Exploring the use of ChatGPT in predicting anterior circulation stroke functional outcomes after mechanical thrombectomy: a pilot study.

BACKGROUND: Accurate prediction of functional outcomes is crucial in stroke management, but this remains challenging. OBJECTIVE: To evaluate the performance of the generative language model ChatGPT in predicting the functional outcome of patients with acute ischemic stroke (AIS) 3 months after mechanical thrombectomy (MT) in order to assess whether ChatGPT can used to be accurately predict the modified Rankin Scale (mRS) score at 3 months post-thrombectomy. METHODS: We conducted a retrospective analysis of clinical, neuroimaging, and procedure-related data from 163 patients with AIS undergoing MT. The agreement between ChatGPT's exact and dichotomized predictions and actual mRS scores was assessed using Cohen's κ. The added value of ChatGPT was measured by evaluating the agreement of predicted dichotomized outcomes using an existing validated score, the MT-DRAGON. RESULTS: ChatGPT demonstrated fair (κ=0.354, 95% CI 0.260 to 0.448) and good (κ=0.727, 95% CI 0.620 to 0.833) agreement with the true exact and dichotomized mRS scores at 3 months, respectively, outperforming MT-DRAGON in overall and subgroup predictions. ChatGPT agreement was higher for patients with shorter last-time-seen-well-to-door delay, distal occlusions, and better modified Thrombolysis in Cerebral Infarction scores. CONCLUSIONS: ChatGPT adequately predicted short-term functional outcomes in post-thrombectomy patients with AIS and was better than the existing risk score. Integrating AI models into clinical practice holds promise for patient care, yet refining these models is crucial for enhanced accuracy in stroke management.

Iron Deficiency and Incident Heart Failure in Older Community-Dwelling Individuals.

AIMS: Among persons with prevalent heart failure (HF), iron deficiency has been linked to HF admissions, and intravenous iron replacement improves HF outcomes. Recent studies in persons with chronic kidney disease (CKD) demonstrate that iron deficiency is associated with incident HF. This study aimed to determine the relationship of iron status with incident HF in community-dwelling older adults irrespective of their kidney function. METHODS: In this case-cohort study, 1,006 Cardiovascular Health Study participants (785 from the random sub-cohort [including 193 HF cases] and 221 additional HF cases [N = 414 total HF cases]) aged ≥ 65 years without HF (41% with CKD), we used weighted Cox models to evaluate associations of iron status with incident HF. Participants were categorized based on quartiles of transferrin saturation and ferritin as "iron replete" (27.3%), "functional iron deficiency" (7.7%), "iron deficiency" (11.8%), "mixed iron deficiency" (5.6%), "high iron" (9.3%) and "non-classified" (38.1%), consistent with prior studies. RESULTS: Compared to older persons who were iron replete, those with iron deficiency were at higher risk of incident HF (HR 1.47; 1.02-2.11) in models adjusting for demographics, HF risk factors, and estimated glomerular filtration rate. Other iron categories did not associate with incident HF. The relationship of iron deficiency with incident HF did not differ by CKD status (interaction P value 0.2). CONCLUSIONS: Among community-dwelling elders, iron deficiency is independently associated with incident HF, an association that was similar irrespective of CKD status. Our findings support conduct of clinical trials of iron replacement for prevention of HF in older adults with iron deficiency.

Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection: The STOP-CAD Study.

BACKGROUND: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation. METHODS: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments. RESULTS: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45-1.12]; P=0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28-2.24]; P=0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35-5.45]; P=0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53-20.13]; P=0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18-0.88]; Pinteraction=0.009). CONCLUSIONS: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings.

Digital flashcards and medical physiology performance: a dose-dependent effect.

