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Retinopathy and albuminuria are associated with hip fracture risk. We investigated whether these disorders and endothelial dysfunction (which underlies microvascular diseases) were associated with low trabecular bone density. No significant associations were found, suggesting that microvascular diseases are not related to fracture risk through low trabecular bone density. PURPOSE: Microvascular diseases of the eye, kidney, and brain are associated with endothelial dysfunction and increased hip fracture risk. To explore the basis for higher hip fracture risk, we comprehensively examined whether markers of microvascular disease and/or endothelial dysfunction are related to trabecular bone mineral density (BMD), a proximate risk factor for osteoporotic fractures. METHODS: Among 6814 participants in the Multi-Ethnic Study of Atherosclerosis study (MESA), we derived thoracic vertebral trabecular BMD from computed tomography of the chest and measured urine albumin to creatinine ratios (UACR), retinal arteriolar and venular widths, flow mediated dilation (FMD) of the brachial artery after 5 min of ischemia; and levels of five soluble endothelial adhesion markers (ICAM-1, VCAM-1, L-selectin, P-selectin, and E-selectin). Linear regression models were used to examine the association of trabecular BMD with markers of microvascular disease and with markers of endothelial dysfunction. RESULTS: We observed no significant associations of UACR, retinal arteriolar or venular widths, or FMD with BMD. We also observed no statistically significant association of spine trabecular BMD with levels of endothelial adhesion markers. Men and women had largely similar results. CONCLUSION: We conclude that there is little evidence to connect thoracic spine trabecular BMD to microvascular disorders or to endothelial dysfunction among multi-ethnic middle-aged and older adults. Other factors beyond trabecular BMD (e.g., bone quality or predisposition to falling) may be responsible for the associations of microvascular disease with osteoporotic fractures.
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Background: There is a yet unmet opportunity to utilize data on taxes and individual behaviors to yield insight for analyzing studies involving alcohol and cigarette use.Objectives: To inform the direction and strength of their mutual associations by leveraging the fact that taxation can affect individual consumption, but individual consumption cannot affect taxation.Methods: We linked state-level data on cigarette and beer taxes in 2009-2020 with individual-level data on self-reported current cigarette and alcohol use from the Behavioral Risk Factor Surveillance System, a telephone survey by the Centers for Disease Control and Prevention that is representative of the population of each state in the United States. We constructed linear and logistic models to examine associations between a $1 increase in cigarette taxes per pack and a $1 increase in beer taxes per gallon and self-reported cigarette use and alcohol consumption (assessed as any current intake, average drinks/day, heavy drinking, and binge drinking), adjusting for survey year and individual characteristics.Results: Among 2,968,839,352 respondents (49% male), a $1 increase in beer taxes was associated with .003 (95% confidence interval [CI] -.013, .008) fewer drinks/day and lower odds of any drinking (odds ratio [OR] = .81 95%CI .80, .83), heavy drinking (OR = .96 95%CI .93, .99), binge drinking (OR = .82 95%CI .80, .83), and smoking (OR = .98 95%CI .96, 1.00). In contrast, a $1 increase in cigarette taxes was associated with lower odds of smoking (OR = .94 95%CI .94, .95) but .007 (95%CI .005, .010) more drinks/day, and higher odds of any drinking (OR = 1.10 95%CI 1.10, 1.11), heavy drinking (OR = 1.02 95%CI 1.01, 1.02), and binge drinking (OR = .82 95%CI .80, .83).Conclusion: Higher beer taxes were associated with lower odds of drinking and smoking, but higher cigarette taxes were associated with lower odds of smoking and higher alcohol consumption. These results suggest that alcohol intake may be a determinant of cigarette use rather than cigarette use as a determinant of alcohol intake.
