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Recent evidence suggests that trimethylamine-N-oxide (TMAO), a metabolite of L-carnitine and choline, is linked to atherosclerosis and cardiovascular diseases. As TMAO content is very high in fish, we raised the following question: why do Japanese people, who consume lots of fish, show a low risk of atherosclerosis? To address this question, we investigated the effects of TMAO and other L-carnitine-related metabolites on carotid intima-media thickness (IMT). Participants were recruited from a small island and a mountainous region. Plasma L-carnitine, γ-butyrobetaine (γBB), TMAO, trimethyllysine (TML), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) levels were measured using liquid or gas chromatography-mass spectrometry. Plasma L-carnitine concentration was higher in men than in women. TMAO and TML were significantly higher in the residents of the island than in the mountainous people. In multiple linear regression analyses in all participants, TML showed a significant inverse association with max-IMT and plaque score (PS), whereas TMAO did not show any associations. In women, L-carnitine was positively associated with max-IMT and PS. TMAO was correlated with both EPA and DHA levels, implying that fish is a major dietary source of TMAO in Japanese people. Our study found that plasma TMAO was not an apparent risk factor for atherosclerosis in elderly Japanese people, whereas a low level of TML might be a potential risk. L-carnitine may be a marker for atherosclerosis in women.
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Aterosclerosis , Grosor Intima-Media Carotídeo , Humanos , Animales , Femenino , Estudios Transversales , Pueblos del Este de Asia , Carnitina , Aterosclerosis/metabolismo , Colina/metabolismo , Metilaminas , ÓxidosRESUMEN
Background: Chronically high blood pressure (HBP) is a known risk factor for cardiovascular diseases. We measured the intensity of hypertensive exposure in young adults and calculated its prognostic significance for subclinical atherosclerosis in middle age. Methods: The Coronary Artery Risk Development in Young Adults (CARDIA) study enrolled 5,115 healthy black and white Americans who were 18-30 years old at baseline (1985-1986). The intensity of hypertensive exposure was calculated as the area under the curve (mm Hg × years) from baseline to year 15. Coronary artery calcium (CAC) was identified at years 15, 20, and 25, and intima-media thickness (IMT) was identified at year 20. Results: At baseline, the mean age was 40.1 years; 55.1% of participants were women, and 46.5% were black. After adjustment, cumulative systolic BP (SBP) was positively associated with CAC [hazard ratio (HR) = 1.23 (1.14, 1.32)] and IMT [ß = 0.022 (0.017, 0.028)]. For CAC, the C-statistic for cumulative SBP was 0.643 (0.619, 0.667); compared to baseline SBP, the net reclassification index (NRI) of cumulative SBP was 0.180 (0.115, 0.256) and the integrated discrimination improvement (IDI) was 0.023 (0.012, 0.036). For IMT, the C-statistic for cumulative SBP was 0.674 (0.643, 0.705), the NRI was 0.220 (0.138, 0.305), and the IDI was 0.008 (0.004, 0.0012). Conclusion: Greater intensity of hypertensive exposure in early adulthood is associated with subclinical atherosclerosis in middle age and provides better prognostic value than baseline BP for early cardiovascular risk.
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Atherosclerosis is a life-threatening disease associated with morbidity and mortality in patients with type 2 diabetes (T2D). This study aimed to characterize a salivary signature of atherosclerosis based on evaluation of carotid intima-media thickness (IMT) to develop a non-invasive predictive tool for diagnosis and disease follow-up. Metabolites in saliva and plasma samples collected at admission and after treatment from 25 T2D patients hospitalized for 2 weeks to undergo medical treatment for diabetes were comprehensively profiled using metabolomic profiling with gas chromatography-mass spectrometry. Orthogonal partial least squares analysis, used to explore the relationships of IMT with clinical markers and plasma and salivary metabolites, showed that the top predictors for IMT included salivary allantoin and 1,5-anhydroglucitol (1,5-AG) at both the baseline examination at admission and after treatment. Furthermore, though treatment induced alterations in salivary levels of allantoin and 1,5-AG, it did not modify the association between IMT and these metabolites (p interaction > 0.05), and models with these metabolites combined yielded satisfactory diagnostic accuracy for the high IMT group even after treatment (area under curve = 0.819). Collectively, this salivary metabolite combination may be useful for non-invasive identification of T2D patients with a higher atherosclerotic burden in clinical settings.
