Prior Events Research Articles

Risk estimation of cardiovascular diseases using the World Health Organization/International Society of Hypertension risk prediction charts in the Azar cohort population: Cross-sectional study.

Cardiovascular disease (CVD) is one of the most important health problems and the leading cause of mortality worldwide. This study aimed to estimate the risk of CVD using the World Health Organization/International Society of Hypertension (WHO/ISH) risk prediction charts. The demographic characteristics of all participants of this study aged 40-70 years who did not have a prior coronary event were collected. The 10-year CVD risk was estimated using the laboratory version of the WHO/ISH risk score charts. The risk scores for 11678 participants of the Azar cohort population were calculated. Participants were classified as low risk, moderate risk, or high risk. According to the WHO/ISH charts, only 0.1 % of the population was classified as high-risk (≥40%), and 96.8% had a 10-year CVD risk of<10%. Also, participants with overweight (P=0.002), obesity, and abdominal obesity had higher CVD risk(P<0.001). There was a low burden of 10-year CVD risk among the Azar cohort population without prior coronary events. It appears the percentage of people in the high-risk group is underestimated in the WHO/ISH risk prediction charts, leading to delays in receiving appropriate management in the population concerned. Therefore, using other charts alongside the WHO/ISH risk prediction charts is advisable.

Bidirectional relationship between epigenetic age and brain health events.

Chronological age offers an imperfect estimate of the molecular changes that occur with aging. Epigenetic age, which is derived from DNA methylation data, provides a more nuanced representation of aging-related biological processes. This study examines the bidirectional relationship between epigenetic age and the occurrence of brain health events (stroke, dementia, and late-life depression). Using data from the Health and Retirement Study, we analyzed blood samples from over 4,000 participants to determine how epigenetic age relates to past and future brain health events. Study participants with a prior brain health event prior to blood collection were 4% epigenetically older (beta 0.04, SE 0.01), suggesting that these conditions are associated with faster aging than that captured by chronological age. Furthermore, a one standard deviation increase in epigenetic age was associated with 70% higher odds of experiencing a brain health event in the next four years after blood collection (OR 1.70, 95%CI 1.16-2.50), indicating that epigenetic age is not just a consequence but also a predictor of poor brain health. Both results were replicated through Mendelian Randomization analyses, supporting their causal nature. Our findings support the utilization of epigenetic age as a useful biomarker to evaluate the role of interventions aimed at preventing and promoting recovery after a brain health event.

Exacerbation-like events in the 12 months prior to identification of chronic respiratory conditions in a primary care population

Initial chronic obstructive lung disease (COPD) pharmacotherapy is based on symptom burden and exacerbation history. Inclusion of inhaled cortico-steroids (ICS) is recommended only for those with a history of exacerbations. This brief report highlights that among individuals with previously unrecognized COPD about 1 in 5 have one or more exacerbation-like events and about 1 in 10 have two or more events in the prior 12 months whether or not they self-report concomitant asthma. Closer attention to prior exacerbation-like event history might lead to more guideline concordant care.In addition, there are two other groups that have impaired but non-obstructive spirometry, some with significant respiratory symptom burden who have frequencies of exacerbation-like events similar to those meeting COPD spirometry criteria. To date we have little guidance for treatment of these individuals.

When leaders and their employees disagree: investigating the consequences of differences in cognitions of workplace event criticality

PurposeCriticality cognitions regarding the same workplace event often differ between leaders and employees. Nevertheless, its consequences on employee work outcomes remain unknown. In this study, we draw on cognitive dissonance theory to examine how and why leader–employee differences in cognitions of workplace event criticality impact employee job-related outcomes.Design/methodology/approachWu used multilevel polynomial regression analyses from a time-lagged, multi-source field study with 145 leader–employee dyads to test our proposed model.FindingsLeader–employee differences in cognitions of workplace event criticality can bring both benefits and perils to employees. Specifically, such differences can cause employee rumination, which in turn leads to an increase in both employee voice and fatigue.Originality/valueThis study contributes to the event and cognitive discrepancy literature in four ways. First, prior event studies largely adopted a singular employee perspective for investigation (e.g. Chen et al., 2021; Lin et al., 2021). By examining the impacts of event criticality from the dual perspective of leaders and employees, we attain a more comprehensive understanding of the implications of workplace events in organizational life. Second, extant studies have predominantly focused on the dark side of cognitive discrepancy (e.g. Bashshur et al., 2011; Erdogan et al., 2004; Grandey et al., 2013). Our study reveals that leader–employee differences in criticality cognitions can have both a bright and a dark side on employee outcomes, offering a more balanced and dialectical view of the consequences of cognitive discrepancy. Third, drawing on cognitive dissonance theory, we introduce employee rumination as an underlying mechanism to explain the impacts of leader–employee differences in criticality cognitions on employee voice and fatigue. Finally, while prior cognitive dissonance research has primarily employed an intrapersonal perspective (e.g. Sivanathan et al., 2008; Pugh et al., 2011; Grandey et al., 2013), our study adopts an interpersonal lens and underscores that interpersonal differences in cognitions can also serve as an example of cognitive discrepancy to instigate internal dissonance processes. By doing so, we enrich our understanding of cognitive dissonance theory.

