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1.
Nutrients ; 12(1)2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31947853

RESUMO

Hyperglycemia is linked to impaired arterial endothelial function (EF), an early sign of cardiovascular disease. We compared the efficacy of low-glycemic index isomaltulose (Palatinose™) with that of sucrose in modulating EF, as assessed by flow-mediated dilation (FMD). In this double-blinded cross-over study, 80 overweight mildly hypertensive subjects were randomized to receive 50 g of either isomaltulose or sucrose. On two non-consecutive days, brachial artery ultrasound FMD scans were obtained prior to and hourly (T0-T3) after carbohydrate load. Blood was drawn immediately after scanning. Glucose and insulin levels were analyzed. Overall, the FMD decrease was attenuated by isomaltulose compared to sucrose (ΔFMD = -0.003% and -0.151%; p > 0.05 for the interaction treatment x period). At T2, FMD was significantly higher after isomaltulose administration compared to that after sucrose administration (FMD = 5.9 ± 2.9% and 5.4 ± 2.6%, p = 0.047). Pearson correlations between FMD and blood glucose showed a trend for a negative association at T0 and T2 independently of the carbohydrate (r-range = -0.20 to -0.23, p < 0.1). Sub-analysis suggested a lower FMD in insulin-resistant (IR) compared to insulin-sensitive subjects. Isomaltulose attenuated the postprandial decline of FMD, particularly in IR persons. These data support the potential of isomaltulose to preserve the endothelial function postprandially and consequently play a favorable role in cardiovascular health.

2.
Eur J Prev Cardiol ; : 2047487319877078, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619084

RESUMO

AIMS: Averaged measurements, but not the progression based on multiple assessments of carotid intima-media thickness, (cIMT) are predictive of cardiovascular disease (CVD) events in individuals. Whether this is true for conventional risk factors is unclear. METHODS AND RESULTS: An individual participant meta-analysis was used to associate the annualised progression of systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with future cardiovascular disease risk in 13 prospective cohort studies of the PROG-IMT collaboration (n = 34,072). Follow-up data included information on a combined cardiovascular disease endpoint of myocardial infarction, stroke, or vascular death. In secondary analyses, annualised progression was replaced with average. Log hazard ratios per standard deviation difference were pooled across studies by a random effects meta-analysis. In primary analysis, the annualised progression of total cholesterol was marginally related to a higher cardiovascular disease risk (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00 to 1.07). The annualised progression of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol was not associated with future cardiovascular disease risk. In secondary analysis, average systolic blood pressure (HR 1.20 95% CI 1.11 to 1.29) and low-density lipoprotein cholesterol (HR 1.09, 95% CI 1.02 to 1.16) were related to a greater, while high-density lipoprotein cholesterol (HR 0.92, 95% CI 0.88 to 0.97) was related to a lower risk of future cardiovascular disease events. CONCLUSION: Averaged measurements of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol displayed significant linear relationships with the risk of future cardiovascular disease events. However, there was no clear association between the annualised progression of these conventional risk factors in individuals with the risk of future clinical endpoints.

3.
N Engl J Med ; 381(16): 1547-1556, 2019 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-31618540

RESUMO

BACKGROUND: Familial hypercholesterolemia is characterized by severely elevated low-density lipoprotein (LDL) cholesterol levels and premature cardiovascular disease. The short-term efficacy of statin therapy in children is well established, but longer follow-up studies evaluating changes in the risk of cardiovascular disease are scarce. METHODS: We report a 20-year follow-up study of statin therapy in children. A total of 214 patients with familial hypercholesterolemia (genetically confirmed in 98% of the patients), who were previously participants in a placebo-controlled trial evaluating the 2-year efficacy and safety of pravastatin, were invited for follow-up, together with their 95 unaffected siblings. Participants completed a questionnaire, provided blood samples, and underwent measurements of carotid intima-media thickness. The incidence of cardiovascular disease among the patients with familial hypercholesterolemia was compared with that among their 156 affected parents. RESULTS: Of the original cohort, 184 of 214 patients with familial hypercholesterolemia (86%) and 77 of 95 siblings (81%) were seen in follow-up; among the 214 patients, data on cardiovascular events and on death from cardiovascular causes were available for 203 (95%) and 214 (100%), respectively. The mean LDL cholesterol level in the patients had decreased from 237.3 to 160.7 mg per deciliter (from 6.13 to 4.16 mmol per liter) - a decrease of 32% from the baseline level; treatment goals (LDL cholesterol <100 mg per deciliter [2.59 mmol per liter]) were achieved in 37 patients (20%). Mean progression of carotid intima-media thickness over the entire follow-up period was 0.0056 mm per year in patients with familial hypercholesterolemia and 0.0057 mm per year in siblings (mean difference adjusted for sex, -0.0001 mm per year; 95% confidence interval, -0.0010 to 0.0008). The cumulative incidence of cardiovascular events and of death from cardiovascular causes at 39 years of age was lower among the patients with familial hypercholesterolemia than among their affected parents (1% vs. 26% and 0% vs. 7%, respectively). CONCLUSIONS: In this study, initiation of statin therapy during childhood in patients with familial hypercholesterolemia slowed the progression of carotid intima-media thickness and reduced the risk of cardiovascular disease in adulthood. (Funded by the AMC Foundation.).