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Introduction: Thyroid hormones affect the cardiovascular system, but the precise mechanisms of their effects on the development of atherosclerosis are not entirely clear. The relationship between subclinical hypothyroidism, dyslipidemia and carotid atherosclerosis has been widely investigated, but the findings were controversial. The aim of the present study was to determine whether female subjects with subclinical hypothyroidism (SHypo) have increased carotid intima-media thickness (IMT) compared with euthyroid subjects, as well as to examine the association of SHypo, carotid atherosclerosis and dyslipidemia.Methods: This research included 100 women aged 30 to 70 years who were divided into two groups: the SHypo group including subjects with signs of subclinical hypothyroidism and the control group of euthyroid subjects. Carotid IMT thickness using B mode ultrasound was determined and its correlation with serum concentrations of fT4, TSH, CRP, and lipid profile including small dense LDL (sdLDL) was analysed.Results: Subjects with SHypo had significantly increased carotid IMT (IMT ≥ 75th centile) in all three measured segments of the right (p <0.001) and the left (p = 0.001) carotid artery compared to the control group, with a significantly more frequent appearance of plaque (25% vs. 9%; p = 0.05). Significant positive correlations were found between higher TSH and higher IMT values. Increased age, LDL cholesterol, and TSH predicted thickening of the carotid artery IMT.Conclusions: It is important to screen people showing early, subclinical signs of thyroid gland dysfunction due to its impact on carotid atherosclerosis development.
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Enfermedades de las Arterias Carótidas , Hipotiroidismo , Adulto , Anciano , Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Grosor Intima-Media Carotídeo , Femenino , Humanos , Hipotiroidismo/complicaciones , Persona de Mediana Edad , Factores de Riesgo , Hormonas TiroideasRESUMEN
BACKGROUND: Arterial stiffness is an independent cardiovascular risk factor. However, the association between sodium/potassium intake and vascular stiffness was inconsistent. Therefore, a large community-based cross-sectional study was performed to try and achieve more definitive conclusion. METHODS: Urinary sodium, potassium, and creatinine levels were tested in spot urine samples during physical examinations of each recruited participant. The 24-h estimated urinary sodium excretion (eUNaE) and estimated urinary potassium excretion (eUKE) levels were determined using the Kawasaki formula (used as a surrogate for intake). Carotid intima-media thickness (IMT) and plaques were measured using ultrasound. RESULTS: In 13,523 subjects aged 18-80 years, the relationships between carotid plaques and IMT with eUNaE, eUKE and their ratios were analyzed. Overall, 30.2% of participants were diagnosed with carotid artery plaques. The ratio of estimated sodium vs. potassium excretion (Na/K ratio) of the individuals with carotid artery plaques was significantly higher than that of participants without plaque (2.14 ± 0.73 vs. 2.09 ± 0.61, P < 0.01). After adjusting for age, gender, and other lifestyle covariates, a significant positive relation was found between carotid plaque and Na/K ratios (OR = 1.06, P < 0.05). In participants without plaque, a similar positive association was observed between Na/K ratios and increased bifurcation carotid IMT (ß = 0.008, P < 0.01), especially in the females (Pinteraction < 0.01). CONCLUSIONS: In this study, in which sodium intake was estimated on the basis of measured urinary excretion, high estimated excretion levels of urinary sodium and/or low estimated excretion levels of urinary potassium might be associated with an increased presence of carotid atherosclerosis in Chinese individuals.
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Aterosclerosis , Enfermedades de las Arterias Carótidas , Sodio en la Dieta , Adulto , Aterosclerosis/epidemiología , Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Grosor Intima-Media Carotídeo , China/epidemiología , Estudios Transversales , Femenino , Humanos , Potasio , SodioRESUMEN
In this review, we describe how technological advances in ultrasound imaging related to transducer construction and image processing fundamentally alter generation of ultrasound images to produce better quality images with higher resolution. However, carotid intima-media thickness (IMT) measurements made from images acquired on modern ultrasound systems are not comparable to historical population nomograms that were used to determine wall thickness thresholds that inform atherosclerotic cardiovascular disease risk. Because it is nearly impossible to replicate instrumentation settings that were used to create the reference carotid IMT nomograms and to place an individual's carotid IMT value in or above a clinically relevant percentile, carotid IMT measurements have a very limited role in clinical medicine, but remain a useful research tool when instrumentation, presets, image acquisition, and measurements can be standardized. In addition to new validation studies, it would be useful for the ultrasound imaging community to reach a consensus regarding technical aspects of ultrasound imaging acquisition, processing, and display for blood vessels so standard presets and imaging approaches could reliably yield the same measurements.
