The impact of patient-reported frailty on cardiovascular outcomes in elderly patients after non-ST-acute coronary syndrome.

BACKGROUND: As life expectancy increases, the population of older individuals with coronary artery disease and frailty is growing. We aimed to assess the impact of patient-reported frailty on the treatment and prognosis of elderly early survivors of non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: Frailty data were obtained from two prospective trials, POPular Age and the POPular Age Registry, which both assessed elderly NSTE-ACS patients. Frailty was assessed one month after admission with the Groningen Frailty Indicator (GFI) and was defined as a GFI-score of 4 or higher. In these early survivors of NSTE-ACS, we assessed differences in treatment and 1-year outcomes between frail and non-frail patients, considering major adverse cardiovascular events (MACE, including cardiovascular mortality, myocardial infarction, and stroke) and major bleeding. RESULTS: The total study population consisted of 2192 NSTE-ACS patients, aged ≥70 years. The GFI-score was available in 1320 patients (79 ± 5 years, 37% women), of whom 712 (54%) were considered frail. Frail patients were at higher risk for MACE than non-frail patients (9.7% vs. 5.1%, adjusted hazard ratio [HR] 1.57, 95% confidence interval [CI] 1.01-2.43, p = 0.04), but not for major bleeding (3.7% vs. 2.8%, adjusted HR 1.23, 95% CI 0.65-2.32, p = 0.53). Cubic spline analysis showed a gradual increase of the risk for clinical outcomes with higher GFI-scores. CONCLUSIONS: In elderly NSTE-ACS patients who survived 1-month follow-up, patient-reported frailty was independently associated with a higher risk for 1-year MACE, but not with major bleeding. These findings emphasize the importance of frailty screening for risk stratification in elderly NSTE-ACS patients.

The potential benefit of statin prescription based on prediction of treatment responsiveness in older individuals: An application to the PROSPER randomised controlled trial.

BACKGROUND & AIMS: Clinical guidelines often recommend to treat individuals based on their cardiovascular risk. We revisit this paradigm and quantify the efficacy of three treatment strategies: (i) overall prescription, i.e. treatment to all individuals sharing the eligibility criteria of a trial; (ii) risk-stratified prescription, i.e. treatment only to those at an elevated outcome risk; and (iii) prescription based on predicted treatment responsiveness. METHODS: We reanalysed the PROSPER randomised controlled trial, which included individuals aged 70-82 years with a history of, or risk factors for, vascular diseases. We conducted the derivation and internal-external validation of a model predicting treatment responsiveness. We compared to placebo (n= 2913): (i) pravastatin (n= 2891); (ii) pravastatin in the presence of previous vascular diseases and placebo in the absence thereof (n= 2925); and (iii) pravastatin in the presence of a favourable prediction of treatment response and placebo in the absence thereof (n= 2890). RESULTS: We found an absolute difference in primary outcome events composed of coronary death, non-fatal myocardial infarction, fatal or non-fatal stroke, per 10 000 person-years equal to: -78 events (95% CI, -144 to -12) when prescribing pravastatin to all participants; -66 events (95% CI, -114 to -18) when treating only individuals with an elevated vascular risk; and -103 events (95% CI, -162 to -44) when restricting pravastatin to individuals with a favourable prediction of treatment response. CONCLUSIONS: Pravastatin prescription based on predicted responsiveness may have an encouraging potential for cardiovascular prevention. Further external validation of our results and clinical experiments are needed.

This study invistigates whether an algorithm to predict how much old age individuals would benefit from a statin treatment could be useful to guide clinicians in their prescription decision-making; the key findings are: About one out of seven individuals included in the study has no predicted benefit of pravastatin; Compared to prescribing pravastatin to all old age individuals at risk of cardiovascular diseases, withholding pravastatin in those with no predicted benefit seems to lead to a better prevention of cardiovascular events.

High residual cardiovascular risk after lipid-lowering: prime time for Predictive, Preventive, Personalized, Participatory, and Psycho-cognitive medicine.

