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1.
Int Psychogeriatr ; : 1-11, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35543307

RESUMO

OBJECTIVES: Higher inflammation has been linked to poor physical and mental health outcomes, and mortality, but few studies have rigorously examined whether changes in perceived stress and depressive symptoms are associated with increased inflammation within family caregivers and non-caregivers in a longitudinal design. DESIGN: Longitudinal Study. SETTING: REasons for Geographic And Racial Differences in Stroke cohort study. PARTICIPANTS: Participants included 239 individuals who were not caregivers at baseline but transitioned to providing substantial and sustained caregiving over time. They were initially matched to 241 non-caregiver comparisons on age, sex, race, education, marital status, self-rated health, and history of cardiovascular disease. Blood was drawn at baseline and approximately 9.3 years at follow-up for both groups. MEASUREMENTS: Perceived Stress Scale, Center for Epidemiological Studies-Depression, inflammatory biomarkers, including high-sensitivity C-reactive protein, D dimer, tumor necrosis factor alpha receptor 1, interleukin (IL)-2, IL-6, and IL-10 taken at baseline and follow-up. RESULTS: Although at follow-up, caregivers showed significantly greater worsening in perceived stress and depressive symptoms compared to non-caregivers, there were few significant associations between depressive symptoms or perceived stress on inflammation for either group. Inflammation, however, was associated with multiple demographic and health variables, including age, race, obesity, and use of medications for hypertension and diabetes for caregivers and non-caregivers. CONCLUSIONS: These findings illustrate the complexity of studying the associations between stress, depressive symptoms, and inflammation in older adults, where these associations may depend on demographic, disease, and medication effects. Future studies should examine whether resilience factors may prevent increased inflammation in older caregivers.

2.
J Thromb Haemost ; 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35426248

RESUMO

BACKGROUND: Thirty to seventy percent of all venous thromboembolism (VTE) events are associated with hospitalization. The absolute and relative risks during and after hospitalization are poorly characterized. OBJECTIVES: Quantify the absolute rate and relative risk of VTE during and up to 3 months after medical and surgical hospitalizations. PATIENTS/METHODS: We conducted an observational cohort study between 2010 and 2016 of patients cared for by the University of Vermont (UVM) Health Network's primary care population. Cox proportional hazard models with hospitalization modeled as a time-varying covariate were used to estimate VTE risk. RESULTS: Over 4.3 years of follow-up, 55 220 hospitalizations (156 per 1000 person-years) and 713 first venous thromboembolism events (2.0 per 1000 person-years) occurred. Among individuals not recently hospitalized, the rate of venous thromboembolism was 1.4 per 1000 person-years and 71.8 per 1000 person-years during hospitalization. During the first, second, and third months after discharge, the rates of venous thromboembolism were 35.1, 11.3, and 5.2 per 1000 person-years, respectively. Relative to those not recently hospitalized, the age- and sex-adjusted HRs of venous thromboembolism were 38.0 (95% CI 28.0, 51.5) during hospitalization, and 18.4 (95% CI 15.0, 22.6), 6.3 (95% CI 4.3, 9.0), and 3.0 (95% CI 1.7, 5.4) during the first, second, and third months after discharge, respectively. Stratified by medical versus surgical services the rates were similar. CONCLUSION: Hospitalization and up to 3 months after discharge were strongly associated with increased venous thromboembolism risk. These data quantify this risk for use in future studies.

3.
Res Pract Thromb Haemost ; 6(2): e12671, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35252737

RESUMO

BACKGROUND: The preponderance of the evidence supports no association between traditional cardiovascular risk factors and venous thromboembolism (VTE), other than obesity. There are limited data in older people. OBJECTIVES: To investigate whether cardiovascular risk factors (body mass index, smoking, alcohol intake, hypertension, and diabetes) are associated with the risk of VTE in elderly and to assess the combined effect between cardiovascular risk factors and genetic risk factors for VTE (factor V Leiden/prothrombin 20210A, positive family history of VTE, and non-O blood group). METHODS: The Age and Thrombosis, Acquired and Genetic risk factors in the Elderly study is a multicenter case-control study performed in Vermont, USA and Leiden, the Netherlands, comprising 401 cases with first VTE and 431 control subjects, all aged ≥70 years. To assess the risk of VTE, odds ratios (OR) with 95% confidence intervals (CIs) were calculated, adjusting for potential confounders. RESULTS: Both height and weight were positively associated with VTE risk: the ORs were 2.2 (95% CI, 1.2-3.9) and 1.5 (95% CI, 1.0-2.4) in the top quartile for height and weight separately. This risk was more pronounced for unprovoked VTE. Smoking, alcohol intake, and diabetes were not associated with VTE. Higher systolic and diastolic blood pressure and hypertension were associated with a decreased risk of VTE. In the presence of a genetic predisposition, height and weight further increased the risk of VTE. CONCLUSIONS: In the elderly, height and weight are positively associated with the risk of VTE. With genetic predisposition, higher levels of height and weight further increase the risk of VTE.

