Association of Left Atrial Function With Incident Chronic Kidney Disease in Older Adults.

Objective: To examine the association of left atrial (LA) function with incident chronic kidney disease (CKD) and assess the clinical utility of adding LA function to a CKD risk prediction equation. Patients and Methods: We included 4002 Atherosclerosis Risk in Communities study participants without prevalent CKD (mean ± SD age, 75±5 years; 58% female, 18% Black). Left atrial function (reservoir, conduit, and contractile strain) was evaluated by 2D-echocardiograms on 2011 to 2013. Chronic kidney disease was defined as greater than 25% decline in estimated glomerular filtration rate of less than 60 mL/min/1.73 m2, end-stage kidney disease, or hospital records. Cox proportional hazards models were used. Risk prediction and decision curve analyses evaluated 5-year CKD risk by diabetes status. Results: Median follow-up was 7.2 years, and 598 participants developed incident CKD. Incidence rate for CKD was 2.29 per 100 person-years. After multivariable adjustments, the lowest quintile of LA reservoir, conduit, and contractile strain (vs highest quintile) had a higher risk of CKD (hazard ratios [95% CIs]: 1.94 [1.42-2.64], 1.62 [1.19-2.20], and 1.49 [1.12-1.99]). Adding LA reservoir strain to the CKD risk prediction equation variables increased the C-index by 0.026 (95% CI: 0.005-0.051) and 0.031 (95% CI: 0.006-0.058) in participants without and with diabetes, respectively. Decision curve analysis found the model with LA reservoir strain had a higher net benefit than the model with CKD risk prediction equation variables alone. Conclusion: Lower LA function is independently associated with incident CKD. Adding LA function to the CKD risk prediction enhances prediction and yields a higher clinical net benefit. These findings suggest that impaired LA function may be a novel risk factor for CKD.

New kinase-deficient PAK2 variants associated with Knobloch syndrome type 2.

The p21-activated kinase (PAK) family of proteins regulates various processes requiring dynamic cytoskeleton organization such as cell adhesion, migration, proliferation, and apoptosis. Among the six members of the protein family, PAK2 is specifically involved in apoptosis, angiogenesis, or the development of endothelial cells. We report a novel de novo heterozygous missense PAK2 variant, p.(Thr406Met), found in a newborn with clinical manifestations of Knobloch syndrome. In vitro experiments indicated that this and another reported variant, p.(Asp425Asn), result in substantially impaired protein kinase activity. Similar findings were described previously for the PAK2 p.(Glu435Lys) variant found in two siblings with proposed Knobloch syndrome type 2 (KNO2). These new variants support the association of PAK2 kinase deficiency with a second, autosomal dominant form of Knobloch syndrome: KNO2.

Percutaneous left atrial appendage occlusion and risk of stroke, hospitalized bleeding and death in Medicare beneficiaries.

PURPOSE: Among patients with atrial fibrillation (AF), a nonpharmacologic option (e.g., percutaneous left atrial appendage occlusion [LAAO]) is needed for patients with oral anticoagulant (OAC) contraindications. Among beneficiaries in the Medicare fee-for-service coverage 20% sample databases (2015-18) who had AF and an elevated CHA2DS2-VASc score, we assessed the association between percutaneous LAAO versus OAC use and risk of stroke, hospitalized bleeding, and death. METHODS: Patients undergoing percutaneous LAAO were matched to up to five OAC users by sex, age, date of enrollment, index date, CHA2DS2-VASc score, and HAS-BLED score. Overall, 17 156 patients with AF (2905 with percutaneous LAAO) were matched (average ± SD 78 ± 6 years, 44% female). Cox proportional hazards model were used. RESULTS: Median follow-up was 10.3 months. After multivariable adjustments, no significant difference for risk of stroke or death was noted when patients with percutaneous LAAO were compared with OAC users (HRs [95% CIs]: 1.14 [0.86-1.52], 0.98 [0.86-1.10]). There was a 2.94-fold (95% CI: 2.50-3.45) increased risk for hospitalized bleeding for percutaneous LAAO compared with OAC use. Among patients 65 to <78 years old, those undergoing percutaneous LAAO had higher risk of stroke compared with OAC users. No association was present in those ≥78 years. CONCLUSION: In this analysis of real-world AF patients, percutaneous LAAO versus OAC use was associated with similar risk of death, nonsignificantly elevated risk of stroke, and an elevated risk of bleeding in the post-procedural period. Overall, these results support results of randomized trials that percutaneous LAAO may be an alternative to OAC use for patients with contraindications.