Use of digital flashcards promotes active recall, spaced repetition, and self-assessment academic principles. This work explores the association and dose-dependent effect of this study method and locomotor (LP) and cardiovascular physiology (CP) grades. A single-faculty cohort study of medical LP and CP students was conducted, and 155 and 676 flashcards, respectively, were created through Moodle. An exploratory analysis examined three exam results (2019), and a confirmatory study used a fourth exam (2021) in another CP cohort. Of 685 students enrolled, 558 participated in the exploratory analysis: 319 (69%) for LP and 311 (84%) for CP, of which 203 LP and 267 CP students were flashcard users. Median grades were higher among flashcard users, and the number of cards reviewed was positively correlated with grades (r = 0.275 to 0.388 for LP and r = 0.239 to 0.432 for CP, P < 0.001). Multiple linear regression models confirmed a positive dose-dependent association between results and the number of flashcards studied: for every 100 LP cards reviewed, exam grades increased 0.44-0.75 on a 0-20 scale range (P < 0.001), and for every 1,000 CP flashcards, results raised 0.81-1.08 values (P < 0.05). These findings were confirmed in the 2021 CP cohort of 269 participants, of whom 67% were flashcard users. Digital flashcard revision has a consistent positive dose-dependent association on LP and CP grades.NEW & NOTEWORTHY Implementing flashcard-based strategies is a feasible way to promote active recall, spaced repetition, and self-assessment, and students are highly adherent to these initiatives. There is a positive dose-dependent association between the number of flashcards reviewed and physiology grades. These results are consistent across different physiology subjects, under different cohorts, over short and medium terms.

A 4-Variable Model to Predict Cardio-Kidney Events and Mortality in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort (CRIC) Study.

INTRODUCTION: Current prognostic models for chronic kidney disease (CKD) are complex and were designed to predict a single outcome. We aimed to develop and validate a simple and parsimonious prognostic model to predict cardio-kidney events and mortality. METHODS: Patients from the CRIC Study (n = 3,718) were randomly divided into derivation (n = 2,478) and validation (n = 1,240) cohorts. Twenty-nine candidate variables were preselected. Multivariable Cox regression models were developed using stepwise selection for various cardio-kidney endpoints, namely, (i) the primary composite outcome of 50% decline in estimated glomerular filtration rate (eGFR) from baseline, end-stage renal disease, or cardiovascular (CV) mortality; (ii) hospitalization for heart failure (HHF) or CV mortality; (iii) 3-point major CV endpoints (3P-MACE); (iv) all-cause death. RESULTS: During a median follow-up of 9 years, the primary outcome occurred in 977 patients of the derivation cohort and 501 patients of the validation cohort. Log-transformed N-terminal pro-B-type natriuretic peptide (NT-proBNP), log-transformed high-sensitive cardiac troponin T (hs-cTnT), log-transformed albuminuria, and eGFR were the dominant predictors. The primary outcome risk score discriminated well (c-statistic = 0.83) with a proportion of events of 11.4% in the lowest tertile of risk and 91.5% in the highest tertile at 10 years. The risk model presented good discrimination for HHF or CV mortality, 3P-MACE, and all-cause death (c-statistics = 0.80, 0.75, and 0.75, respectively). The 4-variable risk model achieved similar c-statistics for all tested outcomes in the validation cohort. The discrimination of the 4-variable risk model was mostly superior to that of published models. CONCLUSION: The combination of NT-proBNP, hs-cTnT, albuminuria, and eGFR in a single 4-variable model provides a unique individual prognostic assessment of multiple cardio-kidney outcomes in CKD.

Paternity data reveal high MHC diversity among sires in a polygynandrous, egalitarian primate.

Evidence from human and nonhuman primates suggests that females avoid breeding with close kin and may choose mates based on MHC diversity, which can improve offspring survival. In despotic societies, female mate choice may be hindered by male sexual coercion, but in egalitarian societies, females may be less constrained. Among northern muriquis-an egalitarian, polygynandrous primate with male philopatry-analyses of new data on paternity and variation at microsatellite and MHC loci, combined with behavioural and life-history data, revealed that sires showed higher MHC diversity than expected by chance and were never close kin of dams, consistent with predictions of female mate choice and close inbreeding avoidance. However, females did not differentially reproduce with males who were more distantly related to them or more dissimilar at the MHC than expected by chance, nor with those who had more MHC alleles distinct from their own. The lack of male dominance may permit females to identify and reproduce preferentially with non-offspring males and with males who are more diverse at the MHC. Nonetheless, the absence of disassortative mating at the MHC and neutral loci suggests that female mate choice may be limited by other factors impacting male fertilization success.

Defining and Measuring Preclinical Mobility Limitation: An Expert Consensus Exercise Informed by a Scoping Review.