4.
JAMA Netw Open ; 5(3): e224205, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35333359

RESUMO

Importance: Previous venous thrombosis (VT) is associated with risk of future VT, but quantification of risk over the life course is poorly understood. More information is needed for clinicians to understand the association of remote history of VT with the risk of VT in older patients. Objective: To assess the association between a remote history of VT and the development of VT in older age. Design, Setting, and Participants: The Age and Thrombosis, Acquired and Genetic Risk Factors in the Elderly case-control study enrolled patients 70 years and older with VT and control individuals 70 years and older without VT between June 2008 and August 2011. The Age and Thrombosis, Acquired and Genetic Risk Factors in the Elderly study is a 2-center, population-based case-control study that was conducted in Burlington, Vermont, in the US and in Leiden, the Netherlands. Consecutively diagnosed patients with an objectively proven episode of VT (deep vein thrombosis of the leg or pulmonary embolism) were included. Control individuals were identified in the same geographic areas as the patients and were randomly selected. Data were analyzed between May 2021 and October 2021. Exposures: Self-reported remote VT (occurring >10 years before to enrollment). Main Outcomes and Measures: The main outcome was the risk of VT at older age. The association of self-reported history of remote VT with VT at older age was assessed by calculating odds ratios (ORs) as estimates of relative risk with 95% CIs. Results: A total of 460 patients with VT and 456 control participants were included. There were slightly more women than men in both groups (60.2% of patients [n = 277] were women and 52.4% of control participants [n = 239] were women), and the mean (range) age of patients was 78.7 (70.0-100.9) years, which was similar to the control participants. Compared with individuals without remote VT, those with a remote history of VT had an increased risk of VT (OR, 2.54; 95% CI, 1.56-4.13). The crude risk estimate was robust to adjustment and time since remote VT, that is, individuals with a VT 10 to 30 years ago (OR, 2.74; 95% CI, 1.34-5.57) and those with a VT more than 30 years ago (OR, 2.42; 95% CI, 1.21-4.84) had a an increased risk of VT. The population-attributable fraction of a remote history of VT was 7.7%. Conclusions and Relevance: In this study, a remote history of VT was associated with risk of VT in older individuals. This quantification could assist clinicians in advising patients on VT prevention.


Assuntos
Trombose Venosa , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Fatores de Risco , Trombose Venosa/epidemiologia , Trombose Venosa/etiologia
5.
Am J Kidney Dis ; 2022 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-35351578

RESUMO

RATIONALE AND OBJECTIVE: Cardiovascular disease (CVD) is a major cause of mortality among people with diabetic kidney disease (DKD). The pathophysiology is inadequately explained by traditional CVD risk factors. Three uremic solutes, trimethylamine-N-oxide (TMAO), asymmetric and symmetric dimethylarginine (ADMA, SDMA), have been linked to CVD in kidney failure with renal replacement therapy (KFRT), but data are limited in populations with diabetes and less severe kidney disease. STUDY DESIGN: Observational cohort. SETTINGS AND PARTICIPANTS: Random subcohort of 555 REGARDS Study participants with diabetes and eGFR <60 ml/min/1.73m2 at study entry. EXPOSURES: ADMA, SDMA and TMAO were assayed by liquid chromatography-mass spectrometry in plasma and urine. OUTCOMES: CV mortality (primary outcome), all-cause mortality and incident KFRT (secondary outcomes). ANALYTIC APPROACH: Plasma and urine:plasma (U/P) ratios of ADMA, SDMA and TMAO were tested for association with outcomes. Adjusted Cox regression models were fitted and hazard ratios (HR) of outcomes presented per standard deviation, log2 increments and interquartile comparisons. RESULTS: Mean baseline eGFR was 44 ml/min/1.73 m2. CV death, overall mortality and KFRT occurred in 120, 285 and 89 participants during mean 6.2 years follow-up. Higher plasma ADMA, and lower U/P ratios of ADMA, SDMA and TMAO were associated with CV mortality by interquartile (HR 1.9-3.9), log2 concentration comparisons (HR 1.4-2.1), and per standard deviation (HR 1.2). Higher plasma concentrations (HR 1.1-2.8) and lower U/P ratios (HR 1.3-2.3) of all three solutes were associated with all-cause mortality. Higher plasma SDMA was associated with incident KFRT (HR 1.2-3.0). LIMITATIONS: Single cohort, restricted to diabetic patients with eGFR <60, potential residual confounding by GFR, no dietary information. CONCLUSIONS: Higher plasma concentrations and lower U/P ratios of uremic solutes were independently associated with CV and all-cause mortality in DKD. Associations of U/P ratios with mortality suggest a connection between renal uremic solute clearance and CVD pathogenesis.