As time has come to translate trial results into individualized medical diagnosis and therapy, we analyzed how to minimize residual risk of cardiovascular disease (CVD) by reviewing papers on "residual cardiovascular disease risk". During this review process we found 989 papers that started off with residual CVD risk after initiating statin therapy, continued with papers on residual CVD risk after initiating therapy to increase high-density lipoprotein-cholesterol (HDL-C), followed by papers on residual CVD risk after initiating therapy to decrease triglyceride (TG) levels. Later on, papers dealing with elevated levels of lipoprotein remnants and lipoprotein(a) [Lp(a)] reported new risk factors of residual CVD risk. And as new risk factors are being discovered and new therapies are being tested, residual CVD risk will be reduced further. As we move from CVD risk reduction to improvement of patient management, a paradigm shift from a reductionistic approach towards a holistic approach is required. To that purpose, a personalized treatment dependent on the individual's CVD risk factors including lipid profile abnormalities should be configured, along the line of P5 medicine for each individual patient, i.e., with Predictive, Preventive, Personalized, Participatory, and Psycho-cognitive approaches.

Coronary calcium score in COVID-19 survivors: Association with cardiac injury and cardiac function after 6 weeks.

Aims: Cardiac manifestations are common in COVID-19, often elevated serum troponin levels or myocardial dysfunction on trans-thoracic echocardiography (TTE) is observed. Both parameters are associated with increased in-hospital mortality. Possibly, subclinical coronary atherosclerosis plays a role, of which severity can be assessed by calculating the coronary artery calcium (CAC) score. This study aims to determine the relation between coronary atherosclerosis and cardiac manifestations in COVID-19 survivors. Methods: This study was conducted at the Leiden University Medical Center. All patients admitted for COVID-19 were included and scheduled for a 6-week follow-up visit with trans-thoracic echocardiography (TTE). CAC was assessed according to an ordinal score on non-gated, non-contrast enhanced computed tomography of the chest. Patients with and without CAC were compared on cardiac injury as reflected by elevated serum troponin levels and impaired cardiac function assessed through TTE. Results: In total, 146 patients were included. Mean age was 62 years and 62 % of the patients were male. During admission, patients with CAC showed significantly higher levels of troponin (19 ng/L vs 10 ng/L; p < 0.01). Overall, mild echocardiographic abnormalities were seen; 12 % showed reduced left ventricular function (left ventricular ejection fraction of <50 %) and 14 % reduced right ventricular function (tricuspid annular planar systolic excursion ≤17 mm). Following multivariable adjustments, there was no significant relation between CAC and myocardial function at 6 weeks. Conclusion: The present study shows that coronary atherosclerosis is associated with cardiac injury in COVID-19 survivors. However, no significant relation with impaired cardiac function was demonstrated.

The Netherlands Heart Tissue Bank : Strengthening the cardiovascular research infrastructure with an open access Cardiac Tissue Repository.

AIM: Cardiac diseases remain a leading cause of cardiovascular disease (CVD) related hospitalisation and mortality. That is why research to improve our understanding of pathophysiological processes underlying cardiac diseases is of great importance. There is a strong need for healthy and diseased human cardiac tissue and related clinical data to accomplish this, since currently used animal and in vitro disease models do not fully grasp the pathophysiological processes observed in humans. This design paper describes the initiative of the Netherlands Heart Tissue Bank (NHTB) that aims to boost CVD-related research by providing an open-access biobank. METHODS: The NHTB, founded in June 2020, is a non-profit biobank that collects and stores biomaterial (including but not limited to myocardial tissue and blood samples) and clinical data of individuals with and without previously known cardiac diseases. All individuals aged ≥ 18 years living in the Netherlands are eligible for inclusion as a potential future donor. The stored samples and clinical data will be available upon request for cardiovascular researchers. CONCLUSION: To improve the availability of cardiac tissue for cardiovascular research, the NHTB will include extensive (cardiac) biosamples, medical images, and clinical data of donors with and without a previously known cardiac disease. As such, the NHTB will function as a translational bridge to boost a wide range of cardiac disease-related fundamental and translational studies.

Resting heart rate and incident atrial fibrillation: A stratified Mendelian randomization in the AFGen consortium.