BACKGROUND: Early change in function in older adults has been termed preclinical disability (PCD). PCD has been understudied compared to other stages of disability because it is unlikely to receive comparative priority in clinical settings. It has major implications for prevention and population health as it may be the optimal time to intervene to prevent further decline. A standardized approach to research in PCD, including a common definition and measurement approaches, is needed to advance this work. METHODS: The process to establish how PCD should be defined and measured was undertaken in 2 stages: (1) a scoping review of the literature, which was used to inform (2) a web-enabled consensus meeting with content experts. RESULTS: The scoping review and the consensus meeting support the use of the term preclinical mobility limitation (PCML) and that it should be measured using both patient-reported and performance-based measures. It was agreed that the definition of PCML should include modification of frequency and/or method of task completion, without overt disability, and that requisite mobility tasks include walking (distance and speed), stairs, and transfers. CONCLUSIONS: Currently, there are few standardized assessments that can identify PCML. PCML is the term that most clearly describes the stage where people experience a change in routine mobility tasks, without a perception of disability. Further evaluation into the reliability, validity, and responsiveness of outcome measures is needed to advance research on PCML.

Examining the Causal Mediating Role of Cardiovascular Disease on the Effect of Subclinical Cardiovascular Disease on Cognitive Impairment via Separable Effects.

BACKGROUND: An important epidemiological question is understanding how vascular risk factors contribute to cognitive impairment. Using data from the Cardiovascular Health Cognition Study, we investigated how subclinical cardiovascular disease (sCVD) relates to cognitive impairment risk and the extent to which the hypothesized risk is mediated by the incidence of clinically manifested cardiovascular disease (CVD), both overall and within apolipoprotein E-4 (APOE-4) subgroups. METHODS: We adopted a novel "separable effects" causal mediation framework that assumes that sCVD has separably intervenable atherosclerosis-related components. We then ran several mediation models, adjusting for key covariates. RESULTS: We found that sCVD increased overall risk of cognitive impairment (risk ratio [RR] = 1.21, 95% confidence interval [CI]: 1.03, 1.44); however, there was little or no mediation by incident clinically manifested CVD (indirect effect RR = 1.02, 95% CI: 1.00, 1.03). We also found attenuated effects among APOE-4 carriers (total effect RR = 1.09, 95% CI: 0.81, 1.47; indirect effect RR = 0.99, 95% CI: 0.96, 1.01) and stronger findings among noncarriers (total effect RR = 1.29, 95% CI: 1.05, 1.60; indirect effect RR = 1.02, 95% CI: 1.00, 1.05). In secondary analyses restricting cognitive impairment to only incident dementia cases, we found similar effect patterns. CONCLUSIONS: We found that the effect of sCVD on cognitive impairment does not seem to be mediated by CVD, both overall and within APOE-4 subgroups. Our results were critically assessed via sensitivity analyses, and they were found to be robust. Future work is needed to fully understand the relationship between sCVD, CVD, and cognitive impairment.

Non-esterified fatty acids and risk of peripheral artery disease in older adults: The cardiovascular health study.

BACKGROUND AND AIMS: Non-esterified fatty acids have been implicated in the pathogenesis of diabetes and cardiovascular disease. No longitudinal study has assessed their effects on peripheral artery disease (PAD). We determined the relationships between NEFAs and incident clinical PAD and abnormal ankle-brachial index (ABI) in a population-based cohort of older persons. METHODS: We evaluated 4575 community living participants aged >65 years who underwent measurement of circulating NEFAs in fasting specimens and ABI in 1992-1993. Participants were assessed annually for clinical PAD until 2015 and underwent repeat ABI in 1998-1999. We used Cox proportional hazards regression to model the associations between NEFAs and risk of clinical PAD and logistic regression to model the associations of NEFAs with incident abnormal ABI. RESULTS: Mean age was 74.8 years, 59% were female, and 17% were Black. NEFAs were associated with higher risk of clinical PAD in unadjusted and adjusted models. The adjusted hazard ratios for incident clinical PAD were 1.51 (95%CI = 1.06-2.13, p = 0.02) across extreme tertiles, and 1.14 (95%CI = 0.99-1.31, p = 0.08) per standard deviation higher NEFA. The corresponding odds ratios for abnormal ABI were 0.95 (95%CI = 0.69-1.32, p = 0.76) across extreme tertiles, and 1.03 (95%CI = 0.89-1.20, p = 0.68) per standard deviation higher NEFA. Relationships appeared similar irrespective of sex, race, or pre-existing cardiovascular disease, but were stronger later than earlier in follow-up. CONCLUSIONS: Higher serum levels of NEFAs are significantly associated with increased likelihood of clinical PAD over long-term follow-up but not with 6-year decline in ABI. NEFAs may offer a potential target for intervention against clinical PAD.