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Aterosclerosis , Grosor Intima-Media Carotídeo , Arterias Carótidas/diagnóstico por imagen , Humanos , Procesamiento de Imagen Asistido por Computador , Tecnología , UltrasonografíaRESUMEN
Age can be evaluated according to many criteria. Of course the objective measure is the calendar age which may differ from the biological age. The biological age more or less correlates with the vascular age. The concept of vascular age is based on the statement that “An individual is as old as his blood vessels”. The process of vascular aging already starts in childhood. Arterial aging may essentially be viewed from two standpoints. First, it involves stiffening of arteries and loss of their elasticity; second, degenerative changes and formation of atherosclerotic plaques occur, being the cause of ischemia, especially in case of the development of atherothrombosis. Both these processes can be monitored: The change of elasticity (arteriosclerosis) mainly by examination of pulse wave velocity (PWV), atherosclerosis then primarily with non-invasive methods, ultrasound or CT angiography examination. From the clinical point of view it is particularly important whether we can influence vascular age in some way. Evidence is available now that atherosclerosis can be affected by hypolipidemic treatment, arteriosclerosis then in particular by ACE inhibitors. The aforementioned possibility of influencing vascular age brings us to another problem, which is compliance of patients. With regard to that it is good that in a situation where we have two drugs affecting vascular age, we can use their fixed combination. It is available as a combination of atorvastatin and perindopril.
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Envejecimiento , Aterosclerosis , Rigidez Vascular , Adolescente , Adulto , Anciano , Envejecimiento/fisiología , Inhibidores de la Enzima Convertidora de Angiotensina , Niño , Elasticidad , Humanos , Persona de Mediana Edad , Perindopril , Análisis de la Onda del Pulso , Adulto JovenRESUMEN
AIM: An identification of the high-risk group of atherosclerotic cardiovascular disease (CVD) is important in the management of patients with diabetes. Metabolomics is a potential tool for the discovery of new biomarkers. With this background, we aimed to identify metabolites associated with atherosclerosis in patients with type 2 diabetes mellitus (T2DM). METHODS: A total of 176 patients with T2DM who have never had a CVD event and 40 who were survivors of coronary artery disease (CAD) events were enrolled. Non-targeted metabolome analysis of fasting plasma samples was performed using gas chromatography coupled with mass spectrometry (GC/MS) highly optimized for multiple measurement of blood samples. First, metabolites were screened by analyzing the association with the established markers of subclinical atherosclerosis (i.e., carotid maximal intima-media thickness (max-IMT) and flow-mediated vasodilation (FMD)) in the non-CVD subjects. Then, the associations between the metabolites detected and the history of CAD were investigated. RESULT: A total of 65 annotated metabolites were detected. Non-parametric univariate analysis identified inositol and indoxyl sulfate as significantly (pï¼0.05) associated with both max-IMT and FMD. These metabolites were also significantly associated with CAD. Moreover, inositol remained to be associated with CAD even after adjustments for traditional coronary risk factors. CONCLUSIONS: We identified novel biomarker candidates for atherosclerosis in Japanese patients with T2DM using GC/MS-based non-targeted metabolomics.