BACKGROUND: Both elevated and low resting heart rates are associated with atrial fibrillation (AF), suggesting a U-shaped relationship. However, evidence for a U-shaped causal association between genetically-determined resting heart rate and incident AF is limited. We investigated potential directional changes of the causal association between genetically-determined resting heart rate and incident AF. METHOD AND RESULTS: Seven cohorts of the AFGen consortium contributed data to this meta-analysis. All participants were of European ancestry with known AF status, genotype information, and a heart rate measurement from a baseline electrocardiogram (ECG). Three strata of instrumental variable-free resting heart rate were used to assess possible non-linear associations between genetically-determined resting heart rate and the logarithm of the incident AF hazard rate: <65; 65-75; and >75 beats per minute (bpm). Mendelian randomization analyses using a weighted resting heart rate polygenic risk score were performed for each stratum. We studied 38,981 individuals (mean age 59±10 years, 54% women) with a mean resting heart rate of 67±11 bpm. During a mean follow-up of 13±5 years, 4,779 (12%) individuals developed AF. A U-shaped association between the resting heart rate and the incident AF-hazard ratio was observed. Genetically-determined resting heart rate was inversely associated with incident AF for instrumental variable-free resting heart rates below 65 bpm (hazard ratio for genetically-determined resting heart rate, 0.96; 95% confidence interval, 0.94-0.99; p = 0.01). Genetically-determined resting heart rate was not associated with incident AF in the other two strata. CONCLUSIONS: For resting heart rates below 65 bpm, our results support an inverse causal association between genetically-determined resting heart rate and incident AF.

Transmural ischemia visualized using routine Chest CTA.

Chest computed tomography (CT) is not routinely used for the diagnosis of myocardial infarction. However, there have been some reports of patients undergoing chest CT for other indications in which ultimately MI was diagnosed due to the presence of areas of myocardial hypoperfusion. The authors present the case of a 60-years old male who is referred due to acute chest pain radiating between the scapulae. Thoracic computed tomography angiography to rule out an aortic dissection revealed an occlusion of the left anterior descending coronary artery with an area of relative hypoperfusion. Hence, the present case demonstrates how using routine thoracic computed tomography angiography, transmural ischemia can be visualized in the setting of an acute myocardial infarction. It should make clinicians aware of the fact it may be beneficial to look for myocardial perfusion abnormalities when assessing chest CT's.

Correlation between quantification of myocardial area at risk and ischemic burden at cardiac computed tomography.

Purpose: This study aims to investigate the correlation between myocardial area at risk at coronary computed tomography angiography (CCTA) and the ischemic burden derived from myocardial computed tomography perfusion (CTP) by using the 17-segment model. Methods: Forty-two patients with chest pain complaints who underwent a combined CCTA and CTP protocol were identified. Patients with reversible ischemia at CTP and at least one stenosis of ≥ 50% at CCTA were selected. Myocardial area at risk was calculated using a Voronoi-based segmentation algorithm at CCTA and was defined as the sum of all territories related to a ≥ 50% stenosis as a percentage of the total left ventricular (LV) mass. The latter was calculated using LV contours which were automatically drawn using a machine learning algorithm. Subsequently, the ischemic burden was defined as the number of segments demonstrating relative hypoperfusion as a percentage of the total amount of segments (=17). Finally, correlations were tested between the myocardial area at risk and the ischemic burden using Pearson's correlation coefficient. Results: A total of 77 coronary lesions were assessed. Average myocardial area at risk and ischemic burden for all lesions was 59% and 23%, respectively. Correlations for ≥ 50% and ≥ 70% stenosis based myocardial area at risk compared to ischemic burden were moderate (r = 0.564; p < 0.01) and good (r = 0.708; p < 0.01), respectively. Conclusion: The relation between myocardial area at risk as calculated by using a Voronoi-based algorithm at CCTA and ischemic burden as assessed by CTP is dependent on stenosis severity.

Utilizing (serial) coronary computed tomography angiography (CCTA) to predict plaque progression and major adverse cardiac events (MACE): results, merits and challenges.