Sex- and race-specific associations of bone mineral density with incident heart failure and its subtypes in older adults.

BACKGROUND: Previous studies have suggested an association between bone mineral density (BMD) and heart failure (HF) risk that may be race-dependent. METHODS: We evaluated the relationship between BMD and incident HF in a cohort of older adults, the Health, Aging, and Body Composition (Health ABC) study (n = 2835), and next performed a pooled analysis involving a second older cohort, the Cardiovascular Health Study (n = 1268). Hip BMD was measured by dual-energy X-ray absorptiometry in both cohorts and spine BMD by computed tomography in a subset from Health ABC. RESULTS: In Health ABC, lower BMD at the total hip was associated with higher incident HF in Black women after multivariable adjustment. Similar associations were found for BMD at the femoral neck and spine. In both cohorts, pooled analysis again revealed an association between lower total hip BMD and increased risk of HF in Black women (HR = 1.41 per 0.1-g/cm2 decrement [95% CI = 1.23-1.62]), and showed the same to be true for White men (HR = 1.12 [1.03-1.21]). There was a decreased risk of HF in Black men (HR 0.80 [0.70-0.91]), but no relationship in White women. The associations were numerically stronger with HFpEF for Black women and White men, and with HFrEF for Black men. Findings were similar for femoral neck BMD. Sensitivity analyses delaying HF follow-up by 2 years eliminated the association in Black men. CONCLUSIONS: Lower BMD was associated with higher risk of HF and especially HFpEF in older Black women and White men, highlighting the need for additional investigation into underlying mechanisms.

Relaxin-2, pathophysiological insights and outcomes in heart failure with preserved ejection fraction: Findings from the NETDiamond cohort.

AIMS: The role of relaxin-2 as a circulating marker in heart failure (HF) with preserved ejection fraction (HFpEF) is poorly understood. We aimed to characterize relaxin-2 circulating levels in a population of chronic HFpEF patients and their association with long-term prognosis. METHODS: Relaxin-2 serum levels were measured in 85 chronic HFpEF patients from a prospective cohort study (NETDiamond). Clinical, imaging, and analytical data were compared across relaxin-2 tertiles. The primary outcome was a composite of cardiovascular death, HF hospitalisation, acute HF episode or diuretic intensification and the secondary outcome a composite of cardiovascular death and total HF hospitalisations. Cox regression and negative binomial models were used to assess the relation between relaxin-2 and the outcomes. RESULTS: Relaxin-2 levels were positively associated with left atrial volume, left ventricular mass and peripheral oedema, and negatively associated with ischemic heart disease and statin use. Higher relaxin-2 levels were associated with an increased risk of primary outcome, even after adjustment for age, B-type natriuretic peptide (BNP) and glomerular filtration rate (eGFR) (adjusted HR = 2.80, 95%CI 1.4-7.3, p = 0.034 for tertile 3). They were also associated with the occurrence of the secondary outcome (Incidence Rate Ratio = 5.28, 95%CI 1.2-23.2, p = 0.027), but this significance was lost when simultaneously adjusted for BNP and eGFR. CONCLUSION: In chronic HFpEF patients, higher relaxin-2 circulating levels were associated with left chambers remodelling, congestion, and adverse prognosis. These findings support a potential role for relaxin-2 as a pathophysiological agent and as a circulating biomarker in HFpEF.

Pooled Cohort Probability Score for Subclinical Airflow Obstruction.

