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1.
Artigo em Inglês | MEDLINE | ID: mdl-31879247

RESUMO

BACKGROUND: National investigations on the interaction of insulin resistance, ß-cell dysfunction, and obesity with the development of diabetes are scarce in China. We aimed to investigate the individual and joint associations of insulin resistance and ß-cell dysfunction with incident diabetes, and to examine the modifying effect of BMI and waist circumference on these associations among adults with normal glucose tolerance and with prediabetes. METHODS: In this nationwide, population-based, prospective cohort study, we analysed data from the China Cardiometabolic Disease and Cancer Cohort Study, which recruited adults aged 40 years or older during 2011-12 (baseline) and invited participants to attend follow-up visits in 2014-16. Patients with diabetes at baseline, missing data for baseline measures of glucose tolerance status, missing data for baseline homoeostasis model assessment (HOMA) indexes, missing data for baseline covariates, and missing data for measures of glucose tolerance status at follow-up visits were excluded. At baseline and follow-up visits, a comprehensive set of questionnaires, clinical measurements, oral glucose tolerance tests, and laboratory examinations were carried out following standardised protocols. Glucose tolerance status and prediabetes were defined according to the American Diabetes Association 2010 criteria. In the main analysis, we examined the contributions of insulin resistance (HOMA of insulin resistance [HOMA-IR]) and ß-cell dysfunction (HOMA of ß-cell function [HOMA-B]) to diabetes risk, and evaluated the impact of obesity on these associations. FINDINGS: 94 952 participants (31 517 men and 63 435 women) were included in the analysis. High HOMA-IR was associated with a greater hazard of diabetes (quartile 4 vs 1: hazard ratio [HR] 6·70, 95% CI 6·08-7·39; per unit increase in Z score: HR 2·17, 95% CI 2·10-2·24) than low HOMA-B (quartile 1 vs 4: 4·08, 3·72-4·48; per unit decrease in Z score: 1·92, 1·85-2·00). Approximately 24·4% (95% CI 23·6-25·2) of the incident diabetes could be attributed to insulin resistance and 12·4% (11·2-13·7) could be attributed to ß-cell dysfunction. The HRs for diabetes were 1·83 (95% CI 1·72-1·95) per unit increase in Z score of HOMA-IR and 2·03 (1·86-2·21) per unit decrease in Z score of HOMA-B among participants with normal weight; the corresponding HRs for diabetes were 2·02 (1·93-2·11) and 1·88 (1·79-1·98) among participants with obesity (pinteraction=0·0091). These associations and interactions were similar for participants with normal glucose tolerance or prediabetes. INTERPRETATION: Insulin resistance shows a stronger association with incident diabetes than does ß-cell dysfunction in Chinese adults, and this association pattern was more prominent among adults with obesity. Given the limitations of HOMA indexes as surrogate measures of insulin resistance and ß-cell dysfunction, these findings should be interpreted with caution. FUNDING: National Natural Science Foundation of China.

2.
Free Radic Biol Med ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31706990

RESUMO

Nitric oxide (NO) participates in many physiological and pathological processes in human. Urine tests tell a lot about health, which are convenient and harmless. Redox stress, including imbalance of reactive nitrogen species and its metabolites NOx, has been gaining increased attention in autism spectrum disorder (ASD) research. However, concentrations of urinary nitrite and nitrate among the ASD population stay unclear. In this study, nitrite and nitrate were precisely measured in urine specimens from 44 ASD children, 30 healthy children (the control group) and 28 healthy adults with an optimized and validated analytic method. For the first time, concentrations of urinary NOx in ASD and healthy children were reported. Nitrite in the ASD population is higher than in the control group, with concentrations of 0.8708 ±â€¯0.1121 µM (0.1556-3.0393 µM) and 0.5938 ±â€¯0.07276 µM (0.1134-2.1004 µM) (p = 0.0420), respectively. Nitrite in the adult groups is 0.5808 ±â€¯0.0985 µM (0.0808-1.9335 µM), which is similar to that in the control group. On the contrary, urinary nitrate concentration in ASD children is lower than that in the control group, which are 2.875 ±â€¯0.2716 mM (0.3264-7.1835 mM) and 4.558 ±â€¯0.5915 mM (1.1860-15.8555 mM) (p = 0.0133), respectively. Nitrate in adults is also significantly lower than that in the control, 2.799 ±â€¯0.3640 mM (0.2507-8.6978 mM) and 4.558 ±â€¯0.5915 mM (p = 0.0146), respectively. Nitrite/nitrate ratios for ASD and the control groups were 0.3496 ±â€¯0.04382 x 10-3 and 0.1604 ±â€¯0.01862 x 10-3 (p = 0.0002), which again indicated the probability of NOx as a novel biomarker. Furthermore, no correlation between NOx and gender, as well as sample collection timing was found. Taken together, the association between NOx and ASD was significant. Urinary nitrite, nitrate and NO2-/NO3-, might serve as a new biomarker for ASD diagnosis during pursuit of harmless, fast, and convenient diagnostic method. Further studies are needed for the metabolic pathways of NOx in ASD pathogenesis.