Assuntos
Doenças Cardiovasculares/prevenção & controle , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Adolescente , Adulto , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Espessura Intima-Media Carotídea , Criança , LDL-Colesterol/sangue , Progressão da Doença , Feminino , Seguimentos , Humanos , Hiperlipoproteinemia Tipo II/sangue , Incidência , Masculino , Intervalo Livre de Progressão , Risco , Inquéritos e Questionários , Adulto Jovem
4.
Circulation ; 138(10): 1000-1007, 2018 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-29748187

RESUMO

BACKGROUND: Lecithin:cholesterol acyltransferase (LCAT) is the sole enzyme that esterifies cholesterol in plasma. Its role in the supposed protection from atherogenesis remains unclear because mutations in LCAT causing fish-eye disease (FED) or familial LCAT deficiency (FLD) have been reported to be associated with more or instead less carotid atherosclerosis, respectively. This discrepancy may be associated with the loss of cholesterol esterification on only apolipoprotein AI (FED) or on both apolipoprotein AI- and apolipoprotein B-containing lipoproteins (FLD), an aspect that has thus far not been investigated. METHODS: Seventy-four heterozygotes for LCAT mutations recruited from Italy and the Netherlands were assigned to FLD (n=33) or FED (n=41) groups and compared with 280 control subjects. Subclinical atherosclerosis was assessed with carotid intima-media thickness. RESULTS: Compared with control subjects, total cholesterol was lower by 16% (-32.9 mg/dL) and 7% (-14.9 mg/dL) and high-density lipoprotein cholesterol was lower by 29% (-16.7 mg/dL) and 36% (-20.7 mg/dL) in the FLD and FED groups, respectively. Subjects with FLD displayed a significant 18% lower low-density lipoprotein cholesterol compared with subjects with FED (101.9±35.0 versus 123.6±47.4 mg/dL; P=0.047) and control subjects (122.6±35.0 mg/dL; P=0.003). Remarkably, all 3 intima-media thickness parameters were lower in subjects with FLD compared with FED and control subjects (accounting for age, sex, body mass index, smoking, hypertension, family history of cardiovascular disease, and plasma lipids). After additional correction for nationality and ultrasonographic methods, average and maximum intima-media thickness remained significantly lower when subjects with FLD were compared with those with FED (0.59 versus 0.73 mm, P=0.003; and 0.87 versus 1.24 mm, P<0.001, respectively). In contrast, the common carotid intima-media thickness (corrected for age, sex, body mass index, smoking, hypertension, family history of cardiovascular disease, and plasma lipids) was higher in subjects with FED compared with control subjects (0.69 versus 0.65 mm; P=0.05), but this significance was lost after adjustment for nationality and ultrasonographic machine. CONCLUSIONS: In this head-to-head comparison, FLD and FED mutations were shown to be associated with decreased and increased atherosclerosis, respectively. We propose that this discrepancy is related to the capacity of LCAT to generate cholesterol esters on apolipoprotein B-containing lipoproteins. Although this capacity is lost in FLD, it is unaffected in FED. These results are important when considering LCAT as a target to decrease atherosclerosis.


Assuntos
Doenças das Artérias Carótidas/etiologia , Deficiência da Lecitina Colesterol Aciltransferase/genética , Mutação , Fosfatidilcolina-Esterol O-Aciltransferase/genética , Adulto , Doenças das Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Marcadores Genéticos , Predisposição Genética para Doença , Heterozigoto , Homozigoto , Humanos , Itália , Deficiência da Lecitina Colesterol Aciltransferase/complicações , Deficiência da Lecitina Colesterol Aciltransferase/diagnóstico , Deficiência da Lecitina Colesterol Aciltransferase/enzimologia , Masculino , Pessoa de Meia-Idade , Países Baixos , Fenótipo , Fosfatidilcolina-Esterol O-Aciltransferase/metabolismo , Medição de Risco , Fatores de Risco
5.
Am J Clin Nutr ; 104(6): 1523-1533, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27797708