Rationale: Early detection of chronic obstructive pulmonary disease (COPD) is a public health priority. Airflow obstruction is the single most important risk factor for adverse COPD outcomes, but spirometry is not routinely recommended for screening. Objectives: To describe the burden of subclinical airflow obstruction (SAO) and to develop a probability score for SAO to inform potential detection and prevention programs. Methods: Lung function and clinical data were harmonized and pooled across nine U.S. general population cohorts. Adults with respiratory symptoms, inhaler use, or prior diagnosis of COPD or asthma were excluded. A probability score for prevalent SAO (forced expiratory volume in 1 second/forced vital capacity < 0.70) was developed via hierarchical group-lasso regularization from clinical variables in strata of sex and smoking status, and its discriminative accuracy for SAO was assessed in the pooled cohort as well as in an external validation cohort (NHANES [National Health and Nutrition Examination Survey] 2011-2012). Incident hospitalizations and deaths due to COPD (respiratory events) were defined by adjudication or administrative criteria in four of nine cohorts. Results: Of 33,546 participants (mean age 52 yr, 54% female, 44% non-Hispanic White), 4,424 (13.2%) had prevalent SAO. The incidence of respiratory events (Nat-risk = 14,024) was threefold higher in participants with SAO versus those without (152 vs. 39 events/10,000 person-years). The probability score, which was based on six commonly available variables (age, sex, race and/or ethnicity, body mass index, smoking status, and smoking pack-years) was well calibrated and showed excellent discrimination in both the testing sample (C-statistic, 0.81; 95% confidence interval [CI], 0.80-0.82) and in NHANES (C-statistic, 0.83; 95% CI, 0.80-0.86). Among participants with predicted probabilities ⩾ 15%, 3.2 would need to undergo spirometry to detect one case of SAO. Conclusions: Adults with SAO demonstrate excess respiratory hospitalization and mortality. A probability score for SAO using commonly available clinical risk factors may be suitable for targeting screening and primary prevention strategies.

Early anticoagulation in atrial fibrillation-related acute ischaemic stroke: efficacy and safety profile.

OBJECTIVES: To evaluate the effects of early anticoagulation on functional outcome, recurrent ischaemic events and haemorrhagic complications in Atrial Fibrillation (AF)-related acute ischaemic strokes (AIS). MATERIALS AND METHODS: We retrospectively evaluated patients hospitalised in a Stroke Unit due to AF-related AIS. Patients were divided according to anticoagulation initiation timing (0-4 days, 5-14 days, no anticoagulation by the 14th day). We assessed the following outcomes at 3 months: favourable functional outcome [modified Rankin Scale (mRS) score 0-2 or equal to pre-stroke], recurrent ischaemic events and haemorrhagic complications after anticoagulation initiation. RESULTS: We included 395 patients. Anticoagulation was initiated at days 0-4 in 33.9% of patients, days 5-14 in 25.3% and not initiated by the day 14 in 40.8%. Factors associated with earlier anticoagulation included lower previous mRS, valvular AF and lower stroke severity. Favourable functional outcome occurred in 40.2% of patients, with lower odds in those anticoagulated at 5-14 versus 0-4 days (OR: 0.47, 95% CI: 0.23-0.94), independently of age, previous mRS and stroke severity. Recurrent ischaemic events occurred in 8.3% of patients, with higher odds in non-anticoagulated patients by the 14th day, compared to the remainder groups (OR: 3.26, 95% CI: 1.29-8.22 vs. 0-4 days and OR: 8.16, 95% CI: 1.76-37.9 vs. 5-14 days). In patients who started anticoagulation (n = 288), haemorrhagic complications occurred in 10.8%, being more frequent in those who started at 0-4 days vs. > 14 days. However, it did not abolish the 0-4-day initiation's benefit on functional outcome. CONCLUSIONS: Early anticoagulation was associated with lower ischaemic recurrence and better functional outcome at 3 months. Additional studies are needed to better clarify its haemorrhagic risk.

Association between serum phosphorus and mortality in NHANES 2003-2006: the effect of gender and renal function.