3.
JAMA Cardiol ; 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31365039

RESUMO

Importance: Whether optimal cardiovascular health metrics may counteract the risk of cardiovascular events among patients with prediabetes or diabetes is unclear. Objective: To investigate the associations of ideal cardiovascular health metrics (ICVHMs) with subsequent development of cardiovascular disease (CVD) among participants with prediabetes or diabetes as compared with participants with normal glucose regulation. Design, Setting, and Participants: The China Cardiometabolic Disease and Cancer Cohort Study was a nationwide, population-based, prospective cohort study of 20 communities from various geographic regions in China. The study included 111 765 participants who were free from CVD or cancer at baseline. Data were analyzed between 2011 and 2016. Exposures: Prediabetes and diabetes were defined according to the American Diabetes Association 2010 criteria. Seven ICVHMs were adapted from the American Heart Association recommendations. Main Outcomes and Measures: The composite of incident fatal or nonfatal CVD, including cardiovascular death, myocardial infarction, stroke, and hospitalized or treated heart failure. Results: Of the 111 765 participants, 24 881 (22.3%) had normal glucose regulation, 61 024 (54.6%) had prediabetes, and 25 860 (23.1%) had diabetes. Mean (SD) age ranged from 52.9 (8.6) years to 59.4 (8.7) years. Compared with participants with normal glucose regulation, among participants with prediabetes, the multivariable-adjusted hazard ratio for CVD was 1.34 (95% CI, 1.16-1.55) for participants who had 1 ICVHM or less and 0.57 (95% CI, 0.43-0.75) for participants who had at least 5 ICVHMs; among participants with diabetes, the hazard ratios for CVD were 2.05 (95% CI, 1.76-2.38) and 0.80 (95% CI, 0.56-1.15) for participants who had 1 ICVHM or less and at least 5 ICVHMs, respectively. Such pattern of association between ICVHM and CVD was more prominent for participants younger than 55 years (prediabetes and at least 5 ICVHMs: hazard ratio [HR], 0.32; 95% CI, 0.16-0.63; 1 ICVHM or less: HR, 1.58, 95% CI, 1.13-2.21; diabetes and at least 5 ICVHMs: HR, 0.99; 95% CI, 0.44-2.26; 1 ICVHM or less: HR, 2.46; 95% CI, 1.71-3.54; compared with normal glucose regulation) than for participants 65 years or older (prediabetes and at least 5 ICVHMs: HR, 0.80; 95% CI, 0.50-1.26; 1 ICVHM or less: HR, 1.01; 95% CI, 0.79-1.31; diabetes and at least 5 ICVHMs: HR, 0.79; 95% CI, 0.46-1.35; 1 ICVHM or less: HR, 1.73; 95% CI, 1.36-2.22, compared with normal glucose regulation; P values for interaction ≤.02). Additionally, the hazard ratio for CVD per additional ICVHM was 0.82 (95% CI, 0.79-0.86) among participants with prediabetes and was 0.85 (95% CI, 0.80-0.89) among participants with diabetes. Conclusions and Relevance: Participants with prediabetes or diabetes who had 5 or more ICVHMs exhibited lower or no significant excess CVD risks compared with the participants with normal glucose regulation.

4.
J Diabetes ; 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31290214

RESUMO

BACKGROUND: Unhealthy diet is one of the important risk factors of diabetes, which is one of the major public health problems in China. The Internet tools provide large-scale passively collected data that show people's dietary preferences and their relationship with diabetes risk. METHODS: 212 341 708 individuals' dietary preference labels were created based on Internet data from online search and shopping software. Metabolic data obtained from the 2010 China Noncommunicable Disease Surveillance, which had 98 658 participants, was used to estimate the relation between dietary preferences geographical distribution and diabetes risk. RESULTS: Chinese dietary preferences had different geographical distribution, which is related to the local climate and consumption level. Fried food preference proportion distribution was significantly positively correlated with diabetes prevalence, hypertension prevalence and body mass index (BMI). Similarly, grilled food preference proportion distribution had significantly positive correlation with the prevalence of diabetes and hypertension. In contrast, spicy food preference proportion distribution was negatively correlated with diabetes prevalence. Sweet food preference proportion distribution was positively related to diabetes prevalence. Using dietary preferences data to predict regional prevalence of diabetes, hypertension and BMI, the average values of error (95% CI) between the three paired predicted and observed values were 9.8% (6.9%-12.7%), 7.5% (5.0%-10.0%) and 1.6% (1.2%-2.0%), respectively. CONCLUSIONS: Fried food, grilled food, and sweet food preferences were positively related to diabetes risk whereas spicy food preference was negatively correlated with diabetes risk. Dietary preferences based on passively collected Internet data could be used to predict regional prevalence of diabetes, hypertension, and BMI and showed good value for public health monitoring.