Fragmentation of the QRS Complex Is Associated with Right Ventricular Dilatation and Mortality in Critically Unwell Coronavirus Disease 2019 Patients.

BACKGROUND: QRS fragmentation (fQRS) is a depolarization disorder that can be detected on routine electrocardiography (ECG). Current evidence suggests that fQRS is a prognosticator of adverse cardiovascular events. This study aimed to assess the relationship between fQRS and all-cause mortality in critically unwell coronavirus disease 2019 (COVID-19) patients and to investigate the significance of associated abnormalities on echocardiography. METHODS: A retrospective cohort study of COVID-19 patients in a critical care setting was performed. Electrocardiography was performed on presentation to hospital, admission to the critical care unit, and at subsequent points according to clinical need. Transthoracic echocardiography was performed at clinical discretion to assess for structural and functional cardiac abnormalities. Primary outcome was in-hospital mortality and secondary outcome was the need for mechanical invasive ventilation. RESULTS: Totally, 212 consecutive patients were included of which 120 (57%) exhibited fQRS and inferior leads were involved in 88% of the patients. Overall, fQRS was a significant predictor of mortality [65% vs. 44% P =.003; multivariate odds ratio = 2.96, 95% confidence interval (CI): 1.42-6.40, P =.005] and inferior fQRS itself was a significant predictor of mortality (P =.03). There was no significant association between fQRS and the need for invasive mechanical ventilation. A total of 112 patients underwent echocardiography. There was a greater incidence of right ventricular (RV) dilatation in the fQRS group (16% vs. 2% respectively, P =.02) and pulmonary hypertension (33% vs. 14% respectively, P =.03) based on echocardiographic criteria. CONCLUSION: Our study demonstrates that fQRS is significantly associated with RV dilation, pulmonary hypertension, and mortality in critically unwell COVID-19 patients.

A polygenic risk score of atrial fibrillation improves prediction of lifetime risk for heart failure.

AIMS: Heart failure (HF) has shared genetic architecture with its risk factors: atrial fibrillation (AF), body mass index (BMI), coronary heart disease (CHD), systolic blood pressure (SBP), and type 2 diabetes (T2D). We aim to assess the association and risk prediction performance of risk-factor polygenic risk scores (PRSs) for incident HF and its subtypes in bi-racial populations. METHODS AND RESULTS: Five PRSs were constructed for AF, BMI, CHD, SBP, and T2D in White participants of the Atherosclerosis Risk in Communities (ARIC) study. The associations between PRSs and incident HF and its subtypes were assessed using Cox models, and the risk prediction performance of PRSs was assessed using C statistics. Replication was performed in the ARIC study Black and Cardiovascular Health Study (CHS) White participants. In 8624 ARIC study Whites, 1922 (31% cumulative incidence) HF cases developed over 30 years of follow-up. PRSs of AF, BMI, and CHD were associated with incident HF (P < 0.001), where PRSAF showed the strongest association [hazard ratio (HR): 1.47, 95% confidence interval (CI): 1.41-1.53]. Only the addition of PRSAF to the ARIC study HF risk equation improved C statistics for 10 year risk prediction from 0.812 to 0.829 (∆C: 0.017, 95% CI: 0.009-0.026). The PRSAF was associated with both incident HF with reduced ejection fraction (HR: 1.43, 95% CI: 1.27-1.60) and incident HF with preserved ejection fraction (HR: 1.46, 95% CI: 1.33-1.62). The associations between PRSAF and incident HF and its subtypes, as well as the improved risk prediction, were replicated in the ARIC study Blacks and the CHS Whites (P < 0.050). Protein analyses revealed that N-terminal pro-brain natriuretic peptide and other 98 proteins were associated with PRSAF. CONCLUSIONS: The PRSAF was associated with incident HF and its subtypes and had significant incremental value over an established HF risk prediction equation.