RESUMO

BACKGROUND: Endothelial dysfunction (ED) is involved in the development of atherosclerosis. Hesperidin, a citrus flavonoid with antioxidant and other biological properties, potentially exerts beneficial effects on endothelial function (EF). OBJECTIVE: We investigated the effect of hesperidin 2S supplementation on EF in overweight individuals. DESIGN: This was a randomized, double-blind, placebo-controlled study in which 68 individuals were randomly assigned to receive hesperidin 2S (450 mg/d) or a placebo for 6 wk. At baseline and after 6 wk of intervention, flow-mediated dilation (FMD), soluble vascular adhesion molecule-1 (sVCAM-1), soluble intracellular adhesion molecule-1 (sICAM-1), soluble P-selectin (sP-selectin), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were assessed. Acute, reversible ED was induced by intake of a high-fat meal (HFM). A second FMD scan was performed 2 h postprandially, and adhesion molecules were assessed 2 and 4 h postprandially. An additional exploratory analysis was performed in subjects with baseline FMD ≥3%. RESULTS: No significant change in fasting or postprandial FMD was observed after 6 wk of hesperidin intake compared with placebo intake. However, there was a trend for a reduction of sVCAM-1, sICAM-1, sP-selectin, SBP, and DBP after 6 wk of hesperidin treatment. In the FMD ≥3% group, hesperidin protected individuals from postprandial ED (P = 0.050) and significantly downregulated sVCAM-1 and sICAM-1 (all P ≤ 0.030). The results reported in the current article were not adjusted for multiplicity. CONCLUSIONS: Six weeks of consumption of hesperidin 2S did not improve basal or postprandial FMD in our total study population. There was a tendency toward a reduction of adhesion molecules and a decrease in SBP and DBP. Further exploratory analyses revealed that, in subjects with baseline FMD ≥3%, hesperidin 2S improved ED after an HFM and reduced adhesion molecules. These results indicate the cardiovascular health benefits of hesperidin 2S in overweight and obese individuals with a relatively healthy endothelium. This trial was registered at clinicaltrials.gov as NCT02228291.


Assuntos
Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Hesperidina/administração & dosagem , Obesidade/sangue , Sobrepeso/sangue , Adulto , Idoso , Pressão Sanguínea/efeitos dos fármacos , Índice de Massa Corporal , Moléculas de Adesão Celular/sangue , Suplementos Nutricionais , Método Duplo-Cego , Regulação para Baixo , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Selectina-P/sangue , Período Pós-Prandial , Resultado do Tratamento , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo
6.
J Am Heart Assoc ; 5(7)2016 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-27381760

RESUMO

BACKGROUND: Kawasaki disease (KD) is a pediatric vasculitis with coronary artery aneurysm (CAA) as a major complication. Controversy exists about cardiovascular risk later in life. The aim of our study was to evaluate whether KD patients are at increased risk, as assessed by carotid intima-media thickness (cIMT). METHODS AND RESULTS: We measured cIMT over 15 years by B-mode ultrasonography in KD patients during follow-up and in unaffected controls (mostly siblings). A multilevel, repeated-measures, linear mixed-effects model was used to evaluate the association between KD and cIMT. A total of 319 patients with 528 measurements were compared with 150 controls. In KD patients, the mean cIMT was increased compared with controls (0.375 mm [95% CI 0.372-0.378 mm] versus 0.363 mm [95% CI 0.358-0.368 mm]; P<0.001). Furthermore, mean cIMT of CAA-negative patients was 0.373 mm (P<0.01 compared with controls), of patients with small-medium CAA was 0.374 mm (P<0.05 compared with controls), and of patients with giant CAA was 0.381 mm (P<0.01 compared with controls). Compared with controls, CAA-negative participants started with an increased cIMT (+0.0193±0.0053 mm, P<0.001) but showed slower progression (-0.0014±0.0006 mm/year, P=0.012). Patients with giant CAA showed a trend toward increased cIMT progression (0.0013±0.0007 mm/year, P=0.058). CONCLUSIONS: We observed a positive correlation between cIMT and KD severity of coronary arteritis at the acute stage. Although initially increased, the cIMT in CAA-negative patients normalized at a later age. In contrast, patients with a history of KD complicated by giant CAA showed a trend toward persistently increased cIMT. These patients may need cardiovascular counseling and follow-up beyond the heart.


Assuntos
Doenças das Artérias Carótidas/epidemiologia , Aneurisma Coronário/epidemiologia , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Adolescente , Adulto , Doenças das Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Modelos Lineares , Masculino , Fatores de Risco , Irmãos , Ultrassonografia , Adulto Jovem
7.
Atherosclerosis ; 251: 476-482, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27341753

RESUMO

Slowing of progression and inducing the regression of atherosclerosis with medical therapy have been shown to be associated with an extensive reduction in risk of cardiovascular events. This proof of concept was obtained with invasive angiographic studies but these are, for obvious reasons, impractical for sequential investigations. Non-invasive imaging has henceforth replaced the more cumbersome invasive studies and has proven extremely valuable in numerous occasions. Because of excellent reproducibility and no radiation exposure, magnetic resonance imaging (MRI) has become the non-invasive method of choice to assess the efficacy of anti-atherosclerotic drugs. The high accuracy of this technology is particularly helpful in rare diseases where the small number of affected patients makes the conduct of outcome-trials in large cohorts impractical. With MRI it is possible to assess the extent, as well as the composition, of atherosclerotic plaques and this further enhances the utility of this technology.


