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BACKGROUND: Accurate assessment of fat intake is essential to examine relationships between diet and disease risk. However, estimating individual intakes of fat quantity by dietary assessment is difficult. OBJECTIVE: We assessed the association of plasma phospholipid fatty acid levels with dietary intake of fatty acids in the INTERMAP/INTERLIPID study, conducted with a standardized protocol. METHODS: The study participants were 1339 men and women ages 40-59 years from five Japanese populations one from Hawaii; four from Japan. Fatty acid intake was estimated from four standardized 24-hour dietary recalls. Plasma phospholipid fatty acid composition was analyzed by gas chromatography. We illustrated the relationship between intake and circulating fatty acid levels using Spearman's rank-correlation coefficients, mean, and median values. RESULTS: Spearman's rank-correlation coefficients between intake (g/d) and circulating fatty acid levels (µg/ml) were -0.03 to 0.21 for saturated fatty acids and monounsaturated fatty acids and -0.04 to 0.32 for trans fatty acids. The coefficients for essential n-3 and n-6 fatty acids were moderate to high, especially for eicosapentaenoic acid (EPA), 0.60; docosahexaenoic acid (DHA), 0.41; and EPA+DHA, 0.51. The circulating levels and intake of marine-derived n-3 fatty acids showed a linear association, at least for the intake of EPA+DHA up to 2.1 g/d. CONCLUSION: We observed high correlation between intake and circulating levels of marine-derived n-3 fatty acids in participants from Japanese and Japanese-American populations with high and low fish intake. Plasma phospholipid marine-derived n-3 fatty acid measurements are a simple and reliable biomarker for assessing dietary intake.
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Ácidos Graxos Ômega-3 , Fosfolipídeos , Feminino , Biomarcadores , Dieta , Ácidos Docosa-Hexaenoicos , Ácido Eicosapentaenoico , Ácidos Graxos , Humanos , Masculino , Adulto , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Depression is associated with inflammation, but the mechanisms underlying this association are unclear. We examined adiposity and smoking as potential pathways through which childhood depression may lead to an elevated inflammatory status among young adults. METHODS: The sample included 294 subjects with histories of depression (probands), 270 never-depressed siblings of probands (high-risk siblings), and 169 controls. C-reactive protein (CRP), interleukin-6 (IL-6), and soluble intercellular adhesion molecule-1 (sICAM-1) were assessed in serum samples. An adiposity score was computed from body mass index and waist circumference. Smoking behavior was evaluated during an interview. Mixed-effects models were used to test whether adiposity and smoking mediate the relationship between depression and inflammation. RESULTS: Probands (p = .004), but not siblings (p = .071), had higher levels of sICAM-1 compared to controls. However, depression history and risk status had no direct effects on CRP (ps > .13) or IL-6 (ps > .16). Importantly, adiposity indirectly mediated the effect of group (probands vs. controls; siblings vs. controls) on all three inflammatory markers. Smoking indirectly mediated the effect of group (probands vs. controls; siblings vs. controls) on sICAM-1 only. CONCLUSIONS: Among young adults, the adverse inflammatory consequences of depression history are significant for sICAM-1. Adiposity and smoking are pathways through which depression can indirectly impact several inflammatory markers, suggesting possible preventive interventions to improve the immunologic and cardiovascular health of depression-prone individuals.
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Adiposidade , Interleucina-6 , Adulto Jovem , Humanos , Criança , Interleucina-6/metabolismo , Depressão , Obesidade , Inflamação , Proteína C-Reativa/análise , Índice de Massa Corporal , Biomarcadores/metabolismo , Fumar/efeitos adversosRESUMO
Background: Preterm delivery (PTD) and poor fetal growth are major contributors to neonatal mortality and morbidity that can extend from birth onward. Although overt maternal nutrient deficiencies are associated with adverse pregnancy outcomes, such deficiencies are rare in developed countries. However, some evidence suggests that even within the normal range, higher levels of antioxidant nutrients are protective against adverse pregnancy outcomes. Materials and Methods: Using data from the prospective Pregnancy Outcomes and Community Health (POUCH) Study (n = 301 preterm; n = 246 term), we examined associations between maternal blood levels of selected antioxidants and pregnancy outcomes. Serum collected at 16-27 weeks' gestation was analyzed for carotenoids, retinol, and α- and γ-tocopherol. Using weighted polytomous regression, these nutrient concentrations were assessed in relation to (1) PTD (<37 weeks gestation) overall and grouped as spontaneous or medically indicated; and (2) small for gestational age (SGA) defined as birthweight-for-gestational age <10th percentile of a national reference population. Results: Women with total serum carotenoids in the upper quartile (Q4) had significantly lower odds of medically indicated PTD compared with women in the lower quartiles (Q1-Q3) even after adjustment for maternal characteristics (aOR = 0.4; 95% CI: 0.2-0.9). Odds ratios for SGA were consistently ≤0.5 among women with any of the serum nutrients in Q4 as compared with Q1-Q3, but final models did not reach statistical significance. Conclusion: Results support the possibility that high maternal serum antioxidants and/or the larger dietary or lifestyle pattern they represent may play a protective role in preventing adverse pregnancy outcomes.