OBJECTIVES: To present an overview of studies using serial coronary computed tomography angiography (CCTA) as a tool for finding both quantitative (changes) and qualitative plaque characteristics as well as epicardial adipose tissue (EAT) volume changes as predictors of plaque progression and/or major adverse cardiac events (MACE) and outline the challenges and advantages of using a serial non-invasive imaging approach for assessing cardiovascular prognosis. METHODS: A literature search was performed in PubMed, Embase, Web of Science, Cochrane Library and Emcare. All observational cohort studies were assessed for quality using the Newcastle-Ottawa Scale (NOS). The NOS score was then converted into Agency for Healthcare Research and Quality (AHRQ) standards: good, fair and poor. RESULTS: A total of 36 articles were analyzed for this review, 3 of which were meta-analyses and one was a technical paper. Quantitative baseline plaque features seem to be more predictive of MACE and/or plaque progression as compared to qualitative plaque features. CONCLUSIONS: A critical review of the literature focusing on studies utilizing serial CCTA revealed that mainly quantitative baseline plaque features and quantitative plaque changes are predictive of MACE and/or plaque progression contrary to qualitative plaque features. Significant questions regarding the clinical implications of these specific quantitative and qualitative plaque features as well as the challenges of using serial CCTA have yet to be resolved in studies using this imaging technique. KEY POINTS: • Use of (serial) CCTA can identify plaque characteristics and plaque changes as well as changes in EAT volume that are predictive of plaque progression and/or major adverse events (MACE) at follow-up. • Studies utilizing serial CCTA revealed that mainly quantitative baseline plaque features and quantitative plaque changes are predictive of MACE and/or plaque progression contrary to qualitative plaque features. • Ultimately, serial CCTA is a promising technique for the evaluation of cardiovascular prognosis, yet technical details remain to be refined.

The challenge of choosing in cardiovascular risk management.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. For many years guidelines have listed optimal preventive therapy. More recently, novel therapeutic options have broadened the options for state-of-the-art CV risk management (CVRM). In the majority of patients with CVD, risk lowering can be achieved by utilising standard preventive medication combined with lifestyle modifications. In a minority of patients, add-on therapies should be considered to further reduce the large residual CV risk. However, the choice of which drug combination to prescribe and in which patients has become increasingly complicated, and is dependent on both the absolute CV risk and the reason for the high risk. In this review, we discuss therapeutic decisions in CVRM, focusing on (1) the absolute CV risk of the patient and (2) the pros and cons of novel treatment options.

2020 ESC Guidelines on acute coronary syndrome without ST-segment elevation : Recommendations and critical appraisal from the Dutch ACS and Interventional Cardiology working groups.

Recently, the European Society of Cardiology (ESC) has updated its guidelines for the management of patients with acute coronary syndrome (ACS) without ST-segment elevation. The current consensus document of the Dutch ACS working group and the Working Group of Interventional Cardiology of the Netherlands Society of Cardiology aims to put the 2020 ESC Guidelines into the Dutch perspective and to provide practical recommendations for Dutch cardiologists, focusing on antiplatelet therapy, risk assessment and criteria for invasive strategy.

Quantification of myocardial ischemia and subtended myocardial mass at adenosine stress cardiac computed tomography: a feasibility study.

Combination of coronary computed tomography angiography (CCTA) and adenosine stress CT myocardial perfusion (CTP) allows for coronary artery lesion assessment as well as myocardial ischemia. However, myocardial ischemia on CTP is nowadays assessed semi-quantitatively by visual analysis. The aim of this study was to fully quantify myocardial ischemia and the subtended myocardial mass on CTP. We included 33 patients referred for a combined CCTA and adenosine stress CTP protocol, with good or excellent imaging quality on CTP. The coronary artery tree was automatically extracted from the CCTA and the relevant coronary artery lesions with a significant stenosis (≥ 50%) were manually defined using dedicated software. Secondly, epicardial and endocardial contours along with CT perfusion deficits were semi-automatically defined in short-axis reformatted images using MASS software. A Voronoi-based segmentation algorithm was used to quantify the subtended myocardial mass, distal from each relevant coronary artery lesion. Perfusion defect and subtended myocardial mass were spatially registered to the CTA. Finally, the subtended myocardial mass per lesion, total subtended myocardial mass and perfusion defect mass (per lesion) were measured. Voronoi-based segmentation was successful in all cases. We assessed a total of 64 relevant coronary artery lesions. Average values for left ventricular mass, total subtended mass and perfusion defect mass were 118, 69 and 7 g respectively. In 19/33 patients (58%) the total perfusion defect mass could be distributed over the relevant coronary artery lesion(s). Quantification of myocardial ischemia and subtended myocardial mass seem feasible at adenosine stress CTP and allows to quantitatively correlate coronary artery lesions to corresponding areas of myocardial hypoperfusion at CCTA and adenosine stress CTP.