Percutaneous left atrial appendage closure for stroke prevention in hypertrophic cardiomyopathy patients with atrial fibrillation

BackgroundPercutaneous left atrial appendage closure (LAAC) is an effective alternative strategy for stroke prevention in patients with atrial fibrillation (AF) at high risk for bleeding with anticoagulation (AC). Efficacy of this strategy in hypertrophic cardiomyopathy (HCM) remains uncertain. ObjectiveThe study aimed to compare risk of stroke in HCM-AF patients treated with LAAC with those treated with AC. MethodsBy use of the TriNetX Global Research Network, HCM-AF patients from 2015 to 2024 were assigned to categories of treatment with LAAC and treatment solely with AC and observed for 3 years for ischemic stroke, systemic embolism, and all-cause mortality. Propensity score matching was used to limit confounders. ResultsOf 14,867 HCM-AF patients identified, 364 (2.5%) were treated with LAAC vs 14,503 (97.5%) treated with AC. HCM LAAC patients were older (72 vs 67 years; P < .001) and had more comorbidities and more prior bleeding events, including higher rate of prior gastrointestinal bleeding (68% vs 18%; P < .001), compared with HCM patients treated solely with AC. After propensity score matching, there was no baseline difference between groups including prior bleeding events (P > .05). During follow-up, HCM patients treated with LAAC had higher rates of ischemic stroke (13% vs 8%; hazard ratio, 1.9; P = .006) and systemic embolism (14% vs 9%; hazard ratio, 1.8; P = .006) but no difference in mortality compared with matched HCM patients receiving AC. ConclusionThese real-world data do not support percutaneous LAAC in HCM-AF patients as the primary treatment strategy during long-term AC to reduce stroke risk. However, LAAC may remain a reasonable option for HCM-AF patients who are unable to tolerate AC because of prohibitive bleeding risk.

Pulmonary hypertension is associated with increased recurrence of atrial fibrillation post-pulmonary vein isolation: a multicenter study insights

Abstract Background Pulmonary vein isolation (PVI) has become an essential therapeutic approach for managing paroxysmal and persistent atrial fibrillation. Besides the fact its application increases, a substantial proportion of patients will suffer from arrhythmia recurrence. Objectives This study aims to determine the clinical and echocardiographic factors that predict fibrillation recurrence following pulmonary vein isolation. Methods In this prospective, multicenter study carried out across 14 medical centers in Israel, we included a cohort of 1002 patients who underwent pulmonary vein isolation from 2019 to 2022. The study involved an assessment of patients' baseline characteristics, electrocardiographic and echocardiographic data, laboratory results, details of the procedure, and their clinical outcomes. We monitored these clinical outcomes for one year after the ablation procedure, focusing mainly on the recurrence of atrial fibrillation, which was verified using electrocardiographic evidence during the post-blanking period. A multivariable analysis revealed the clinical and echocardiographic predictors for atrial fibrillation recurrence post-PVI. Results Our study evaluated 1002 patients with an average age of 64.4 ±11.3 years, including 37.5% females (376 patients). The cohort predominantly, about two-thirds, had paroxysmal AFIB, with an average arrythmia duration of 4.1 years. Frequent pre-existing conditions included ischemic heart disease in 17.3% and congestive heart failure in 13.8% of the patients. Additionally, diabetes was present in a quarter of the cohort, with 9% having a prior cerebrovascular event. The median LVEF was 60 (IQR 53-60), and the average left atrial diameter was 42.6 mm±8.8. The median pulmonary artery pressure was noted at 31 (IQR 25-38), with 13% of patients exhibiting elevated levels above 45 mmHg. Within the first year after the ablation, 11.7% of patients experienced AFIB recurrence in the post-blanking period. Our multivariate COX analysis established clinical and echocardiographic models for predicting post-PVI AFIB recurrence. Gender was a significant predictor, with women showing a higher recurrence rate (HR 1.85, 95% CI 1.29-2.7, P&amp;lt;0.01), in addition to persistent AFIB and a non-sinus rhythm at the time of the procedure. Echocardiographic predictors of recurrence included a left atrial diameter greater than 40 mm (HR 2.16, 95% CI 1.3-3.6, P&amp;lt;0.01) and pulmonary hypertension, notably when pulmonary artery pressure exceeded 55 mmHg, which correlated with almost a fourfold increase in AFIB recurrence risk within the first-year post-procedure (HR 4.25, 95% CI 1.57-11.5, P&amp;lt;0.01). Conclusions Pulmonary hypertension, especially with pulmonary artery pressure above 55 mmHg, significantly elevates the risk of atrial fibrillation recurrence post-pulmonary vein isolation, underscoring its importance in patient prognosis and management.