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Aterosclerosis/sangre , Biomarcadores/sangre , Diabetes Mellitus Tipo 2/sangre , Indicán/sangre , Inositol/sangre , Anciano , Aterosclerosis/complicaciones , Grosor Intima-Media Carotídeo , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Japón/epidemiología , Masculino , Metaboloma , Metabolómica , Persona de Mediana Edad , Isquemia Miocárdica/patología , SolventesRESUMEN
OBJECTIVE: To observe the characteristics of carotid intima-media thickness (IMT) and cerebral blood flow velocity in patients with mild-to-moderate hypertension, and to evaluate the effects of acupuncture on carotid IMT and blood flow velocity of middle cerebral artery and vertebral-basilar artery. METHODS: A total of 240 patients with mild-to-moderate hypertension who met the inclusion criteria were treated with Huoxue Sanfeng acupuncture method proposed by academician SHI Xue-min. The acupoints of Renying (ST 9), Quchi (LI 11), Hegu (LI 4), Zusanli (ST 36) and Taichong (LR 3) were selected. The treatment was given once a day, five times a week for 3 months. The carotid ultrasonography and transcranial color Doppler were performed before treatment and 3 months after treatment to evaluate the improvements of carotid IMT and brain blood flow velocity. RESULTS: Among 175 patients, 94.3% suffered from impaired carotid IMT. After acupuncture intervention, 7.7%-10.9% patients had improved IMT but 4.6%-6.3% had aggravated carotid IMT. There was no significant difference of carotid IMT before and after treatment (P>0.05). About 50% patients had abnormal intracranial blood flow velocity; after acupuncture intervention, 27.4%-33.3% patients who had the abnormal blood flow velocity had normal one, but 27.0%-52.5% patients who had normal blood flow velocity had abnormal one. After acupuncture intervention, the low-speed blood flow of MCA, VA and BA in female patients aged 41-60 years and the low-speed blood flow of MCA and VA in female patients aged 61-70 years were significantly improved (all P<0.05); the high-speed blood flow of MCA and VA in male patients aged 61-70 years and the high-speed blood flow of VA and BA in female patients aged 41-60 years were significantly decreased (all P<0.05). CONCLUSION: Nearly 95% of patients with mild-to-moderate hypertension had carotid IMT, and about 50% had abnormal blood flow velocity of intracranial artery. The present study failed to found significant effects of acupuncture on carotid IMT, but it shows acupuncture can generally improve the low blood flow velocity in women with mild-to-moderate hypertension.
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Terapia por Acupuntura , Hipertensión , Adulto , Anciano , Velocidad del Flujo Sanguíneo , Grosor Intima-Media Carotídeo , Circulación Cerebrovascular , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE@#To observe the characteristics of carotid intima-media thickness (IMT) and cerebral blood flow velocity in patients with mild-to-moderate hypertension, and to evaluate the effects of acupuncture on carotid IMT and blood flow velocity of middle cerebral artery and vertebral-basilar artery.@*METHODS@#A total of 240 patients with mild-to-moderate hypertension who met the inclusion criteria were treated with acupuncture method proposed by academician . The acupoints of Renying (ST 9), Quchi (LI 11), Hegu (LI 4), Zusanli (ST 36) and Taichong (LR 3) were selected. The treatment was given once a day, five times a week for 3 months. The carotid ultrasonography and transcranial color Doppler were performed before treatment and 3 months after treatment to evaluate the improvements of carotid IMT and brain blood flow velocity.@*RESULTS@#Among 175 patients, 94.3% suffered from impaired carotid IMT. After acupuncture intervention, 7.7%-10.9% patients had improved IMT but 4.6%-6.3% had aggravated carotid IMT. There was no significant difference of carotid IMT before and after treatment (>0.05). About 50% patients had abnormal intracranial blood flow velocity; after acupuncture intervention, 27.4%-33.3% patients who had the abnormal blood flow velocity had normal one, but 27.0%-52.5% patients who had normal blood flow velocity had abnormal one. After acupuncture intervention, the low-speed blood flow of MCA, VA and BA in female patients aged 41-60 years and the low-speed blood flow of MCA and VA in female patients aged 61-70 years were significantly improved (all <0.05); the high-speed blood flow of MCA and VA in male patients aged 61-70 years and the high-speed blood flow of VA and BA in female patients aged 41-60 years were significantly decreased (all <0.05).@*CONCLUSION@#Nearly 95% of patients with mild-to-moderate hypertension had carotid IMT, and about 50% had abnormal blood flow velocity of intracranial artery. The present study failed to found significant effects of acupuncture on carotid IMT, but it shows acupuncture can generally improve the low blood flow velocity in women with mild-to-moderate hypertension.
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Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia por Acupuntura , Velocidad del Flujo Sanguíneo , Grosor Intima-Media Carotídeo , Circulación Cerebrovascular , HipertensiónRESUMEN
BACKGROUND: Cardiovascular disease is prevalent in children on dialysis and accounts for almost 30% of all deaths. Randomised trials in adults suggest that haemodiafiltration (HDF) with high convection volumes is associated with reduced cardiovascular mortality compared to high-flux haemodialysis (HD); however paediatric data are scarce. We designed the haemodiafiltration, heart and height (3H) study to test the hypothesis that children on HDF have an improved cardiovascular risk profile, growth and nutritional status and quality of life, compared to those on conventional HD. We performed a non-randomised parallel-arm intervention study within the International Paediatric Haemodialysis Network Registry comparing children on HDF and conventional HD to determine annualised change in cardiovascular end-points and growth. Here we present the 3H study design and baseline characteristics of the study population. METHODS: 190 children were screened and 177 (106 on HD and 71 on HDF) recruited from 28 centres in 10 countries. There was no difference in age, underlying diagnosis, comorbidities, previous dialysis therapy, dialysis vintage, residual renal function, type of vascular access or blood flow between HD and HDF groups. High flux dialysers were used in 63% of HD patients and ultra-pure water was available in 52%. HDF patients achieved a median convection volume of 13.3 L/m2; this was associated with the blood flow rate only ((p = 0.0004, r = 0.42) and independent of access type (p = 0.38). DISCUSSION: This is the largest study on dialysis outcomes in children that involves deep phenotyping across a wide range of cardiovascular, anthropometric, nutritional and health-related quality of life measures, to test the hypothesis that HDF leads to improved cardiovascular and growth outcomes compared to conventional HD. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02063776 . The trial was prospectively registered on the 14 Feb 2014.