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Antioxidantes , Nascimento Prematuro , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Gravidez , Nascimento Prematuro/epidemiologia , Estudos ProspectivosRESUMO
AIM: The haptoglobin (Hp) 2-2 genotype has been shown to increase the risk of coronary artery disease, kidney dysfunction and mortality from cardiovascular and renal causes in type 1 diabetes (T1D). Similar associations, however, have not been observed in those without diabetes. As cardiac autonomic neuropathy (CAN) is a cardiovascular disease risk factor, we assessed the presence of an association between the Hp 2-2 genotype and CAN. METHODS: The study included 216 individuals with childhood-onset T1D and 200 individuals with normal glucose tolerance (NGT) of similar age and gender distribution to their counterparts with T1D. CAN was assessed using an electrocardiogram as an abnormal, age-specific, heart rate response to deep breathing. Multivariable logistic regression models were used to assess the association between the Hp 2-2 genotype and CAN. RESULTS: Compared with NGT, participants with T1D had a similar proportion of Hp 2-2 carriers (41.5% vs. 32.0%, p = 0.05) but a greater CAN prevalence (28.2% vs. 5.0%, p < 0.0001). In multivariable logistic regression models, those carrying the Hp 2-2 genotype had significantly higher odds of CAN compared with Hp 1-1 or Hp 2-1 carriers (OR = 2.27, p = 0.01). The presence of T1D (OR = 4.20, p = 0.0003), hypertension (OR = 2.08, p = 0.03), eGFR (OR = 0.98, p = 0.01) and WBC count (OR = 1.21, p = 0.02) were also associated with CAN. There was no T1D by Hp interaction (p = 0.92), although in stratified analyses, the Hp-CAN association was significant only in T1D. CONCLUSIONS: The Hp 2-2 genotype was independently associated with greater odds of CAN in T1D though no definitive conclusions could be made in NGT.
Assuntos
Doenças Cardiovasculares/genética , Diabetes Mellitus Tipo 1/complicações , Haptoglobinas/genética , Adolescente , Adulto , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Criança , Pré-Escolar , Feminino , Seguimentos , Genótipo , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: High-sensitivity cardiac troponin (hs-cTn) elevations are associated with incident cardiovascular disease events in primary prevention samples. However, the mechanisms underlying this association remain unclear. METHODS: We studied 458 men without known cardiovascular disease who participated in the cardiovascular disease substudy of the Multicenter AIDS Cohort Study and had cardiac CT angiography. We used multivariable linear and logistic regression models to examine the cross-sectional associations between coronary artery stenosis, coronary artery plaque, indexed left ventricular mass (LVMi), and the outcome of hs-cTnI. We also evaluated the associations between HIV serostatus or use of highly active antiretroviral therapy (HAART) and hs-cTnI. RESULTS: The mean age was 54 years, 54% were white, and 61% were HIV infected. In multivariable-adjusted logistic models, comparing the highest quartile of LVMi with the lowest quartile, the odds ratio (OR) of hs-cTnI ≥75th percentile was 2.59 (95% CI, 1.20-5.75). There was no significant association between coronary stenosis severity or plaque type and hs-cTnI in linear models; however, in logistic regression models, coronary artery stenosis ≥70% (8% of sample) was marginally associated with a higher likelihood (OR, 2.75 [95% CI, 1.03, 7.27]) of having hs-cTnI ≥75th percentile. There were no associations between HIV serostatus or HAART use and hs-cTnI in either linear or logistic models. CONCLUSION: Among primary prevention men with or at risk for HIV, hs-cTnI concentrations were strongly associated with LVMi but were not associated with HIV infection or treatment status or with coronary plaque type or stenosis until the extremes of severity (≥70% stenosis).