#2251 Long-term systolic blood pressure variability as an independent risk factor for cardiovascular events in kidney transplant recipients

Abstract Background and Aims Cardiovascular (CV) events represent the main cause of death in patients undergoing renal transplantation. Several studies have described the role of blood pressure variability (BPV) in predicting all-cause mortality and fatal and non-fatal CV events in the general population and in diabetic patients. Systolic blood pressure variability (SBPV) has recently been proposed as a predictor of clinical outcomes in patients with chronic kidney disease. However, evidence is still scarce about the prognostic role of BPV in the setting of renal transplantation. The aim of the study was to evaluate the role of long-term SBPV in the development of fatal and non-fatal CV events (myocardial infarction, unstable angina or revascularization, stroke and hospitalization for heart failure) in subjects undergoing kidney transplantation. Method We performed a single-center retrospective observational analysis in a cohort of 272 kidney transplant patients (mean age 64 ± 13 years, 66% men), with a transplant duration ≥12 months and with at least 6 blood pressure measurements at defined intervals (3 months ±15 days) over an assessment period of 18 months. BPV was expressed as standard deviation of ambulatory systolic blood pressure (SBP) and patients were accordingly classified in tertiles (low &amp;lt;9.3 mmHg, medium 9.3-13 mmHg, high &amp;gt;13 mmHg). The role of SBPV was analyzed by Kaplan-Meier (logrank) and its independent effect by Cox Regression. Results Over a mean follow-up of 58.7 ± 17.2 months, 27 subjects (9.9%) developed CV events. For each increase of 2.7 mmHg in SBP standard deviation, the risk for fatal or non-fatal CV events increased almost 3-folds (P = 0.02) and patients in the highest tertile of SBP standard deviation showed a 4-fold increased risk (P = 0.01) (Fig. 1). This relationship was maintained even after incremental adjustment for time-averaged pulse pressure, age, diabetes, prior CV event, and dialysis vintage (HR 3.2, 95% CI 1.1–10.0, p 0.04) (Table 1). Conclusion Long-term BPV represents an independent risk factor for CV events in kidney transplant patients. It is therefore essential to seek for stable long-term blood pressure levels in this population in order to minimize the residual CV risk.

#1275 Post-transplant renal anaemia: a call to action from a national study in routine clinical practice