6.
Am J Epidemiol ; 2022 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-35279711

RESUMO

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults comprising 14 established United States (US) prospective cohort studies. Starting as early as 1971, C4R cohorts have collected data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R links this pre-COVID phenotyping to information on SARS-CoV-2 infection and acute and post-acute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and reflects the racial, ethnic, socioeconomic, and geographic diversity of the US. C4R ascertains SARS-CoV-2 infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations, and high-quality events surveillance. Extensive pre-pandemic data minimize referral, survival, and recall bias. Data are harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these will be pooled and shared widely to expedite collaboration and scientific findings. This resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including post-acute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term trajectories of health.

7.
Neurology ; 2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35264422

RESUMO

BACKGROUND AND OBJECTIVES: Both genetic and environmental factors contribute to stroke risk. We sought to identify novel metabolites associated with incident stroke in the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, and determine whether they reflected genetic or environmental variation. METHODS: This was a stroke case-cohort observational study nested in REGARDS. Cases were defined as incident stroke and metabolomic profiles were compared to a randomly selected control cohort. In baseline plasma samples, 162 metabolites were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Cox proportional hazards models were adjusted for age, sex, race, and age-by-race in the base model. Fully adjusted models included traditional stroke risk factors. Mediation analyses conducted for these stroke risk factors used the metabolite as mediator. Genome wide associations with the leading candidate metabolites were calculated using array data. Replication analyses in the Jackson Heart Study (JHS) were conducted using random effects meta-analysis. RESULTS: There were 2,043 participants who were followed over an average period of 7.1 years, including 1,075 stroke cases and 968 random controls. Nine metabolites were associated with stroke in the base model, eight of which were measured and remained significant in meta-analysis with JHS. In the fully adjusted model in REGARDS, guanosine [Hazard ratio (HR)=1.34; 95%CI=1.18-1.53; P=7.26x10-6] and pseudouridine [HR=1.28; 95% CI=1.13-1.45; P=1.03x10-4] were associated with incident ischemic stroke following Bonferroni adjustment. Guanosine also partially mediated the relationship between hypertension and stroke (17.6%), and pseudouridine did not mediate any risk factor. Genome-wide association analysis identified loci rs34631560 and rs34631560 associated with pseudouridine, but these did not explain the association of pseudouridine with stroke. DISCUSSION: Guanosine and pseudouridine are nucleosides associated with incident ischemic stroke independently of other risk factors. Genetic and mediation analyses suggest that environmental exposures rather than genetic variation link nucleoside levels to stroke risk. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that guanosine and pseudouridine are associated with incident stroke.