The first multicentre study on coronary anomalies in the Netherlands: MuSCAT.

BACKGROUND: Current guidelines on coronary anomalies are primarily based on expert consensus and a limited number of trials. A gold standard for diagnosis and a consensus on the treatment strategy in this patient group are lacking, especially for patients with an anomalous origin of a coronary artery from the opposite sinus of Valsalva (ACAOS) with an interarterial course. AIM: To provide evidence-substantiated recommendations for diagnostic work-up, treatment and follow-up of patients with anomalous coronary arteries. METHODS: A clinical care pathway for patients with ACAOS was established by six Dutch centres. Prospectively included patients undergo work-up according to protocol using computed tomography (CT) angiography, ischaemia detection, echocardiography and coronary angiography with intracoronary measurements to assess anatomical and physiological characteristics of the ACAOS. Surgical and functional follow-up results are evaluated by CT angiography, ischaemia detection and a quality-of-life questionnaire. Patient inclusion for the first multicentre study on coronary anomalies in the Netherlands started in 2020 and will continue for at least 3 years with a minimum of 2 years of follow-up. For patients with a right or left coronary artery originating from the pulmonary artery and coronary arteriovenous fistulas a registry is maintained. RESULTS: Primary outcomes are: (cardiac) death, myocardial ischaemia attributable to the ACAOS, re-intervention after surgery and intervention after initially conservative treatment. The influence of work-up examinations on treatment choice is also evaluated. CONCLUSIONS: Structural evidence for the appropriate management of patients with coronary anomalies, especially (interarterial) ACAOS, is lacking. By means of a structured care pathway in a multicentre setting, we aim to provide an evidence-based strategy for the diagnostic evaluation and treatment of this patient group.

Interplay of circulating leptin and obesity in cognition and cerebral volumes in older adults.

We aimed to investigate whether circulating leptin and body mass index (BMI) associate independently with cognitive function (decline) and brain volumes using magnetic resonance imaging (MRI) in older individuals at risk of cardiovascular disease. We studied the cross-sectional and longitudinal associations in participants enrolled in the PROSPER study (Prospective Study of Pravastatin in the Elderly at Risk). Cognitive function was tested at baseline and repeated during a mean follow-up time of 3.2 years. Analyses were performed with multivariable (repeated) linear regression models and adjusted for demographics, cardiovascular risk-factors, and stratified by sex. We included 5623 dementia-free participants (52 % female, mean age 75 years) with a mean BMI of 26.9 (SD = 4.1). In a sub-study, 527 participants underwent brain MRI. At baseline, individuals with a BMI > 30 had a worse performance on the Stroop test (ß 5.0 s, 95 %CI 2.6;7.5) and larger volumes of the amygdala (ß 234 mm3, 95 %CI 3;464) and hippocampus (ß 590 mm3, 95 %CI 181;999), independent of intracranial volume and serum leptin levels, compared with individuals with the reference BMI (BMI 18-25 kg/m2). Per log ng/mL higher serum leptin, independent of BMI, a 135 mm3 (95 %CI 2;268) higher volume of the amygdala was found, but no association was observed with cognitive tests nor with other brain volumes. Stratification for sex did not materially change the results. Whereas higher BMI associated with worse cognitive function independent of leptin levels, our study provided evidence that leptin and BMI independently associate with amygdala volume suggesting potential distinct biological associations.