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Consumo de Bebidas Alcoólicas , Cerveja , Sistema de Vigilância de Fator de Risco Comportamental , Impostos , Produtos do Tabaco , Humanos , Impostos/economia , Masculino , Feminino , Cerveja/economia , Consumo de Bebidas Alcoólicas/economia , Consumo de Bebidas Alcoólicas/epidemiologia , Adulto , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Produtos do Tabaco/economia , Adulto Jovem , Fumar Cigarros/economia , Fumar Cigarros/epidemiologia , Adolescente , Idoso , Fumar/economia , Fumar/epidemiologiaRESUMO
BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer death in US adults but can be reduced by screening. The roles of individual and contextual factors, and especially physician supply, in attaining universal CRC screening remains uncertain. METHODS: We used data from adults 50-75 years old participating in the 2018 New York (NY) Behavioural Risk Factor Surveillance System linked to county-level covariates, including primary care physician (PCP) density and gastroenterologist (GI) density. Data were analysed in 2023-2024. Our analyses included (1) ecological and geospatial analyses of county-level CRC screening prevalence and (2) individual-level Poisson regression models of receipt of screening, adjusted for socioeconomic and county-level contextual variables. RESULTS: Mean prevalence of up-to-date CRC screening was 71% (95% CI 70% to 73%) across NY's 62 counties. County-level CRC screening demonstrated significant spatial patterning (Global Moran's I=0.14, p=0.04), consistent with the existence of county-level contextual factors. In both county-level and individual-level analyses, lack of health insurance was associated with lower likelihood of up-to-date screening (ß=-1.09 (95% CI -2.00 to -0.19); adjusted prevalence ratio 0.68 (95% CI 0.60 to 0.77)), even accounting for age, race/ethnicity and education. In contrast, county-level densities of both PCPs and GIs were completely unassociated with screening at either the county or individual level. As expected, other determinants at the individual level included education status and age. CONCLUSION: In this state-wide representative analysis, physician density was completely unassociated with CRC screening, although health insurance status remains strongly related. In similar screening environments, broadened insurance coverage for CRC screening is likely to improve screening far more effectively than increased physician supply.
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Neoplasias Colorretais , Detecção Precoce de Câncer , Humanos , Neoplasias Colorretais/diagnóstico , Pessoa de Meia-Idade , Idoso , Detecção Precoce de Câncer/estatística & dados numéricos , Masculino , Feminino , New York , Sistema de Vigilância de Fator de Risco Comportamental , Análise Espacial , Fatores Socioeconômicos , Médicos de Atenção PrimáriaRESUMO
Hypertension guidelines recommend team-based care for the treatment of high blood pressure (BP). Clinical pharmacists can help patients get to goal BP with rapid medication titration in conjunction with telehealth visits. We conducted a pharmacist-led home BP monitoring pilot program from June 2020 to September 2021. Forty-two patients with a SBP ≥140 despite using ≤2 antihypertensive medications were referred for pharmacist telehealth with expedited medication titration to achieve a BP goal <130/80. The mean enrollment SBP/DBP was 155.2 (SD, 15.8)/89.7 (SD, 11.5) mm Hg, and the mean completion SBP/DBP was 132.1 (SD, 10.9)/77.6 (SD, 10). The number of hypertension medications prescribed increased from 1.3 to 1.6 with no instances of falls or hypotension. At completion, 31% of patients had an automated office blood pressure (AOBP) with SBP <130 mm Hg and DBP <80 mm Hg. A pharmacist-led, home BP monitoring telehealth pilot program helped patients safely achieve BP goals.
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Hipertensão , Telemedicina , Humanos , Hipertensão/tratamento farmacológico , Farmacêuticos , Melhoria de Qualidade , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/fisiologiaRESUMO
Importance: The consequences of low levels of environmental lead exposure, as found commonly in US household water, have not been established. Objective: To examine whether commonly encountered levels of lead in household water are associated with hematologic toxicity among individuals with advanced kidney disease, a group known to have disproportionate susceptibility to environmental toxicants. Design, Setting, and Participants: Cross-sectional analysis of household water lead concentrations and hematologic outcomes was performed among patients beginning dialysis at a Fresenius Medical Care outpatient facility between January 1, 2017, and December 20, 2021. Data analysis was performed from April 1 to August 15, 2023. Exposure: Concentrations of lead in household water were examined in categorical proportions of the Environmental Protection Agency's allowable threshold (15 µg/L) and continuously. Main Outcomes and Measures: Hematologic toxic effects were defined by monthly erythropoiesis-stimulating agent (ESA) dosing during the first 90 days of incident kidney failure care and examined as 3 primary outcomes: a proportion receiving maximum or higher dosing, continuously, and by a resistance index that normalized to body weight and hemoglobin concentrations. Secondarily, hemoglobin concentrations for patients with data prior to kidney failure onset were examined, overall and among those with concurrent iron deficiency, thought to increase gastrointestinal absorption of ingested lead. Results: Among 6404 patients with incident kidney failure (male, 4182 [65%]; mean [SD] age, 57 [14] years) followed up for the first 90 days of dialysis therapy, 12% (n = 742) had measurable lead in household drinking water. A higher category of household lead contamination was associated with 15% (odds ratio [OR], 1.15 [95% CI, 1.04-1.27]) higher risk of maximum monthly ESA dosing, 4.5 (95% CI, 0.8-8.2) µg higher monthly ESA dose, and a 0.48% (95% CI, 0.002%-0.96%) higher monthly resistance index. Among patients with pre-kidney failure hemoglobin measures (n = 2648), a higher household lead categorization was associated with a 0.12 (95% CI, -0.23 to -0.002) g/dL lower hemoglobin concentration, particularly among those with concurrent iron deficiency (multiplicative interaction, P = .07), among whom hemoglobin concentrations were 0.25 (95% CI, -0.47 to -0.04) g/dL lower. Conclusion: The findings of this study suggest that levels of lead found commonly in US drinking water may be associated with lead poisoning among susceptible individuals.
