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1.
Front Cardiovasc Med ; 8: 599341, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33778019

RESUMO

Background: Psychosocial stress correlates with cardiovascular (CV) events; however, associations between physiologic measures of stressors and CVD remain incompletely understood, especially in racial/ethnic minority populations in resource-limited neighborhoods. We examined associations between chronic stress-related neural activity, measured by amygdalar 18Fluorodeoxyglucose (18FDG) uptake, and aortic vascular FDG uptake (arterial inflammation measure) in a community-based cohort. Methods: Forty participants from the Washington, DC CV Health and Needs Assessment (DC-CHNA), a study of a predominantly African-American population in resource-limited urban areas and 25 healthy volunteers underwent detailed phenotyping, including 18FDG PET/CT for assessing amygdalar activity (AmygA), vascular FDG uptake, and hematopoietic (leukopoietic) tissue activity. Mediation analysis was used to test whether the link between AmygA and vascular FDG uptake was mediated by hematopoietic activity. Results: AmygA (1.11 ± 0.09 vs. 1.05 ± 0.09, p = 0.004) and vascular FDG uptake (1.63 ± 0.22 vs. 1.55 ± 0.17, p = 0.05) were greater in the DC-CHNA cohort compared to volunteers. Within the DC-CHNA cohort, AmygA associated with vascular FDG uptake after adjustment for Framingham score and body mass index (ß = 0.41, p = 0.015). The AmygA and aortic vascular FDG uptake relationship was in part mediated by splenic (20.2%) and bone marrow (11.8%) activity. Conclusions: AmygA, or chronic stress-related neural activity, associates with subclinical CVD risk in a community-based cohort. This may in part be mediated by the hematopoietic system. Our findings of this hypothesis-generating study are suggestive of a potential relationship between chronic stress-related neural activity and subclinical CVD in an African American community-based population. Taken together, these findings suggest a potential mechanism by which chronic psychosocial stress, such as stressors that can be experienced in adverse social conditions, promotes greater cardiovascular risk amongst resource-limited, community-based populations most impacted by cardiovascular health disparities. However, larger prospective studies examining these findings in other racially and ethnically diverse populations are necessary to confirm and extend these findings.

2.
JCI Insight ; 5(22)2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-33104056

RESUMO

BACKGROUNDPsoriasis is a chronic inflammatory skin disease associated with increased obesity, noncalcified coronary artery burden (NCB), and incident myocardial infarction. Here, we sought to assess the relationship among inflammation, visceral adipose tissue (VAT), and NCB. Furthermore, we evaluated whether improvement in VAT would be associated with reduction in NCB over time in psoriasis.METHODSConsecutive psoriasis patients underwent coronary CT angiography to quantify NCB and abdominal CT to calculate VAT at baseline (n = 237), 1 year (n = 176), and 4 years (n = 50).RESULTSPatients with high levels of high-sensitivity C-reactive protein (hs-CRP) had significantly greater visceral adiposity (17,952.9 ± 849.2 cc3 vs. 13370.7 ± 806.8 cc3, P < 0.001) and noncalcified coronary burden (1.26 ± 0.03 vs. 1.07 ± 0.02 mm2) than those with low levels of hs-CRP. Those with higher levels of VAT had more systemic inflammation (hs-CRP, median [IQR], 2.5 mg/L [1.0-5.3 mg/L] vs. 1.2 mg/L [0.6-2.9 mg/L]), with approximately 50% higher NCB (1.42 ± 0.6 mm2 vs. 0.91 ± 0.2 mm2, P < 0.001). VAT associated with NCB in fully adjusted models (ß = 0.47, P < 0.001). At 1-year follow-up, patients who had worsening hs-CRP had an increase in VAT (14,748.7 ± 878.1 cc3 to 15,158.7 ± 881.5 cc3; P = 0.03), whereas those who had improved hs-CRP improved their VAT (16,876.1 ± 915.2 cc3 to 16310.4 ± 889.6 cc3; P = 0.04). At 1 year, there was 10.3% reduction in NCB in those who had decreased VAT (ß = 0.26, P < 0.0001), which persisted in a subset of patients at 4 years (ß = 0.39, P = 0.003).CONCLUSIONSInflammation drives development of VAT, increased cardiometabolic risk, and NCB in psoriasis. Reduction of inflammation associated with reduction in VAT and associated with longitudinal improvement in NCB. These findings demonstrate the important role of inflammation in the development of VAT in humans and its effect on early atherogenesis.TRIAL REGISTRATIONClinicalTrials.gov NCT01778569.FUNDINGThis study was supported by the National Heart, Lung, and Blood Institute Intramural Research Program (HL006193-05), the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation (no. 2014194), the American Association for Dental Research, the Colgate-Palmolive Company, Genentech, and Elsevier as well as private donors.


