correlating with eGFR were selected a priori among 36 plasma biomarkers reflecting endothelial and vascular function, and haemostasis. Adjusted Cox regression were used to study their association with the composite outcome of myocardial infarction, ischemic stroke, heart failure or death. Interaction with eGFR strata above or below 60 ml/min/1.73 m2 was tested. RESULTS: Tissue factor, proteinase-activated receptor, soluble urokinase plasminogen activator surface receptor (suPAR), thrombomodulin, adrenomedullin, renin, and angiotensinogen correlated inversely with eGFR and were selected for the Cox regression. Mean follow-up was 5.2 years during which 428 events occurred. Adrenomedullin, suPAR, and renin were independently associated with the composite outcome. Adrenomedullin showed interaction with eGFR strata (p = 0.010) and was associated with increased risk (HR 1.88; CI 1.44-2.45) only in patients with eGFR ≥60 ml/min/ 1.73 m2. CONCLUSIONS: Adrenomedullin, suPAR, and renin were associated with the composite outcome in all. Adrenomedullin, involved in endothelial protection, showed a significant interaction with renal function and outcome, and was associated with the composite outcome only in patients with preserved kidney function.