BACKGROUND: The impact of high serum phosphorus in the general population is still debated. Studies are heterogeneous, most lack an adjustment for parathyroid hormone, vitamin D and phosphorus intake and the effect might differ by gender and renal function. We investigated the association between serum phosphorus and mortality in American adults. METHODS: We prospectively analyzed 5698 non-pregnant and non-CKD adults from the National Health and Nutrition Examination Survey (NHANES) 2003-2006. Serum phosphorus and potential confounders including parathyroid hormone, 25(OH)vitamin D and phosphorus intake were evaluated. All-cause, cardiovascular- and cancer-related deaths were recorded through December 31st, 2015. Sex-specific terciles of serum phosphorus were used to fit adjusted Cox proportional hazard models for mortality. Analysis was stratified by gender and renal function. RESULTS: A total of 590 deaths were recorded over a median follow-up of 81 months. Women showed higher serum phosphorus than men. The adjusted hazard ratio (HR) for all-cause mortality was 1.35 (95% CI 1.08-1.58) (p = 0.033) for the third tercile (versus second tercile). This increased risk was present in participants with estimated glomerular filtration rate (eGFR) below 90 ml/min/1.73 m2 but not above, although interaction was not significant (p = 0.12). Interaction by gender, phosphorus intake, PTH and fasting time was also not detected. For cardiovascular and cancer mortality, the adjusted HR was 0.81 (95% CI 0.33-2.00) (p = NS) and 1.45 (95% CI 0.77-2.72) (p = NS), respectively. CONCLUSIONS: We demonstrated that the highest tercile of serum phosphorus is associated with increased all-cause mortality, irrespective of PTH, 25(OH)vitamin D or phosphorus intake. This association may differ by gender and renal function, but larger studies testing for effect modification are needed.

Urocortin-2 in Acute Heart Failure: Role as a Marker of Volume Overload and Pulmonary Hypertension.

Urocortin (Ucn)-2 has shown promising therapeutic effects on heart failure (HF). However, there are still significant knowledge gaps regarding the role and modulation of the endogenous Ucn-2 axis in the cardiovascular system and, specifically, in acute HF. We evaluated Ucn-2 levels in admission serum samples of 80 acute HF patients and assessed their association with clinical, analytical and echocardiographic parameters. Median age was 76.5 years, and 37 patients (46%) were male. Median serum Ucn-2 was 2.3ng/mL. Ucn-2 levels were positively associated with peripheral edemas (P = 0.022), hepatomegaly (P = 0.007) and sodium retention score (ρ = 0.37, P = 0.001) and inversely correlated with inferior vena cava collapse at inspiration (ρ = -0.37, P = 0.001). Additionally, patients with higher Ucn-2 levels had a higher prevalence of right atrial dilation (P = 0.027), right ventricle dilation (P = 0.008), and higher systolic pulmonary artery pressure (ρ = 0.34, P = 0.002). Regarding analytical parameters, Ucn-2 correlated positively with log BNP (r = 0.22, P = 0.055) and inversely with uric acid (r = 0.24, P = 0.029) and total (r = -0.30, P = 0.007) and low-density lipoprotein cholesterol (r = -0.23, P = 0.038). No associations were found between Ucn-2 and age, sex or left heart structure or function. In conclusion, Circulating Ucn-2 was associated with clinical and echocardiographic markers of volume overload and pulmonary hypertension in acute HF patients.

Anticoagulation after intracerebral hemorrhage in patients with atrial fibrillation: between Scylla and Charybdis.

BACKGROUND: Oral anticoagulants (OAC) are indicated in patients with atrial fibrillation (AF) and high risk of ischemic stroke. However, the introduction of anticoagulation in patients with AF and previous intracerebral hemorrhage (ICH) is controversial. We aimed to better understand the efficacy and safety of OAC in this context and to assess the factors that may influence this decision. METHODS: In a single-center retrospective observational study, patients with AF and ICH who survived hospitalization at a level A Stroke Unit between 2009 and 2018 were included. Patients were followed for two years after discharge. Data were collected regarding the introduction or not of OAC and the occurrence of major thrombotic/hemorrhagic events and death. RESULTS: Ninety-five patients (75.2 ± 9.9 years) were included and 40 patients (42.1%) started OAC. Patients were more likely to initiate anticoagulation if they had: mechanical prosthetic valves, previous AF (p = 0.005) and previous OAC therapy (p < 0001); and less if they had previous hemorrhagic stroke (p < 0.005). During follow-up, 10.5% had at least one major hemorrhagic event (60% anticoagulated), 20% had at least one major thrombotic event (all non-anticoagulated) and 20% died. The only factor associated with the risk of bleeding was ICH score (OR:2.49 per 1-point increase; 95%CI:1.14-5.46). Patients who initiated anticoagulation had lower mortality than non-anticoagulated (OR:0.296; 95%CI:0.090-0-975). Previous ICH and higher CHA2DS2-VASc were associated with higher mortality. CONCLUSION: In this retrospective series, anticoagulation reduced thrombotic events and overall mortality in patients admitted for ICH and AF, without a significant increase in bleeding risk.