8.
Artigo em Inglês | MEDLINE | ID: mdl-35137178

RESUMO

BACKGROUND: Black adults experience more type 2 diabetes mellitus and also higher inflammatory markers, including C-reactive protein (CRP), compared to White adults. Inflammatory markers are associated with risk of incident diabetes but the impact of inflammation on racial differences in incident diabetes is unknown. We assessed whether CRP mediated the Black-White incident diabetes disparity. METHODS: The REasons for Geographic And Racial Differences in Stroke (REGARDS) study enrolled 30,239 US Black and White adults aged ≥45 years in 2003-2007 with a second visit approximately 10-years later. Among participants without baseline diabetes, adjusted sex- and race-stratified risk ratios (RR) for incident diabetes at the second visit by CRP level were calculated using modified Poisson regression. Inverse odds weighting estimated the percent mediation of the racial disparity by CRP. RESULTS: Of 11,073 participants without baseline diabetes (33% Black, 67% White), 1,389 (12.5%) developed diabetes. Black participants had higher CRP at baseline and greater incident diabetes than White participants. Relative to CRP <3 mg/L, CRP ≥3 mg/L was associated with greater risk of diabetes in all race-sex strata. Black participants had higher risk of diabetes at CRP <3 mg/L, but not at CRP ≥3mg/L. In women, CRP mediated 10.0% of the racial difference in incident diabetes. This mediation was not seen in men. CONCLUSIONS: Higher CRP is a risk factor for incident diabetes, but the excess burden of diabetes in Black adults was only seen in those with lower CRP, suggesting that inflammation is unlikely to be the main driver of this racial disparity.

11.
Am J Nephrol ; 53(2-3): 182-190, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35100591

RESUMO

INTRODUCTION: The association of apolipoprotein L1 (APOL1) nephropathy risk variants (APOL1), unique to African-ancestry (African-American [AA]) populations, with systemic inflammation, a contributor to chronic kidney disease (CKD) and end-stage kidney disease (ESKD) is ill-defined. This study aimed to describe the role of inflammatory markers in the relationship between APOL1 and incident kidney outcomes using a prospective cohort study. METHODS: APOL1 high-risk status under a recessive genetic model was studied in 10,605 AA adults aged ≥45 years from the Reasons for Geographic and Racial Differences in Stroke study. The primary variables of interest were inflammatory markers: C-reactive protein (mg/dL), white blood cell count (cells/mm3), and serum albumin (sALB) (mg/dL). High inflammation status was defined if at least one of these inflammatory markers exceeded clinical threshold. The association between APOL1 and biomarkers were assessed using regression models adjusting for age, sex, ancestry, hypertension, lipid medications, albumin-to-creatinine ratio, and estimated glomerular filtration rate (eGFR). Models were stratified by diabetes status. We identified incident ESKD using USRDS linkage, and we defined incident CKD as an eGFR <60 mL/min/1.73 m2 and ≥25% decline in the eGFR and normal baseline eGFR and tested for mediation of APOL1 and outcomes by biomarkers using the causal inference approach. RESULTS: Among 7,151 participants with data available on all inflammation markers, 4,479 participants had ≥1 marker meeting the clinical threshold. APOL1 high-risk status was associated with lower adjusted odds of reduced sALB {odds ratio (OR) (95% confidence interval [CI]): 0.59 [0.36, 0.96])}, and this association was significant in people with diabetes (OR [95% CI]: 0.40 [0.18, 0.89]) but not in those without diabetes. There was no association of APOL1 high-risk status with other markers or high inflammation status. APOL1 was independently associated with ESKD (OR [95% CI] = 1.78 [1.28, 2.48]) and CKD (OR [95% CI] = 1.38 [1.00, 1.91]). On mediation analysis, the direct effect between APOL1 and ESKD strengthened after accounting for sALB, but the estimated mediated effect was not statistically significant (OR [95% CI]: 0.98 [0.92, 1.05], p = 0.58). CONCLUSION: APOL1 high-risk variants were associated with sALB. However, sALB did not statistically mediate the association between APOL1 and incident ESKD.


Assuntos
Apolipoproteína L1 , Insuficiência Renal Crônica , Adulto , Apolipoproteína L1/genética , Estudos de Coortes , Taxa de Filtração Glomerular/genética , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/genética , Fatores de Risco , Albumina Sérica
12.
JAMA ; 327(3): 227-236, 2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-35040887