Assuntos
Biomarcadores/metabolismo , Doença da Artéria Coronariana/patologia , Inflamação/complicações , Gordura Intra-Abdominal/patologia , Psoríase/fisiopatologia , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
3.
JACC Cardiovasc Imaging ; 13(2 Pt 1): 465-477, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-30448131

RESUMO

OBJECTIVES: This study hypothesized that there is an association between chronic stress (as indexed by resting amygdalar activity [AmygA]), hematopoietic system activity (HMPA), and subclinical cardiovascular indexes (aortic vascular inflammation [VI] and noncalcified coronary plaque burden [NCB]) in psoriasis (PSO). The study also hypothesized that treatment of PSO would improve these parameters. BACKGROUND: PSO is a stress-related chronic inflammatory condition that is associated with increased prevalence of subclinical cardiovascular disease (CVD). In individuals without PSO, stress has been linked to CVD through a serial biological pathway that involves the amygdala, hematopoietic tissues, and atherosclerotic plaques. METHODS: A total of 164 consecutive patients with PSO and 47 healthy volunteers underwent 18-fluorodeoxyglucose positron emission tomography/computed tomography scans for assessment of AmygA, HMPA, and VI, as well as coronary computed tomography angiography scans for quantifying NCB. Furthermore, a consecutive subset of 30 patients with severe PSO (Psoriasis Area Severity Index Score >10) were followed at 1 year to assess the relationship between skin disease improvement and AmygA, HMPA, VI, and NCB. RESULTS: The PSO cohort was middle-aged (mean age: 50 years), had low cardiovascular risk (Framingham risk score: median: 3) and had mild to moderate PSO activity (median Psoriasis Area Severity Index Score: 5.6). AmygA was higher in patients with PSO compared to volunteer participants. AmygA was associated with HMPA (bone marrow activity: ß = 0.20, p = 0.01) and subclinical CVD (VI: ß = 0.31, p < 0.001; NCB: ß = 0.27, p < 0.001) The AmygA-CVD association was in part mediated by HMPA (VI: 20.9%, NCB: 36.7%). Following 1 year of PSO treatment in those with severe disease, improvement in skin disease was accompanied by a reduction in AmygA, bone marrow activity, and VI, with no progression of NCB. CONCLUSIONS: In PSO, a chronic inflammatory disease state, AmygA, which is a manifestation of chronic stress, substantially contributes to the risk of subclinical CVD. Additional studies that use psychometric measures of stress are required to explore therapeutic impact.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Doenças Cardiovasculares/etiologia , Sistema Hematopoético/fisiopatologia , Psoríase/complicações , Estresse Psicológico/etiologia , Adulto , Idoso , Tonsila do Cerebelo/diagnóstico por imagem , Anti-Inflamatórios/uso terapêutico , Doenças Assintomáticas , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/fisiopatologia , Estudos de Casos e Controles , Doença Crônica , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Estudos Transversais , Feminino , Fluordesoxiglucose F18/administração & dosagem , Sistema Hematopoético/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Valor Preditivo dos Testes , Estudos Prospectivos , Psoríase/diagnóstico por imagem , Psoríase/tratamento farmacológico , Psoríase/fisiopatologia , Compostos Radiofarmacêuticos/administração & dosagem , Fatores de Risco , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Estresse Psicológico/diagnóstico por imagem , Estresse Psicológico/fisiopatologia , Resultado do Tratamento , Estados Unidos/epidemiologia
4.
JAMA Dermatol ; 156(2): 151-157, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31746956