Abstract Background and Aims Post-transplant anaemia (PTA) is common, frequently unnoticed and carries associated risks. Current guidelines consider the same treatment recommendations and goals for these patients as for chronic kidney disease-non dialysis (CKD-NDD). Previous reports demonstrated low awareness and management that could improve. Aims: To describe current anaemia management, goals, and adherence to guidelines in a representative sample of kidney transplant (KT) recipients. Method Retrospective nationwide multicentre study including patients from 8 KT hospitals. Nephrologists collected demographics, comorbidities, KT data and immunosuppressive therapy and data related to anaemia management (laboratory values, previously prescribed treatments, and subsequent adjustments) from electronic medical records. We classified as early anaemia that within the first 6 months. The European statement on KDIGO guidelines was the reference for definitions, drug prescriptions and targets. Results We included 297 recipients with PTA aged 62.8 y (SD 13.6) and 60% male. They had received a graft from donors after cardiac death or brain death) (61.6%. 31.1% respectively) a median of 2.5 years [0.5-8.7] before. A total of 158 patients were on treatment with erythropoietin stimulating agents (ESAs) and the distribution of haemoglobin (Hb) and iron are summarized in Table 1. Among 110 patients on ESA treatment but without iron prescription, 44 had an indication to receive iron and 30 of them had absolute iron deficiency (ID). Only 39/158 patients exceeded the ESA resistance index (ERI) limit, and this condition was more frequent in early PTA (26.1 vs 9.2%). Absolute or functional ID accounted for the majority of ESA resistance (28.2 vs 17.1; p &amp;lt; 0.001). Conclusion Hemoglobin levels in these patients are within the upper KDIGO. Iron therapy continues to be underused (especially intravenous), while iron deficiency and prior events explain most of ESA hyporesponsiveness. We identify missed opportunities for accurate prescription targeting and adherence to guidelines.

Residual risk of thromboembolic events despite anticoagulation in Middle Eastern patients with atrial fibrillation. The JoFib study

ObjectivesTo investigate residual risk of thromboembolic events despite anticoagulation in patients with atrial fibrillation form the Middle East. Materials and methodsUsing data from the JoFib registry, we described the characteristics of patients treated with anticoagulants (n = 1654) and calculated the incidence rate for thromboembolic events. We constructed multivariable Cox proportional hazard models and calculated the population-attributable fraction to determine clinical factors predictive of residual thromboembolic events. ResultsDuring the one-year follow-up, 57 thromboembolic events occurred (incidence rate 4.1 per 100 person-years). In multivariable time-to-event analysis, prior thromboembolic events (aHR 3.8, 95 %CI 2.2–6.4, p < 0.001) and diabetes (aHR 2.3, 95 %CI 1.3–4.1, p = 0.004) were independently predictive of residual thromboembolism. Percentage of thromboembolic risk attributable to prior thromboembolic events was 30.9 % (95 %CI 13.9–44.6, p = 0.001) and was 37.1 % (95 %CI 8.8–56.6, p = 0.015) for diabetes. Furthermore, the effect of diabetes on thromboembolic events depends on the type of anticoagulant, with diabetes being significantly predictive of thromboembolic events in patients anticoagulated with warfarin (aHR 4.11, 95 %CI 1.81–9.37, p = 0.001), but not non-vitamin K antagonist oral anticoagulants (aHR 1.23, 95 %CI 0.51–2.97, p = 0.643) with a p = 0.045 for interaction. Prior thromboembolism was independently predictive of thromboembolic events in both anticoagulants (aHR 2.67, 95 %CI 1.28–5.58, p = 0.009; aHR 7.33, 95 %CI 3.05–17.65, p < 0.001; respectively; p = 0.084 for interaction). ConclusionsMiddle Eastern patients with atrial fibrillation remain at significant risk of thromboembolism and its recurrence despite anticoagulation, and especially in diabetic patients. Therefore, management should focus on controlling diabetes as well as other modifiable risk factors in addition to antithrombotic therapy.

Reward enhancement of item-location associative memory spreads to similar items within a category

ABSTRACT The experience of a reward appears to enhance memory for recent prior events, adaptively making that information more available to guide future decision-making. Here, we tested whether reward enhances memory for associative item-location information and also whether the effect of reward spreads to other categorically-related but unrewarded items. Participants earned either points (Experiment 1) or money (Experiment 2) through a time-estimation reward task, during which stimuli-location pairings around a 2D-ring were shown followed by either high-value or low-value rewards. All stimuli were then tested for location memory or recognition (yes/no), immediately and after a 24-hour delay. Across both experiments (combined analysis), there was a robust improvement in location memory following high-value rewards, even though evidence supporting this effect was reliable in Experiment 2 but not in Experiment 1. The memory-enhancing effect of reward was observed on both the immediate and delayed location-memory tests. Reward-enhanced memory for both directly rewarded stimuli and categorically related stimuli that were not directly rewarded. No reliable effect of reward value on yes/no recognition-memory performance was observed in either experiment. We hypothesise that reward enhances the consolidation of recent experience and conceptually related memories to make these more available for future decisions.