RESUMO

Importance: Platelets represent a potential therapeutic target for improved clinical outcomes in patients with COVID-19. Objective: To evaluate the benefits and risks of adding a P2Y12 inhibitor to anticoagulant therapy among non-critically ill patients hospitalized for COVID-19. Design, Setting, and Participants: An open-label, bayesian, adaptive randomized clinical trial including 562 non-critically ill patients hospitalized for COVID-19 was conducted between February 2021 and June 2021 at 60 hospitals in Brazil, Italy, Spain, and the US. The date of final 90-day follow-up was September 15, 2021. Interventions: Patients were randomized to a therapeutic dose of heparin plus a P2Y12 inhibitor (n = 293) or a therapeutic dose of heparin only (usual care) (n = 269) in a 1:1 ratio for 14 days or until hospital discharge, whichever was sooner. Ticagrelor was the preferred P2Y12 inhibitor. Main Outcomes and Measures: The composite primary outcome was organ support-free days evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and, for those who survived to hospital discharge, the number of days free of respiratory or cardiovascular organ support up to day 21 of the index hospitalization (range, -1 to 21 days; higher scores indicate less organ support and better outcomes). The primary safety outcome was major bleeding by 28 days as defined by the International Society on Thrombosis and Hemostasis. Results: Enrollment of non-critically ill patients was discontinued when the prespecified criterion for futility was met. All 562 patients who were randomized (mean age, 52.7 [SD, 13.5] years; 41.5% women) completed the trial and 87% received a therapeutic dose of heparin by the end of study day 1. In the P2Y12 inhibitor group, ticagrelor was used in 63% of patients and clopidogrel in 37%. The median number of organ support-free days was 21 days (IQR, 20-21 days) among patients in the P2Y12 inhibitor group and was 21 days (IQR, 21-21 days) in the usual care group (adjusted odds ratio, 0.83 [95% credible interval, 0.55-1.25]; posterior probability of futility [defined as an odds ratio <1.2], 96%). Major bleeding occurred in 6 patients (2.0%) in the P2Y12 inhibitor group and in 2 patients (0.7%) in the usual care group (adjusted odds ratio, 3.31 [95% CI, 0.64-17.2]; P = .15). Conclusions and Relevance: Among non-critically ill patients hospitalized for COVID-19, the use of a P2Y12 inhibitor in addition to a therapeutic dose of heparin, compared with a therapeutic dose of heparin only, did not result in an increased odds of improvement in organ support-free days within 21 days during hospitalization. Trial Registration: ClinicalTrials.gov Identifier: NCT04505774.


Assuntos
Anticoagulantes/administração & dosagem , COVID-19/tratamento farmacológico , Heparina/administração & dosagem , Pacientes Internados , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , COVID-19/sangue , COVID-19/mortalidade , Clopidogrel/administração & dosagem , Clopidogrel/efeitos adversos , Comorbidade , Oxigenação por Membrana Extracorpórea/estatística & dados numéricos , Feminino , Hemorragia/induzido quimicamente , Heparina/efeitos adversos , Mortalidade Hospitalar , Humanos , Masculino , Futilidade Médica , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Oxigenoterapia/estatística & dados numéricos , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Receptores Purinérgicos P2Y12 , Respiração Artificial/estatística & dados numéricos , Trombose/epidemiologia , Ticagrelor/administração & dosagem , Ticagrelor/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
13.
J Am Heart Assoc ; 11(2): e022921, 2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-35023350

RESUMO

Background It is unknown if stroke symptoms in the absence of a stroke diagnosis are a sign of subtle cardioembolic phenomena. The objective of this study was to examine associations between atrial fibrillation (AF) and stroke symptoms among adults with no clinical history of stroke or transient ischemic attack (TIA). Methods and Results We evaluated associations between AF and self-reported stroke symptoms in the national, prospective REGARDS (Reasons for Geographic and Racial Differences in Stroke) cohort. We conducted cross-sectional (n=27 135) and longitudinal (n=21 932) analyses over 8 years of follow-up of REGARDS participants without stroke/transient ischemic attack and stratified by anticoagulant or antiplatelet agent use. The mean age was 64.4 (SD±9.4) years, 55.3% were women, and 40.8% were Black participants; 28.6% of participants with AF reported stroke symptoms. In the cross-sectional analysis, comparing participants with and without AF, the risk of stroke symptoms was elevated for adults with AF taking neither anticoagulants nor antiplatelet agents (odds ratio [OR], 2.22; 95% CI, 1.89-2.59) or antiplatelet agents only (OR, 1.92; 95% CI, 1.61-2.29) but not for adults with AF taking anticoagulants (OR, 1.08; 95% CI, 0.71-1.65). In the longitudinal analysis, the risk of stroke symptoms was also elevated for adults with AF taking neither anticoagulants nor antiplatelet agents (hazard ratio [HR], 1.41; 95% CI, 1.21-1.66) or antiplatelet agents only (HR, 1.23; 95% CI, 1.04-1.46) but not for adults with AF taking anticoagulants (HR, 0.86; 95% CI, 0.62-1.18). Conclusions Stroke symptoms in the absence of a stroke diagnosis may represent subclinical cardioembolic phenomena or "whispering strokes." Future studies examining the benefit of stroke symptom screening may be warranted.