Assuntos
Aterosclerose/diagnóstico por imagem , Angiografia por Ressonância Magnética , Imagem por Ressonância Magnética , Placa Aterosclerótica/diagnóstico por imagem , Aterosclerose/patologia , Biomarcadores , Ensaios Clínicos como Assunto , Progressão da Doença , Desenho de Drogas , Humanos , Processamento de Imagem Assistida por Computador , Placa Aterosclerótica/patologia , Reprodutibilidade dos Testes , Resultado do Tratamento
8.
Environ Health Perspect ; 124(11): 1700-1706, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27258721

RESUMO

BACKGROUND: Subclinical atherosclerosis has been associated with long-term exposure to particulate matter (PM), but the relevance of particle size and sources of exposure remains unclear. OBJECTIVES: We investigated the association of long-term exposure to PM10 (≤ 10 µm), PM2.5 (≤ 2.5 µm: total mass, vehicular, and crustal sources), and ultrafine particles [UFP < 0.1 µm: particle number concentration (PNC) and lung-deposited surface area (LDSA)] with carotid intima-media thickness (CIMT). METHODS: We used data from 1,503 participants ≥ 50 years old who participated in the third examination of the Swiss SAPALDIA cohort. Exposures were obtained from dispersion models and land-use regression models. Covariate information, including previous cardiovascular risk factors, was obtained from the second and third SAPALDIA examinations. RESULTS: The adjusted percent difference in CIMT associated with an exposure contrast between the 10th and 90th percentile was 1.58% (95% CI: -0.30, 3.47%) for PM10, 2.10% (95% CI: 0.04, 4.16%) for PM2.5, 1.67% (95% CI: -0.13, 3.48%) for the vehicular source of PM2.5, -0.58% (95% CI: -3.95, 2.79%) for the crustal source of PM2.5, 2.06% (95% CI: 0.03, 4.10%) for PNC, and 2.32% (95% CI: 0.23, 4.40%) for LDSA. Stronger associations were observed among diabetics, subjects with low-educational level, and those at higher cardiovascular risk. CONCLUSIONS: CIMT was associated with exposure to PM10, PM2.5, and UFP. The PM2.5 source-specific analysis showed a positive association for the vehicular source but not for the crustal source. Although the effects of PNC and LDSA were similar in magnitude, two-pollutant and residual-based models suggested that LDSA may be a better marker for the health relevance of UFP. Citation: Aguilera I, Dratva J, Caviezel S, Burdet L, de Groot E, Ducret-Stich RE, Eeftens M, Keidel D, Meier R, Perez L, Rothe T, Schaffner E, Schmit-Trucksäss A, Tsai MY, Schindler C, Künzli N, Probst-Hensch N. 2016. Particulate matter and subclinical atherosclerosis: associations between different particle sizes and sources with carotid intima-media thickness in the SAPALDIA study. Environ Health Perspect 124:1700-1706; http://dx.doi.org/10.1289/EHP161.


Assuntos
Aterosclerose/etiologia , Espessura Intima-Media Carotídea , Exposição Ambiental , Material Particulado/toxicidade , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Escolaridade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho da Partícula , Material Particulado/análise , Material Particulado/química , Suíça
9.
Arch Dis Child ; 101(7): 637-9, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26644401

RESUMO

BACKGROUND AND AIMS: Inhaled corticosteroids (ICS) reduce growth during the first year of treatment, but this growth suppressing effect does not continue during further treatment. Decreasing adherence may play a role in explaining this. The aim of this study was to examine the relationship between cumulative real exposure (with objectively assessed adherence) to ICS and height growth in children with asthma. METHODS: We investigated 99 prepubertal children with asthma, 2-13 years of age, who had been using ICS in guideline-recommended dosages for ≥3 months, and continued to do so during 1-year follow-up. ICS adherence was assessed by electronic monitoring devices, allowing calculation of true cumulative exposure to ICS. We analysed the relationship between cumulative ICS dose and height growth velocity (assessed as change in height SD score) over 1 year. RESULTS: Median (IQR) adherence over 1 year was 84 (68-92) %. Mean cumulative fluticasone dose was 64.6 (SD, 27.8) mg, reflecting a daily dose of 167 (SD, 7) µg. The negative correlation between cumulative ICS dose and height growth velocity (r=-0.266; p=0.008) became non-significant after adjustment for age and sex in a multiple regression model (adjusted r=-0.188; p=0.066). CONCLUSIONS: One year of ICS treatment in guideline-recommended dosages with high adherence did not result in significant or relevant growth suppression. Unaffected growth can be maintained for at least 1 year in children with asthma during ICS treatment with high adherence.