Systematic review and meta-analysis of the visual mismatch negativity in schizophrenia.

Mismatch negativity (MMN) is an event-related potential component automatically elicited by events that violate predictions based on prior events. To elicit this component, researchers use stimulus repetition to induce predictions, and the MMN is obtained by subtracting the brain response to rare or unpredicted stimuli from that of frequent stimuli. Under the Predictive Processing framework, one increasingly popular interpretation of the mismatch response postulates that MMN represents a prediction error. In this context, the reduced MMN amplitude to auditory stimuli has been considered a potential biomarker of Schizophrenia, representing a reduced prediction error and the inability to update the mental model of the world based on the sensory signals. It is unclear, however, whether this amplitude reduction is specific for auditory events or if the visual MMN reveals a similar pattern in schizophrenia spectrum disorder. This review and meta-analysis aimed to summarise the available literature on the vMMN in schizophrenia. A systematic literature search resulted in 10 eligible studies that resulted in a combined effect size of g = -.63, CI [-.86, -.41], reflecting lower vMMN amplitudes in patients. These results are in line with the findings in the auditory domain. This component offers certain advantages, such as less susceptibility to overlap with components generated by attentional demands. Future studies should use vMMN to explore abnormalities in the Predictive Processing framework in different stages and groups of the SSD and increase the knowledge in the search for biomarkers in schizophrenia.

Evaluation of blood pressure variation in recovered COVID-19 patients at one-year follow-up: a retrospective cohort study

BackgroundCoronavirus disease 2019 (COVID-19) has various sequelae, one of which might be hypertension. We aimed to evaluate COVID-19’s impact on blood pressure (BP) in non-hospitalized patients at one-year follow-up.MethodA total of 7,950 consecutive COVID-19 patients regularly visiting our cardiology clinic were retrospectively screened. Patients’ electronic medical records including demographics, comorbidities, vital signs, treatments, and outcomes, were reviewed by two physicians. Individuals with at least one BP measurement in the three months preceding COVID-19 and one measurement in 12 months or more following recovery were included. BP levels before and after COVID-19 were compared using the paired t-test.Results5,355 confirmed COVID-19 patients (mean age 55.51 ± 15.38 years) were included. Hypertension (56.9%) and diabetes mellitus (34%) were the predominant comorbidities, and 44.3% had prior major adverse cardiovascular events. Both systolic (126.90 ± 20.91 vs. 139.99 ± 23.94 mmHg, P < 0.001) and diastolic BP (80.54 ± 13.94 vs. 86.49 ± 14.40 mmHg, P < 0.001) were significantly higher post-COVID-19 vs. pre-COVID-19. Notably, 456 (14%) hypertensive patients experienced exacerbated hypertension, while 408 (17%) patients developed new-onset hypertension, overall 864 (16%) of patients had exacerbation or new hypertension. Linear regression analysis revealed that advanced age, smoking, previous cardiovascular events, hypertension, and diabetes mellitus predict increased BP following COVID-19 (P < 0.001).ConclusionCOVID-19 raised systolic and diastolic BP in the long term in non-hospitalized patients, with over one-sixth developing new-onset or exacerbated hypertension. All patients should be evaluated regarding BP, following COVID-19 recovery, particularly those with the mentioned predictive factors. (clinicaltrial.gov: NCT05798208)

Myocardial Infarction in Chronic Myeloid Leukemia: Results from the Nationwide Readmission Database