5.
Osong Public Health Res Perspect ; 10(3): 123-136, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31263661

RESUMO

Objectives: Cardiovascular disease (CVD) has a substantial financial impact on healthcare systems in the US. This study aimed to examine the impact of CVD on health insurance coverage and health service use under economic stress as indicated by the Great Recession in the US (December 2007-June 2009). Methods: Data of 26,483 adults aged ≥ 20 years from the 2003-2012 National Health and Nutrition Examination Survey were analyzed. There were 9,479 adults assigned to the group "before the Great Recession" (2003-2006), 5,674 adults assigned to "during the Great Recession" (2007-2008), and 11,330 adults assigned to "after the Great Recession" (2009-2012). Results: Patients with CVD from low-income families were more likely to have health insurance during the recession (OR:1.57, 95% CI: 1.01,2.45). Those participants without CVD, who were from low-income families or < 65 years, were more likely to use the emergency room rather than primary care facilities to gain access to routine healthcare (p < 0.05). Patients with CVD from high-income families were also more likely to use the emergency room (p < 0.05). Patients with CVD but not those without CVD, who reported a high family income or were ≥ 65 years old, were less likely to use mental health services during the recession than before the recession. Conclusion: Effective strategies need to be developed to promote primary care use among the general adult American population. In addition, use of mental health services among patients with CVD needs to be improved when financial stress occurs.

6.
Diabetes Care ; 42(8): 1539-1548, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31152120

RESUMO

OBJECTIVE: Uncertainty remains regarding the predictive value of various glycemic measures as they relate to the risk of diabetes and its complications. Using the cutoffs recommended by the American Diabetes Association's 2010 criteria, we determined the associations of fasting plasma glucose (FPG), 2-h postload glucose (2h-PG), and HbA1c with the outcomes. RESEARCH DESIGN AND METHODS: Baseline medical history, FPG, 2h-PG, and HbA1c were obtained from a population-based cohort of 193,846 adults aged ≥40 years in China during 2011-2012. A follow-up visit was conducted during 2014-2016 in order to assess incident diabetes, cardiovascular disease (CVD), cancer, and mortality. RESULTS: We documented 8,063 cases of diabetes, 3,014 CVD-related events, 1,624 cases of cancer, and 2,409 deaths during up to 5 years of follow-up. Multivariable-adjusted risk ratios (95% CIs) of diabetes associated with prediabetes based on FPG of 100-125 mg/dL, 2h-PG of 140-199 mg/dL, or HbA1c of 5.7-6.4% (39-47 mmol/mol) were 1.60 (1.43-1.79), 2.72 (2.43-3.04), and 1.49 (1.36-1.62), respectively. Restricted cubic spline analyses suggested J-shaped associations of FPG, 2h-PG, and HbA1c levels with CVD, cancer, and mortality. Multivariable-adjusted hazard ratios (95% CIs) associated with untreated diabetes based on FPG ≥126 mg/dL, 2h-PG ≥200 mg/dL, or HbA1c ≥6.5% (48 mmol/mol) were 1.18 (1.05-1.33), 1.31 (1.18-1.45), and 1.20 (1.07-1.34) for CVD; 1.10 (0.92-1.32), 1.44 (1.25-1.67), and 1.08 (0.92-1.28) for cancer; and 1.37 (1.20-1.57), 1.57 (1.41-1.76), and 1.33 (1.17-1.52) for mortality, respectively. 2h-PG remained significantly associated with outcomes in models including FPG and HbA1c as spline terms. Furthermore, 2h-PG significantly improved the ability of the C statistic to predict diabetes, CVD, and mortality. CONCLUSIONS: 2h-PG remains independently predictive of outcomes in models including FPG and HbA1c. Therefore, in addition to FPG and HbA1c, routine testing of 2h-PG should be considered in order to better assess the risks of outcomes.

7.
J Med Virol ; 91(9): 1660-1667, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31144332

RESUMO

Cocaine is commonly used among HIV-infected people and may worsen HIV disease progression. In addition, existing evidence suggests a link between antiretroviral regimens and endothelial dysfunction. This study aimed to examine whether the associations of antiretroviral therapy (ART) regimens with endothelial dysfunction may be modified by cocaine use in adults with HIV infection. Between 2003 and 2014, 466 HIV-positive participants residing in Baltimore, Maryland, were enrolled in a study investigating comorbidities associated with HIV/ART. The associations between various risk factors and endothelial dysfunction indicators were examined by robust regression models fitted for the overall subjects and cocaine subgroups, separately. Duration of nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based therapy was negatively associated with plasma vWF:Ag levels in cocaine non-users (ß = -.715, SE = .220, P < .05). However, cocaine users on longer-term NNRTI-based regimens had greater plasma endothelin-1 (ET-1) concentrations than their counterparts (ß = .003, SE = .001, P < .05). In addition, current cigarette smoking was significantly positively associated with ET-1 concentrations in both cocaine non-users (ß = .609, SE = .164, P < .05) and cocaine users (ß = .331, SE = .086, P < .05). In conclusion, cocaine use modified the potential effects of NNRTI-based therapy on biomarkers of endothelial dysfunction. These findings suggested that reduction in cocaine use may improve endothelial function in HIV-infected cocaine users.