Assuntos
Asma/tratamento farmacológico , Broncodilatadores/efeitos adversos , Fluticasona/efeitos adversos , Glucocorticoides/efeitos adversos , Transtornos do Crescimento/induzido quimicamente , Administração por Inalação , Adolescente , Antropometria/métodos , Asma/fisiopatologia , Estatura/efeitos dos fármacos , Broncodilatadores/administração & dosagem , Broncodilatadores/uso terapêutico , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Fluticasona/administração & dosagem , Fluticasona/uso terapêutico , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Guias de Prática Clínica como Assunto
10.
Eur J Prev Cardiol ; 23(2): 194-205, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25416041

RESUMO

BACKGROUND: Large-scale epidemiological evidence on the role of inflammation in early atherosclerosis, assessed by carotid ultrasound, is lacking. We aimed to quantify cross-sectional and longitudinal associations of inflammatory markers with common-carotid-artery intima-media thickness (CCA-IMT) in the general population. METHODS: Information on high-sensitivity C-reactive protein, fibrinogen, leucocyte count and CCA-IMT was available in 20 prospective cohort studies of the PROG-IMT collaboration involving 49,097 participants free of pre-existing cardiovascular disease. Estimates of associations were calculated within each study and then combined using random-effects meta-analyses. RESULTS: Mean baseline CCA-IMT amounted to 0.74 mm (SD = 0.18) and mean CCA-IMT progression over a mean of 3.9 years to 0.011 mm/year (SD = 0.039). Cross-sectional analyses showed positive linear associations between inflammatory markers and baseline CCA-IMT. After adjustment for traditional cardiovascular risk factors, mean differences in baseline CCA-IMT per one-SD higher inflammatory marker were: 0.0082 mm for high-sensitivity C-reactive protein (p < 0.001); 0.0072 mm for fibrinogen (p < 0.001); and 0.0025 mm for leucocyte count (p = 0.033). 'Inflammatory load', defined as the number of elevated inflammatory markers (i.e. in upper two quintiles), showed a positive linear association with baseline CCA-IMT (p < 0.001). Longitudinal associations of baseline inflammatory markers and changes therein with CCA-IMT progression were null or at most weak. Participants with the highest 'inflammatory load' had a greater CCA-IMT progression (p = 0.015). CONCLUSION: Inflammation was independently associated with CCA-IMT cross-sectionally. The lack of clear associations with CCA-IMT progression may be explained by imprecision in its assessment within a limited time period. Our findings for 'inflammatory load' suggest important combined effects of the three inflammatory markers on early atherosclerosis.


Assuntos
Aterosclerose/sangue , Proteína C-Reativa/análise , Progressão da Doença , Fibrinogênio/análise , Contagem de Leucócitos , Biomarcadores/sangue , Espessura Intima-Media Carotídea , Humanos , Inflamação/sangue
11.
Circ J ; 79(12): 2682-7, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26439324

RESUMO

BACKGROUND: Kawasaki disease (KD) is an acute pediatric vasculitis with coronary artery aneurysms (CAA) as its main complication. Concerns have been raised regarding the possibility of a predisposition of KD to premature cardiovascular disease (CVD) risk later in life. Our aim was to assess carotid intima-media thickness (cIMT), as a surrogate marker of CVD risk, in patients with a history of KD compared with unaffected controls. METHODS AND RESULTS: B-mode ultrasound cIMT measurements were performed in 168 patients with a history of KD, and 82 controls; 7 patients were excluded because of incomplete cIMT assessments. Mean cIMT (±SD) was increased in patients with KD compared with controls (0.378±0.030 mm vs. 0.360±0.027 mm, respectively; P adjusted <0.0001). If the cIMTs of CAA-negative patients and controls were plotted against age, increased cIMT was only apparent at young age. In patients with CAA, increased cIMT was observed over the entire age range. CONCLUSIONS: Our findings show that arterial wall thickening is more apparent in patients with a history of KD as compared with controls. In CAA-negative patients, cIMT is indistinguishable from controls at older age, whereas an increased cIMT is observed at any age in patients with CAA, suggesting a more general and severe effect of KD on the arterial wall.


Assuntos
Espessura Intima-Media Carotídea , Aneurisma Coronário , Síndrome de Linfonodos Mucocutâneos , Adolescente , Adulto , Criança , Aneurisma Coronário/diagnóstico por imagem , Aneurisma Coronário/etiologia , Humanos , Masculino , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico por imagem , Fatores de Risco
12.
Clin Infect Dis ; 61(10): 1606-14, 2015 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-26215596