Upper Reference Limits for High-Sensitivity Cardiac Troponin T and N-Terminal Fragment of the Prohormone Brain Natriuretic Peptide in Patients With CKD.

RATIONALE & OBJECTIVE: The utility of conventional upper reference limits (URL) for N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hsTnT) in chronic kidney disease (CKD) remains debated. We analyzed the distribution of hsTnT and NT-proBNP in people with CKD in ambulatory settings to examine the diagnostic value of conventional URL in this population. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: We studied participants of the Chronic Renal Insufficiency Cohort (CRIC) with CKD and no self-reported history of cardiovascular disease. EXPOSURE: Estimated glomerular filtration rate (eGFR). OUTCOME: NT-proBNP and hsTnT at baseline. ANALYTICAL APPROACH: We described the proportion of participants above the conventional URL for NT-proBNP (125pg/mL) and hsTnT (14ng/L) overall and by eGFR. We then estimated 99th percentile URL for NT-proBNP and hsTnT. Using quantile regression of the 99th percentile, we modeled the association of eGFR with NT-proBNP and hsTnT. RESULTS: Among 2,312 CKD participants, 40% and 43% had levels of NT-proBNP and hsTnT above the conventional URL, respectively. In those with eGFR <30mL/min/1.73m2, 71% and 68% of participants had concentrations of NT-proBNP and hsTnT above the conventional URL, respectively. Among all CKD participants, the 99th percentile for NT-proBNP was 3,592 (95% CI, 2,470-4,849) pg/mL and for hsTnT it was 126 (95% CI, 100-144) ng/L. Each 15mL/min/1.73m2 decrement in eGFR was associated with a ~40% higher threshold for the 99th percentile of NT-proBNP (1.43 [95% CI, 1.21-1.69]) and hsTnT (1.45 [95% CI, 1.31-1.60]). LIMITATIONS: Study included ambulatory patients, and we could not test the accuracy of the URL of NT-proBNP and hsTnT in the acute care setting. CONCLUSIONS: In this ambulatory CKD population with no self-reported history of cardiovascular disease, a range of 40%-88% of participants had concentrations of NT-proBNP and hsTnT above the conventional URL, depending on eGFR strata. Developing eGFR-specific thresholds for these commonly used cardiac biomarkers in the setting of CKD may improve their utility for evaluation of suspected heart failure and myocardial infarction.

Higher Serum Brain-Derived Neurotrophic Factor Levels Are Associated With a Lower Risk of Cognitive Decline: A 2-Year Follow Up Study in Community-Dwelling Older Adults.

OBJECTIVE: To assess the relationship of serum brain-derived neurotrophic factor (BDNF) levels with the subsequent short-term decline in cognitive functioning in community-dwelling older adults. DESIGN: Two-year prospective, observational study. SETTING AND PARTICIPANTS: The study included 405 adults aged 65-84 years, initially free of a dementia diagnosis who were living in Tokyo, Japan. METHODS: Participants underwent health assessments at baseline (2011) and follow-up (2013). Serum BDNF levels and scores from the Montreal Cognitive Assessment-Japanese version (MoCA-J) were systematically measured. Logistic regression was used to estimate the odds of cognitive decline between baseline and follow-up assessments in the full MoCA-J scale (operationally defined as a decrease of two or more points), as well as in MoCA-J subscales (decline of one or more points in a specific subscale), as a function of serum BDNF level, adjusting for baseline demographics, prevalent chronic diseases, and baseline cognitive scores. RESULTS: Among individuals who performed worse on the full MoCA-J at baseline (i.e., scores in the bottom quartile [≤21], which is consistent with a mild cognitive impairment status), but not among those who performed better (top 3 quartiles), those with highest baseline serum BDNF levels (top quartile) had lower odds of subsequent decline in the full MoCA-J scale than those with lowest (bottom quartile); i.e., odds ratio (OR): 0.10 (95% confidence interval [CI]: 0.02-0.62; p = 0.013). Regarding MoCA-J subscales, adjusted odds of decline in the executive function subscale, but not in the other five subscales, were substantially low among those with highest baseline serum BDNF levels (top quartile), as compared to those with the lowest (bottom quartile), i.e., OR: 0.27 (95% CI:0.13-0.60; p < 0.001). CONCLUSION AND IMPLICATIONS: Higher serum BDNF levels were associated with a lower risk of decline in cognitive function in a sample of community-dwelling older Japanese adults. Risk varied across cognitive subdomains and according to baseline cognition. This warrants further research to evaluate the added-value of serum BDNF in health promotion initiatives directed toward cognitive decline prevention in community-dwelling older adults.