Introduction: Chronic myeloid leukemia (CML) is a hematological malignancy with an excellent prognostic outcome. After the advancements in CML treatment and the introduction of different tyrosine kinase inhibitors (TKIs), the life expectancy of CML patients has become equivalent to that of the general population. As a result, coronary artery disease is anticipated to be the leading cause of death among CML patients. Moreover, TKI use is associated with a risk of endothelial dysfunction, thrombosis, and cardiovascular events, including myocardial infarction. In this study, we compare the outcomes of percutaneous coronary intervention (PCI) in patients with CML to their matched non-CML counterparts. Method: This is a retrospective cohort study using the Nationwide Readmission Database from January 2016 to December 2020. Adults with or without CML hospitalized for acute myocardial infarction and underwent PCI were included. The patients were identified using ICD-10 codes. The primary outcomes were in-hospital mortality and 30-day readmission rates. The secondary outcomes were PCI complications rates. Results: Out of 2,727,619 patients with myocardial infarction, 2,124 CML patients were identified. A total of 888 CML patients underwent PCI. CML patients were significantly older (mean age: 68.34 ± 11.14 vs. 64.40 ± 12.61 years, p < 0.001) than non-CML patients without a difference in sex distribution. Hypertension (85.45% vs. 78.64%), diabetes (45.48% vs. 37.29), stroke (11.84% vs. 7.78) at baseline were significantly higher in the CML group. Prior myocardial infarction events (20.51% vs. 15.17%) and prior PCI procedure (24.47% vs. 16.89%) were significantly higher in the CML group. CML patients had a significantly longer hospital stay (4.66 ± 4.40 vs. 3.75 ± 4.62 days, p = 0.001). The primary outcomes did not differ between the comparison groups. The risk of post-PCI complications did not differ between the comparison groups in the propensity matched analysis except for coronary artery dissection (odds ratio [OR]: 0.10; 95% confidence interval [CI]: 0.02–0.65, p = 0.016) and ischemic stroke (OR: 0.35; 95% CI: 0.14–0.93, p = 0.034) which were lower in the CML group. Conclusion: This analysis showed no statistically significant difference in mortality, 30-day readmission, and post PCI complications rates between CML and non-CML patients. However, interestingly, CML patients may experience lower coronary artery dissection and ischemic stroke events than those without CML diagnosis.

Consecutive or selectively included high bleeding risk patients in the MASTER DAPT screening log and trial

AimsScreening logs have the potential to appraise the actual prevalence and distribution of predefined patient subsets, avoiding selection biases, which are inevitably and potentially present in randomised trials and real-world registries, respectively. We aimed to assess the prevalence of high bleeding risk (HBR) characteristics in the real world and the external validity of the MASTER DAPT trial. Methods and resultsAll consecutive patients who underwent percutaneous coronary intervention (PCI) for at least two consecutive weeks across 65 sites participating in the trial were entered into a screening log. Of 2,847 consecutive patients, 1,098 (38.6 %) were HBR and 109 (9.9 %) consented for trial participation. PRECISE-DAPT score ≥ 25 was the most frequent HBR feature, followed by advanced age, use of oral anticoagulation (OAC) and anaemia. Compared with consecutive HBR patients, consenting patients were older (≥ 75 years: 69 % versus 62 %, absolute standardized difference [SD] 0.16), more frequently male (78 % versus 71 %, absolute SD 0.18), had higher use of OAC (38 % versus 20 %, absolute SD 0.39), treatment with steroids or nonsteroidal anti-inflammatory drugs (10 % versus 5 %, SD 0.16), and prior cerebrovascular events (10 % versus 6 %, absolute SD 0.18) but lower PRECISE DAPT score ≥ 25 (54 % versus 66 %, absolute SD 0.24). ConclusionsThe HBR criteria distribution differed between consecutive versus selectively included HBR patients, suggesting the existence of selection biases in the trial population.

Association of COVID-19 vaccination with risks of hospitalization due to cardiovascular and other diseases: A study using data from the UK Biobank