RESUMO

BACKGROUND: In sub-Saharan Africa, the number of persons living with human immunodeficiency virus (HIV) has increased immensely. In parallel, rates of noncommunicable diseases, especially cardiovascular disease, are rising rapidly in resource-limited settings. This study aims to evaluate the relation between subclinical atherosclerosis and HIV-related and traditional cardiovascular risk factors in HIV-infected patients in rural South Africa. METHODS: A cross-sectional study was performed among HIV-infected patients visiting a health center in Limpopo, South Africa. Demographic and HIV-related information was collected, and cardiovascular risk was assessed. Carotid intima media thickness (CIMT) was measured and the prevalence of subclinical atherosclerosis (CIMT >0.78 mm) was calculated. The association between cardiovascular or HIV-related determinants with CIMT was analyzed using linear and logistic regression models adjusted for age and sex. RESULTS: The median CIMT in 866 subjects (median age [interquartile range], 41 [35-48] years; 69% female) was 0.589 mm (interquartile range, 0.524-0.678 mm), and values seemed higher than in healthy Western reference populations. In fact 12% of subjects (106 of 866) had subclinical atherosclerosis. Hypertension, high body mass index, previous cardiovascular event, diabetes mellitus, total and low-density lipoprotein cholesterol, estimated glomerular filtration rate, metabolic syndrome, and the Framingham Heart Risk score were independently associated with CIMT. No HIV-related determinants were associated with CIMT. CONCLUSIONS: In a predominantly female HIV-infected population in South Africa, CIMT values are considerably high and associated with cardiovascular risk factors, rather than HIV-related factors. This finding emphasizes the need to screen for cardiovascular disease among persons with HIV infection in resource-limited settings. Ideally, this screening would be integrated into care for chronic HIV infection, posing a major challenge for the future.


Assuntos
Aterosclerose/epidemiologia , Doenças Cardiovasculares/patologia , Espessura Intima-Media Carotídea , Infecções por HIV/complicações , Adulto , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , População Rural , África do Sul
13.
PLoS One ; 10(7): e0130878, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26161783

RESUMO

PURPOSE: Different in-plane resolutions have been used for carotid 3T MRI. We compared the reproducibility, as well as the within- and between reader variability of high and routinely used spatial resolution in scans of patients with atherosclerotic carotid artery disease. Since no consensus exists about the optimal segmentation method, we analysed all imaging data using two different segmentation methods. MATERIALS AND METHODS: In 31 patient with carotid atherosclerosis a high (0.25 × 0.25 mm2; HR) and routinely used (0.50 × 0.50 mm2; LR) spatial resolution carotid MRI scan were performed within one month. A fully blinded closed and a simultaneously open segmentation were used to quantify the lipid rich necrotic core (LRNC), calcified and loose matrix (LM) plaque area and the fibrous cap (FC) thickness. RESULTS: No significant differences were observed between scan-rescan reproducibility for HR versus LR measurements, nor did we find any significant difference between the within-reader and between-reader reproducibility. The same applies for differences between the open and closed reads. All intraclass correlation coefficients between scans and rescans for the LRNC, calcified and LM plaque area, as well as the FC thickness measurements with the open segmentation method were excellent (all above 0.75). CONCLUSIONS: Increasing the spatial resolution at the expense of the contrast-to-noise ratio does not improve carotid plaque component scan-rescan reproducibility in patients with atherosclerotic carotid disease, nor does using a different segmentation method.


Assuntos
Artérias Carótidas/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Placa Aterosclerótica/diagnóstico por imagem , Idoso , Artérias Carótidas/patologia , Feminino , Fibrose , Humanos , Masculino , Pessoa de Meia-Idade , Necrose , Placa Aterosclerótica/diagnóstico , Radiografia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
14.
PLoS One ; 10(6): e0128991, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26035590

RESUMO

INTRODUCTION: Regular physical activity has been shown to reduce cardiovascular disease risk in the general population. While smaller studies in specified groups (highly trained versus untrained individuals) indicate a certain dose-dependent effect of physical activity on the reduction of carotid stiffness (an indicator of subclinical vascular disease), it is unclear whether this association is present in a representative sample. Thus, we investigated this question cross-sectionally in participants from the population-based Swiss Cohort Study on Air Pollution And Lung and Heart Diseases In Adults (SAPALDIA). METHODS: Self-reported total, moderate and vigorous physical activity and distensibility as a measure of local arterial stiffness among 1636 participants aged 50 to 81 years without clinically manifest diseases were evaluated. Mixed regression models were used to examine associations of physical activity intensity with distensibility. RESULTS: Vigorous physical activity, but not total nor moderate physical activity, was significantly associated with increased distensibility (= reduced carotid stiffness) in univariate analyses (percent change in the geometric mean and 95% confidence interval per 1 standard deviation increment in vigorous physical activity = 2.54 (0.69; 4.43), p < 0.01; in total physical activity = 1.62 (-0.22; 3.50), p = 0.08; in moderate physical activity = 0.70 (-1.12; 2.56), p = 0.45). These associations disappeared when we additionally adjusted for age. CONCLUSION: After adjustment for the most important confounders and risk factors, we found no evidence for an association of physical activity with carotid stiffness in the general middle aged to elderly population.