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Chumbo , Insuficiência Renal Crônica , Humanos , Masculino , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Chumbo/sangue , Insuficiência Renal Crônica/epidemiologia , Idoso , Exposição Ambiental/efeitos adversos , Hematínicos/administração & dosagem , Hematínicos/efeitos adversos , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/efeitos adversos , Diálise RenalRESUMO
RATIONALE: Cannabis use is rapidly growing in the United States, but its health implications are poorly understood, particularly when compared with cigarette smoking. Previous research conducted on animal models or non-representative populations with small sample sizes has yielded mixed results on the impact of marijuana use on hemoglobin levels, which may reflect subclinical hypoxemia and/or carbon monoxide exposure. OBJECTIVES: We evaluated the association between marijuana use and hemoglobin levels in a nationally representative sample of U.S. adults. METHODS: This cross-sectional study included 16,038 individuals aged 18 to 59 years enrolled in the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2018. We related current and former marijuana use with measured hemoglobin levels, with adjustment for demographics, education, housing, and cigarette smoking status in multivariable analyses that incorporated complex survey weights. As candidate positive and negative control exposures, we used similar methods to relate cigarette smoking and benzodiazepine use, respectively, with hemoglobin concentrations. RESULTS: Current marijuana use was associated with significantly higher hemoglobin concentrations. After multivariable adjustment, compared with never use, current marijuana use was associated with a 0.111, 95% CI [0.021,0.201] g/dL higher hemoglobin concentration, whereas former use was associated with a 0.047, 95% CI [-0.018,0.113] g/dL higher concentration (linear trend p=0.01). As hypothesized, cigarette smoking was also associated with higher hemoglobin concentrations, while benzodiazepine use was not. CONCLUSIONS: Among American adults, current marijuana use was associated with higher hemoglobin concentrations, as is cigarette smoking but not benzodiazepine use. These results suggest the possibility that marijuana smoking induces subclinical hypoxemia stimulating hemoglobin production. Further confirmation of this observational finding is needed, in light of the increasing medical and recreational use of smoked marijuana products.
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Introduction: Substantial barriers to screening exist for medically underserved populations, especially adults with limited English proficiency (LEP). We examined the proportion of US adults aged 45-75 up-to-date with colorectal cancer (CRC) screening by LEP after 2018. The American Cancer Society began recommending CRC screening for adults 45-49 in 2018. Methods: We analyzed cross-sectional data of adults 45-75 years old participating in the 2019 or 2021 National Health Interview Survey (N = 25,611). Adults were considered up-to-date with screening if they reported any stool test within 1 year, stool-DNA testing within 3 years, or colonoscopy within 10 years. Adults who interviewed in a language other than English were considered to have LEP. Adults not up-to-date with screening were asked if a healthcare professional (HCP) recommended screening, and if so which test(s). Regression models conducted in 2022-2023 evaluated receipt of screening, adjusting for sociodemographics, year, and healthcare access. Results: Overall, 54.0 % (95 % CI 53.1-54.9 %) of participants were up-to-date with screening (9.4 % aged 45-49 vs 75.5 % aged 65-75); prevalence increased from 2019 (52.9 %) to 2021(55.2 %). Adults with LEP (vs English proficiency) were less likely to be up-to-date with screening (31.6 % vs. 56.8 %, [aPR 0.86 (0.77-0.96)]). Among adults not up-to-date, 15.0 % reported their HCP recommended screening (8.4 % among adults with LEP). Conclusions: Nearly half of US adults were not up-to-date with CRC screening in 2019 and 2021 and few reported being recommended screening. Adults with LEP and those 45-49 were least likely to be screened suggesting targeted interventions are needed for these populations.