RESUMO

Importance: Psoriasis, a chronic inflammatory skin disease associated with accelerated noncalcified coronary burden (NCB) by coronary computed tomography angiography (CCTA), accelerates lipoprotein oxidation in the form of oxidized modified lipoproteins. A transmembrane scavenger receptor for these oxidized modified lipoproteins is lectinlike oxidized low-density lipoprotein receptor-1 (LOX-1), which has been reported to be associated with coronary artery disease. It is unknown whether this receptor is associated with coronary artery disease in psoriasis. Objective: To assess the association between soluble LOX-1 (sLOX-1) and NCB in psoriasis over time. Design, Setting, and Participants: In a cohort study at the National Institutes of Health, 175 consecutive patients with psoriasis were referred from outpatient dermatology practices between January 1, 2013, and October 1, 2017. A total of 138 consecutively recruited patients with psoriasis were followed up at 1 year. Exposures: Circulating soluble lectinlike oxidized low-density lipoprotein receptor-1 levels were measured blindly by field scientists running undiluted serum using an enzyme-linked immunosorbent assay. Main Outcomes and Measures: Coronary computed tomography angiography scans were performed to quantify NCB in all 3 major epicardial coronary arteries by a reader blinded to patient demographics, visit, and treatment status. Results: Among the 175 patients with psoriasis, the mean (SD) age was 49.7 (12.6) years and 91 were men (55%). The cohort had relatively low median cardiovascular risk by Framingham risk score (median, 2.0 [interquartile range (IQR), 1.0-6.0]) and had a mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) suggestive of overweight profiles (29.6 [6.0]). Elevated sLOX-1 levels were found in patients with psoriasis compared with age- and sex-matched controls (median, 210.3 [IQR, 110.9-336.2] vs 83.7 [IQR, 40.1-151.0]; P < .001), and were associated with Psoriasis Area Severity Index (PASI) score (ß = 0.23; 95% CI, 0.082-0.374; P = .003). Moreover, sLOX-1 was associated with NCB independent of hyperlipidemia status (ß = 0.11; 95% CI, 0.016-0.200; P = .023), an association which persisted after adjusting for traditional cardiovascular risk factors, statin use, and biologic psoriasis treatment (ß = 0.10; 95% CI, 0.014-0.193; P = .03). At 1 year, in those who had clinical improvement in PASI (eg, >50% improvement), a reduction in sLOX-1 (median, 311.1 [IQR, 160.0-648.8] vs median, 224.2 [IQR, 149.1 - 427.4]; P = .01) was associated with a reduction in NCB (ß = 0.14; 95% CI, 0.028-0.246; P = .02). Conclusions and Relevance: Soluble lectinlike oxidized low-density lipoprotein receptor-1 levels were elevated in patients with psoriasis and were associated with severity of skin disease. Moreover, sLOX-1 associated with NCB independent of hyperlipidemia status, suggesting that inflammatory sLOX-1 induction may modulate lipid-rich NCB in psoriasis. Improvement of skin disease was associated with a reduction of sLOX-1 at 1 year, demonstrating the potential role of sLOX-1 in inflammatory atherogenesis in psoriasis.


Assuntos
Angiografia por Tomografia Computadorizada , Doença da Artéria Coronariana/diagnóstico por imagem , Psoríase/complicações , Receptores Depuradores Classe E/sangue , Adulto , Estudos de Coortes , Doença da Artéria Coronariana/sangue , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Psoríase/patologia , Índice de Gravidade de Doença , Fatores de Tempo
5.
Atherosclerosis ; 289: 44-50, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31450013

RESUMO

BACKGROUND AND AIMS: Vitamin D exists as an inactive 25-hydroxyvitamin D (25(OH)D) in the bloodstream, which is converted to active 1,25-dihydroxyvitaminD (1,25(OH)2D) in target tissues. Cohort studies reporting cardiovascular disease among individuals with low vitamin D are inconsistent and solely measure 25(OH)D. Psoriasis, a chronic inflammatory disease, is a vitamin D deficient state and is associated with increased cardiovascular disease risk. While serum 25(OH)D is routinely measured, we hypothesized that measurement of 1,25(OH)2D in psoriasis may perform better than 25(OH)D in capturing cardiovascular risk. METHODS: Consecutive psoriasis patients (N = 122) at baseline underwent FDG PET/CT and CCTA scans to measure visceral adipose volume, aortic vascular uptake of FDG, and coronary plaque burden respectively. Blood levels of both 1,25(OH)2D and 25(OH)D were measured by chemiluminescence (LIAISON XL DIaSorin, Stillwater, MN). RESULTS: The psoriasis cohort was middle-aged (mean ±â€¯SD: 49.6 ±â€¯13.0), predominantly male (n = 71, 58%), in majority Caucasians (n = 98, 80%), and had moderate-to-severe skin disease [psoriasis area severity index score, PASI score, med. (IQR): 5.5 (3.2-10.7)], with almost one-fourth of the cohort on biologic psoriasis therapy for skin disease management (n = 32, 27%) at baseline. Interestingly, serum levels of 1,25(OH)2D but not 25(OH)D were found to be inversely associated with visceral adipose, a marker of cardiometabolic risk in fully adjusted models (ß = - 0.43, p = 0.026 and ß = -0.26 p = 0.13). Similarly, we found an inverse relationship between 1,25(OH)2D, but not 25(OH)D, and aortic vascular uptake of FDG independent of traditional risk factors (ß = -0.19, p = 0.01). Finally, we found that serum 1,25(OH)2D, but not 25(OH)D, was inversely associated with non-calcified coronary plaque burden, as measured by CCTA independent of traditional risk factors (ß = -0.18, p = 0.03). CONCLUSIONS: In conclusion, we demonstrate that low 1,25(OH)2D levels were associated with visceral adipose volume, vascular uptake of FDG and coronary plaque burden independent of traditional risk factors, suggesting that 1,25(OH)2D may better capture the cardiometabolic risk associated with vitamin D deficient states.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/complicações , Psoríase/sangue , Psoríase/complicações , Vitamina D/análogos & derivados , Adiposidade , Idoso , Angiografia Coronária , Vasos Coronários/fisiopatologia , Feminino , Fluordesoxiglucose F18 , Humanos , Imunoensaio , Gordura Intra-Abdominal , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/sangue , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Prospectivos , Risco , Vitamina D/sangue
6.
JAMA Cardiol ; 3(10): 949-956, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30208407