8.
Int J STD AIDS ; 30(3): 223-230, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30381028

RESUMO

HIV infection and/or antiretroviral therapy may increase the risk of subclinical coronary atherosclerosis. However, patients with chronic kidney disease (CKD) and those without IV access cannot undergo contrast-enhanced coronary CT angiography (CCTA). This study was to explore the relationship between cardiac troponin T (cTnT) levels and the extent of coronary plaque burden, as assessed by CCTA in those with HIV infection. Between June and September 2017, 58 HIV-infected participants were recruited and underwent contrast-enhanced CCTA. cTnT was measured with the Elecsys Troponin T Gen 5 STAT assay, and noncalcified plaque burden was quantified using coronary plaque analysis. Robust regression model was employed to perform primary statistical analysis. Univariate robust regression analysis indicated that male gender, cardiovascular risk score defined by the 2013 ACC/AHA cardiovascular risk score algorithm, and cTnT levels were significantly associated with noncalcified plaque volume index (NCPI). Final robust regression analyses showed that only cTnT (log scale) was independently associated with the NCPI (regression coefficient: 0.0453 with 95% CI: 0.0151, 0.0755, p = 0.003). These results of this study suggest that cTnT may be a promising marker for coronary plaque burden, especially in patients with HIV-associated CKD or without IV access.


Assuntos
Doença da Artéria Coronariana/sangue , Infecções por HIV/complicações , Placa Aterosclerótica/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Troponina T/sangue , Biomarcadores/sangue , Calcinose/diagnóstico por imagem , Doença da Artéria Coronariana/diagnóstico por imagem , Estudos Transversais , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Placa Aterosclerótica/epidemiologia , Placa Aterosclerótica/etiologia
9.
Magn Reson Med ; 81(2): 1157-1164, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30387903

RESUMO

PURPOSE: Gadolinium-based contrast agents (GBCAs) for MRI are generally administrated in direct relationship to body weight. Instead, we propose a model for GBCA dosing on the basis of blood volume. The new method was tested by exploring the associations between MRI T1 mapping indices and weight in the MESA (Multi-Ethnic Study of Atherosclerosis. METHODS: Empirically derived methods based on sex and body habitus were used to calculate blood volumes. GBCA dose (in mL) in blood (in L) was calculated as the injected volume divided by the blood volume (i.e., DBV). Of the 1219 participants with cardiac MRI T1 mapping, 845 studies had standard dose of 0.15 mmol/kg (cohort 1) and 166 studies had 30 mL of GBCA regardless of weight (cohort 2). We also created a specific cohort with similar DBV (N = 357; cohort 3). RESULTS: Postcontrast blood relaxation rate R1blood and DBV were significantly correlated (R = 0.641; P < 0.001). R1blood was significantly associated with weight in cohort 1 and 2, but the correlation coefficient was positive for cohort 1 and negative for cohort 2, indicating GBCA overdosing in cohort 1 and underdosing in cohort 2 in heavy relative to lean subjects. R1blood was not associated with weight in cohort 3. Simulated results demonstrated that less contrast should be administrated for heavy subjects compared to the conventional weight-based dose. CONCLUSION: GBCA dosing on the basis of blood volume could improve the efficacy and safety of contrast-enhanced MRI studies. This method could be implemented to standardize dose and augment precision in study comparisons.

10.
Atherosclerosis ; 278: 7-14, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30227267

RESUMO

BACKGROUND AND AIMS: Coronary artery disease (CAD) is now an important cause of premature death in people with HIV but the causes of accelerated CAD are poorly understood. Epicardial adipose tissue (EAT) is metabolically-active and thought to contribute to CAD development. We tested the hypothesis that abnormal coronary endothelial function (CEF), an early marker and mediator of atherosclerosis, is related to the amount of local pericoronary EAT in HIV. METHODS: We studied 36 participants with HIV and no CAD (HIV+ CAD-), 15 participants with HIV and known CAD (HIV+ CAD+), and 14 age-matched, healthy participants without HIV (HIV-CAD-). To measure CEF, coronary MRI was performed before and during isometric handgrip exercise (IHE), an endothelial-dependent stressor. EAT was measured with MRI at the same imaging plane as CEF. RESULTS: CEF was significantly depressed, as measured by IHE-induced % coronary cross sectional area (CSA) change, in HIV+ CAD- and HIV+ CAD+ as compared to HIV-CAD-participants (p<0.0001). EAT thickness was significantly greater in HIV+ CAD- and HIV+ CAD+ participants as compared to HIV-CAD-participants (p=0.001). There was a significant inverse relationship between CEF and local EAT thickness and area (R = -0.48 and R = -0.51 respectively, p<0.0001 for both) among participants with HIV even after adjustment for cardiovascular risk factors. In participants with multiple CEF measures, CEF was lower in segments with higher EAT, other factors being equivalent. CONCLUSIONS: There is a significant relationship between increased metabolically-active EAT and depressed local CEF in people with HIV, consistent with the hypothesis that increased epicardial fat contributes to accelerated CAD in persons with HIV.