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BACKGROUND AND OBJECTIVE: Preliminary evidence suggests a possible preventive effect of tumor necrosis factor-α inhibitors (TNFi) on incident dementia. The objective of the analysis was to investigate the association between TNFi and the risk of incident dementia in a population undergoing treatment for rheumatological disorders. METHODS: We followed patients aged ≥ 65 years with dementia and rheumatological conditions in two cohort studies, DANBIO (N = 21,538), a Danish clinical database, and AOK PLUS (N = 7112), a German health insurance database. We defined incident dementia using diagnostic codes and/or medication use and used Cox regression to compare the associations of TNFi with other rheumatological therapies on the risk of dementia. To ensure that the patients were receiving long-term medication, we included patients with rheumatic diseases and systemic therapies. RESULTS: We observed similar trends towards a lower risk of dementia associated with TNFi versus other anti-inflammatory agents in both cohorts (hazard ratios were 0.92 [95% confidence interval 0.76, 1.10] in DANBIO and 0.89 [95% confidence interval 0.63, 1.24] in AOK PLUS, respectively). CONCLUSIONS: Tumor necrosis factor-α inhibitors may decrease the risk of incident dementia although the association did not reach statistical significance in this analysis. Further research, ideally with randomization, is needed to gauge the potential of repurposing TNFi for dementia prevention and/or treatment.
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Demência , Fator de Necrose Tumoral alfa , Humanos , Demência/epidemiologia , Demência/induzido quimicamente , Idoso , Masculino , Feminino , Estudos de Coortes , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Idoso de 80 Anos ou mais , Incidência , Doenças Reumáticas/tratamento farmacológico , Dinamarca/epidemiologiaRESUMO
BACKGROUND: Age at menarche, reproductive lifespan, and age at menopause are associated with several cardiovascular diseases, but their relationship with atrial fibrillation (AF) is uncertain. METHODS: We linked information on all women who participated in the third survey of the population-based, longitudinal HUNT study in Norway with medical records from all local hospitals. A total of 14,632 women aged 60 or more were followed for validated incident AF. We retrieved age at menarche and age at menopause from the HUNT questionnaires. Reproductive lifespan was defined as the difference between age at menarche and age at menopause. We used Cox proportional hazards regression models to assess associations between AF and age at menarche, reproductive lifespan, and age at menopause. RESULTS: During a median follow-up of 8.17 years (136,494 person-years), 1217 (8.3 %) participants developed AF. In multivariable-adjusted analyses, we observed no associations between early or late age at menarche and AF (hazard ratios (HRs): <12 years: 0.85 [95 % confidence interval (CI), 0.65-1.12]; ≥16 years: 0.99 [95 % CI, 0.80-1.24] compared to those who attained menarche at 13-14 years). The HR for a reproductive lifespan shorter than 30 years was 0.91 [95 % CI, 0.72-1.15] compared to 34-37 years. Likewise, there was no clear association between premature or early age at menopause and AF (HRs: <40 years: 1.21 [95 % CI, 0.83-1.75]; 40-44 years: 0.97 [95 % CI, 0.77-1.22] compared to 50-54 years). CONCLUSIONS: In this population of women aged 60 years and over, the risk of AF was not associated with age at menarche, reproductive lifespan, or age at menopause.
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Fibrilação Atrial , Menarca , Menopausa , Modelos de Riscos Proporcionais , Humanos , Menarca/fisiologia , Feminino , Menopausa/fisiologia , Pessoa de Meia-Idade , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/etiologia , Fatores Etários , Idoso , Noruega/epidemiologia , Fatores de Risco , Estudos Longitudinais , Reprodução/fisiologia , Inquéritos e Questionários , AdolescenteRESUMO
AIMS: Although parity, infertility, and age at first birth are important for later development of cardiovascular disease, research on their association with atrial fibrillation (AF) is limited. METHODS: We linked data from the population-based HUNT study, the Medical Birth Registry of Norway (MBRN) and validated medical records from local hospitals. A total of 24,015 women aged 45 years or older were followed for verified incident AF. Parity and age at first birth were retrieved from the MBRN or from self-reported questionnaires in the HUNT. History of infertility was self-reported on the HUNT questionnaire. Cox-proportional hazard models were used to calculate hazard ratios (HR) for the multivariable-adjusted associations of parity, infertility, and age at first birth with risk of AF. RESULTS: During a median follow-up of 12.8 years, 1,448 (6.0%) participants developed AF. Women with higher parity (four or more births vs. two births) were at 21% higher risk of AF (HR 1.21, 95% confidence interval (CI), 1.05-1.39). History of infertility was also associated with risk of AF (HR 1.20, 95% CI, 1.02-1.42). Among parous women, younger age at first birth (<20 years vs. 20-29 years) was associated with a 20% higher risk of AF (HR 1.20, 95% CI, 1.03-1.40). CONCLUSION: Women with four or more births, or a history of infertility, or younger age at first birth have approximately a 20% higher risk of AF among women over 45 years old.