Assuntos
Fibrilação Atrial , Ataque Isquêmico Transitório , Acidente Vascular Cerebral , Adulto , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Estudos Transversais , Feminino , Humanos , Ataque Isquêmico Transitório/diagnóstico , Ataque Isquêmico Transitório/epidemiologia , Ataque Isquêmico Transitório/etiologia , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia
14.
J Am Soc Nephrol ; 33(1): 213-224, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34706968

RESUMO

BACKGROUND: α-Globin is expressed in endothelial cells of resistance arteries, where it limits endothelial nitric oxide signaling and enhances α-adrenergic-mediated vasoconstriction. α-Globin gene (HBA) copy number is variable in people of African descent and other populations worldwide. Given the protective effect of nitric oxide in the kidney, we hypothesized that HBA copy number would be associated with kidney disease risk. METHODS: Community-dwelling Black Americans aged ≥45 years old were enrolled in a national longitudinal cohort from 2003 through 2007. HBA copy number was measured using droplet digital PCR. The prevalence ratio (PR) of CKD and the relative risk (RR) of incident reduced eGFR were calculated using modified Poisson multivariable regression. The hazard ratio (HR) of incident ESKD was calculated using Cox proportional hazards multivariable regression. RESULTS: Among 9908 participants, HBA copy number varied from 2 to 6. In analyses adjusted for demographic, clinical, and genetic risk factors, a one-copy increase in HBA was associated with 14% greater prevalence of CKD (PR, 1.14; 95% CI, 1.07 to 1.21; P<0.0001). While HBA copy number was not associated with incident reduced eGFR (RR, 1.06; 95% CI, 0.94 to 1.19; P=0.38), the hazard of incident ESKD was 32% higher for each additional copy of HBA (HR, 1.32; 95% CI, 1.09 to 1.61; P=0.005). CONCLUSIONS: Increasing HBA copy number was associated with a greater prevalence of CKD and incidence of ESKD in a national longitudinal cohort of Black Americans.


Assuntos
Afro-Americanos/estatística & dados numéricos , Dosagem de Genes , Falência Renal Crônica/etnologia , Falência Renal Crônica/genética , alfa-Globinas/genética , Idoso , Feminino , Taxa de Filtração Glomerular , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prevalência , Modelos de Riscos Proporcionais
15.
Am J Hypertens ; 35(3): 281-288, 2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-34655288

RESUMO

BACKGROUND: Neurotensin, a neuropeptide with direct cardiac effects, has been associated with prospective risk of hypertension-related conditions through measurement of its precursor, pro-neurotensin/neuromedin N (pro-NT/NMN). Its association with incident hypertension has not been evaluated. METHODS: From 2003 to 2007, the REasons for Geographic And Racial Differences in Stroke (REGARDS) study enrolled 30,239 Black or White adults age ≥45. Pro-NT/NMN was measured in 1,692 participants without baseline hypertension (self-reported antihypertensive use or blood pressure ≥140/90 mm Hg) who underwent follow-up assessment in 2013-2016. A sensitivity analysis was conducted using a lower threshold (≥130/80 mm Hg) to define hypertension. Three robust Poisson regression models were fitted to risk of incident hypertension, adding demographics, cardiometabolic risk factors, and dietary covariates. RESULTS: Six hundred and fourteen participants developed hypertension over 9.4 years of follow-up. Pro-NT/NMN ranged from 14 to 1,246 pmol/l, with median [interquartile range] 154 [112, 206] pmol/l. Pro-NT/NMN was not associated with hypertension overall (fully adjusted incidence rate ratio per SD increment log pro-NT/NMN 1.03, 95% confidence interval 0.95-1.11). Results of sensitivity analysis did not differ substantially. CONCLUSIONS: Baseline pro-NT/NMN was not associated with incident hypertension. This may be a result of neurotensin's long-term interactions with other molecular regulators of blood pressure, such as the renin-angiotensin-aldosterone system.