The Acute and Chronic Effects of Lion's Mane Mushroom Supplementation on Cognitive Function, Stress and Mood in Young Adults: A Double-Blind, Parallel Groups, Pilot Study.

BACKGROUND: Given the bioactive properties and limited work to date, Hericium erinaceus (Lion's mane) shows promise in improving cognitive function and mood. However, much of the human research has concentrated on chronic supplementation in cognitively compromised cohorts. OBJECTIVE: The current pilot study investigated the acute and chronic (28-day) cognitive and mood-enhancing effects of Hericium erinaceus in a healthy, young adult cohort. DESIGN: This randomized, double-blind, placebo-controlled, parallel-groups design investigated the acute (60 min post dose) and chronic (28-day intervention) effects of 1.8 g Hericium erinaceus in 41 healthy adults aged 18-45 years. RESULTS: Analysis revealed that following a single dose of Hericium erinaceus, participants performed quicker on the Stroop task (p = 0.005) at 60 min post dose. A trend towards reduced subjective stress was observed following 28-day supplementation (p = 0.051). CONCLUSIONS: The findings tentatively suggest that Hericium erinaceus may improve speed of performance and reduce subjective stress in healthy, young adults. However, null and limited negative findings were also observed. Given the small sample size, these findings should be interpreted with caution. Further investigation in larger sample sizes is crucial, however the findings of this trial offer a promising avenue of interest.

Association of Atrial Fibrillation With Stroke and Dementia Accounting for Left Atrial Function and Size.

BACKGROUND: Atrial fibrillation (AF) is associated with higher risks of ischemic stroke (IS) and dementia. Whether alterations in left atrial (LA) function or size-atrial myopathy-confound these associations remains unknown. OBJECTIVES: The purpose of this study was to examine the association of prevalent and incident AF with ischemic stroke and dementia in the ARIC (Atherosclerosis Risk In Communities) study, adjusting for LA function and size. METHODS: Participants at visit 5 (2011-2013) with echocardiographic LA function (reservoir, conduit, contractile strain, and emptying fraction) and size (maximal, minimal volume index) data, and without prevalent stroke or dementia were followed through 2019. For analysis, we used time-varying Cox regression. RESULTS: Among 5,458 participants (1,193 with AF, mean age of 76 years) in the stroke analysis and 5,461 participants (1,205 with AF, mean age of 75 years) in the dementia analysis, 209 participants developed ischemic stroke, and 773 developed dementia over 7.1 years (median). In a demographic and risk factor-adjusted model, AF was significantly associated with ischemic stroke (HR, 1.63; 95% CI: 1.11-2.37) and dementia (HR: 1.38, 95% CI: 1.13-1.70). After additionally adjusting for LA reservoir strain, these associations were attenuated and no longer statistically significant (stroke [HR: 1.33, 95% CI: 0.88-2.00], dementia [HR: 1.15, 95% CI: 0.92-1.43]). Associations with ischemic stroke and dementia were also attenuated and not statistically significant after adjustment for LA contractile strain, emptying fraction, and minimal volume index. CONCLUSIONS: AF-ischemic stroke and AF-dementia associations were not statistically significant after adjusting for measures of atrial myopathy. This proof-of-concept analysis does not support AF as an independent risk factor for ischemic stroke and dementia.

Risk Factors for Sudden Cardiac Arrest Among Hispanic or Latino Adults in Southern California: Ventura PRESTO and HCHS/SOL.