A higher number of births and younger age at first birth are associated with a higher risk of cardiovascular disease (CVD). However, there is limited evidence on the associations between parity, age at first birth and atrial fibrillation (AF). Moreover, the association between infertility and AF remains largely unexplored. We have investigated the association between parity, infertility, age at first birth and AF in the population-based cohort from Norway (the HUNT study) among women over 45 years old. Our findings reveal that women with four or more births, or a history of infertility, or younger age at first birth have approximately a 20% higher risk of AF.
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BACKGROUND: Self-measured blood pressure (SMBP) monitoring is increasingly used for remote hypertension management, but the real-world performance of home blood pressure (BP) devices is unknown. We examined BP measurements from patients' home devices using the American Medical Association's (AMA) SMBP Device Accuracy Test tool. METHODS: Patients at a single internal medicine clinic underwent up to five seated, same-arm BP readings using a home device and an automated BP device (Omron HEM-907XL). Following the AMA's three-step protocol, we used the patient's home device for the first, second, and fourth measurements and the office device for the third and fifth (if needed) measurements. Device agreement failure was defined as an absolute difference in systolic BP >10 mm Hg between the home and office devices in either of two confirmatory steps. Performance was examined by brand (Omron vs. non-Omron). Moreover, we examined patient factors associated with agreement failure via logistic regression models adjusted for demographic characteristics. RESULTS: We evaluated 152 patients (mean age 60â ±â 15 years, 58% women, 31% Black) seen between October 2020 and November 2021. Device agreement failure occurred in 22.4% (95% CI: 16.4%, 29.7%) of devices tested, including 19.1% among Omron devices and 27.6% among non-Omron devices (Pâ =â 0.23). No patient characteristics were associated with agreement failure. CONCLUSIONS: Over one-fifth of home devices did not agree based on the AMA SMBP device accuracy protocol. These findings confirm the importance of office-based device comparisons to ensure the accuracy of home BP monitoring.
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Determinação da Pressão Arterial , Hipertensão , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , Pressão Sanguínea/fisiologia , Determinação da Pressão Arterial/métodos , Reprodutibilidade dos Testes , Esfigmomanômetros , Hipertensão/diagnóstico , Monitorização Ambulatorial da Pressão Arterial/métodosRESUMO
INTRODUCTION: Markers of hemostasis such as procoagulant factors and peak thrombin generation are associated with cardiovascular outcomes, but their associations with dementia risk are unclear. We aimed to evaluate prospective associations of selected procoagulant factors and peak thrombin generation with dementia risk. METHODS: We measured levels of 7 hemostatic factors (fibrinogen, factor VII coagulant activity [FVIIc], activated factor VII [FVIIa], factor VIIa-antithrombin [FVIIa-AT], factor XI antigen [FXI], peak thrombin generation, and platelet count) among participants in the Cardiovascular Health Study, a cohort of older adults free of dementia in 1992/1993 (n = 3185). Dementia was adjudicated and classified by DSM-IV criteria through 1998/1999. Cox proportional hazards models estimated hazard ratios (HRs) for any dementia associated with 1-standard deviation (SD) differences, adjusting for sociodemographic and clinical factors and APOE genotype. Secondary analyses separately evaluated the risk of vascular dementia, Alzheimer's disease, and mixed dementia. RESULTS: At baseline, participants had a median age of 73 years. Over 5.4 years of follow-up, we identified 448 dementia cases. There was no evidence of linear associations between levels of these hemostatic factors with any dementia risk (HRs per 1-SD difference ranged from 1.0 to 1.1; 95 % confidence intervals included 1.0). Results of secondary analyses by dementia subtype were similar. CONCLUSIONS: In this prospective study, there was no strong evidence of linear associations between levels of fibrinogen, FVIIc, FVIIa, FVIIa-AT, FXI, peak thrombin generation, or platelet count with dementia risk. Despite their associations with cardiovascular disease, higher levels of these biomarkers measured among older adults may not reflect dementia risk.