Assuntos
Hipertensão , Neuropeptídeos , Adulto , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Neurotensina , Fragmentos de Peptídeos , Estudos Prospectivos , Fatores de Risco
16.
Ann Epidemiol ; 66: 13-19, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34742867

RESUMO

PURPOSE: Relative to White adults, Black adults have a substantially higher prevalence of hypertension and diabetes, both key risk factors for stroke, cardiovascular disease, cognitive impairment, and dementia. Blood biomarkers have shown promise in identifying contributors to racial disparities in many chronic diseases. METHODS: We outline the study design and related statistical considerations for a nested cohort study, the Biomarker Mediators of Racial Disparities in Risk Factors (BioMedioR) study, within the 30,239-person biracial REasons for Geographic And Racial Differences in Stroke (REGARDS) study (2003-present). Selected biomarkers will be assessed for contributions to racial disparities in risk factor development over median 9.4 years of follow-up, with initial focus on hypertension, and diabetes. Here we outline study design decisions and statistical considerations for the sampling of 4,400 BioMedioR participants. RESULTS: The population for biomarker assessment was selected using a random sample study design balanced across race and sex to provide the optimal opportunity to describe association of biomarkers with the development of hypertension and diabetes. Descriptive characteristics of the BioMedioR sample and analytic plans are provided for this nested cohort study. CONCLUSIONS: This nested biomarker study will examine pathways with the target to help explain racial differences in hypertension and diabetes incidence.


Assuntos
Afro-Americanos , Adulto , Biomarcadores , Estudos de Coortes , Humanos , Fatores de Risco
17.
Hypertension ; 79(1): 196-206, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34784734

RESUMO

Social vulnerabilities increase the risk of developing hypertension and lower life expectancy, but the effect of an individual's overall vulnerability burden is unknown. Our objective was to determine the association of social vulnerability count and the risk of developing hypertension or dying over 10 years and whether these associations vary by race. We used the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) and included participants without baseline hypertension. The primary exposure was the count of social vulnerabilities defined across economic, education, health and health care, neighborhood and built environment, and social and community context domains. Among 5425 participants of mean age 64±10 SD years of which 24% were Black participants, 1468 (31%) had 1 vulnerability and 717 (15%) had ≥2 vulnerabilities. Compared with participants without vulnerabilities, the adjusted relative risk ratio for developing hypertension was 1.16 (95% CI, 0.99-1.36) and 1.49 (95% CI, 1.20-1.85) for individuals with 1 and ≥2 vulnerabilities, respectively. The adjusted relative risk ratio for death was 1.55 (95% CI, 1.24-1.93) and 2.30 (95% CI, 1.75-3.04) for individuals with 1 and ≥2 vulnerabilities, respectively. A greater proportion of Black participants developed hypertension and died than did White participants (hypertension, 38% versus 31%; death, 25% versus 20%). The vulnerability count association was strongest in White participants (P value for vulnerability count×race interaction: hypertension=0.046, death=0.015). Overall, a greater number of socially determined vulnerabilities was associated with progressively higher risk of developing hypertension, and an even higher risk of dying over 10 years.


Assuntos
Hipertensão/mortalidade , Determinantes Sociais da Saúde , Vulnerabilidade Social , Idoso , Pressão Sanguínea/fisiologia , Feminino , Disparidades nos Níveis de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Sexuais , Taxa de Sobrevida
18.
J Stroke Cerebrovasc Dis ; 31(2): 106237, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34896817

RESUMO

OBJECTIVES: The opioid neuropeptide pro-enkephalin A (PENK-A) may be a circulating marker of cardiovascular risk, with prior findings relevant to heart failure, kidney disease, and vascular dementia. Despite these findings, the association of PENK-A with ischemic stroke is unknown, so we examined this association in a prospective cohort study and analyzed differences by race and sex. MATERIALS AND METHODS: The REasons for Geographic and Racial Differences in Stroke study (REGARDS) is a prospective cohort study of 30,239 Black and White adults. Plasma PENK-A was measured in 473 participants that developed first-time ischemic stroke over 5.9 years and 899 randomly selected participants. Cox models adjusted for demographics and stroke risk factors were used to calculate hazard ratios (HRs) of stroke by baseline PENK-A. RESULTS: PENK-A was higher with increasing age, female sex, White race, lower body mass index, and antihypertensive medication use. Each SD higher increment of PENK-A was associated with an adjusted HR of 1.20 (95% CI 1.01-1.42) for stroke, with minimal confounding by stroke risk factors. Spline plots suggested a U-shaped relationship, particularly in White men, with an adjusted HR 3.88 (95% CI 1.94-7.77) for the 95th versus 50th percentile of PENK-A in White men. CONCLUSIONS: Higher baseline plasma PENK-A was independently associated with future stroke risk in REGARDS. This association was most apparent among White men. There was little confounding by established stroke risk factors, suggesting a possible causal role in stroke etiology. Further research is needed to understand the role of endogenous opioids in stroke pathogenesis.