Background Out-of-hospital sudden cardiac arrest (SCA) is a leading cause of mortality, making prevention of SCA a public health priority. No studies have evaluated predictors of SCA risk among Hispanic or Latino individuals in the United States. Methods and Results In this case-control study, adult SCA cases ages 18-85 (n=1,468) were ascertained in the ongoing Ventura Prediction of Sudden Death in Multi-Ethnic Communities (PRESTO) study (2015-2021) in Ventura County, California. Control subjects were selected from 3033 Hispanic or Latino participants who completed Visit 2 examinations (2014-2017) at the San Diego site of the HCHS/SOL (Hispanic Community Health Survey/Study of Latinos). We used logistic regression to evaluate the association of clinical factors with SCA. Among Hispanic or Latino SCA cases (n=295) and frequency-matched HCHS/SOL controls (n=590) (70.2% men with mean age 63.4 and 61.2 years, respectively), the following clinical variables were associated with SCA in models adjusted for age, sex, and other clinical variables: chronic kidney disease (odds ratio [OR], 7.3 [95% CI, 3.8-14.3]), heavy drinking (OR, 4.5 [95% CI, 2.3-9.0]), stroke (OR, 3.1 [95% CI, 1.2-8.0]), atrial fibrillation (OR, 3.7 [95% CI, 1.7-7.9]), coronary artery disease (OR, 2.9 [95% CI, 1.5-5.9]), heart failure (OR, 2.5 [95% CI, 1.2-5.1]), and diabetes (OR, 1.5 [95% CI, 1.0-2.3]). Conclusions In this first population-based study, to our knowledge, of SCA risk predictors among Hispanic or Latino adults, chronic kidney disease was the strongest risk factor for SCA, and established cardiovascular disease was also important. Early identification and management of chronic kidney disease may reduce SCA risk among Hispanic or Latino individuals, in addition to prevention and treatment of cardiovascular disease.

Warning symptoms associated with imminent sudden cardiac arrest: a population-based case-control study with external validation.

BACKGROUND: Sudden cardiac arrest is a global public health problem with a mortality rate of more than 90%. Prearrest warning symptoms could be harnessed using digital technology to potentially improve survival outcomes. We aimed to estimate the strength of association between symptoms and imminent sudden cardiac arrest. METHODS: We conducted a case-control study of individuals with sudden cardiac arrest and participants without sudden cardiac arrest who had similar symptoms identified from two US community-based studies of patients with sudden cardiac arrest in California state, USA (discovery population; the Ventura Prediction of Sudden Death in Multi-Ethnic Communities [PRESTO] study), and Oregon state, USA (replication population; the Oregon Sudden Unexpected Death Study [SUDS]). Participant data were obtained from emergency medical services reports for people aged 18-85 years with witnessed sudden cardiac arrest (between Feb 1, 2015, and Jan 31, 2021) and an inclusion symptom. Data were also obtained from corresponding control populations without sudden cardiac arrest who were attended by emergency medical services for similar symptoms (between Jan 1 and Dec 31, 2019). We evaluated the association of symptoms with sudden cardiac arrest in the discovery population and validated our results in the replication population by use of logistic regression models. FINDINGS: We identified 1672 individuals with sudden cardiac arrest from the PRESTO study, of whom 411 patients (mean age 65·7 [SD 12·4] years; 125 women and 286 men) were included in the analysis for the discovery population. From a total of 76 734 calls to emergency medical services, 1171 patients (mean age 61·8 [SD 17·3] years; 643 women, 514 men, and 14 participants without data for sex) were included in the control group. Patients with sudden cardiac arrest were more likely to have dyspnoea (168 [41%] of 411 vs 262 [22%] of 1171; p<0·0001), chest pain (136 [33%] vs 296 [25%]; p=0·0022), diaphoresis (50 [12%] vs 90 [8%]; p=0·0059), and seizure-like activity (43 [11%] vs 77 [7%], p=0·011). Symptom frequencies and patterns differed significantly by sex. Among men, chest pain (odds ratio [OR] 2·2, 95% CI 1·6-3·0), dyspnoea (2·2, 1·6-3·0), and diaphoresis (1·7, 1·1-2·7) were significantly associated with sudden cardiac arrest, whereas among women, only dyspnoea was significantly associated with sudden cardiac arrest (2·9, 1·9-4·3). 427 patients with sudden cardiac arrest (mean age 62·2 [SD 13·5]; 122 women and 305 men) were included in the analysis for the replication population and 1238 patients (mean age 59·3 [16·5] years; 689 women, 548 men, and one participant missing data for sex) were included in the control group. Findings were mostly consistent in the replication population; however, notable differences included that, among men, diaphoresis was not associated with sudden cardiac arrest and chest pain was associated with sudden cardiac arrest only in the sex-stratified multivariable analysis. INTERPRETATION: The prevalence of warning symptoms was sex-specific and differed significantly between patients with sudden cardiac arrest and controls. Warning symptoms hold promise for prediction of imminent sudden cardiac arrest but might need to be augmented with additional features to maximise predictive power. FUNDING: US National Heart Lung and Blood Institute.