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Cardiomiopatias/sangue , Cardiomiopatias/diagnóstico por imagem , Angiografia por Tomografia Computadorizada , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Troponina/sangue , Idoso , Biomarcadores , Cardiomiopatias/epidemiologia , Comorbidade , Angiografia por Tomografia Computadorizada/métodos , Doença da Artéria Coronariana/epidemiologia , Infecções por HIV , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Sensibilidade e Especificidade , Troponina C/sangue , Troponina T/sangueRESUMO
BACKGROUND: Carotid plaque has emerged as a marker of coronary heart disease (CHD) risk. Comparison of carotid plaque burden between different race/ethnic groups may provide a relative estimate of their future CHD risk. METHODS: We conducted a population-based study among apparently healthy middle-aged men aged 40-49â¯years (ERA JUMP study (nâ¯=â¯924)) and recruited 310 Whites in Pittsburgh, US, 313 Japanese in Otsu, Japan, and 301 Koreans in Ansan, South Korea. The number of carotid plaque and CHD risk factors was assessed using a standardized protocol across all centers. The burden of carotid plaque was compared between race/ethnic groups after adjustment for age and BMI, and after multivariable adjustment for other CHD risk factors using marginalized zero-inflated Poisson regression models. Cross-sectional associations of risk factors with plaque were examined. RESULTS: Whites (22.8%) had more than four-fold higher prevalence (pâ¯<â¯0.01) of carotid plaque than Japanese men (4.8%) while the prevalence among Koreans was 10.6%. These differences remained significant after adjustment for age, BMI as well as other risk factors - incidence density ratio (95% confidence interval) for plaque was 0.13 (0.07, 0.24) for Japanese and 0.32 (0.18, 0.58) for Koreans as compared to Whites. Age, hypertension and diabetes were the only risk factors significantly associated with presence of carotid plaque in the overall population. CONCLUSION: Whites have significantly higher carotid plaque burden than men in Japan and Korea. Lower carotid plaque burden among Japanese and Koreans is independent of traditional CVD risk factors.
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Povo Asiático/etnologia , Doenças das Artérias Carótidas/etnologia , Espessura Intima-Media Carotídea , Placa Aterosclerótica/etnologia , População Branca/etnologia , Adulto , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/fisiopatologia , Espessura Intima-Media Carotídea/tendências , Estudos Transversais , Humanos , Japão/etnologia , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/sangue , Placa Aterosclerótica/fisiopatologia , República da Coreia/etnologia , Fatores de Risco , Estados Unidos/etnologiaRESUMO
Haptoglobin's (Hp) main role is to bind free hemoglobin (Hb), reducing its oxidative potential. The Hp-Hb complex formed is cleared from the circulation by macrophage receptor CD163. In diabetes, impaired Hp 2-2-Hb CD163 clearance and abnormal glomerular permeability allow the large Hp 2-2-Hb complex to cross the barrier, where its redox active iron leads to cellular toxicity. Although Hp 2-2 predicts renal function decline, whether renal iron deposition differs by Hp is unknown. We used renal quantitative T2* magnetic resonance imaging to estimate iron level in the cortex and medullar of type 1 diabetes (T1D) adults [15 Hp 1-1 and 15 Hp 2-2 carriers of similar age (53 years), duration (45 years), and gender]. Total kidney iron level was estimated as the sum of the cortex and medullar iron. Albuminuria was defined as urinary albumin to creatinine ratio >30 mg/g in two of three samples. Total kidney iron did not differ by gender or Hp but was higher in those with albuminuria (p = 0.05), an association confined to Hp 2-2 carriers (p = 0.04 vs. p = 0.51 in Hp 1-1). These data lead to the hypothesis that kidney iron deposition is increased among Hp 2-2 carriers with albuminuria in T1D. Antioxid. Redox Signal. 29, 735-741.
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Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/metabolismo , Haptoglobinas/genética , Heterozigoto , Ferro/análise , Ferro/metabolismo , Rim/metabolismo , Imageamento por Ressonância Magnética , Diabetes Mellitus Tipo 1/diagnóstico , Feminino , Haptoglobinas/metabolismo , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-IdadeRESUMO
Arterial stiffness is established as an independent predictor of cardiovascular morbidity and mortality. The objective was to prospectively evaluate association of aortic calcification burden with progression of arterial stiffness in population-based samples of healthy middle-aged men from ERA JUMP cohort (Electron-Beam Computed Tomography and Risk Factor Assessment in Japanese and US Men in the Post-World War II Birth Cohort). Men (n=635) aged 40 to 49 years (207 white American, 45 black American, 142 Japanese American, and 241 Japanese in Japan) were examined at baseline and 4 to 7 years later. Aortic calcification was evaluated from level of aortic arch to iliac bifurcation. Arterial stiffness progression was measured as annual change in brachial-ankle pulse wave velocity. Multivariable-adjusted general linear models were applied to investigate associations of longitudinal change in aortic calcification with arterial stiffness progression in participants overall, as well as in subgroups without or with prevalent aortic calcification at baseline. Annual change in aortic calcification was positively and significantly associated with arterial stiffness progression. In participants with annual changes in aortic calcium score of ≤0, 1 to 10, 11 to 100, and >100, the adjusted means (SD) for the annual change in brachial-ankle pulse wave velocity were 3.8 (2.2), 7.2 (2.2), 12.2 (1.8), and 15.6 (2.6) cm/s, respectively (P for trend <0.01) adjusted for baseline aortic calcification, arterial stiffness, and standard cardiovascular risk factors. Arterial stiffness was associated with the incidence of aortic calcification over the follow-up period among participants without aortic calcification (n=297) and with an increase in aortic calcification among participants with prevalent aortic calcification at baseline (n=388). Our findings suggest aortic calcification may be causally linked to arterial stiffness.