Identification of IgG1 isotype phosphorylcholine antibodies for the treatment of inflammatory cardiovascular diseases.

BACKGROUND: Phosphorylcholine (PC) is an important pro-inflammatory damage-associated molecular pattern. Previous data have shown that natural IgM anti-PC protects against cardiovascular disease. We aimed to develop a monoclonal PC IgG antibody with anti-inflammatory and anti-atherosclerotic properties. METHODS: Using various techniques PC antibodies were validated and optimized. In vivo testing was performed in a femoral artery cuff model in ApoE3*Leiden mice. Safety studies are performed in rats and cynomolgus monkeys. RESULTS: A chimeric anti-PC (PC-mAb(T15), consisting of a human IgG1 Fc and a mouse T15/E06 Fab) was produced, and this was shown to bind specifically to epitopes in human atherosclerotic tissues. The cuff model results in rapid induction of inflammatory genes and altered expression of genes associated with ER stress and choline metabolism in the lesions. Treatment with PC-mAb(T15) reduced accelerated atherosclerosis via reduced expression of endoplasmic reticulum stress markers and CCL2 production. Recombinant anti-PC Fab fragments were identified by phage display and cloned into fully human IgG1 backbones creating a human monoclonal IgG1 anti-PC (PC-mAbs) that specifically bind PC, apoptotic cells and oxLDL. Based on preventing macrophage oxLDL uptake and CCL2 production, four monoclonal PC-mAbs were selected, which to various extent reduced vascular inflammation and lesion development. Additional optimization and validation of two PC-mAb antibodies resulted in selection of PC-mAb X19-A05, which inhibited accelerated atherosclerosis. Clinical grade production of this antibody (ATH3G10) significantly attenuated vascular inflammation and accelerated atherosclerosis and was tolerated in safety studies in rats and cynomolgus monkeys. CONCLUSIONS: Chimeric anti-PCs can prevent accelerated atherosclerosis by inhibiting vascular inflammation directly and through reduced macrophage oxLDL uptake resulting in decreased lesions. PC-mAb represents a novel strategy for cardiovascular disease prevention.

Blood transfusion and ischaemic outcomes according to anemia and bleeding in patients with non-ST-segment elevation acute coronary syndromes: Insights from the TAO randomized clinical trial.

BACKGROUND: The benefits and risks of blood transfusion in patients with acute myocardial infarction who are anemic or who experience bleeding are debated. We sought to study the association between blood transfusion and ischemic outcomes according to haemoglobin nadir and bleeding status in patients with NST-elevation myocardial infarction (NSTEMI). METHODS: The TAO trial randomized patients with NSTEMI and coronary angiogram scheduled within 72h to heparin plus eptifibatide versus otamixaban. After exclusion of patients who underwent coronary artery bypass surgery, patients were categorized according to transfusion status considering transfusion as a time-varying covariate. The primary ischemic outcome was the composite of all-cause death or MI within 180 days of randomization. Subgroup analyses were performed according to pre-transfusion hemoglobin nadir and bleeding status. RESULTS: 12,547 patients were enrolled. Among these, blood transfusion was used in 489 (3.9%) patients. Patients who received transfusion had a higher rate of death or MI (29.9% vs. 8.1%, p<0.01). This excess risk persisted after adjustment on GRACE score and nadir of hemoglobin (HR 3.36 95%CI 2.63-4.29 p<0.01). Subgroup analyses showed that blood transfusion was associated with a higher risk in patients without overt bleeding (adjusted HR 6.25 vs. 2.85; p-interaction 0.001) as well as in those with hemoglobin nadir > 9.0 g/dl (HR 4.01; p-interaction<0.0001). CONCLUSION: In patients with NSTEMI, blood transfusion was associated with an overall increased risk of ischaemic events. However, this was mainly driven by patients without overt bleeding and those hemoglobin nadir > 9.0g/dl. This suggests possible harm of transfusion in those groups.

The association between leptin concentration and blood coagulation: Results from the NEO study.

