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Background: Cognitive impairment is common in patients with heart failure (HF) and impacts patients' life. Sex differences in HF-characteristics are well-established. We hypothesized that women and men with HF also differ in cognitive functioning and that this may be related to sex differences in HF-characteristics and vascular brain injury., Methods: In the Heart-Brain Connection Study, 162 clinically stable HF patients (mean age 69.7 ± 10.0, 33 % women) underwent neuropsychological assessments and brain-MRI. Test results were standardized into z-scores for memory, language, attention/speed, executive functioning, and global cognition. Using linear models adjusted for age and education, we calculated sex differences (women-to-men: W-M∆) in cognitive functioning and examined effects of HF- and vascular brain injury-characteristics on these differences., Results: Men more often had an ischemic cause of HF and lower NYHA-classes, whereas women more often had preserved left ventricular ejection fractions (LVEF). Women had a higher volume of white matter hyperintensities (WMHs) whereas non-lacunar infarcts and microbleeds were more prevalent in men. Women performed better on global cognition than men (W-M∆ in z-score 0.20, 95 %CI 0.03-0.37), predominantly on memory (0.40, 0.02-0.78). These differences were associated with ischemic HF-etiology, as adjustment attenuated these sex differences. After adjustment for non-lacunar infarcts, global cognition difference persisted, but the difference in memory functioning attenuated. Adjustments for NYHA-class, LVEF, WMHs, and microbleeds did not change the results., Conclusion: Women and men with HF differ in cognitive functioning, predominantly in memory functioning, these differences were related to some sex differences in HF-characteristics and vascular brain injury, but not to all., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Angina without angiographic evidence of obstructive coronary artery disease (ANOCA) is a highly prevalent condition with insufficient pathophysiological knowledge and lack of evidence-based medical therapies. This affects ANOCA patients prognosis, their healthcare utilization and quality of life. In current guidelines, performing a coronary function test (CFT) is recommended to identify a specific vasomotor dysfunction endotype. The NetherLands registry of invasive Coronary vasomotor Function testing (NL-CFT) has been designed to collect data on ANOCA patients undergoing CFT in the Netherlands., Methods: The NL-CFT is a web-based, prospective, observational registry including all consecutive ANOCA patients undergoing clinically indicated CFT in participating centers throughout the Netherlands. Data on medical history, procedural data and (patient reported) outcomes are gathered. The implementation of a common CFT protocol in all participating hospitals promotes an equal diagnostic strategy and ensures representation of the entire ANOCA population. A CFT is performed after ruling out obstructive coronary artery disease. It comprises of both acetylcholine vasoreactivity testing as well as bolus thermodilution assessment of microvascular function. Optionally, continuous thermodilution or Doppler flow measurements can be performed. Participating centers can perform research using own data, or pooled data will be made available upon specific request via a secure digital research environment, after approval of a steering committee., Conclusion: NL-CFT will be an important registry by enabling both observational and registry based (randomized) clinical trials in ANOCA patients undergoing CFT., Competing Interests: Declaration of Competing Interest NL-CFT is supported by research grants from Dutch Cardiovascular Alliance consortium IMPRESS (2020B004), Philips and Abbott. Damman P received research grants, lecture and consultancy fees from Phillips, and research grants and lecture fees from Abbott Vascular. Van Royen N has received research grants from Philips, Biotronik, Medtronic and Abbott and speaker fees from Microport, Rainmed and Abbott. Van ‘t Hof A received research grants and lecture fees from Abbott Vascular, Medtronic, Boehringer Ingelheim, Astra Zeneca and AMGEN not related to this work. Van de Hoef T received institutional research grants and consultancy fees from Philips and Abbott Vascular. Appelman Y received research grant from Dutch Heart Foundation IMPRESS, lecture and consultancy fees from Abbott Vascular and Phillips. Woudstra P received lecture fees from Philips. All other authors have no disclosures., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Elevated serum levels of growth differentiation factor-15 (GDF-15), is an established risk factor for a range of cardiovascular diseases. We aimed to evaluate the predictive value of plasma GDF-15 as a biomarker for secondary cardiovascular events (CVE) in patients with atherosclerosis undergoing carotid endarterectomy (CEA). Secondly, we determined whether plasma GDF-15 was associated with carotid plaque characteristics., Methods: Circulating GDF-15 levels were determined by Luminex assay in a cohort of 1056 patients from the Athero-Express biobank. Composite endpoint was defined as major CVE, death and peripheral vascular interventions. Findings were validated in 473 patients from the independent Carotid Plaque Imaging Project biobank., Results: GDF-15 levels did not associate with secondary CVE in the total cohort. However, following a significant interaction with sex, it was found to be strongly, independently predictive of secondary CVE in women but not men (quartile 4 vs. quartile 1: HR 3.04 [95% CI 1.35-6.86], p=0.007 in women vs. HR 0.96 [95% CI 0.66-1.40], p=0.845 in men). This was also observed in the validation cohort (women: HR 2.28 [95% CI 1.04-5.05], p=0.041), albeit dependent upon renal function. In addition, GDF-15 was associated with the presence of plaque smooth muscle cells and calcification., Conclusion: High circulating GDF-15 levels are predictive of secondary CVE in women but not in men with carotid atherosclerotic disease undergoing CEA, suggesting a potential use for GDF-15 as a biomarker for secondary prevention in women. Sex differences in the role of GDF-15 in atherosclerotic disease deserve further interest., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Medical guidelines increasingly use risk stratification and implicitly assume that individuals classified in the same risk category form a homogeneous group, while individuals with similar, or even identical, predicted risks can still be very different. We evaluate a strategy to identify homogeneous subgroups typically comprising predicted risk categories to allow further tailoring of treatment allocation and illustrate this strategy empirically for cardiac surgery patients with high postoperative mortality risk., Methods: Using a dataset of cardiac surgery patients (n=6517) we applied cluster analysis to identify homogenous subgroups of patients comprising the high postoperative mortality risk group (EuroSCORE ≥ 15%). Cluster analyses were performed separately within younger (<75 years) and older (≥ 75 years) patients. Validity measures were calculated to evaluate quality and robustness of the identified subgroups., Results: Within younger patients two distinct and robust subgroups were identified, differing mainly in preoperative state and indication of recent myocardial infarction or unstable angina. In older patients, two distinct and robust subgroups were identified as well, differing mainly in preoperative state, presence of chronic pulmonary disease, previous cardiac surgery, neurological dysfunction disease and pulmonary hypertension., Conclusions: We illustrated a feasible method to identify homogeneous subgroups of individuals typically comprising risk categories. This allows a single treatment strategy--optimal only on average, across all individuals in a risk category--to be replaced by subgroup-specific treatment strategies, bringing us another step closer to individualized care. Discussions on allocation of cardiac surgery patients to different interventions may benefit from focusing on such specific subgroups., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)