Assuntos
Doenças da Aorta/etnologia , Etnicidade , População , Medição de Risco/métodos , Calcificação Vascular/etnologia , Rigidez Vascular/fisiologia , Adulto , Índice Tornozelo-Braço , Doenças da Aorta/diagnóstico , Doenças da Aorta/fisiopatologia , Progressão da Doença , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Tomografia Computadorizada Multidetectores , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Fatores de Tempo , Estados Unidos/epidemiologia , Calcificação Vascular/diagnóstico , Calcificação Vascular/fisiopatologiaRESUMO
OBJECTIVE: A few studies have examined the longitudinal association of blood pressure (BP) with arterial stiffness progression, and the results were inconsistent. The objective of this study was to investigate the roles of initial BP and its longitudinal change on the progression of arterial stiffness measured using brachial-ankle pulse wave velocity (baPWV). METHOD: Study participants (nâ=â656) were from population-based samples of healthy men aged 40-49 years at baseline (213 White Americans, 47 African-Americans, 152 Japanese Americans and 244 Japanese in Japan). BP measures, baPWV and other factors were examined at baseline and 4-7 years later. General linear regression was applied for statistical analyses. RESULT: Annual change in SBP (standardized coefficient: 0.33, Pâ<â0.001), but not its baseline level (standardized coefficient: 0.03, Pâ=â0.495), had a positive significant association with the progression of baPWV after adjusting for a wide range of standard cardiovascular risk factors. Similarly, annual changes in DBP (standardized coefficient: 0.35, Pâ<â0.001), pulse pressure (standardized coefficient: 0.15, Pâ=â0.001) and mean arterial pressure (standardized coefficient: 0.37, Pâ<â0.001) were positively associated with the progression of baPWV. None of the baseline measures were related to the progression of baPWV. CONCLUSION: Our findings imply that, regardless of initial BP, effective monitoring and controlling of BP is important to slow down arterial wall stiffening and hence reduce cardiovascular risk.
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Pressão Sanguínea/fisiologia , Rigidez Vascular , Adulto , Negro ou Afro-Americano , Pressão Arterial/fisiologia , Asiático , Diástole , Voluntários Saudáveis , Humanos , Japão , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Sístole , Estados Unidos , População BrancaRESUMO
Recent studies suggest that the ability to produce equol, a metabolite of the soya isoflavone daidzein, is beneficial to coronary health. Equol, generated by bacterial action on isoflavones in the human gut, is biologically more potent than dietary sources of isoflavones. Not all humans are equol producers. We investigated whether equol-producing status is favourably associated with risk factors for CHD following an intervention by dietary soya isoflavones. We systematically reviewed randomised controlled trials (RCT) that evaluated the effect of soya isoflavones on risk factors for CHD and that reported equol-producing status. We searched PubMed, EMBASE, Ovid Medline and the Cochrane Central Register for Controlled Trials published up to April 2015 and hand-searched bibliographies to identify the RCT. Characteristics of participants and outcomes measurements were extracted and qualitatively analysed. From a total of 1671 studies, we identified forty-two articles that satisfied our search criteria. The effects of equol on risk factors for CHD were mainly based on secondary analyses in these studies, thus with inadequate statistical power. Although fourteen out of the forty-two studies found that equol production after a soya isoflavone intervention significantly improved a range of risk factors including cholesterol and other lipids, inflammation and blood pressure variables, these results need further verification by sufficiently powered studies. The other twenty-eight studies primarily reported null results. RCT of equol, which has recently become available as a dietary supplement, on CHD and its risk factors are awaited.
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OBJECTIVE: Although a significant positive association of vitamin D deficiency with coronary heart disease has been demonstrated in cross-sectional as well as prospective studies, only a few studies have examined the association of vitamin D deficiency with subclinical atherosclerosis. We examined whether vitamin D deficiency is associated with subclinical atherosclerosis, as measured by coronary artery calcification (CAC) in asymptomatic adults. METHODS: In a population-based cross-sectional study, 195 men aged 40 to 49 years without cardiovascular disease were randomly selected (98 Caucasian and 97 Japanese American men). Liquid chromatography-tandem mass spectrometry was utilized to measure serum vitamin D. CAC was examined by electron beam computed tomography using standardized protocols and read centrally at the University of Pittsburgh using Agatston's methods. To investigate an association between vitamin D deficiency (defined as 25-hydroxyvitamin D [25(OH)D] < 20 ng/mL) and CAC (defined as Agatston score ≥ 10), we utilized multivariable logistic regression models. RESULTS: Prevalence of CAC and vitamin D deficiency was 27.2% and 10.3%, respectively. Participants with CAC were significantly older, had significantly higher body mass index (BMI), and had higher rates of smoking. Those with CAC were 3.31 times likely to be vitamin D deficient, after adjusting for traditional cardiovascular risk factors (odds ratio [OR] = 3.31, 95% confidence interval [CI], 1.12-9.77). CONCLUSIONS: In this population-based study of healthy middle-aged men, vitamin D deficiency had a significant positive association with the presence of CAC.