SGLT2 Inhibitors Are Associated With Reduced Cardiovascular Disease in Patients With Type 2 Diabetes: An Analysis of Real-World Data.

OBJECTIVE: To assess the association between sodium-glucose cotransporter-2 (SGLT2) inhibitors and other second-line diabetes therapies with risk of cardiovascular disease (CVD), as well as conduct head-to-head comparisons between SGLT2 inhibitors. PATIENTS AND METHODS: Using data from the MarketScan databases (January 1, 2013, through December 31, 2019), SGLT2 inhibitor users were matched with up to five other second-line therapy users by age, sex, date of enrollment, and date of second-line therapy initiation. The primary composite outcome included stroke, atrial fibrillation, myocardial infarction, and heart failure. Hazard ratios were estimated, adjusting for demographics and a propensity score reflecting comorbidities and medications. RESULTS: In this study population of 313,396 patients (mean age 53±10 years; 47% female), 9787 incident CVD events occurred over a median follow-up of 1.36 years. After multivariable adjustments, SGLT2 inhibitor users had a lower risk of CVD than other second-line therapy users (HR, 0.66; 95% CI, 0.62 to 0.71). Significant associations were also observed when each CVD outcome was assessed separately. No differences were noted when comparing individual SGLT2 inhibitors. CONCLUSION: SGLT2 inhibitors were associated with a clinically meaningfully lower CVD risk in the real-world setting. In head-to-head comparisons, the different SGLT2 inhibitors were consistent in their protective associations with CVD. This suggests that as a class, SGLT2 inhibitors may have widespread benefit in preventing CVD among patients with type 2 diabetes.

Diagnosed Gonorrhea Among Privately Insured Women: Analysis of United States Claims Data.

Background: Gonorrhea incidence in the United States has risen by nearly 50% in the last decade, while screening rates have increased. Gonorrhea sequelae rates could indicate whether increased gonorrhea incidence is due to better screening. We estimated the association of gonorrhea diagnosis with pelvic inflammatory disease (PID), ectopic pregnancy (EP), and tubal factor infertility (TFI) in women and detected changes in associations over time. Materials and Methods: This retrospective cohort study included 5,553,506 women aged 18-49 tested for gonorrhea in the IBM MarketScan claims administrative database from 2013-2018 in the United States. We estimated incidence rates and hazard ratios (HRs) of gonorrhea diagnosis for each outcome, adjusting for potential confounders using Cox proportional hazards models. We tested the interaction between gonorrhea diagnosis and the initial gonorrhea test year to identify changes in associations over time. Results: We identified 32,729 women with a gonorrhea diagnosis (mean follow-up time in years: PID = 1.73, EP = 1.75, TFI = 1.76). A total of 131,500 women were diagnosed with PID, 64,225 had EP, and 41,507 had TFI. Women with gonorrhea diagnoses had greater incidence per 1000 person-years for all outcomes (PID = 33.5, EP = 9.4, TFI = 5.3) compared to women without gonorrhea diagnoses (PID = 13.9, EP = 6.7, TFI = 4.3). After adjustment, HRs were higher in women with a gonorrhea diagnosis vs. those without [PID = 2.29 (95% confidence interval, CI: 2.15-2.44), EP = 1.57, (95% CI: 1.41-1.76), TFI = 1.70 (95% CI: 1.47-1.97)]. The interaction of gonorrhea diagnosis and test year was not significant, indicating no change in relationship by initial test year. Conclusion: The relationship between gonorrhea and reproductive outcomes has persisted, suggesting a higher disease burden.

Cardiovascular Autonomic Function and Incident Chronic Obstructive Pulmonary Disease Hospitalizations in Atherosclerosis Risk in Communities.