Assuntos
Doenças das Artérias Carótidas/epidemiologia , Exercício , Rigidez Vascular , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Suíça/epidemiologia
15.
Acta Paediatr ; 104(9): 916-21, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26033420

RESUMO

AIM: The prevalence of true therapy-resistant asthma among children whose asthma remains uncontrolled, despite daily controller therapy, is unknown. The aim of this study was to investigate the underlying causes in children with uncontrolled asthma. METHODS: This was a retrospective chart review of 142 children aged from five to 17 years over a five-year period. The patients had uncontrolled asthma and were referred by general practitioners to a hospital-based paediatric asthma clinic. RESULTS: An underlying cause for uncontrolled asthma was found in 138 children (97.2%). The causes were poor adherence (n = 53, 37.3%), ongoing exposure to environmental triggers (n = 40, 28.2%), comorbidities (n = 28, 19.7%), incorrect inhaler technique (n = 11, 7.7%) and incorrect diagnosis (n = 6, 4.2%). After properly addressing these basics in asthma management, the asthma was well controlled in all 138 patients and lung function was normal. Only four children (2.8%) fulfilled the criteria for true therapy-resistant asthma. CONCLUSION: A remedial cause in the basics of asthma management could be found in 97% of children with uncontrolled asthma referred to a hospital-based asthma clinic. True therapy-resistant asthma was found to be very rare in children.


Assuntos
Asma/etiologia , Asma/terapia , Adolescente , Alérgenos/efeitos adversos , Antiasmáticos/uso terapêutico , Asma/diagnóstico , Criança , Pré-Escolar , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Masculino , Adesão à Medicação , Encaminhamento e Consulta , Estudos Retrospectivos , Falha de Tratamento
16.
Nutrients ; 7(5): 3138-53, 2015 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-25942487

RESUMO

Polyphenols in grape and wine have been suggested to contribute to the cardiovascular health benefits of the Mediterranean lifestyle. The reported effects of grape products on blood pressure (BP) remain, however, equivocal. In a double-blind placebo controlled crossover study, the effect of two grape extracts on BP and vascular function was assessed in 60 untreated, mildly hypertensive subjects after four weeks intervention. Both extracts (grape-red wine and grape alone) had high concentrations of anthocyanins and flavonols, but the grape alone was relatively poor in catechins and procyanidins. Parameters measured included ambulatory and office BP, flow-mediated vasodilation, arterial distensibility, platelet function and plasma lipoproteins. Results showed that 24-hour ambulatory systolic/diastolic BPs were significantly lower in the grape-wine extract intervention (135.9 ± 1.3/84.7 ± 0.8 mmHg; mean ± SEM) compared to placebo (138.9 ± 1.3/86.6 ± 1.2 mmHg), predominantly during daytime. Plasma concentrations of the vasoconstrictor endothelin-1 decreased by 10%, but other measures of vascular function were not affected. Grape juice extract alone had no effect on BP or any measures of vascular function. Polyphenol-rich food products, and may be specifically catechins and procyanidins, may thus help sustain a healthy BP and contribute to the healthy Mediterranean lifestyle.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Hipertensão/fisiopatologia , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Vitis/química , Vinho , Adulto , Idoso , Antocianinas/análise , Biflavonoides/análise , Catequina/análise , Estudos Cross-Over , Método Duplo-Cego , Endotelina-1/sangue , Feminino , Flavonóis/análise , Humanos , Hipertensão/tratamento farmacológico , Lipoproteínas/sangue , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/química , Testes de Função Plaquetária , Proantocianidinas/análise , Rigidez Vascular/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Vitis/metabolismo
17.
Obesity (Silver Spring) ; 23(6): 1239-43, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25960049

RESUMO

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) has been recognized as an independent risk factor for cardiovascular disease in adults. It has not been established whether NAFLD is related to early atherosclerotic changes in children. METHODS: In a cross-sectional study, 78 non diabetic, non smoking children with severe obesity were evaluated for NAFLD. Proton magnetic resonance spectroscopy was used to detect liver steatosis and serum ALT was used as a surrogate marker for steatohepatitis. Carotid intima-media thickness (CIMT) and arterial wall stiffness were measured using ultrasound. RESULTS: Steatosis was present in 41 (53%) of subjects. Of these children, 26 out of 41 (63%) had elevated ALT levels. No differences in CIMT and arterial wall stiffness were observed between those without and with steatosis and those with steatosis plus elevated ALT levels [CIMT = 0.47 (±0.06), 0.48 (±0.06) and 0.48 (±0.07) mm, respectively; stiffness = 2.78 (±0.50), 3.00 (±0.81), and 2.90 (±0.78), respectively]. Steatosis and ALT were not correlated to CIMT (r = -0.02 and -0.14, respectively) or arterial wall stiffness (r = 0.13 and -0.11, respectively). CONCLUSIONS: In this study, no relationship between NAFLD and early atherosclerotic changes in children was observed. An atherogenic effect of steatohepatitis (NASH) on pediatric age and long-term atherogenic consequences of simple steatosis cannot be excluded based on this study.