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Doença da Artéria Coronariana/complicações , Calcificação Vascular/complicações , Deficiência de Vitamina D/complicações , Adulto , Asiático , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Estudos Transversais , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Tomografia Computadorizada por Raios X , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/epidemiologia , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , População BrancaRESUMO
OBJECTIVE: Cross-sectional studies suggest that lipopolysaccharide-binding protein (LBP) may be associated with obesity and metabolic disorders. However, prospective studies examining LBP are lacking. This prospective study investigated the association between LBP and metabolic abnormalities in 580 African ancestry men (mean age, 59.1 ± 10.5 years). RESEARCH DESIGN AND METHODS: We measured fasting serum LBP at baseline. Changes in adiposity and glucose homeostasis as well as case subjects with new type 2 diabetes and impaired fasting glucose (IFG) were assessed at a follow-up visit ~6 years later. Baseline LBP values were tested across quartiles for linear trend with metabolic measures. Multivariable logistic regression was used to determine the odds of new cases of IFG or diabetes per 1-SD greater baseline LBP. RESULTS: LBP was significantly associated with baseline BMI, waist circumference, whole-body and trunk fat, skeletal muscle density, fasting serum insulin, and HOMA-insulin resistance (IR) (all P < 0.01). Greater baseline LBP was significantly associated with longitudinal increases in the percentage of trunk fat (P = 0.025) and HOMA-IR (P = 0.034), but only borderline so with a decrease in skeletal muscle density (P = 0.057). In men with normal glucose, baseline LBP was associated with increased odds of having IFG at follow-up after adjustment for age, baseline trunk fat, and lifestyle factors (odds ratio per 1-SD LBP: 1.51; 95% CI 1.02-2.21). This association was attenuated after additional adjustment for change in trunk fat (P = 0.067). CONCLUSIONS: LBP may be a marker of prediabetes. Some of this association appears to be mediated through increased central and ectopic skeletal muscle adiposity.
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Adiposidade/fisiologia , Proteínas de Transporte/sangue , Glicoproteínas de Membrana/sangue , Estado Pré-Diabético/sangue , Proteínas de Fase Aguda/fisiologia , Adulto , Idoso , Envelhecimento/sangue , Envelhecimento/fisiologia , Biomarcadores/sangue , População Negra , Glicemia/análise , Glicemia/metabolismo , Proteínas de Transporte/fisiologia , Estudos Transversais , Humanos , Masculino , Glicoproteínas de Membrana/fisiologia , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/fisiopatologia , Estado Pré-Diabético/fisiopatologia , Estudos ProspectivosRESUMO
AIMS: Haptoglobin (Hp) genotype 2-2 increases cardiovascular diabetes complications. In type 2 diabetes, α-tocopherol was shown to lower cardiovascular risk in Hp 2-2, potentially through HDL function improvements. Similar type 1 diabetes data are lacking. We conducted a randomized crossover pilot of α-tocopherol supplementation on HDL function [i.e., cholesterol efflux (CE) and HDL-associated lipid peroxides (LP)] and lipoprotein subfractions in type 1 diabetes. METHODS: Hp genotype was assessed in members of two Allegheny County, PA, type 1 diabetes registries and the CACTI cohort; 30 were randomly selected within Hp genotype, and 28 Hp 1-1, 31 Hp 2-1 and 30 Hp 2-2 were allocated to daily α-tocopherol or placebo for 8 weeks with a 4-week washout. RESULTS: Baseline CE decreased with the number of Hp 2 alleles (p-trend = 0.003). There were no differences in LP or lipoprotein subfractions. In intention-to-treat analysis stratified by Hp, α-tocopherol increased CE in Hp 2-2 (ß = 0.79, p = 0.03) and LP in Hp 1 allele carriers (ß Hp 1-1 = 0.18, p = 0.05; ß Hp 2-1 = 0.21, p = 0.07); reduced HDL particle size (ß = -0.07, p = 0.03) in Hp 1-1 carriers; increased LDL particle concentration in Hp 1-1; and decreased it in Hp 2-2 carriers. However, no significant interactions were observed by Hp. CONCLUSIONS: In this type 1 diabetes study, HDL function worsened with the number of Hp 2 alleles. α-Tocopherol improved HDL function in Hp 2-2 carriers and appeared to adversely affect lipid peroxides and lipoprotein subfractions among Hp 1 allele carriers. As no significant interactions were observed, findings require replication in larger studies.
