Background: Numerous studies have shown inverse associations between serum magnesium (Mg) levels and risk of cardiovascular disease (CVD), but studies of dietary Mg have not been consistent. Aim: T...

Background: Nocturnal hypoxemia may better capture disease burden than obstructive sleep apnea (OSA). Using a subset of participants from the Atherosclerosis Risk in Communities (ARIC) study who pa...

Introduction: Oral anticoagulants (OAC) are a standard and highly efficacious treatment for venous thromboembolism (VTE), with newer direct oral anticoagulants (DOACs; rivaroxaban and apixaban) equ...

Introduction: Psychosocial factors (social isolation, social support, trait anger, and depressive symptoms) are associated with cardiovascular disease risk factors and incidence; few studies invest...

Introduction: Diabetes has been tied to infection risk in mechanistic studies. However, the relationship between diabetes and infection hasn't been well documented in epidemiologic studies, especia...

Introduction: Hypertension in midlife, but not late life, is a robust predictor of subsequent dementia. However, the fraction of dementia attributable to hypertension might vary depending on the ag...

Introduction: Diabetes is associated with both dementia and death. Ignoring the competing risk of mortality may result in overestimation of the lifetime of dementia. Hypothesis: The lifetime cumula...

Background: Atrial fibrillation (AF) is a significant risk factor for stroke, with oral anticoagulants (OACs) recommended for stroke prevention. However, a nonpharmacologic option is needed for pat...

Introduction: Medication non-adherence increases the risk of hospitalization and mortality in older adults. Evidence from previous studies was not conclusive due to small sample size or lack of adj...

Background: Recent evidence indicates that abnormal P-wave parameters (PWPs)-ECG markers of

Background: Hypertension (HTN) while asleep is strongly associated with cardiovascular disease (CVD) and death. Whether HTN while supine in clinic is a risk factor for CVD independent of seated BP ...

Rationale: The autonomic nervous system extensively innervates the lungs but its role in COPD outcomes has not been well-studied. Objective: We assessed relationships between cardiovascular autonom...

Personal health literacy (PHL) has recently been defined by the US Department of Health and Human Services in Healthy People 2030 as “the degree in which individuals have the ability to find, under...

<p>Habitual physical activity (PA) impacts the plasma proteome and reduces the risk of developing type 2 diabetes (T2D). Using a large-scale proteome-wide approach in Atherosclerosis Risk in Communities Study participants, we aimed to identify plasma proteins associated with PA and determine which of these may be causally related to lower T2D risk. PA was associated with 92 plasma proteins in discovery (p&amp;lt;1.01x10−5), and 40 remained significant in replication (p&amp;lt;5.43x10−4). Eighteen of these proteins were independently associated with incident T2D (p&amp;lt;1.25x10−3) including neuronal growth regulator 1 (NeGR1) (HR per SD: 0.85; p-value=7.5x10−11). Two-sample Mendelian randomization inverse variance weighted analysis indicated that higher NeGR1 reduces T2D risk (OR per SD: 0.92; p=0.03) and was consistent with MR-Egger, weighted median, and weighted mode sensitivity analyses. A stronger association was observed for the single cis-acting NeGR1 genetic variant (OR per SD: 0.80; p=6.3x10−5). Coupled with previous evidence that low circulating NeGR1 levels promote adiposity, its association with PA and potential causal role in T2D shown here suggest that NeGR1 may link PA exposure with metabolic outcomes. Further research is warranted to confirm our findings and examine the interplay of PA, NeGR1, adiposity, and metabolic health.</p>