RESUMO

Importance: Inflammation is critical to atherosclerosis. Psoriasis, a chronic inflammatory disease associated with early cardiovascular events and increased aortic vascular inflammation (VI), provides a model to study the process of early atherogenesis. Fludeoxyglucose F 18 positron emission tomography/computed tomography (18F-FDG PET/CT) helps quantify aortic VI, and coronary computed tomography angiography provides coronary artery disease (CAD) assessment through evaluation of total plaque burden (TB) and noncalcified coronary plaque burden (NCB), luminal stenosis, and high-risk plaques (HRP). To our knowledge, association between aortic VI and broad CAD indices has not yet been assessed in a chronic inflammatory disease state. Such a study may provide information regarding the utility of aortic VI in capturing early CAD. Objective: To assess the association between aortic VI and CAD indices, including TB, NCB, luminal stenosis, and HRP prevalence, in psoriasis. Design, Setting, and Participants: In a cross-sectional cohort study at the National Institutes of Health, 215 consecutive patients with psoriasis were recruited from surrounding outpatient dermatology practices. All patients underwent 18F-FDG PET/CT for aortic VI assessment, and 190 of 215 patients underwent coronary computed tomography angiography to characterize CAD. The study was conducted between January 1, 2013, and May 31, 2017. Data were analyzed in March 2018. Exposures: Aortic VI assessed by 18F-FDG PET/CT. Main Outcomes and Measures: Primary outcome: TB and NCB. Secondary outcomes: luminal stenosis and HRP. Results: Among 215 patients with psoriasis (mean [SD] age, 50.4 [12.6] years; 126 men [59%]), patients with increased aortic VI had increased TB (standardized ß = 0.48; P < .001), and higher prevalence of luminal stenosis (OR, 3.63; 95% CI, 1.71-7.70; P = .001) and HRP (OR, 3.05; 95% CI, 1.42-6.47; P = .004). The aortic VI and TB association was primarily driven by NCB (ß = 0.49; P < .001), whereas the aortic VI and HRP association was driven by low-attenuation plaque (OR, 5.63; 95% CI, 1.96-16.19; P = .001). All associations of aortic VI remained significant after adjustment for cardiovascular risk factors: aortic VI and TB (ß = 0.23; P < .001), NCB (ß = 0.24; P < .001), luminal stenosis (OR, 3.40; 95% CI, 1.40-8.24; P = .007), and HRP (OR, 2.72; 95% CI, 1.08-6.83; P = .03). No association was found between aortic VI and dense-calcified coronary plaque burden. Conclusions and Relevance: Aortic VI is associated with broad CAD indices, suggesting that aortic VI may be a surrogate for early CAD. Larger prospective studies need to assess these associations longitudinally and examine treatment effects on these outcomes.


Assuntos
Aorta/diagnóstico por imagem , Doença da Artéria Coronariana/diagnóstico por imagem , Inflamação/diagnóstico por imagem , Psoríase/complicações , Adulto , Angiografia por Tomografia Computadorizada , Estudos Transversais , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Prospectivos
7.
Am Heart J ; 204: 109-118, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30092412