Assuntos
Diabetes Mellitus Tipo 1/genética , Haptoglobinas/genética , Lipoproteínas HDL/metabolismo , Vitamina E/uso terapêutico , Vitaminas/uso terapêutico , Adulto , Idoso , Alelos , Estudos de Coortes , Estudos Cross-Over , Diabetes Mellitus Tipo 1/terapia , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Genótipo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Lipoproteínas LDL/sangue , Lipoproteínas LDL/metabolismo , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: We sought to determine whether midpregnancy antioxidant levels are associated with preeclampsia, overall and by timing of onset. STUDY DESIGN: We carried out a case-control study, nested within a cohort of 5337 pregnant women in Montreal, Quebec, Canada. Blood samples obtained at 24-26 weeks were assayed for nonenzymatic antioxidant levels among cases of preeclampsia (n = 111) and unaffected controls (n = 441). We excluded women diagnosed with gestational hypertension only. We used logistic regression with the z-score of each antioxidant level as the main predictor variable for preeclampsia risk. We further stratified early-onset (<34 weeks) and late-onset preeclampsia and carried out multinomial logistic regression. Finally, we assessed associations between antioxidant biomarkers and timing of onset (in weeks) by Cox regression, with appropriate selection weights. We summed levels of correlated biomarkers (r(2) > 0.3) and log-transformed positively skewed distributions. We adjusted for body mass index, nulliparity, preexisting diabetes, hypertension, smoking, and proxies for ethnicity and socioeconomic status. RESULTS: The odds ratios for α-tocopherol, α-tocopherol:cholesterol, lycopene, lutein, and carotenoids (sum of α-carotene, ß-carotene, anhydrolutein, α-cryptoxanthin, and ß-cryptoxanthin) suggested an inverse association between antioxidant levels and overall preeclampsia risk; however, only lutein was significantly associated with overall preeclampsia in adjusted models (odds ratio, 0.60; 95% confidence interval, 0.46-0.77) per SD. In multinomial logistic models, the relative risk ratio (RRR) estimates for the early-onset subgroup were farther from the null than those for the late-onset subgroup. The ratio of α-tocopherol to cholesterol and retinol were significantly associated with early- but not late-onset preeclampsia: RRRs (95% confidence intervals) for early-onset preeclampsia 0.67 (0.46-0.99) and 1.61 (1.12-2.33), respectively. Lutein was significantly associated with both early- and late-onset subtypes in adjusted models; RRRs 0.53 (0.35-0.80) and 0.62 (0.47-0.82), respectively. Survival analyses confirmed these trends. CONCLUSION: Most antioxidants were more strongly associated with early-onset preeclampsia, suggesting that oxidative stress may play a greater role in the pathophysiology of early-onset preeclampsia. Alternatively, reverse causality may explain this pattern. Lutein was associated with both early- and late-onset preeclampsia and may be a promising nutrient to consider in preeclampsia prevention trials, if this finding is corroborated.
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Antioxidantes/análise , Pré-Eclâmpsia/sangue , Adulto , Carotenoides/sangue , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Pré-Eclâmpsia/epidemiologia , Gravidez , Segundo Trimestre da Gravidez , Quebeque/epidemiologia , Medição de Risco , Adulto Jovem , alfa-Tocoferol/sangueRESUMO
The haptoglobin (Hp) 2 allele directly predicts coronary artery disease in type 1 diabetes, potentially due to its decreased antioxidative/anti-inflammatory properties. We measured the concentrations of oxidative/inflammatory biomarkers (urinary 15-isoprostane F(2t) [IsoP], α- and γ-tocopherol, tumor necrosis factor α [TNF-α], high-sensitivity C-reactive protein [hsCRP], white blood cell [WBC] count, fibrinogen, and adiponectin) thrice during 20 years of follow-up among 454 individuals with childhood-onset type 1 diabetes (mean baseline age, 28 years and diabetes duration, 19 years). Differences in biomarkers by Hp were assessed both at baseline (i.e., the first time point of measurements) and over time (with mixed models). No differences by Hp were observed at baseline with the exception of a significant trend toward higher IsoP concentrations with the number of Hp 2 alleles (p=0.01). In multivariable mixed models, the concentrations of IsoP (ß=0.05, p=0.01) and WBC count (ß=0.20, p=0.06) overtime increased incrementally with the number of Hp 2 alleles. No other biomarker assessed related to Hp. Reported elevated IsoP and WBC count concentrations over time among Hp 2 allele carriers lead to the hypothesis that the antioxidative and anti-inflammatory capacity of the Hp 2 is inferior to that of the Hp 1 allele in type 1 diabetes.