Rationale: The autonomic nervous system extensively innervates the lungs, but its role in chronic obstructive pulmonary disease (COPD) outcomes has not been well studied. Objective: We assessed relationships between cardiovascular autonomic nervous system measures (heart rate variability [HRV] and orthostatic hypotension [OH]) and incident COPD hospitalization in the multicenter ARIC (Atherosclerosis Risk In Communities) study. Methods: We used Cox proportional hazards regression models to estimate hazard ratios and 95% confidence intervals between baseline (1987-1989) autonomic function measures (HRV measures from 2-minute electrocardiograms and OH variables) and incident COPD hospitalizations through 2019. Adjusted analyses included demographic data, smoking status, lung function, comorbidities, and physical activity. We also performed analyses stratified by baseline airflow obstruction. Results: Of the 11,625 participants, (mean age, 53.8 yr), 56.5% were female and 26.3% identified as Black. Baseline mean percentage predicted forced expiratory volume in 1 second was 94 ± 17% (standard deviation), and 2,599 participants (22.4%) had airflow obstruction. During a median follow-up time of 26.9 years, there were 2,406 incident COPD hospitalizations. Higher HRV (i.e., better autonomic function) was associated with a lower risk of incident COPD hospitalization. Markers of worse autonomic function (OH and greater orthostatic changes in systolic and diastolic blood pressure) were associated with a higher risk of incident COPD hospitalization (hazard ratio for the presence of OH, 1.5; 95% confidence interval, 1.25-1.92). In stratified analyses, results were more robust in participants without airflow obstruction at baseline. Conclusions: In this large multicenter prospective community cohort, better cardiovascular autonomic function at baseline was associated with a lower risk of subsequent hospitalization for COPD, particularly among participants without evidence of lung disease at baseline.

Elevated FOXG1 in glioblastoma stem cells cooperates with Wnt/ß-catenin to induce exit from quiescence.

Glioblastoma (GBM) stem cells (GSCs) display phenotypic and molecular features reminiscent of normal neural stem cells and exhibit a spectrum of cell cycle states (dormant, quiescent, proliferative). However, mechanisms controlling the transition from quiescence to proliferation in both neural stem cells (NSCs) and GSCs are poorly understood. Elevated expression of the forebrain transcription factor FOXG1 is often observed in GBMs. Here, using small-molecule modulators and genetic perturbations, we identify a synergistic interaction between FOXG1 and Wnt/ß-catenin signaling. Increased FOXG1 enhances Wnt-driven transcriptional targets, enabling highly efficient cell cycle re-entry from quiescence; however, neither FOXG1 nor Wnt is essential in rapidly proliferating cells. We demonstrate that FOXG1 overexpression supports gliomagenesis in vivo and that additional ß-catenin induction drives accelerated tumor growth. These data indicate that elevated FOXG1 cooperates with Wnt signaling to support the transition from quiescence to proliferation in GSCs.

Sudden cardiac arrest during the COVID-19 pandemic: A two-year prospective evaluation in a North American community.

BACKGROUND: Early during the coronavirus disease 2019 (COVID-19) pandemic, higher sudden cardiac arrest (SCA) incidence and lower survival rates were reported. However, ongoing effects on SCA during the evolving pandemic have not been evaluated. OBJECTIVE: The purpose of this study was to assess the impact of COVID-19 on SCA during 2 years of the pandemic. METHODS: In a prospective study of Ventura County, California (2020 population 843,843; 44.1% Hispanic), we compared SCA incidence and outcomes during the first 2 years of the COVID-19 pandemic to the prior 4 years. RESULTS: Of 2222 out-of-hospital SCA cases identified, 907 occurred during the pandemic (March 2020 to February 2022) and 1315 occurred prepandemic (March 2016 to February 2020). Overall age-standardized annual SCA incidence increased from 39 per 100,000 (95% confidence [CI] 37-41) prepandemic to 54 per 100,000 (95% CI 50-57; P <.001) during the pandemic. Among Hispanics, incidence increased by 77%, from 38 per 100,000 (95% CI 34-43) to 68 per 100,000 (95% CI 60-76; P <.001). Among non-Hispanics, incidence increased by 26%, from 39 per 100,000 (95% CI 37-42; P <.001) to 50 per 100,000 (95% CI 46-54). SCA incidence rates closely tracked COVID-19 infection rates. During the pandemic, SCA survival was significantly reduced (15% to 10%; P <.001), and Hispanics were less likely than non-Hispanics to receive bystander cardiopulmonary resuscitation (45% vs 55%; P = .005) and to present with shockable rhythm (15% vs 24%; P = .003). CONCLUSION: Overall SCA rates remained consistently higher and survival outcomes consistently lower, with exaggerated effects during COVID infection peaks. This longer evaluation uncovered higher increases in SCA incidence among Hispanics, with worse resuscitation profiles. Potential ethnicity-specific barriers to acute SCA care warrant urgent evaluation and intervention.