RESUMO

BACKGROUND: Cardiovascular disease is a leading economic and medical burden in the United States (US). As an important risk factor for cardiovascular disease, hypertension represents a critical point of intervention. Less is known about longitudinal effects of neighborhood deprivation on blood pressure outcomes, especially in light of new hypertension guidelines. METHODS: Longitudinal data from the Dallas Heart Study facilitated multilevel regression analysis of the relationship between neighborhood deprivation, blood pressure change, and incident hypertension over a 9-year period. Factor analysis explored neighborhood perception, which was controlled for in all analyses. Neighborhood deprivation was derived from US Census data and divided into tertiles for analysis. Hypertension status was compared using pre-2017 and 2017 hypertension guidelines. RESULTS: After adjusting for covariates, including moving status and residential self-selection, we observed significant associations between residing in the more deprived neighborhoods and 1) increasing blood pressure over time and 2) incident hypertension. In the fully adjusted model of continuous blood pressure change, significant relationships were seen for both medium (SBP: ß = 4.81, SE = 1.39, P = .0005; DBP: ß = 2.61, SE = 0.71, P = .0003) and high deprivation (SBP: ß = 7.64, SE = 1.55, P < .0001; DBP: ß = 4.64, SE = 0.78, P < .0001). In the fully adjusted model of incident hypertension, participants in areas of high deprivation had 1.69 higher odds of developing HTN (OR 1.69; 95% CI 1.02, 2.82), as defined by 2017 hypertension guidelines. Results varied based on definition of hypertension used (pre-2017 vs. 2017 guidelines). CONCLUSION: These findings highlight the potential impact of adverse neighborhood conditions on cardiometabolic outcomes, such as hypertension.


Assuntos
Status Econômico , Hipertensão/epidemiologia , Áreas de Pobreza , Características de Residência/estatística & dados numéricos , Adulto , Feminino , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Texas/epidemiologia
8.
J Adolesc Health ; 62(5): 583-590, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29477492

RESUMO

PURPOSE: Decreased cardiorespiratory fitness (CRF) is associated with an increased risk of cardiovascular disease. However, little is known how the interaction of diet, physical activity (PA), and sedentary time (ST) affects CRF among adolescents. By using a nationally representative sample of U.S. adolescents, we used cluster analysis to investigate the interactions of these behaviors with CRF. We hypothesized that distinct clustering patterns exist and that less healthy clusters are associated with lower CRF. METHODS: We used 2003-2004 National Health and Nutrition Examination Survey data for persons aged 12-19 years (N = 1,225). PA and ST were measured objectively by an accelerometer, and the American Heart Association Healthy Diet Score quantified diet quality. Maximal oxygen consumption (V˙O2​max) was measured by submaximal treadmill exercise test. We performed cluster analysis to identify sex-specific clustering of diet, PA, and ST. Adjusting for accelerometer wear time, age, body mass index, race/ethnicity, and the poverty-to-income ratio, we performed sex-stratified linear regression analysis to evaluate the association of cluster with V˙O2​max. RESULTS: Three clusters were identified for girls and boys. For girls, there was no difference across clusters for age (p = .1), weight (p = .3), and BMI (p = .5), and no relationship between clusters and V˙O2​max. For boys, the youngest cluster (p < .01) had three healthy behaviors, weighed less, and was associated with a higher V˙O2​max compared with the two older clusters. CONCLUSIONS: We observed clustering of diet, PA, and ST in U.S. adolescents. Specific patterns were associated with lower V˙O2​max for boys, suggesting that our clusters may help identify adolescent boys most in need of interventions.


Assuntos
Aptidão Cardiorrespiratória/fisiologia , Exercício Físico , Comportamentos Relacionados com a Saúde , Comportamento Sedentário , Acelerometria/métodos , Adolescente , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Masculino , Inquéritos Nutricionais , Estado Nutricional , Fatores Sexuais , Estados Unidos
9.
Prev Med Rep ; 9: 42-48, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29340269

RESUMO

Sedentary time (ST) and neighborhood environment (NE) are predictors of cardiovascular (CV) health. However, little is known about ST's relationship with NE. We examined associations of perceived and objective NE with ST in the predominantly African American faith-based population of the Washington, D.C. CV Health and Needs Assessment. After using community-based research principles, participants reported NE perceptions, including sidewalks, recreational areas, and crime presence. Factor analysis was conducted to explore pertinent constructs; factor sums were created and combined as Total Perception Score (TPS) (higher score = more favorable perception). Objective NE was assessed using Google Maps and the Active Neighborhood Checklist (ANC). ST was self-reported. Linear regression determined relationships between TPS and ST, and ANC scores and ST, for 1) overall population, 2) lower median-income D.C. areas, and 3) higher median-income DC and Maryland areas. For the sample (N = 98.9% African-American, 78% female), lower median-income areas had significantly lower mean TPS and ANC scores than higher median-income areas (p < 0.001). Three factors (neighborhood violence, physical/social environment, and social cohesion) were associated with overall NE perception. Among those in lower median-income areas, there was a negative association between TPS and ST that remained after covariate adjustment; this was not observed in higher median-income areas. There was no association between ANC scores and ST. Poorer NE perception is associated with greater ST for those in lower income areas, while objective environment is not related to ST. Multi-level interventions are needed to improve NE perceptions in lower-median income areas, reduce ST, and improve CV health.