Assuntos
Encefalinas , Disparidades nos Níveis de Saúde , AVC Isquêmico , Precursores de Proteínas , Adulto , Biomarcadores/sangue , Encefalinas/sangue , Feminino , Geografia , Humanos , AVC Isquêmico/sangue , AVC Isquêmico/etnologia , Masculino , Estudos Prospectivos , Precursores de Proteínas/sangue , Fatores Raciais , Fatores de Risco , /estatística & dados numéricos
19.
Res Pract Thromb Haemost ; 5(8): e12632, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34934895

RESUMO

BACKGROUND: Higher D-dimer is a risk factor for cardiovascular diseases and venous thromboembolism. In the general population, D-dimer and other thrombo-inflammatory biomarkers are higher among Black individuals, who also have higher risk of these conditions compared to White people. OBJECTIVE: To assess whether Black individuals have an exaggerated correlation between D-dimer and thrombo-inflammatory biomarkers characteristic of cardiovascular diseases. METHODS: Linear regression was used to assess correlations of 11 thrombo-inflammatory biomarkers with D-dimer in a cross-sectional study of 1068 participants of the biracial Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. RESULTS: Adverse levels of most biomarkers, especially fibrinogen, factor VIII, C-reactive protein, N-terminal pro-B-type natriuretic peptide, and interleukin (IL)-6, were associated with higher D-dimer. Several associations with D-dimer differed significantly by race. For example, the association of factor VIII with D-dimer was more than twice as large in Black compared to White participants. Specifically, D-dimer was 26% higher per standard deviation (SD) higher factor VIII in Black adults and was only 11% higher per SD higher factor VIII in White adults. In Black but not White adults, higher IL-10 and soluble CD14 were associated with higher D-dimer. CONCLUSIONS: Findings suggest that D-dimer might relate to Black/White differences in cardiovascular diseases and venous thromboembolism because it is a marker of amplified thrombo-inflammatory response in Black people. Better understanding of contributors to higher D-dimer in the general population is needed.

20.
BMC Public Health ; 21(1): 2255, 2021 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-34895192

RESUMO

BACKGROUND: Understanding health care experiences during the COVID-19 pandemic may provide insights into patient needs and inform policy. The objective of this study was to describe health care experiences by race and social determinants of health. METHODS: We conducted a telephone survey (July 6, 2020-September 4, 2021) among 9492 Black and White participants in the longitudinal REasons for Geographic And Racial Differences in Stroke cohort study, age 58-105 years, from the continental United States. Among participants with symptoms of COVID-19, outcomes were: 1. Sought care or advice for the illness; 2. Received a SARS-CoV-2 test for the illness; and 3. Tested positive. Among participants without symptoms of COVID-19, outcomes were: 1. Wanted a test; 2. Wanted and received a test; 3. Did not want but received a test; and 4. Tested positive. We examined these outcomes overall and in subgroups defined by race, household income, marital status, education, area-level poverty, rural residence, Medicaid expansion, public health infrastructure ranking, and residential segregation. RESULTS: The average age of participants was 76.8 years, 36% were Black, and 57% were female. Among participants with COVID-19 symptoms (n = 697), 74% sought care or advice for the illness, 50% received a SARS-CoV-2 test, and 25% had a positive test (50% of those tested). Among participants without potential COVID-19 symptoms (n = 8795), 29% wanted a SARS-CoV-2 test, 22% wanted and received a test, 8% did not want but received a test, and 1% tested positive; a greater percentage of participants who were Black compared to White wanted (38% vs 23%, p < 0.001) and received tests (30% vs 18%, p < 0.001) and tested positive (1.4% vs 0.8%, p = 0.005). CONCLUSIONS: In this national study of older US adults, many participants with potential COVID-19 symptoms and asymptomatic participants who desired testing did not receive COVID-19 testing.


Assuntos
COVID-19 , Adulto , Idoso , Idoso de 80 Anos ou mais , Teste para COVID-19 , Estudos de Coortes , Atenção à Saúde , Feminino , Humanos , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2 , Determinantes Sociais da Saúde , Estados Unidos/epidemiologia
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