Performance of the Pooled Cohort Equations to Estimate Atherosclerotic Cardiovascular Disease Risk by Body Mass Index.

Importance: Obesity is a global health challenge and a risk factor for atherosclerotic cardiovascular disease (ASVCD). Performance of the pooled cohort equations (PCE) for ASCVD risk by body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is unknown. Objective: To assess performance of the PCE across clinical BMI categories. Design, Setting, and Participants: This cohort study used pooled individual-level data from 8 community-based, prospective, longitudinal cohort studies with 10-year ASCVD event follow-up from 1996 to 2016. We included all adults ages 40 to 79 years without baseline ASCVD or statin use, resulting in a sample size of 37 311 participants. Data were analyzed from August 2017 to July 2020. Exposures: Participant BMI category: underweight (<18.5), normal weight (18.5 to <25), overweight (25 to <30), mild obesity (30 to <35), and moderate to severe obesity (≥35). Main Outcomes and Measures: Discrimination (Harrell C statistic) and calibration (Nam-D'Agostino χ2 goodness-of-fit test) of the PCE across BMI categories. Improvement in discrimination and net reclassification with addition of BMI, waist circumference, and high-sensitivity C-reactive protein (hsCRP) to the PCE. Results: Among 37 311 participants (mean [SD] age, 58.6 [11.8] years; 21 897 [58.7%] women), 380 604 person-years of follow-up were conducted. Mean (SD) baseline BMI was 29.0 (6.2), and 360 individuals (1.0%) were in the underweight category, 9937 individuals (26.6%) were in the normal weight category, 13 601 individuals (36.4%) were in the overweight category, 7783 individuals (20.9%) were in the mild obesity category, and 5630 individuals (15.1%) were in the moderate to severe obesity category. Median (interquartile range [IQR]) 10-year estimated ASCVD risk was 7.1% (2.5%-15.4%), and 3709 individuals (9.9%) developed ASCVD over a median (IQR) 10.8 [8.5-12.6] years. The PCE overestimated ASCVD risk in the overall cohort (estimated/observed [E/O] risk ratio, 1.22; 95% CI, 1.18-1.26) and across all BMI categories except the underweight category. Calibration was better near the clinical decision threshold in all BMI groups but worse among individuals with moderate or severe obesity (E/O risk ratio, 1.36; 95% CI, 1.25-1.47) and among those with the highest estimated ASCVD risk ≥20%. The PCE C statistic overall was 0.760 (95% CI, 0.753-0.767), with lower discrimination in the moderate or severe obesity group (C statistic, 0.742; 95% CI, 0.721-0.763) compared with the normal-range BMI group (C statistic, 0.785; 95% CI, 0.772-0.798). Waist circumference (hazard ratio, 1.07 per 1-SD increase; 95% CI, 1.03-1.11) and hsCRP (hazard ratio, 1.07 per 1-SD increase; 95% CI, 1.05-1.09), but not BMI, were associated with increased ASCVD risk when added to the PCE. However, these factors did not improve model performance (C statistic, 0.760; 95% CI, 0.753-0.767) with or without added metrics. Conclusions and Relevance: These findings suggest that the PCE had acceptable model discrimination and were well calibrated at clinical decision thresholds but overestimated risk of ASCVD for individuals in overweight and obese categories, particularly individuals with high estimated risk. Incorporation of the usual clinical measures of obesity did not improve risk estimation of the PCE. Future research is needed to determine whether incorporation of alternative high-risk obesity markers (eg, weight trajectory or measures of visceral or ectopic fat) into the PCE may improve risk prediction.