<h3>Importance</h3><p>Factors associated with the risk of dementia remain to be fully understood. Systemic infections are hypothesized to be such factors and may be targets for prevention and screening.</p><h3>Objective</h3><p>To investigate the association between hospitalization with infection and incident dementia.</p><h3>Design, Setting, and Participants</h3><p>Data from the community-based Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study, were used. Enrollment occurred at 4 research centers in the US, initiated in 1987 to 1989. The present study includes data up to 2019, for 32 years of follow-up. Data analysis was performed from April 2021 to June 2022.</p><h3>Exposures</h3><p>Hospitalizations with infections were identified via medical record review for selected<i>International Classification of Diseases, Ninth Revision</i>(<i>ICD-9</i>) and<i>International Statistical Classification of Diseases and Related Health Problems, Tenth Revision</i>(<i>ICD-10</i>) codes, from baseline until administrative censoring or dementia diagnosis. Participants were considered unexposed until first hospitalization with infection and exposed thereafter. Selected infection subtypes were also considered.</p><h3>Main Outcomes and Measures</h3><p>Incident dementia and time-to-event data were identified through surveillance of<i>ICD-9 </i>and<i>ICD-10</i>hospitalization and death certificate codes, in-person assessments, and telephone interviews. A sensitivity analysis was conducted excluding cases occurring within 3 years or beyond 20 years from exposure. Data were collected before study hypothesis formulation.</p><h3>Results</h3><p>Of the 15 792 ARIC study participants, an analytical cohort of 15 688 participants who were dementia free at baseline and of Black or White race were selected (8658 female [55.2%]; 4210 Black [26.8%]; mean [SD] baseline age, 54.7 [5.8] years). Hospitalization with infection occurred among 5999 participants (38.2%). Dementia was ascertained in 2975 participants (19.0%), at a median (IQR) of 25.1 (22.2-29.1) years after baseline. Dementia rates were 23.6 events per 1000 person-years (95% CI, 22.3-25.0 events per 1000 person-years) among the exposed and 5.7 events per 1000 person-years (95% CI, 5.4-6.0 events per 1000 person-years) among the unexposed. Patients hospitalized with infection were 2.02 (95% CI, 1.88-2.18;<i>P</i> &lt; .001) and 1.70 (95% CI, 1.55-1.86;<i>P</i> &lt; .001) times more likely to experience incident dementia according to unadjusted and fully adjusted Cox proportional hazards models compared with individuals who were unexposed. When excluding individuals who developed dementia less than 3 years or more than 20 years from baseline or the infection event, the adjusted hazard ratio was 5.77 (95% CI, 4.92-6.76;<i>P</i> &lt; .001). Rates of dementia were significantly higher among those hospitalized with respiratory, urinary tract, skin, blood and circulatory system, or hospital acquired infections. Multiplicative and additive interactions were observed by age and<i>APOE-ε</i>genotype.</p><h3>Conclusions and Relevance</h3><p>Higher rates of dementia were observed among participants who experienced hospitalization with infection. These findings support the hypothesis that infections are factors associated with higher risk of dementias.</p>

Cancer survivors may have elevated atherosclerotic cardiovascular disease (ASCVD) risk. Therefore, we tested how accurately the American College of Cardiology/American Heart Association 2013 pooled cohort equations (PCEs) predict 10-year ASCVD risk in cancer survivors. To estimate the calibration and discrimination of&nbsp;the PCEs in cancer survivors compared to non-cancer participants in the Atherosclerosis Risk in Communities (ARIC) study. We evaluated the PCEs’ performance among 1244 cancer survivors and 3849 cancer-free participants who were free of ASCVD at the start of follow-up. Each cancer survivor was incidence-density matched with up to five controls by age, race, sex, and study center. Follow-up began at the first study visit at least 1&nbsp;year after the diagnosis date of the cancer survivor and finished at the ASCVD event, death, or end of follow-up. Calibration and discrimination were assessed and compared between cancer survivors and cancer-free participants. Cancer survivors had higher PCE-predicted risk, at 26.1%, compared with 23.1% for cancer-free participants. There were 110 ASCVD events in cancer survivors and 332 ASCVD events in cancer-free participants. The PCEs overestimated ASCVD risk in cancer survivors and cancer-free participants by 45.6% and 47.4%, respectively, with poor discrimination in both groups (C-statistic for cancer survivors = 0.623; for cancer-free participants, C = 0.671). The PCEs overestimated ASCVD risk in all participants. The performance of the PCEs was similar in cancer survivors and cancer-free participants. Our findings suggest that ASCVD risk prediction tools tailored to survivors of adult cancers may not be needed.