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Biomarcadores/metabolismo , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/metabolismo , Haptoglobinas/genética , Adulto , Alelos , Biomarcadores/urina , F2-Isoprostanos/urina , Feminino , Seguimentos , Genótipo , Humanos , Contagem de Leucócitos , Masculino , Estresse Oxidativo , Adulto JovemRESUMO
Poor renal function is associated with increased rates of bone loss and osteoporotic fractures in Caucasian men. The importance of kidney function for skeletal health in African ancestry men, who are a population segment with a high prevalence of chronic kidney disease as well as high peak bone mass, is not well known. We examined the relationship between estimated glomerular filtration rate (eGFR) and rates of bone loss in a large population cohort of otherwise healthy Afro-Caribbean men aged 40 years and older. Dual X-ray absorptiometry of the proximal femur and quantitative computed tomography of the proximal radius and tibia were obtained approximately 6 years apart. We calculated eGFR from serum creatinine that was measured in fasting samples in 1451 men. Impaired kidney function (IKF, eGFR<60 ml/min/1.7 m(2)) was observed in 8.6% of the cohort. The relationship between IKF and baseline BMD and annualized rate of change in BMD was analyzed controlling for potentially important confounders. IKF was not associated with baseline BMD. In contrast, men with IKF experienced a rate of decline in areal BMD at the total hip, femoral neck and trochanter and cortical volumetric BMD compared to those with normal kidney function (p<0.05 for all). Impaired kidney function was not associated with changes in trabecular volumetric BMD. In conclusion, poorer kidney function is associated with accelerated bone loss among otherwise healthy Afro-Caribbean men even after controlling for age and other important medical and lifestyle related variables.
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Densidade Óssea , Doenças Ósseas Metabólicas/diagnóstico por imagem , Doenças Ósseas Metabólicas/etnologia , Falência Renal Crônica/diagnóstico por imagem , Falência Renal Crônica/etnologia , Rim/fisiopatologia , Absorciometria de Fóton , Adulto , Idoso , Idoso de 80 Anos ou mais , Antropometria , População Negra , Peso Corporal , Osso e Ossos/patologia , Região do Caribe , Estudos de Coortes , Densitometria , Fêmur/diagnóstico por imagem , Colo do Fêmur/diagnóstico por imagem , Taxa de Filtração Glomerular , Quadril/diagnóstico por imagem , Humanos , Rim/fisiologia , Testes de Função Renal , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: We hypothesized that higher concentrations of LDL particles (LDL-P) and leptin, and lower concentrations of HDL particles (HDL-P), and total and high molecular weight (HMW) adiponectin, would predict incident coronary heart disease (CHD) among severely obese postmenopausal women. METHODS: In a case-cohort study nested in the Women's Health Initiative Observational Study, we sampled 677 of the 1852 white or black women with body mass index (BMI) ≥40 kg/m2 and no prevalent cardiovascular disease (CVD), including all 124 cases of incident CHD over mean 5.0 year follow-up. Biomarkers were assayed on stored blood samples. RESULTS: In multivariable-adjusted weighted Cox models, higher baseline levels of total and small LDL-P, and lower levels of total and medium HDL-P, and smaller mean HDL-P size were significantly associated with incident CHD. In contrast, large HDL-P levels were inversely associated with CHD only for women without diabetes, and higher total and HMW adiponectin levels and lower leptin levels were associated with CHD only for women with diabetes. Higher total LDL-P and lower HDL-P were associated with CHD risk independently of confounders including CV risk factors and other lipoprotein measures, with adjusted HR (95%CIs) of 1.55(1.28, 1.88) and (0.70 (0.57, 0.85), respectively, and similar results for medium HDL-P. CONCLUSIONS: Higher CHD risk among severely obese postmenopausal women is strongly associated with modifiable concentrations of LDL-P and HDL-P, independent of diabetes, smoking, hypertension, physical activity, BMI and waist circumference. GENERAL SIGNIFICANCE: Severely obese postmenopausal women should be considered high risk candidates for lipid lowering therapy.
RESUMO
OBJECTIVE: To describe associations between maternal lipids and birthweight and to determine whether pre-pregnancy body mass index (BMI) modifies these associations. DESIGN: Cohort study. SETTING: Multiple communities in Michigan, USA. POPULATION: Participants were a sub-cohort of women from the multi-community Pregnancy Outcomes and Community Health (POUCH) study (1998-2004). METHODS: Maternal total cholesterol, high-density lipoprotein (HDLc), and low-density lipoprotein (LDLc) cholesterol, and triglycerides were assessed at 16-27 weeks' gestation. Women were classified as having normal (< 25 kg/m(2) ) or overweight/obese (≥ 25 kg/m(2) ) pre-pregnancy BMI. MAIN OUTCOME MEASURES: Sex- and gestational-age-specific body weight z-score (BWz). RESULTS: Regression models examined associations among lipids (low: 1st quartile, referent: middle quartiles, high: 4th quartile) and BWz for the total sample and stratified by pre-pregnancy BMI. In adjusted analyses (n = 1207), low HDLc was associated with lower BWz (ß = -0.23, 95% CI -0.40 to -0.06), whereas high triglycerides were associated with higher BWz (ß = 0.23, 95% CI 0.06-0.41). Once stratified by pre-pregnancy BMI, low total cholesterol was associated with lower BWz in normal BMI women (ß = -0.25, 95% CI -0.47 to -0.03), whereas in overweight/obese BMI women, high HDLc was inversely (ß = -0.29, 95% CI -0.54 to -0.04) and high triglycerides were directly associated with BWz (ß = 0.32, 95% CI 0.07-0.54). Removing women with gestational diabetes/hypertensive disorders did not alter the results. CONCLUSIONS: The associations between maternal lipids and BWz vary by lipid measure and pre-pregnancy BMI. Future work should examine whether lipids and pre-pregnancy BMI make unique contributions to the fetal programming of disease.