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Demência , Hemostáticos , Humanos , Idoso , Trombina , Estudos Prospectivos , Fator VIIa , Antitrombinas , Anticoagulantes , Antitrombina III , Fibrinogênio/análiseRESUMO
BACKGROUND: Gait impairment leads to increased mobility decline and may have neurological contributions. This study explores how neurological biomarkers are related to gait in older adults. METHODS: We studied participants in the Cardiovascular Health Study, a population-based cohort of older Americans, who underwent a serum biomarker assessment from samples collected in 1996-1997 for neurofilament light chain (NfL), glial fibrillary acidic protein, ubiquitin carboxy-terminal hydrolase L1, and total tau (nâ =â 1 959, mean ageâ =â 78.0 years, 60.8% female). In a subsample (nâ =â 380), cross-sectional associations with quantitative gait measures were explored. This subsample was assessed on a mat for gait speed, step length, double support time, step time, step length variability, and step time variability. Gait speed was also measured over a 15-ft walkway annually from 1996-1997 to 1998-1999 for longitudinal analyses. Linear regression models assessed cross-sectional associations of biomarkers with gait measures, whereas mixed effects models assessed longitudinal gait speed change from baseline to 1998-1999. RESULTS: Neurofilament light chain was significantly associated with annual gait speed decline (standardized ßâ =â -0.64 m/s, 95% CI: [-1.23, -0.06]) after adjustment for demographic and health factors. Among gait mat-assessed phenotypes, NfL was also cross-sectionally associated with gait speed (ßâ =â 0.001 m/s [0.0003, 0.002]) but not with other gait measures. None of the remaining biomarkers were significantly related to gait in either longitudinal or cross-sectional analyses. CONCLUSIONS: Higher NfL levels were related to greater annual gait speed decline. Gait speed decline may be related to axonal degeneration. The clinical utility of NfL should be explored.
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Sistema Cardiovascular , Marcha , Humanos , Feminino , Idoso , Masculino , Estudos Transversais , Biomarcadores , Pulmão , Proteína Glial Fibrilar ÁcidaRESUMO
Background: Sphingolipids are implicated in neurodegeneration and neuroinflammation. We assessed the potential role of circulating ceramides and sphingomyelins in subclinical brain pathology by investigating their association with brain magnetic resonance imaging (MRI) measures and circulating biomarkers of brain injury, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) in the Cardiovascular Health Study (CHS), a large and intensively phenotyped cohort of older adults. Methods: Brain MRI was offered twice to CHS participants with a mean of 5 years between scans, and results were available from both time points in 2,116 participants (mean age 76 years; 40% male; and 25% APOE ε4 allele carriers). We measured 8 ceramide and sphingomyelin species in plasma samples and examined the associations with several MRI, including worsening grades of white matter hyperintensities and ventricular size, number of brain infarcts, and measures of brain atrophy in a subset with quantitative measures. We also investigated the sphingolipid associations with serum NfL and GFAP. Results: In the fully adjusted model, higher plasma levels of ceramides and sphingomyelins with a long (16-carbon) saturated fatty acid were associated with higher blood levels of NfL [ß = 0.05, false-discovery rate corrected P (PFDR) = 0.004 and ß = 0.06, PFDR = < 0.001, respectively]. In contrast, sphingomyelins with very long (20- and 22-carbon) saturated fatty acids tended to have an inverse association with levels of circulating NfL. In secondary analyses, we found an interaction between ceramide d18:1/20:0 and sex (P for interaction = <0.001), such that ceramide d18:1/20:0 associated with higher odds for infarcts in women [OR = 1.26 (95%CI: 1.07, 1.49), PFDR = 0.03]. We did not observe any associations with GFAP blood levels, white matter grade, ventricular grade, mean bilateral hippocampal volume, or total brain volume. Conclusion: Overall, our comprehensive investigation supports the evidence that ceramides and sphingomyelins are associated with increased aging brain pathology and that the direction of association depends on the fatty acid attached to the sphingosine backbone.