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Estatura/fisiología , Enfermedades Cardiovasculares/prevención & control , Desarrollo Infantil/fisiología , Corazón/fisiología , Hemodiafiltración/tendencias , Fallo Renal Crónico/terapia , Adolescente , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/psicología , Niño , Preescolar , Femenino , Hemodiafiltración/métodos , Hemodiafiltración/psicología , Humanos , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/psicología , Masculino , Estudios Prospectivos , Calidad de Vida/psicología , Diálisis Renal/métodos , Diálisis Renal/psicología , Diálisis Renal/tendencias , Resultado del Tratamiento , Adulto JovenRESUMEN
Objective We aimed to investigate the relationships among chronic kidney disease (CKD), symptomatic ischaemic stroke, and carotid atherosclerosis. Methods We enrolled 455 patients who underwent carotid ultrasonography in our hospital, including 311 patients with symptomatic ischaemic stroke and 144 patients without symptomatic ischaemic stroke. Carotid intima-media thickness (IMT), the rate of internal carotid artery stenosis, and maximal plaque size were evaluated. Results The mean age of the patients was 68.5 ± 11.0 years and the mean estimated glomerular filtration rate (eGFR) was 68.8 ± 18.2 mL/min/1.73 m2. After adjustment for cardiovascular risk factors, the mean IMT was significantly higher in patients with CKD than in those without CKD. The IMT and eGFR were negatively correlated in patients with stroke (r = -0.169). Multiple logistic regression analyses showed that mean IMT, plaque size, and internal carotid artery stenosis were significant determinants of symptomatic ischaemic stroke after adjustment of multivariate risk factors. Furthermore, the eGFR was a negative determinant of symptomatic ischaemic stroke after adjusting for classical risk factors (odds ratio [95% confidence interval] = 0.868 [0.769-0.979]). Conclusion CKD might be associated with the carotid atherosclerosis and symptomatic ischaemic stroke.
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Arteria Carótida Interna/diagnóstico por imagen , Estenosis Carotídea/diagnóstico por imagen , Insuficiencia Renal Crónica/complicaciones , Accidente Cerebrovascular/complicaciones , Anciano , Grosor Intima-Media Carotídeo , Estenosis Carotídea/complicaciones , Estudios Transversales , Femenino , Tasa de Filtración Glomerular , Humanos , Persona de Mediana Edad , Insuficiencia Renal Crónica/diagnóstico , Estudios Retrospectivos , Factores de Riesgo , UltrasonografíaRESUMEN
AIMS: Recent studies suggested that subclasses of high-density lipoprotein (HDL) may be a better biomarker to predict the risk of atherosclerotic disorders. We aimed to examine the association of HDL2- and HDL3-cholesterol (HDL2-C and HDL3-C) with carotid intima-media thickness (IMT) using a new method to quantify the HDL-C subclasses. METHODS: Participants were 657 Japanese subjects (434 women) who received a health examination (mean age: 73 years). Serum samples were analyzed by the homogenous assay for HDL-C and HDL3-C. HDL2-C was calculated indirectly by subtracting HDL3-C from HDL-C. HDL3-C measured by this assay was well correlated with that measured by ultracentrifugation (r=0.898, pï¼0.001). The maximum IMT (max-IMT) and plaque score (PS) were evaluated by ultrasonography following the standard protocol. RESULTS: HDL3-C was associated with age both in men (r=ï¼0.322, pï¼0.0001) and women (r=ï¼0.315, pï¼0.0001). In a simple regression analysis, max-IMT showed an inverse association with HDL3-C, whereas no significant association was observed with HDL2-C. A multiple linear regression analysis indicated, however, that the association between HDL3-C and max-IMT was not significant in both aged and younger populations when age was included in the analysis. Further, not only HDL2-C but also HDL3-C was not a significant predictor of 'atherosclerotic arteries' defined as the max-IMT ≥1.5 mm. Similar results were observed in the analysis on PS. CONCLUSIONS: Neither HDL3-C nor HDL2-C was significantly associated with carotid atherosclerosis in the Japanese population in this study.