Assuntos
Aterosclerose/etiologia , Fígado Gorduroso/etiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Obesidade/complicações , Obesidade Pediátrica/complicações , Adolescente , Adulto , Aterosclerose/patologia , Doenças Cardiovasculares/diagnóstico , Espessura Intima-Media Carotídea , Criança , Estudos Transversais , Fígado Gorduroso/patologia , Feminino , Humanos , Masculino , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade Pediátrica/patologia , Espectroscopia de Prótons por Ressonância Magnética , Fatores de Risco , Rigidez Vascular
18.
Rev Esp Cardiol (Engl Ed) ; 68(10): 869-77, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25804320

RESUMO

INTRODUCTION AND OBJECTIVES: Recent studies have identified several genetic variants associated with coronary artery disease. Some of these genetic variants are not associated with classical cardiovascular risk factors and the mechanism of such associations is unclear. The aim of the study was to determine whether these genetic variants are related to subclinical atherosclerosis measured by carotid intima media thickness, carotid stiffness, and ankle brachial index. METHODS: A cross-sectional study nested in the follow-up of the REGICOR cohort was undertaken. The study included 2667 individuals. Subclinical atherosclerosis measurements were performed with standardized methods. Nine genetic variants were genotyped to assess associations with subclinical atherosclerosis, individually and in a weighted genetic risk score. A systematic review and meta-analysis of previous studies that analyzed these associations was undertaken. RESULTS: Neither the selected genetic variants nor the genetic risk score were significantly associated with subclinical atherosclerosis. In the meta-analysis, the rs1746048 (CXCL12; n = 10581) risk allele was directly associated with carotid intima-media thickness (ß = 0.008; 95% confidence interval, 0.001-0.015), whereas the rs6725887 (WDR12; n = 7801) risk allele was inversely associated with this thickness (ß = -0.013; 95% confidence interval, -0.024 to -0.003). CONCLUSIONS: The analyzed genetic variants seem to mediate their association with coronary artery disease through different mechanisms. Our results generate the hypothesis that the CXCL12 variant appears to influence coronary artery disease risk through arterial remodeling and thickening, whereas the WDR12 risk variant could be related to higher plaque vulnerability.


Assuntos
Aterosclerose , Quimiocina CXCL12/genética , Doença da Artéria Coronariana , Vasos Coronários/diagnóstico por imagem , Predisposição Genética para Doença , Proteínas Nucleares/genética , Alelos , Aterosclerose/complicações , Aterosclerose/diagnóstico , Aterosclerose/genética , Quimiocina CXCL12/metabolismo , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/genética , Genótipo , Humanos , Proteínas Nucleares/metabolismo , Fatores de Risco
19.
Swiss Med Wkly ; 144: w14052, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25356963

RESUMO

QUESTIONS UNDER STUDY: As the burden of cardiovascular disease (CVD) increases globally, its prevention and risk assessment becomes ever more important. We thus investigated the longitudinal association of the cardiovascular risk scores in the population-based cohort SAPALDIA with carotid intima media thickening (CIMT), an indicator of sub-clinical disease, and CVD incidence. METHODS: In 2,832 SAPALDIA participants, the Swiss and ESC heart risk score (AGLA, SCORE) were calculated based on 2001 data and CIMT was measured in 2010/11. We ran multi-level linear regression analyses between scores and CIMT, stratified for CVD status and gender, and logistic analyses for doctor-diagnosed CVD incidence. Path analyses investigated direct and indirect effects on CIMT. RESULTS: AGLA and SCORE were positively associated with increasing CIMT in both healthy and CVD diagnosed subjects and men and women. Participants in highest risk categories showed a significant CIMT difference of >0.20 mm compared to the reference risk category (<1%), even larger in CVD healthy subjects and men. With increasing risk the odds of CVD incidence increased (Ref. <1%; 10 yr. risk AGLA >10% OR 2.1, >20% OR 3.7). Path analyses yield risk factors' direct and indirect effects through blood pressure. CONCLUSION: The positive longitudinal association between risk estimations and CIMT confirms the use of risk scores in assessing individuals and populations at risk. Systolic blood pressure appears to be a main pathological mechanism, underscoring the importance of optimal blood pressure control and the importance of prevention strategies of risk factors, indirectly affecting CIMT through the haemodynamic pathway.


Assuntos
Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Espessura Intima-Media Carotídea/estatística & dados numéricos , Remodelação Vascular , Adulto , Idoso , Biomarcadores , Pressão Sanguínea , Pesos e Medidas Corporais , Estudos de Coortes , Diagnóstico Precoce , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Incidência , Estilo de Vida , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Pós-Menopausa , Medição de Risco , Fatores de Risco , Fumar/epidemiologia , Fatores Socioeconômicos , Suíça/epidemiologia
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