<p> Aging adults experience increased health vulnerability and compromised abilities to cope with stressors, which are the clinical manifestations of frailty. Frailty is complex, and efforts to identify biomarkers to detect frailty and pre‐frailty in the clinical setting are rarely reproduced across cohorts. We developed a predictive model incorporating biological and clinical frailty measures to identify robust biomarkers across data sets. Data were from two large cohorts of older adults: “ <italic>Invecchiare in Chianti</italic> (Aging in Chianti, InCHIANTI Study”) ( <italic>n</italic>  = 1453) from two small towns in Tuscany, Italy, and replicated in the Atherosclerosis Risk in Communities Study (ARIC) ( <italic>n</italic>  = 6508) from four U.S. communities. A complex systems approach to biomarker selection with a tree‐boosting machine learning (ML) technique for supervised learning analysis was used to examine biomarker population differences across both datasets. Our approach compared predictors with robust, pre‐frail, and frail participants and examined the ability to detect frailty status by race. Unique biomarker features identified in the InCHIANTI study allowed us to predict frailty with a model accuracy of 0.72 (95% confidence interval (CI) 0.66–0.80). Replication models in ARIC maintained a model accuracy of 0.64 (95% CI 0.66–0.72). Frail and pre‐frail Black participant models maintained a lower model accuracy. The predictive panel of biomarkers identified in this study may improve the ability to detect frailty as a complex aging syndrome in the clinical setting. We propose several concrete next steps to keep research moving toward detecting frailty with biomarker‐based detection methods. </p>

Diabetes Care 2023;46(4):1-9 | https://doi.org/10.2337/dc22-1830 ARTICLE HIGHLIGHTS • Plasma protein signatures preceding diabetes can improve our understanding of diabetes pathogenesis. • The aims of this study were to discover and validate (internally and externally) associations for nearly 5,000 ap-tamer measurements of the plasma proteome in midlife with incident diabetes. We also conducted a pathway analysis and examined causality using genetic instruments. • We identified 47 plasma proteins predictive of incident diabetes, established causal effects for 3 proteins (SHBG, ATP1B2, and GSTA1), and identified diabetes-associated inflammation and lipid pathways with potential implications for diagnosis and therapy.

<p>Background: Reduced kidney function is related to brain atrophy and higher risk of dementia. It is not known whether kidney impairment is associated with higher levels of circulating amyloid-β and brain amyloid-β deposition, which could contribute to elevated risk of dementia. Objective: To investigate whether kidney impairment is associated with higher levels of circulating amyloid-β and brain amyloid-β deposition. Methods: This cross-sectional study was performed within the community–based Atherosclerosis Risk in Communities (ARIC) Study cohort. We used estimated glomerular filtration rate (eGFR) based on serum creatinine and cystatin C levels and urine albumin-to-creatinine ratio (ACR) to assess kidney function. Amyloid positivity was defined as a standardized uptake value ratios &gt;  1.2 measured with florbetapir positron emission tomography (PET) (n = 340). Plasma amyloid-β 1 - 40 and amyloid-β 1 - 42 were measured using a fluorimetric bead-based immunoassay (n = 2,569). Results: Independent of demographic and cardiovascular risk factors, a doubling of ACR was associated with 1.10 (95% CI: 1.01,1.20) higher odds of brain amyloid positivity, but not eGFR (odds ratio per 15 ml/min/1.73 m2 lower eGFR: 1.08; 95% CI: 0.95,1.23). A doubling of ACR was associated with a higher level of plasma amyloid-β 1 - 40 (standardized difference: 0.12; 95% CI: 0.09,0.14) and higher plasma amyloid-β 1 - 42 (0.08; 95% CI: 0.05,0.10). Lower eGFR was associated with higher plasma amyloid-β 1 - 40 (0.36; 95% CI: 0.33,0.39) and higher amyloid-β 1 - 42 (0.32; 95% CI: 0.29,0.35). Conclusion: Low clearance of amyloid-β and elevated brain amyloid positivity may link impaired kidney function with elevated risk of dementia. kidney function should be considered in interpreting amyloid biomarker results in clinical and research setting.</p>