ObjectivesTo explore whether COVID-19 vaccination protects against hospital admission by preventing infections and severe disease. MethodsWe leveraged the UK Biobank and studied associations of COVID-19 vaccination (BioNTech-BNT162b2 or Oxford-AstraZeneca-ChAdOx1) with hospitalizations from cardiovascular and other selected diseases (N = 393,544; median follow-up = 54 days among vaccinated individuals). Multivariable Cox, Poisson regression, propensity score matching, and inverse probability treatment weighting analyses were performed. We also performed adjustment using prescription-time distribution matching, and prior event rate ratio. ResultsWe observed that COVID-19 vaccination (at least one dose), compared with no vaccination, was associated with reduced short-term risks of hospitalizations from stroke (hazard ratio [HR] = 0.178, 95% confidence interval [CI]: 0.127-0.250, P = 1.50e-23), venous thromboembolism (HR = 0.426, CI: 0.270-0.673, P = 2.51e-4), dementia (HR = 0.114, CI: 0.060-0.216; P = 2.24e-11), non-COVID-19 pneumonia (HR = 0.108, CI: 0.080-0.145; P = 2.20e-49), coronary artery disease (HR = 0.563, CI: 0.416-0.762; P = 2.05e-4), chronic obstructive pulmonary disease (HR = 0.212, CI: 0.126-0.357; P = 4.92e-9), type 2 diabetes (HR = 0.216, CI: 0.096-0.486, P = 2.12e-4), heart failure (HR = 0.174, CI: 0.118-0.256, P = 1.34e-18), and renal failure (HR = 0.415, CI: 0.255-0.677, P = 4.19e-4), based on standard Cox regression models. Among the previously mentioned results, reduced hospitalizations for stroke, heart failure, non-COVID-19 pneumonia, and dementia were consistently observed across regression, propensity score matching/inverse probability treatment weighting, prescription-time distribution matching, and prior event rate ratio. The results for two-dose vaccination were similar. ConclusionsTaken together, this study provides further support to the safety and benefits of COVID-19 vaccination, and such benefits may extend beyond reduction of infection risk or severity per se. However, causal relationship cannot be concluded and further studies are required.

Contingent Reasoning and Dynamic Public Goods Provision

Contributions toward public goods often reveal information that is useful to others considering their own contributions. This experiment compares static and dynamic contribution decisions to determine how contingent reasoning differs in dynamic decisions where equilibrium requires understanding how future information can inform about prior events. This identifies partially cursed individuals who can only extract partial information from contingent events, others who are better at extracting information from past rather than future or concurrent events, and Nash players who effectively perform contingent thinking. Contrary to equilibrium, the dynamic provision mechanism does not lead to lower contributions than the static mechanism. (JEL C92, D71, D82, D91, H41)

Looking for the oldest diatoms

Paleontological observations of ancient flora and fauna provide powerful insights into past diversity and relationship dynamics between organisms and their environments. Diatoms are globally distributed protists that influence major biogeochemical cycles and sustain oceanic food webs. The fossil diatom record extends 120 million years back to the Early Cretaceous where rare deposits were discovered worldwide and are occasionally represented by diverse communities. However scarce, the taxonomic richness and geographical spread of these diatom communities suggest prior evolutionary events and therefore earlier deposits. To complement the existing fossil information and to discover diatom deposits predating 120 Ma, we examined 33 study sites from cores and outcrops across oceans and continents. These efforts did not generate new fossil discoveries, however. Our assessment suggests biogenic silica that comprises the cell wall of diatoms was likely dissolved from Mesozoic sediments through diagenetic processes. Altogether, the search for the oldest diatoms must continue but should target sediments that experienced shallow burial and concretions.

Women With a History of Preeclampsia Exhibit Accelerated Aging and Unfavorable Profiles of Senescence Markers.

Senescence, a mechanism of cellular aging, which is characterized by irreversible proliferation arrest and a proinflammatory secretory phenotype, has been documented in women with preeclampsia. As cellular senescence can persist and progress, we postulated that it is associated with accelerated aging phenotype and accumulation of comorbidities in women with a history of preeclampsia. We included a cohort of women with a history of preeclampsia (n=40) age- and parity-matched to a group of referent women with normotensive pregnancies (n=40). Women with prior major cardiovascular events, neurological, or autoimmune conditions were excluded. We collected urine and blood samples to study markers of aging, data on multimorbidity at the time of enrollment, and prospectively followed them for events over the course of 6 years, on average. Women with a history of preeclampsia exhibited unfavorable aging profiles compared with referent women, including decreased urinary α-Klotho (P=0.018); increased leptin (P=0.016) and leptin/adiponectin ratio (P=0.027), and increased extracellular vesicles positive for tissue factor (P=0.025). Women with a history of preeclampsia likewise had a higher rate of comorbidities at the time of enrollment (P=0.003) and had a 4× higher risk of developing major cardiovascular events compared with referent women (P=0.003). Our data suggest that a history of preeclampsia is associated with accelerated aging as indicated by senescence marker differences and the accumulation of multimorbidity later in life. Targeting cellular senescence may offer novel, mechanism-based approaches for the diagnosis and treatment of adverse health outcomes in women with a history of preeclampsia.