Associations between MICA and MICB Genetic Variants, Protein Levels, and Colorectal Cancer: Atherosclerosis Risk in Communities (ARIC).

BACKGROUND: The MHC class I chain-related protein A (MICA) and protein B (MICB) participate in tumor immunosurveillance and may be important in colorectal cancer, but have not been examined in colorectal cancer development. METHODS: sMICA and sMICB blood levels were measured by SomaScan in Visit 2 (1990-92, baseline) and Visit 3 (1993-95) samples in cancer-free participants in the Atherosclerosis Risk in Communities Study. We selected rs1051792, rs1063635, rs2516448, rs3763288, rs1131896, rs2596542, and rs2395029 that were located in or in the vicinity of MICA or MICB and were associated with cancer or autoimmune diseases in published studies. SNPs were genotyped by the Affymetrix Genome-Wide Human SNP Array. We applied linear and Cox proportional hazards regressions to examine the associations of preselected SNPs with sMICA and sMICB levels and colorectal cancer risk (236 colorectal cancers, 8,609 participants) and of sMICA and sMICB levels with colorectal cancer risk (312 colorectal cancers, 10,834 participants). In genetic analyses, estimates adjusted for ancestry markers were meta-analyzed. RESULTS: Rs1051792-A, rs1063635-A, rs2516448-C, rs3763288-A, rs2596542-T, and rs2395029-G were significantly associated with decreased sMICA levels. Rs2395029-G, in the vicinity of MICA and MICB, was also associated with increased sMICB levels. Rs2596542-T was significantly associated with decreased colorectal cancer risk. Lower sMICA levels were associated with lower colorectal cancer risk in males (HR = 0.68; 95% confidence interval, 0.49-0.96) but not in females (Pinteraction = 0.08). CONCLUSIONS: Rs2596542-T associated with lower sMICA levels was associated with decreased colorectal cancer risk. Lower sMICA levels were associated with lower colorectal cancer risk in males. IMPACT: These findings support an importance of immunosurveillance in colorectal cancer.

Association of abnormal p-wave parameters with brain MRI morphology: The atherosclerosis risk in communities neurocognitive study (ARIC-NCS).

BACKGROUND: Recent evidence indicates that abnormal P-wave parameters (PWPs)-ECG markers of atrial myopathy-are associated with incident dementia, independent of atrial fibrillation (AF) and clinical ischemic stroke. However, the mechanisms remain unclear and may include subclinical vascular brain injury. Hence, we evaluated the association of abnormal PWPs with brain MRI correlates of vascular brain injury in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS). METHODS: ARIC-NCS participants who underwent 3T brain MRI scans in 2011-2013 were included. PWPs were measured from standard 12-lead ECGs. Brain MRI outcomes included cortical infarcts, lacunar infarcts, cerebral microhemorrhages, brain volumes, and white matter disease (WMD) volume. We used weighted multivariable logistic and linear regression to evaluate the associations of abnormal PWPs with brain MRI outcomes. RESULTS: Among 1715 participants (mean age, 76.1 years; 61% women; 29% Black), 797 (46%) had ≥1 abnormal PWP. After multivariable adjustment, including adjusting for prevalent AF, abnormal P-wave terminal force in lead V1 (aPTFV1) and prolonged P-wave duration (PPWD) were associated with increased odds of both cortical (OR 1.41; 95% CI, 1.14 to 1.74 and OR 1.30; 95% CI, 1.04 to 1.63, respectively) and lacunar infarcts (OR 1.36; 95% CI, 1.15 to 1.63 and OR 1.37; 95% CI, 1.15 to 1.65, respectively). Advanced interatrial block (aIAB) was associated with higher odds of subcortical microhemorrhage (OR 2.04; 95% CI, 1.36 to 3.06). Other than a significant association between aPTFV1 with lower parietal lobe volume, there were no other significant associations with brain or WMD volume. CONCLUSION: In this exploratory analysis of a US community-based cohort, ECG surrogates of atrial myopathy are associated with a higher prevalence of brain infarcts and microhemorrhage, suggesting subclinical vascular brain injury as a possible mechanism underlying the association of atrial myopathy with dementia.