Assuntos
Tecido Adiposo/fisiopatologia , Doença da Artéria Coronariana/complicações , Infecções por HIV/complicações , Pericárdio/fisiopatologia , Adulto , Estudos de Casos e Controles , Comorbidade , Doença da Artéria Coronariana/fisiopatologia , Vasos Coronários/fisiopatologia , Endotélio Vascular/patologia , Exercício , Feminino , Infecções por HIV/fisiopatologia , Força da Mão , Coração/fisiopatologia , Cardiopatias/complicações , Cardiopatias/fisiopatologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fatores de Risco
11.
Am Heart J ; 197: 85-93, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29447788

RESUMO

BACKGROUND: The xanthine oxidase (XO) system is a significant source of vascular oxidative stress, which is believed to impair endothelial function, an important contributor to atherosclerotic disease. We tested whether febuxostat, a potent XO inhibitor, improves coronary endothelial function (CEF) in patients with stable coronary artery disease (CAD) in a single-center, randomized, placebo-controlled, double-blind crossover trial. METHODS: CEF was measured using noninvasive magnetic resonance imaging (MRI) assessment of changes in 30 patients with stable CAD and baseline impaired CEF. Patients received either febuxostat or placebo for 6 weeks and then were crossed over to the alternative for an additional 6 weeks. MRI-detected changes in coronary flow and in coronary cross-sectional area from rest to isometric handgrip exercise, a known endothelial-dependent stressor, were measured at the end of each 6 week period. RESULTS: Mean serum urate levels were lower at the end of the 6-week febuxostat period (2.9±0.8mg/dL) than at the end of the 6-week placebo period (5.9±0.04, P<.001). However, there were no significant differences in any of the CEF parameters measured at the end of the febuxostat and placebo periods. CONCLUSIONS: In summary, although XO inhibition with febuxostat was well tolerated and lowered serum urate, it did not improve the primary end point of the study, CEF measured using MRI after 6 weeks of treatment. In conclusion, these findings suggest that short-term inhibition of XO does not significantly improve impaired CEF in patients with stable CAD.


Assuntos
Doença da Artéria Coronariana , Vasos Coronários , Endotélio Vascular , Febuxostat/administração & dosagem , Xantina Oxidase , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/metabolismo , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/fisiopatologia , Estudos Cross-Over , Método Duplo-Cego , Monitoramento de Medicamentos/métodos , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Feminino , Supressores da Gota/administração & dosagem , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Resultado do Tratamento , Xantina Oxidase/antagonistas & inibidores , Xantina Oxidase/metabolismo
12.
Prog Neuropsychopharmacol Biol Psychiatry ; 84(Pt A): 11-17, 2018 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-29410247

RESUMO

BACKGROUND: Although cocaine use may induce/accelerate HIV-associated comorbidities in HIV-infected individuals on antiretroviral therapy (ART), and that HIV itself may accelerate aging, the issue of whether cocaine use plays a role in HIV-associated aging in HIV-infected cocaine users has not been reported. The goals of this study were (1) to explore factor(s) associated with peripheral blood leukocyte telomere length, a marker of cellular replicative history, and telomere shortening in HIV-infected individuals, and (2) to assess whether cocaine use plays a role in accelerating telomere shortening in cocaine users with HIV infection. METHODS: Between June 2010 and December 2016, 147 HIV-infected participants in Baltimore, Maryland, were enrolled in a cross-sectional study investigating factor(s) associated with telomere length. Of these 147, 93 participated in a follow-up study to examine factor(s) associated with telomere shortening. Robust regression model was used to analyze cross-sectional data and the generalized estimating equation approach was used to analyze follow-up data. RESULTS: Cross-sectional analyses demonstrated that (1) both daily alcohol consumption and use of non-nucleoside reverse transcriptase inhibitors (NNRTIs) were independently associated with telomere length, and cocaine use modified the associations of daily alcohol use and NNRTI use with telomere length. Longitudinal analyses suggested that both daily alcohol consumption and duration of NNRTI use were independently associated with telomere shortening, and (2) cocaine use induced/accelerated telomere shortening in HIV-infected individuals. CONCLUSIONS: Our findings suggest that cocaine use may promote premature aging in HIV-infected individuals who are on ART. Our results emphasize the importance of cocaine abstinence/reduced use, which may retard HIV-associated premature aging.


Assuntos
Cocaína/efeitos adversos , Infecções por HIV/genética , Encurtamento do Telômero/efeitos dos fármacos , Estudos Transversais , Etanol/efeitos adversos , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Inibidores da Transcriptase Reversa/efeitos adversos , Homeostase do Telômero/efeitos dos fármacos
13.
Int J STD AIDS ; 29(8): 781-789, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29471762