Assuntos
Peso ao Nascer , Colesterol/sangue , Lipídeos/sangue , Obesidade/sangue , Complicações na Gravidez/sangue , Triglicerídeos/sangue , Adulto , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Segundo Trimestre da Gravidez/sangue , Aumento de PesoRESUMO
The nuclear receptor farnesoid X receptor (FXR) (nuclear receptor subfamily 1, group H, member 4, or NR1H4) is highly expressed in the liver and intestine. Previous reports have suggested beneficial functions of FXR in the homeostasis of bile acids, lipids, and glucose, as well as in promoting liver regeneration and inhibiting carcinogenesis. To investigate the effect of chronic FXR activation in vivo, we generated transgenic mice that conditionally and tissue specifically express the activated form of FXR in the liver and intestine. Unexpectedly, the transgenic mice showed several intriguing phenotypes, including partial neonatal lethality, growth retardation, and spontaneous liver toxicity. The transgenic mice also displayed heightened sensitivity to a high-cholesterol diet-induced hepatotoxicity but resistance to the gallstone formation. The phenotypes were transgene specific, because they were abolished upon treatment with doxycycline to silence the transgene expression. The perinatal toxicity, which can be rescued by a maternal vitamin supplement, may have resulted from vitamin deficiency due to low biliary bile acid output as a consequence of inhibition of bile acid formation. Our results also suggested that the fibroblast growth factor-inducible immediate-early response protein 14 (Fn14), a member of the proinflammatory TNF family, is a FXR-responsive gene. However, the contribution of Fn14 induction in the perinatal toxic phenotype of the transgenic mice remains to be defined. Because FXR is being explored as a therapeutic target, our results suggested that a chronic activation of this nuclear receptor may have an unintended side effect especially during the perinatal stage.
Assuntos
Colesterol/toxicidade , Mucosa Intestinal/metabolismo , Fígado/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Animais , Ácidos e Sais Biliares/metabolismo , Dieta Hiperlipídica , Intestinos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Hepatopatias/metabolismo , Camundongos , Camundongos Transgênicos , Receptores Citoplasmáticos e Nucleares/genética , Receptores do Fator de Necrose Tumoral/genética , Receptores do Fator de Necrose Tumoral/metabolismo , Receptor de TWEAK , Vitamina A/sangue , Vitamina E/sangueRESUMO
AIMS/HYPOTHESIS: At the same level of BMI, white people have less visceral adipose tissue (VAT) and are less susceptible to developing type 2 diabetes than Japanese people. No previous population-based studies have compared insulin resistance and insulin secretion between these two races in a standardised manner that accounts for VAT. We compared HOMA-IR, HOMA of beta cell function (HOMA-ß%) and disposition index (DI) in US white men and Japanese men in Japan. METHODS: We conducted a population-based, cross-sectional study, comprising 298 white men and 294 Japanese men aged 40-49 years without diabetes. Insulin, glucose, VAT and other measurements were performed at the University of Pittsburgh. We used ANCOVA to compare geometric means of HOMA-IR, HOMA-ß% and DI, adjusting for VAT and other covariates. RESULTS: White men had higher HOMA-IR, HOMA-ß% and DI than Japanese men, and the difference remained significant (p < 0.01) after adjusting for VAT (geometric mean [95% CI]): 3.1 (2.9, 3.2) vs 2.5 (2.4, 2.6), 130.8 (124.6, 137.3) vs 86.7 (82.5, 91.0), and 42.4 (41.0, 44.0) vs 34.8 (33.6, 36.0), respectively. Moreover, HOMA-IR, HOMA-ß% and DI were significantly higher in white men even after further adjustment for BMI, impaired fasting glucose and other risk factors. CONCLUSIONS/INTERPRETATION: The higher VAT-adjusted DI in white men than Japanese men may partly explain lower susceptibility of white people than Japanese people to developing type 2 diabetes. The results, however, should be interpreted with caution because the assessment of insulin indices was made using fasting samples and adjustment was not made for baseline glucose tolerance. Further studies using formal methods to evaluate insulin indices are warranted.