Autoimmune disease and risk of postpartum venous thromboembolism.

Background: The risk of pregnancy-related mortality in the United States has nearly doubled since 1990, with venous thromboembolism (VTE) accounting for approximately 10% of these deaths. Objectives: The objective of this study was to assess whether preexisting autoimmune disease is a risk factor for postpartum VTE. Methods: Using the MarketScan Commercial and Medicare Supplemental administrative databases, a retrospective cohort study analyzed whether postpartum persons with autoimmune disease had a higher risk of postpartum VTE incidence than postpartum persons without autoimmune disease. Using International Classification of Diseases codes, we identified 757,303 individuals of childbearing age who had a valid delivery date with at least 12 weeks of follow-up. Results: Individuals were, on average, 30.7 years old (SD, 5.4), and 3.7% (N = 27,997 of 757,303) of them had evidence of preexisting autoimmune disease. In covariate-adjusted models, postpartum persons with preexisting autoimmune disease had higher rates of postpartum VTE than postpartum persons without autoimmune disease (hazard ratio [HR], 1.33; 95% CI, 1.07-1.64). When analyzed by individual autoimmune disease, those with systemic lupus erythematosus (HR, 2.49; 95% CI, 1.47-4.21) and Crohn's disease (HR, 2.49; 95% CI, 1.34-4.64) were at an elevated risk of postpartum VTE compared with those without autoimmune disease. Conclusion: Autoimmune disease was associated with a higher rate of postpartum VTE, with evidence that the association was most pronounced among individuals with systemic lupus erythematosus and Crohn's disease. These findings suggest that postpartum persons of childbearing age with autoimmune disease may require more monitoring and prophylactic care after delivery to prevent potentially fatal VTE events.

Sudden Cardiac Arrest During Sports Activity in Older Adults.

BACKGROUND: Sports activity among older adults is rising, but there is a lack of community-based data on sports-related sudden cardiac arrest (SrSCA) in the elderly. OBJECTIVES: In this study, the authors investigated the prevalence and characteristics of SrSCA among subjects ≥65 years of age in a large U.S. METHODS: All out-of-hospital sudden cardiac arrests (SCAs) were prospectively ascertained in the Portland, Oregon, USA, metro area (2002-2017), and Ventura County, California, USA (2015-2021) (catchment population ∼1.85 million). Detailed information was obtained for SCA warning symptoms, circumstances, and lifetime clinical history. Subjects with SCA during or within 1 hour of cessation of sports activity were categorized as SrSCA. RESULTS: Of 4,078 SCAs among subjects ≥65 years of age, 77 were SrSCA (1.9%; 91% men). The crude annual SrSCA incidence among age ≥65 years was 3.29/100,000 in Portland and 2.10/100,000 in Ventura. The most common associated activities were cycling, gym activity, and running. SrSCA cases had lower burden of cardiovascular risk factors (P = 0.03) as well as comorbidities (P < 0.005) compared with non-SrSCA. Based on conservative estimates of community residents ≥65 years of age who participate in sports activity, the SrSCA incidence was 28.9/100,000 sport participation years and 18.4/100,000 sport participation years in Portland and Ventura, respectively. Crude survival to hospital discharge rate was higher in SrSCA, but the difference was nonsignificant after adjustment for confounding factors. CONCLUSIONS: Among free-living community residents age ≥65 years, SrSCA is uncommon, predominantly occurs in men, and is associated with lower disease burden than non-SrSCA. These results suggest that the risk of SrSCA is low, and probably outweighed by the high benefit of exercise.