RESUMO

Previous studies have demonstrated a link between protease inhibitor (PI)-based therapy and lipid dysregulation. The main objective of this study was to examine whether cocaine use may modify PI-associated dyslipidemia in adults. Between June 2003 and June 2014, 957 human immunodeficiency virus (HIV)-infected participants in Baltimore, Maryland were enrolled in a study that investigated HIV/antiretroviral therapy-associated comorbidities. Multiple linear and logistic regression models were fitted to examine the associations between PI therapy and lipid profiles for the pooled sample and cocaine use subgroups, respectively. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), TC/high-density lipoprotein cholesterol (HDL-C) ratio, and atherogenic index of plasma (AIP) levels were positively associated with duration of PI-based therapy in long-term cocaine users (all p < 0.05). However, longer-term PI therapy was significantly associated with increased HDL-C in non-chronic cocaine users (ß = 0.109, SE = 0.042, p < 0.05). The participants who received PI therapy ≥12 months and used cocaine ≥15 years were more likely to have hypertriglyceridemia (OR = 2.82, 95% CI = 1.63, 4.88) and abnormal AIP (OR = 1.73, 95% CI = 1.08, 2.79) as compared to their counterparts. Our findings showed that long-term cocaine use may exacerbate adverse effects of PI therapy on lipid metabolism, suggesting that reduced cocaine use may be considered an alternative approach to managing PI-associated dyslipidemia in chronic cocaine users with HIV infection.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/complicações , Dislipidemias/induzido quimicamente , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/efeitos adversos , Metabolismo dos Lipídeos/efeitos dos fármacos , Adulto , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Transtornos Relacionados ao Uso de Cocaína/epidemiologia , Dislipidemias/sangue , Dislipidemias/epidemiologia , Dislipidemias/virologia , Feminino , Infecções por HIV/sangue , Infecções por HIV/epidemiologia , Inibidores da Protease de HIV/uso terapêutico , Humanos , Masculino , Maryland/epidemiologia , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento
14.
J Am Coll Cardiol ; 70(25): 3102-3109, 2017 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-29268924

RESUMO

BACKGROUND: Serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) is considered a marker that is expressed in response to myocardial strain and possibly fibrosis. However, the relationship to myocardial fibrosis in a community-based population is unknown. OBJECTIVES: The authors evaluated the relationship between cardiac magnetic resonance (CMR) measures of fibrosis and NT-proBNP levels in the MESA (Multi-Ethnic Study of Atherosclerosis) study. METHODS: A total of 1,334 participants (52% white, 23% black, 11% Chinese, 14% Hispanic, and 52% men with a mean age of 67.6 years) at 6 sites had both serum NT-proBNP measurements and CMR with T1 mapping of indices of fibrosis at 1.5 T. Univariate and multivariable regression analyses adjusting for demographics, cardiovascular risk factors, and left ventricular (LV) mass were performed to examine the association of log NT-proBNP with CMR T1 mapping indices. RESULTS: In the fully adjusted model, each 1-SD increment (0.44 pg/ml) of log NT-proBNP was associated with a 0.62% increment in extracellular volume fraction (p < 0.001), 0.011 increment in partition coefficient (p < 0.001), and 4.7-ms increment in native T1 (p = 0.001). Results remained unchanged after excluding individuals with clinical cardiovascular disease or late gadolinium enhancement (n = 167), and after replacing LV mass by LV end-diastolic volume in the regression models. CONCLUSIONS: Elevated NT-proBNP is related to subclinical fibrosis in a community-based setting. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487).


Assuntos
Aterosclerose/sangue , Cardiomiopatias/sangue , Grupos Étnicos , Ventrículos do Coração/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética/métodos , Miocárdio/patologia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/diagnóstico , Aterosclerose/etnologia , Cardiomiopatias/diagnóstico , Cardiomiopatias/etnologia , Diástole , Feminino , Fibrose/sangue , Fibrose/diagnóstico , Fibrose/etnologia , Ventrículos do Coração/fisiopatologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Precursores de Proteínas , Estados Unidos/epidemiologia , Função Ventricular Esquerda
15.
J Stroke Cerebrovasc Dis ; 26(11): 2510-2518, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28709742

RESUMO

BACKGROUND: Previous findings on the association between serum 25(OH)D level and stroke have been controversial. We aimed to examine whether these controversial findings could be possibly due to difference in study participant characteristics, especially age and gender differences in these studies, by analyzing the data from a representative sample of the general US population. METHODS: Data of 13,642 adults 20 years or older who participated in the 2001-2006 National Health and Nutrition Examination Survey were analyzed in this study. Serum 25(OH)D was used to reflect vitamin D status. Stroke history was self-reported using questionnaires. Unadjusted and adjusted logistic regression models were fitted using SAS survey procedures to investigate the associations between 25(OH)D level and stroke for the pooled sample and age-gender subgroups (men versus women, <50 years old versus ≥50 years old), respectively. RESULTS: After adjusting for demographic and lifestyle covariates, vitamin D deficiency (defined as serum 25(OH)D < 12 ng/mL) was significantly associated with increased risk of stroke (adjusted odds ratio [OR] = 1.62, 95% confidence interval [CI] = 1.11, 2.36), and higher vitamin D levels were significantly associated with reduced risk of stroke (adjusted OR = .70, 95% CI = .51, .96). The association between high levels of serum 25(OH)D and stroke was particularly evident among young females (age ≤20 years to <50 years) (adjusted OR = .26, 95% CI = .14, .49). CONCLUSIONS: The findings add to the evidence suggesting maintaining ideal 25(OH)D levels may reduce the risk of stroke among US adults, particularly in adult women younger than 50 years.