10.
Physiol Rep ; 6(2)2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29380958

RESUMO

Early pioneering investigators discovered, in anesthetized dogs, a protective period within the cardiac cycle. The protective period was a time within the cardiac cycle when a precisely timed stimulus prevented the initiation of ventricular fibrillation caused by an earlier stimulus. Thus, in addition to the susceptible period of repolarization discussed by Wiggers and Wegria (Am. J. Physiol. 131:296, 1940; Am. J. Physiol. 128:500, 1940), there is also a nearby protective period. This report describes a protective period within the cardiac cycle of conscious mice when a precisely timed stimulus prevented the initiation of ventricular tachycardia caused by an earlier stimulus. In addition, we tested the hypothesis that this precisely timed pulse within the protective period prevents reperfusion-induced ventricular tachyarrhythmias in conscious mice. Mice (n = 6) were prepared to record arterial blood pressure and the electrocardiogram. In addition, a vascular occluder was placed around the left main coronary artery, and stimulating electrodes were secured onto the left ventricle. A single precisely timed electrical pulse (5 msec pulse width and 2.5 V) to the left ventricle arriving 13.9 ± 1.1 msec after the R-wave, caused ventricular tachycardia occurring 24.9 ± 0.9 msec after the R-wave. Importantly, a second precisely timed electrical pulse arriving 18.8 ± 0.5 msec after the first stimulus blocked the induction of ventricular tachycardia caused by the earlier stimulus. On an alternate day, the susceptibility to sustained ventricular tachycardia produced by 3.5 min of occlusion and reperfusion of the coronary artery was determined in conscious mice by use of the vascular occluder. Reperfusion resulted in ventricular tachycardia in all six mice. A precisely timed pulse within the protective period prevented ventricular tachycardia in all mice.


Assuntos
Estimulação Elétrica , Frequência Cardíaca/fisiologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Taquicardia Ventricular/fisiopatologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Isquemia Miocárdica/complicações , Isquemia Miocárdica/fisiopatologia , Traumatismo por Reperfusão Miocárdica/complicações , Taquicardia Ventricular/etiologia
11.
JACC Cardiovasc Imaging ; 11(2 Pt 2): 349-357, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29055628

RESUMO

OBJECTIVES: The authors sought to examine the relationship between visceral adipose tissue (VAT) and vascular inflammation (VI) by 18F-Fluorodeoxyglucose (18F-FDG) positron-emission tomography (PET)/computed tomography (CT) in psoriasis (PSO). Furthermore, we evaluated whether treatment of PSO modulated VAT and VI. BACKGROUND: PSO, a chronic inflammatory skin disease, is associated with VI by 18F-FDG PET/CT and increased cardiometabolic risk including adipose tissue dysregulation. Recently, VI was associated with future cardiovascular events; however, the relationship of visceral and subcutaneous adiposity with VI in PSO has yet to be evaluated. METHODS: Consecutive PSO patients (N = 77) underwent 18F-FDG PET/CT scans to measure VI and abdominal adiposity. A subset of PSO patients with severe skin disease was scanned at 1 year following PSO treatment (N = 13). RESULTS: The cohort was middle aged (51.8 ± 12.6 years), predominantly male (n = 44, 57%), had low cardiovascular risk by Framingham 10-year risk (median 4 years [interquartile range (IQR): 2 to 7 years]), and mild-to-moderate skin disease (5.2 [IQR: 3.0 to 8.5]). PSO disease severity associated with VAT (ß = 0.33; p = 0.004) beyond SAT (ß = 0.30; p = 0.005). VAT (ß = 0.55; p < 0.001), but not SAT (ß = 0.15; p = 0.11), associated with VI beyond cardiovascular risk factors. We followed a subset of severe PSO patients treated aggressively for PSO and observed improvement in PSO severity and VAT, which was associated with an improvement in VI at 1 year beyond cardiovascular risk factors (ß = 0.53; p = 0.049). CONCLUSIONS: Volume-based CT measurement of VAT may capture metabolic risk associated with VI compared to subcutaneous adipose tissue in PSO. PSO treatment associated with a decrease in VAT as well as decrease in VI suggesting VAT as a relevant biomarker related to VI in PSO.