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BACKGROUND: Accurate quantification of sodium intake based on self-reported dietary assessments has been a persistent challenge. We aimed to apply machine-learning (ML) algorithms to predict 24-hour urinary sodium excretion from self-reported questionnaire information. METHODS AND RESULTS: We analyzed 3454 participants from the NHS (Nurses' Health Study), NHS-II (Nurses' Health Study II), and HPFS (Health Professionals Follow-Up Study), with repeated measures of 24-hour urinary sodium excretion over 1 year. We used an ensemble approach to predict averaged 24-hour urinary sodium excretion using 36 characteristics. The TOHP-I (Trial of Hypertension Prevention I) was used for the external validation. The final ML algorithms were applied to 167 920 nonhypertensive adults with 30-year follow-up to estimate confounder-adjusted hazard ratio (HR) of incident hypertension for predicted sodium. Averaged 24-hour urinary sodium excretion was better predicted and calibrated with ML compared with the food frequency questionnaire (Spearman correlation coefficient, 0.51 [95% CI, 0.49-0.54] with ML; 0.19 [95% CI, 0.16-0.23] with the food frequency questionnaire; 0.46 [95% CI, 0.42-0.50] in the TOHP-I). However, the prediction heavily depended on body size, and the prediction of energy-adjusted 24-hour sodium excretion was modestly better using ML. ML-predicted sodium was modestly more strongly associated than food frequency questionnaire-based sodium in the NHS-II (HR comparing Q5 versus Q1, 1.48 [95% CI, 1.40-1.56] with ML; 1.04 [95% CI, 0.99-1.08] with the food frequency questionnaire), but no material differences were observed in the NHS or HPFS. CONCLUSIONS: The present ML algorithm improved prediction of participants' absolute 24-hour urinary sodium excretion. The present algorithms may be a generalizable approach for predicting absolute sodium intake but do not substantially reduce the bias stemming from measurement error in disease associations.
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Hipertensão , Aprendizado de Máquina , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Hipertensão/urina , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Sódio/urina , Idoso , Sódio na Dieta/urina , Algoritmos , Valor Preditivo dos Testes , Autorrelato , Fatores de Tempo , Reprodutibilidade dos Testes , Estados Unidos , Urinálise/métodosRESUMO
INTRODUCTION: Whether circulating levels of sphingolipids are prospectively associated with cognitive decline and dementia risk is uncertain. METHODS: We measured 14 sphingolipid species in plasma samples from 4488 participants (mean age 76.2 years; 40% male; and 25% apolipoprotein E (APOE) ε4 allele carriers). Cognitive decline was assessed annually across 6 years using modified Mini-Mental State Examination (3MSE) and Digital Symbol Substitution Test (DSST). Additionally, a subset of 3050 participants were followed for clinically adjudicated dementia. RESULTS: Higher plasma levels of sphingomyelin-d18:1/16:0 (SM-16) were associated with a faster cognitive decline measured with 3MSE, in contrast, higher levels of sphingomyelin-d18:1/22:0 (SM-22) were associated with slower decline in cognition measured with DSST. In Cox regression, higher levels of SM-16 (hazard ration [HR] = 1.24 [95% confidence interval [CI]: 1.08-1.44]) and ceramide-d18:1/16:0 (Cer-16) (HR = 1.26 [95% CI: 1.10-1.45]) were associated with higher risk of incident dementia. DISCUSSION: Several sphingolipid species appear to be involved in cognitive decline and dementia risk. Highlights: Plasma levels of sphingolipids were associated with cognitive decline and dementia risk.Ceramides and sphingomyelins with palmitic acid were associated with faster annual cognitive decline and increased risk of dementia.The direction of association depended on the covalently bound saturated fatty acid chain length in analysis of cognitive decline.
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Mounting evidence indicates that blueberry consumption is associated with a variety of health benefits. It has been suggested that regular consumption of blueberries can support and/or protect against cardiovascular disease and function, pre-diabetes and type 2 diabetes, and brain and cognitive function in individuals with health conditions and age-related decline. Further, mechanistic investigations highlight the role of blueberry anthocyanins in mediating these health benefits, in part through interactions with gut microbiota. Also, nutritional interventions with blueberries have demonstrated the ability to improve recovery following exercise-induced muscle damage, attributable to anti-inflammatory effects. Despite these advancements in blueberry health research, research gaps persist which affects the generalizability of findings from clinical trials. To evaluate the current state of knowledge and research gaps, a blueberry health roundtable with scientific experts convened in Washington, DC (December 6-7, 2022). Discussions centered around five research domains: cardiovascular health, pre-diabetes and diabetes, brain health and cognitive function, gut health, and exercise recovery. This article synthesizes the outcomes of a blueberry research roundtable discussion among researchers in these domains, offering insights into the health benefits of blueberries and delineating research gaps and future research directions.