Assuntos
Envelhecimento/fisiologia , Caracteres Sexuais , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia , Vitamina D/análogos & derivados , Adulto , Fatores Etários , Feminino , Inquéritos Epidemiológicos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Estudos Retrospectivos , Acidente Vascular Cerebral/terapia , Estados Unidos/epidemiologia , Vitamina D/sangue , Adulto Jovem
16.
Nat Med ; 23(7): 859-868, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28628112

RESUMO

Emerging evidence has linked the gut microbiome to human obesity. We performed a metagenome-wide association study and serum metabolomics profiling in a cohort of lean and obese, young, Chinese individuals. We identified obesity-associated gut microbial species linked to changes in circulating metabolites. The abundance of Bacteroides thetaiotaomicron, a glutamate-fermenting commensal, was markedly decreased in obese individuals and was inversely correlated with serum glutamate concentration. Consistently, gavage with B. thetaiotaomicron reduced plasma glutamate concentration and alleviated diet-induced body-weight gain and adiposity in mice. Furthermore, weight-loss intervention by bariatric surgery partially reversed obesity-associated microbial and metabolic alterations in obese individuals, including the decreased abundance of B. thetaiotaomicron and the elevated serum glutamate concentration. Our findings identify previously unknown links between intestinal microbiota alterations, circulating amino acids and obesity, suggesting that it may be possible to intervene in obesity by targeting the gut microbiota.


Assuntos
DNA Bacteriano/análise , Disbiose/microbiologia , Microbioma Gastrointestinal/genética , Metaboloma , Obesidade/microbiologia , Adiposidade , Adulto , Animais , Bacteroides/genética , Bacteroides thetaiotaomicron/genética , Cirurgia Bariátrica , Estudos de Casos e Controles , Disbiose/metabolismo , Feminino , Fusobacterium/genética , Gastrectomia , Ácido Glutâmico/sangue , Humanos , Masculino , Metagenoma , Camundongos , Obesidade/metabolismo , Obesidade/cirurgia , Ganho de Peso , Adulto Jovem
17.
PLoS One ; 12(6): e0179947, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28640873

RESUMO

BACKGROUND: Understanding the relationship of cardiovascular structure and function to age is confounded by the high prevalence of traditional risk factors in the United States. The purpose of the study is to compare left ventricular (LV) and aortic structural, and functional parameters in individuals with and without traditional risk factors in a population-based cohort. METHODS AND RESULTS: 3015 study participants (48% men, age 55-94, mean 69.01±9.17 years) in the Multi-Ethnic Study of Atherosclerosis (MESA) underwent cardiovascular magnetic resonance (CMR) imaging from 2010-2012. Absence of cardiovascular (CV) risk factors (no hypertension, diabetes or impaired fasting glucose, obesity, smoking or hypercholesterolemia) was infrequent, occurring in just 314 (10.4%, 38% men) of 3015 participants. In multivariable analyses adjusting for age, sex and race, individuals with CV risk factors had significantly larger LV mass index (by 17%) and lower LV contractibility (circumference strain, lower by 14%). Indexed LV volumes and stroke volume were inversely associated with age, but such relationships were not statistically significant in risk-free male subjects (p>0.05). Men with CV risk factors showed positive association of CMR T1 indices of myocardial fibrosis with age. Aortic function was similar in individuals with and without risk factors; age was associated with decline of aortic function in both CV and no CV risk factor groups. CONCLUSION: Our results support that LV structure and function are better preserved in senescent hearts in the absence of traditional cardiovascular risk factors, and such protection is more prominent in men than in women.


Assuntos
Envelhecimento/fisiologia , Aterosclerose/fisiopatologia , Saúde , Ventrículos do Coração , Função Ventricular Esquerda , Idoso , Idoso de 80 Anos ou mais , Feminino , Ventrículos do Coração/fisiopatologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fatores de Risco
18.
Drug Alcohol Depend ; 177: 84-92, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28578226

RESUMO

BACKGROUND: It has been recognized that myocardial and hepatic steatosis may be more prevalent in HIV-infected individuals on antiretroviral therapy (ART); however, factors associated with these conditions have not been thoroughly investigated. The goals of this study were (1) to identify the risk factors for myocardial and hepatic steatosis in HIV-infected African Americans (AAs) and explore whether ART use is independently associated with myocardial and hepatic steatosis, and (2) to examine whether and how cocaine use influences any associations of ART use with myocardial and hepatic steatosis. METHODS: Between June 2010 and December 2013, 220 HIV-infected AAs in Baltimore, Maryland, were enrolled in a study investigating HIV/ART-associated myocardial and hepatic damage. Proton magnetic resonance spectroscopy was performed to quantify myocardial and hepatic triglyceride contents. Sociodemographic, medical and laboratory data were also obtained. Robust regression model was employed to perform primary statistical analysis. RESULTS: Robust regression analyses showed that (1) duration of protease inhibitor (PI) use was independently associated with myocardial and hepatic triglyceride contents, (2) duration of PI use was independently associated with myocardial triglyceride in cocaine users (p=0.025), but not in cocaine never-users (p=0.84), and (3) duration of PI use was independently associated with hepatic triglyceride in cocaine users, but not in cocaine never-users (p=0.52). CONCLUSIONS: Cocaine use may trigger/exacerbate the toxicity of PI in ART-associated myocardial and hepatic steatosis, suggesting that cocaine abstinence/reduced use may retard these ART-associated comorbidities. Clinical trials should be conducted to examine whether reduced cocaine use improves HIV/AIDS-associated myocardial and hepatic steatosis.