Assuntos
Adiposidade , Fluordesoxiglucose F18/administração & dosagem , Gordura Intra-Abdominal/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Psoríase/diagnóstico por imagem , Compostos Radiofarmacêuticos/administração & dosagem , Gordura Subcutânea/diagnóstico por imagem , Vasculite/diagnóstico por imagem , Adulto , Feminino , Humanos , Gordura Intra-Abdominal/fisiopatologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Psoríase/fisiopatologia , Psoríase/terapia , Fatores de Risco , Gordura Subcutânea/fisiopatologia , Fatores de Tempo , Vasculite/fisiopatologia , Vasculite/terapia , Imagem Corporal Total
12.
Obesity (Silver Spring) ; 25(12): 2149-2155, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29086471

RESUMO

OBJECTIVE: The objective of this study was to quantify the impact of crime on physical activity location accessibility, leisure-time physical activity (LTPA), and obesity among African American women. METHODS: An agent-based model was developed in 2016 to represent resource-limited Washington, DC, communities and their populations to simulate the impact of crime on LTPA and obesity among African American women under different circumstances. RESULTS: Data analysis conducted between 2016 and 2017 found that in the baseline scenario, African American women had a 25% probability of exercising. Reducing crime so more physical activity locations were accessible (increasing from 10% to 50%) decreased the annual rise in obesity prevalence by 2.69%. Increasing the probability of African American women to exercise to 37.5% further increased the impact of reducing crime on obesity (2.91% annual decrease in obesity prevalence). CONCLUSIONS: These simulations showed that crime may serve as a barrier to LTPA. Reducing crime and increasing propensity to exercise through multilevel interventions (i.e., economic development initiatives to increase time available for physical activity and subsidized health care) may promote greater than linear declines in obesity prevalence. Crime prevention strategies alone can help prevent obesity, but combining such efforts with other ways to encourage physical activity can yield even greater benefits.


Assuntos
Crime/tendências , Exercício Físico/psicologia , Obesidade/epidemiologia , Adolescente , Adulto , Negro ou Afro-Americano , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade/psicologia , Prevalência , Estados Unidos , Adulto Jovem
13.
JAMA Cardiol ; 2(9): 1013-1018, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28564678

RESUMO

Importance: Inflammation is critical in the development of atherosclerosis. Psoriasis is a chronic inflammatory skin disease that is associated with increased vascular inflammation by 18fluorodeoxyglucose positron emission tomography/computed tomography in vivo and future cardiovascular events. It provides a human model to understand the effect of treating inflammation in a target organ (eg, the skin) on vascular diseases. Objective: To investigate the association between change in skin disease severity and change in vascular inflammation at 1 year and to characterize the impact of 1 year of anti-tumor necrosis factor therapy on vascular inflammation. Design, Setting, and Participants: In this prospective cohort study, 220 participants from outpatient practices were recruited at the US National Institutes of Health. A total of 115 consecutively recruited patients with psoriasis were followed up at 1 year. The study was conducted from January 1, 2013, through October 31, 2016, with data analyzed in November 2016. Exposure: Skin inflammation measured as Psoriasis Area and Severity Index (PASI) score. Main Outcomes and Measures: Vascular inflammation assessed as target-to-background ratio by 18fluorodeoxyglucose positron emission tomography/computed tomography. Results: Among the 115 patients, the mean (SD) age at 1-year follow-up was 50.8 (12.8) years and 68 were men (59%). The cohort had a low cardiovascular risk by Framingham risk score and mild-to-moderate psoriasis, with a median PASI score of 5.2 (interquartile range, 3.0-8.9). At follow-up, the total cohort had a median improvement in PASI score of 33%, with use of topical therapy (60%), biological therapy (66%, mostly anti-tumor necrosis factor) and phototherapy (15%) (P < .001). Moreover, improvement in PASI score was associated with improvement in target-to-background ratio of 6%, mainly driven by those with higher responses in PASI score (P < .001). This association persisted beyond traditional risk factors (ß = 0.19; 95% CI, 0.012-0.375; P = .03) and was the strongest in those initiated with anti-tumor necrosis factor therapy (ß = 0.79; 95% CI, 0.269-1.311; P = .03). Conclusions and Relevance: Improvement in psoriasis skin disease severity was associated with improvement in aortic vascular inflammation by 18fluorodeoxyglucose positron emission tomography/computed tomography, with greater improvement in aortic vascular inflammation observed in those who had higher than 75% reduction in skin disease severity. These findings suggest that controlling remote target organ inflammation (eg, in the skin) may improve vascular diseases; however, randomized clinical trials are needed to confirm these findings.