BACKGROUND: The adipocyte-derived hormone leptin has been associated with altered blood coagulation in in vitro studies. However, it is unclear whether this association is relevant in vivo and to what extent this association is influenced by total body fat. Therefore, we aimed to examine the association between serum leptin and blood coagulation while taking total body fat into account in a population-based cohort study. METHODS: We performed a cross-sectional analysis with baseline measurements of 5797 participants of the Netherlands Epidemiology of Obesity (NEO) study, a population-based cohort of middle-aged men and women. We examined associations between serum leptin concentration and coagulation factor concentrations and parameters of platelet activation in linear regression analyses. All analyses were adjusted for multiple covariates, including total body fat. RESULTS: In multivariable adjusted analyses a 1 µg/L higher serum leptin concentration was associated with a 0.22 IU/dL (95% CI: 0.11, 0.32) higher FVIII concentration and a 0.20 IU/dL (95% CI: 0.14, 0.27) higher FIX concentration (3.5 IU/dL FVIII and 3.2 IU/dL FIX per SD leptin). Serum leptin concentration was not associated with FXI, fibrinogen, platelet count, mean platelet volume and platelet distribution width in multivariable adjusted analyses. DISCUSSION: This study showed that serum leptin concentration was associated with higher concentrations of FVIII and FIX in an observational study, which could be clinically relevant.

Genome-wide meta-analysis of variant-by-diuretic interactions as modulators of lipid traits in persons of European and African ancestry.

Hypertension (HTN) is a significant risk factor for cardiovascular morbidity and mortality. Metabolic abnormalities, including adverse cholesterol and triglycerides (TG) profiles, are frequent comorbid findings with HTN and contribute to cardiovascular disease. Diuretics, which are used to treat HTN and heart failure, have been associated with worsening of fasting lipid concentrations. Genome-wide meta-analyses with 39,710 European-ancestry (EA) individuals and 9925 African-ancestry (AA) individuals were performed to identify genetic variants that modify the effect of loop or thiazide diuretic use on blood lipid concentrations. Both longitudinal and cross sectional data were used to compute cohort-specific interaction results, which were then combined through meta-analysis in each ancestry. These ancestry-specific results were further combined through trans-ancestry meta-analysis. Analysis of EA data identified two genome-wide significant (p < 5 × 10-8) loci with single nucleotide variant (SNV)-loop diuretic interaction on TG concentrations (including COL11A1). Analysis of AA data identified one genome-wide significant locus adjacent to BMP2 with SNV-loop diuretic interaction on TG concentrations. Trans-ancestry analysis strengthened evidence of association for SNV-loop diuretic interaction at two loci (KIAA1217 and BAALC). There were few significant SNV-thiazide diuretic interaction associations on TG concentrations and for either diuretic on cholesterol concentrations. Several promising loci were identified that may implicate biologic pathways that contribute to adverse metabolic side effects from diuretic therapy.

Correction to: Guidelines for the management of myocardial infarction/injury with non-obstructive coronary arteries (MINOCA): a position paper from the Dutch ACS working group.

Correction to: Neth Heart J 2019 https://doi.org/10.1007/s12471-019-01344-6 The reference to the term acute coronary syndrome with normal or near-normal (non-obstructive) coronary arteries (ACSNNOCA) from Manolis et al. (2018) was inadvertently omitted to the original published article. Therefore, ….

Indications for an early invasive strategy in NSTE-ACS patients.

An early invasive strategy in patients who have acute coronary syndrome without ST-elevation (NSTE-ACS) can improve clinical outcome in high-risk subgroups. According to the current guidelines of the European Society of Cardiology (ESC), the majority of NSTE-ACS patients are classified as "high-risk". We propose to prioritise patients with a global registry of acute coronary events (GRACE) risk score >140 over patients with isolated troponin rise or electrocardiographic changes and a GRACE risk score <140. We also acknowledge that same-day transfer for all patients at a high risk is not necessary in the Netherlands since the majority of Dutch cardiology departments are equipped with a catheterisation laboratory where diagnostic coronary angiography is routinely performed in NSTE-ACS patients. Therefore, same-day transfer should be restricted to true high-risk patients (in addition to those NSTE-ACS patients with very high-risk (VHR) criteria) in centres without coronary angiography capabilities.