Assuntos
Afro-Americanos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Transtornos Relacionados ao Uso de Cocaína/epidemiologia , Fígado Gorduroso/epidemiologia , Infecções por HIV/epidemiologia , Miocárdio/patologia , Adulto , Baltimore/epidemiologia , Transtornos Relacionados ao Uso de Cocaína/diagnóstico , Estudos Transversais , Fígado Gorduroso/induzido quimicamente , Fígado Gorduroso/diagnóstico , Feminino , Infecções por HIV/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Espectroscopia de Prótons por Ressonância Magnética/métodos , Fatores de Risco
19.
AIDS ; 31(9): 1281-1289, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28353539

RESUMO

OBJECTIVE: HIV-positive (HIV+) individuals experience an increased burden of coronary artery disease (CAD) not adequately accounted for by traditional CAD risk factors. Coronary endothelial function (CEF), a barometer of vascular health, is depressed early in atherosclerosis and predict future events but has not been studied in HIV+ individuals. We tested whether CEF is impaired in HIV+ patients without CAD as compared with an HIV-negative (HIV-) population matched for cardiac risk factors. DESIGN/METHODS: In this observational study, CEF was measured noninvasively by quantifying isometric handgrip exercise-induced changes in coronary vasoreactivity with MRI in 18 participants with HIV but no CAD (HIV+CAD-, based on prior imaging), 36 age-matched and cardiac risk factor-matched healthy participants with neither HIV nor CAD (HIV-CAD-), 41 patients with no HIV but with known CAD (HIV-CAD+), and 17 patients with both HIV and CAD (HIV+CAD+). RESULTS: CEF was significantly depressed in HIV+CAD- patients as compared with that of risk-factor-matched HIV-CAD- patients (P < 0.0001) and was depressed to the level of that in HIV- participants with established CAD. Mean IL-6 levels were higher in HIV+ participants (P < 0.0001) and inversely related to CEF in the HIV+ patients (P = 0.007). CONCLUSION: Marked coronary endothelial dysfunction is present in HIV+ patients without significant CAD and is as severe as that in clinical CAD patients. Furthermore, endothelial dysfunction appears inversely related to the degree of inflammation in HIV+ patients as measured by IL-6. CEF testing in HIV+ patients may be useful for assessing cardiovascular risk and testing new CAD treatment strategies, including those targeting inflammation.


Assuntos
Vasos Coronários/patologia , Endotélio Vascular/patologia , Infecções por HIV/complicações , Idoso , Vasos Coronários/diagnóstico por imagem , Endotélio Vascular/diagnóstico por imagem , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade
20.
J Epidemiol ; 27(5): 228-234, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28142049

RESUMO

BACKGROUND: As an endocrine disruptor, bisphenol A (BPA) exposure has been implicated as a potential risk factor in childhood obesity, which is defined using percentiles of body mass index for age. We aimed to examine the associations between BPA exposure, reflected by urinary BPA concentration, and body composition in American children. METHODS: Data of 1860 children aged 8-19 years who participated in the 2003-2006 National Health and Nutrition Examination Survey (NHANES) were analyzed in this study. Urinary BPA concentration (ng/mL) was used to indicate BPA status in the body. Body composition was measured by dual-energy X-ray absorptiometry (DXA). Multivariate linear regression models were fitted using survey procedures to investigate the associations between urinary BPA level and body composition separately for boys and girls. RESULTS: After adjusting for demographic and lifestyle covariates, higher quartiled and log-transformed urinary BPA levels were significantly associated with elevated lean body mass index (LBMI) z-scores in boys (p < 0.05), and significantly associated with elevated fat mass index (FMI) z-scores in girls (p < 0.05). Lower urinary BPA concentration was associated with lower percentage of trunk fat in girls (compared to 1st quartile, 2nd-quartile: ß = 2.85, 95% CI, 0.92-4.78; 3rd-quartile: ß = 2.57, 95% CI, 0.28-4.85; 4th-quartile: ß = 2.79, 95% CI, 0.44-5.14; all p < 0.05). Such patterns were not observed in boys. CONCLUSIONS: Higher BPA levels may be associated with elevated LBM in boys, but not in girls, while higher BPA levels may be associated with elevated FM in girls, but not in boys.


Assuntos
Compostos Benzidrílicos/urina , Composição Corporal , Exposição Ambiental , Obesidade/induzido quimicamente , Fenóis/urina , Adolescente , Índice de Massa Corporal , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Inquéritos Nutricionais , Análise de Regressão , Caracteres Sexuais , Fatores Sexuais , Estados Unidos/epidemiologia , Adulto Jovem
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