Assuntos
Antirreumáticos/uso terapêutico , Aorta/diagnóstico por imagem , Inflamação/epidemiologia , Psoríase/epidemiologia , Adulto , Proteína C-Reativa/imunologia , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos de Coortes , Feminino , Fluordesoxiglucose F18 , Humanos , Inflamação/diagnóstico por imagem , Inflamação/imunologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fototerapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Estudos Prospectivos , Psoríase/imunologia , Psoríase/terapia , Compostos Radiofarmacêuticos , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/antagonistas & inibidores
14.
Artigo em Inglês | MEDLINE | ID: mdl-28282878

RESUMO

Optimization of existing measurement tools is necessary to explore links between aspects of the neighborhood built environment and health behaviors or outcomes. We evaluate a scoring method for virtual neighborhood audits utilizing the Active Neighborhood Checklist (the Checklist), a neighborhood audit measure, and assess street segment representativeness in low-income neighborhoods. Eighty-two home neighborhoods of Washington, D.C. Cardiovascular Health/Needs Assessment (NCT01927783) participants were audited using Google Street View imagery and the Checklist (five sections with 89 total questions). Twelve street segments per home address were assessed for (1) Land-Use Type; (2) Public Transportation Availability; (3) Street Characteristics; (4) Environment Quality and (5) Sidewalks/Walking/Biking features. Checklist items were scored 0-2 points/question. A combinations algorithm was developed to assess street segments' representativeness. Spearman correlations were calculated between built environment quality scores and Walk Score®, a validated neighborhood walkability measure. Street segment quality scores ranged 10-47 (Mean = 29.4 ± 6.9) and overall neighborhood quality scores, 172-475 (Mean = 352.3 ± 63.6). Walk scores® ranged 0-91 (Mean = 46.7 ± 26.3). Street segment combinations' correlation coefficients ranged 0.75-1.0. Significant positive correlations were found between overall neighborhood quality scores, four of the five Checklist subsection scores, and Walk Scores® (r = 0.62, p < 0.001). This scoring method adequately captures neighborhood features in low-income, residential areas and may aid in delineating impact of specific built environment features on health behaviors and outcomes.


Assuntos
Planejamento Ambiental , Projetos de Pesquisa , Características de Residência , Algoritmos , Ciclismo , District of Columbia , Comportamentos Relacionados com a Saúde , Humanos , Pobreza , Meios de Transporte , Caminhada
15.
Auton Neurosci ; 201: 24-31, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27594686

RESUMO

Mice may now be the preferred animal model for biomedical research due to its anatomical, physiological, and genetic similarity to humans. However, little is known about accentuated antagonism of chronotropic and dromotropic properties in conscious mice. Accordingly, we describe the complex and interacting influence of the autonomic nervous system on cardiac electrophysiology in conscious mice. Specifically, we report the effects of single and combined cardiac autonomic blockade on measurements of pulse interval (heart rate), atrio-ventricular interval, sinus node recovery time (SNRT), SNRT corrected for spontaneous sinus cycle, and Wenckebach cycle length in conscious mice free of the confounding influences of anesthetics and surgical trauma. Autonomic influences were quantified as the change in parameter induced by its selective blocker (Sympathetic or Parasympathetic Effect) or as the difference between the intrinsic value and the value after a selective blocker (Sympathetic or Parasympathetic Tonus). Sympatho-Vagal Balance (SVB) was assessed as the ratio of control interval to intrinsic interval. SVB suggests slight parasympathetic dominance in the control of cardiac electrophysiology intervals. Furthermore, results documents a complex interaction between the sympathetic and parasympathetic divisions of the autonomic nervous system in the control of cardiac electrophysiology parameters. Specifically, the parasympathetic effect was greater than the parasympathetic tonus in the control of cardiac electrophysiology parameters. In contrast, the sympathetic effect was smaller than the sympathetic tonus in the control of cardiac electrophysiology parameters. Results have important implications because actions of pharmacological agents that alter the autonomic control of cardiac electrophysiology are transformed by these interacting mechanisms.


Assuntos
Sistema Nervoso Autônomo/fisiologia , Coração/fisiologia , Sistema Nervoso Parassimpático/fisiologia , Antagonistas Adrenérgicos beta/farmacologia , Animais , Sistema Nervoso Autônomo/efeitos dos fármacos , Eletrocardiografia Ambulatorial , Coração/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Antagonistas Muscarínicos/farmacologia , Sistema Nervoso Parassimpático/efeitos dos fármacos , Telemetria
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