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As there are effective treatments to reduce hip fractures, identification of patients at high risk of hip fracture is important to inform efficient intervention strategies. To obtain a new tool for hip fracture prediction, we developed a protein-based risk score in the Cardiovascular Health Study using an aptamer-based proteomic platform. The proteomic risk score predicted incident hip fractures and improved hip fracture discrimination in two Trøndelag Health Study validation cohorts using the same aptamer-based platform. When transferred to an antibody-based proteomic platform in a UK Biobank validation cohort, the proteomic risk score was strongly associated with hip fractures (hazard ratio per s.d. increase, 1.64; 95% confidence interval 1.53-1.77). The proteomic risk score, but not available polygenic risk scores for fractures or bone mineral density, improved the C-index beyond the fracture risk assessment tool (FRAX), which integrates information from clinical risk factors (C-index, FRAX 0.735 versus FRAX + proteomic risk score 0.776). The developed proteomic risk score constitutes a new tool for stratifying patients according to hip fracture risk; however, its improvement in hip fracture discrimination is modest and its clinical utility beyond FRAX with information on femoral neck bone mineral density remains to be determined.
Assuntos
Proteínas Sanguíneas , Fraturas do Quadril , Proteômica , Humanos , Fraturas do Quadril/sangue , Fraturas do Quadril/epidemiologia , Feminino , Masculino , Medição de Risco/métodos , Proteômica/métodos , Idoso , Fatores de Risco , Proteínas Sanguíneas/metabolismo , Proteínas Sanguíneas/análise , Pessoa de Meia-Idade , Densidade ÓsseaRESUMO
Hip fractures are associated with significant disability, high cost, and mortality. However, the exact biological mechanisms underlying susceptibility to hip fractures remain incompletely understood. In an exploratory search of the underlying biology as reflected through the circulating proteome, we performed a comprehensive Circulating Proteome Association Study (CPAS) meta-analysis for incident hip fractures. Analyses included 6430 subjects from two prospective cohort studies (Cardiovascular Health Study and Trøndelag Health Study) with circulating proteomics data (aptamer-based 5 K SomaScan version 4.0 assay; 4979 aptamers). Associations between circulating protein levels and incident hip fractures were estimated for each cohort using age and sex-adjusted Cox regression models. Participants experienced 643 incident hip fractures. Compared with the individual studies, inverse-variance weighted meta-analyses yielded more statistically significant associations, identifying 23 aptamers associated with incident hip fractures (conservative Bonferroni correction 0.05/4979, P < 1.0 × 10-5). The aptamers most strongly associated with hip fracture risk corresponded to two proteins of the growth hormone/insulin growth factor system (GHR and IGFBP2), as well as GDF15 and EGFR. High levels of several inflammation-related proteins (CD14, CXCL12, MMP12, ITIH3) were also associated with increased hip fracture risk. Ingenuity pathway analysis identified reduced LXR/RXR activation and increased acute phase response signaling to be overrepresented among those proteins associated with increased hip fracture risk. These analyses identified several circulating proteins and pathways consistently associated with incident hip fractures. These findings underscore the usefulness of the meta-analytic approach for comprehensive CPAS in a similar manner as has previously been observed for large-scale human genetic studies. Future studies should investigate the underlying biology of these potential novel drug targets.
Hip fractures are associated with significant disability, high cost, and mortality. However, the exact biological mechanisms underlying susceptibility to hip fractures remain incompletely understood. To increase the understanding of the underlying mechanisms, we performed a meta-analysis of the associations between 4860 circulating proteins and risk of fractures using two large cohorts, including 6430 participants with 643 incident hip fractures. We identified 23 proteins/aptamers associated with incident hip fractures. Two proteins of the growth hormone/insulin growth factor system (GHR and IGFBP2), as well as GDF15 and EGFR were most strongly associated with hip fracture risk. High levels of several inflammation-related proteins were also associated with increased hip fracture risk. Pathway analysis identified reduced LXR/RXR activation and increased acute phase response signaling to be overrepresented among those proteins associated with increased hip fracture risk. Future mechanistic studies should investigate the underlying biology of these novel protein biomarkers which may be potential drug targets.