Impact of anticoagulants, antiplatelet agents, and oral antidiabetic drugs on the risk of stroke in patients with diabetes and nonvalvular atrial fibrillation: A case-referent study

BackgroundType 2 diabetes mellitus (T2DM) and atrial fibrillation are risk factors for stroke. The potential preventive effects of cardiovascular and antidiabetic treatments on stroke risk in patients with these diseases remain insufficiently documented. Sulfonylureas have also been reported to be associated with stroke. This study aimed to assess the risk of stroke according to the use of drugs (anticoagulants, antiplatelet agents, and oral antidiabetic drugs [OADs]) in patients with T2DM and nonvalvular atrial fibrillation (NVAF). MethodsPatients with a history of T2DM and NVAF were identified from two systematic registries: a registry of patients with stroke and a registry of patients with atrial fibrillation. Patients with stroke were randomly matched to patients without prior stroke events based on age, sex, body mass index, and index date. All treatments administered 12 months before the index date were documented. The associations between anticoagulants, antiplatelet agents, and OADs and stroke were assessed using multivariate conditional logistic models that yielded adjusted odds ratios (aORs) and 95 % confidence intervals, controlling for risk factors identified in the univariate comparison of cases and matched referents. ResultsThree-hundred and fifteen patients with stroke with both diabetes and NVAF were matched to 523 referents with both diabetes and NVAF but no history of stroke. The aORs for the use of drugs and stroke were 0.24 [0.15–0.40] for direct oral anticoagulants (DOACs), 0.42 [0.27–0.67] for vitamin K agonists (VKA), 0.80 [0.52–1.24] for antiplatelet agents, and 0.68 [0.45–1.02] for OADs. No significant associations were found between individual OAD use and stroke risk. Similar results were obtained for ischemic stroke. Only VKAs were significantly associated with hemorrhagic stroke (odds ratio = 4.25 [1.16–15.64]). ConclusionsAnticoagulant use was associated with a protective effect against the risk of stroke in patients with diabetes and NVAF, with no increase in the risk of hemorrhagic stroke for DOAC. No increased risk of stroke was observed because of any OAD, including sulfonylureas.

LONG-TERM SYSTOLIC BLOOD PRESSURE VARIABILITY AS AN INDEPENDENT RISK FACTOR FOR CARDIOVASCULAR EVENTS IN KIDNEY TRANSPLANT RECIPIENTS

Objective: Cardiovascular (CV) events represent the main cause of death in patients undergoing renal transplantation. Several studies have described the role of blood pressure variability (BPV) in predicting all-cause mortality and fatal and non-fatal CV events in the general population and in diabetic patients. Systolic blood pressure variability (SBPV) has recently been proposed as a predictor of clinical outcomes in patients with chronic kidney disease. However, evidence is still scarce about the prognostic role of BPV in the setting of renal transplantation. The aim of our study was to evaluate the role of long-term SBPV in the development of fatal and non-fatal CV events (myocardial infarction, unstable angina or revascularization, stroke and hospitalization for heart failure) in subjects undergoing kidney transplantation. Design and method: We performed a single-center retrospective observational analysis in a cohort of 272 kidney transplant patients (mean age 64±13 years, 66% men), with a transplant duration beyond 12 months and with at least 6 blood pressure measurements at defined intervals (3 months ± 15 days) over an assessment period of 18 months. BPV was expressed as standard deviation of ambulatory systolic blood pressure (SBP) and patients were accordingly classified in tertiles (low &lt;9.3 mmHg, medium 9.3-13 mmHg, high &gt;13 mmHg). The role of SBPV was analyzed by Kaplan-Meier (logrank) and its independent effect by Cox Regression. Results: Over a mean follow-up of 58.7±17.2 months, 27 subjects (9.9%) developed CV events. For each increase of 2.7 mmHg in SBP standard deviation, the risk for fatal or non-fatal CV events increased almost 3-folds (P=0.02) and patients in the highest tertile of SBP standard deviation showed a 4-fold increased risk (P= 0.01) (Figure 1). This relationship was maintained even after incremental adjustment for time-averaged pulse pressure, age, diabetes, prior CV event, and dialysis vintage (HR 3.2, 95% CI 1.1–10.0, p 0.04) (Table 1). Conclusions: Long-term BPV represents an independent risk factor for CV events in kidney transplant patients. It is therefore essential to seek for stable long-term blood pressure levels in this population in order to minimize the residual CV risk.