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Grosor Intima-Media Carotídeo , Lipoproteínas HDL/sangre , Adulto , Anciano , Aterosclerosis/metabolismo , Arterias Carótidas/patología , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Estudios de Cohortes , Femenino , Humanos , Japón , Lipoproteínas HDL/clasificación , Masculino , Persona de Mediana Edad , Análisis de Regresión , UltrasonografíaRESUMEN
Objective • To study the relationship between homocysteine (HCY) in plasma and carotid atherosclerosis in the elderly patients and its clinical significance. Methods • The intima-media thickness (IMT) of the common carotid arteries and the sclerotic lesions at the carotid arteries bulbs were evaluated by color Doppler ultrasonography in 99 elderly in-patients (65 years old or above). Fasting venous blood was drew from the patients for the determination of plasma HCY and other indexes. According to the plasma HCY concentration, the patients were divided into two groups, i.e., control group (HCY<15 μmol/L) and high HCY group (HCY ≥ 15 μmol/L). General clinical data, carotid plaque number, plaque thickness, plaque stability and carotid IMT were investigated in the two group of patients. Results • The numbers (P=0.015), stability (P=0.013) and thickness (P=0.001) of carotid plaques between the two groups were significantly different. After balancing the effects of age by the partial correlation analysis, plasma HCY concentration was positively correlated with the number (partial correlation coefficient=0.133, P=0.049), instability (partial correlation coefficient=0.046, P=0.023) and thickness (partial correlation coefficient=0.119, P=0.024) of carotid plaques. Nevertheless, the difference in the IMT of carotid arteries between the two groups was not significant (P=0.057). Conclusion • Plasma HCY concentration is correlated with the number, stability and thickness of carotid plaques.
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PURPOSE: To determine the effects of omega-3 supplementation on liver fat and carotid intima-media thickness (IMT) and to assess accuracy of ultrasound (US) for grading liver steatosis. MATERIALS AND METHODS: In this one-way crossover pilot study, we assigned children with obesity and liver steatosis to receive 1.2 g daily of omega-3 supplementation vs. inactive sunflower oil for 24 or 12 weeks. Liver fat content was assessed by magnetic resonance spectroscopy (MRS), magnetic resonance imaging (MRI) and US, and common carotid IMT by US. Statistical analysis included Chi-square, Student's t-tests, ANOVA tests and receiver operating characteristic (ROC) curves. RESULTS: Omega-3 supplementation was associated with a trend towards decrease in MRS-determined liver fat fraction (0.7% and 2.1% decrease in the 24-week and 12-week omega-3 group, respectively) compared with the sunflower oil group (1.0% increase). These changes were not significant, whether assessed by MRS (P = 0.508), MRI (P = 0.508) or US (P = 0.678). Using US, the area under the ROC curves were 0.964, 0.817 and 0.783 for distinguishing inferred steatosis grades 0 vs. 1-2-3, 0-1 vs. 2-3 and 0-1-2 vs. 3, respectively, indicating good accuracy of US-based fat grading. Omega-3 supplementation was associated with a decrease in US-determined IMT (0.05-mm decrease in the 24-week omega-3 group. A 0.015-mm increase was found in the 12-week omega-3 group, and a 0.007-mm decrease in the sunflower oil group (P = 0.003). CONCLUSION: Omega-3 supplementation had no significant effect on liver fat fraction, but led to carotid IMT decrease in children with obesity and liver steatosis.
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BACKGROUND: Carotid intima media thickness (IMT) is a noninvasive marker of the extent and severity of subclinical atherosclerosis. Micronutrient intake may affect atherosclerosis and play a major role in the development of cardiovascular diseases (CVDs). OBJECTIVE: The primary aim of this review was to synthesize the evidence regarding the association between carotid IMT and selected micronutrients. METHOD: The authors searched PubMed, Cochrane, and EMBASE databases from inception to June 2016 for selected micronutrients, CVD, carotid IMT, and antioxidants. Thirty-five original studies met the inclusion criteria and were reviewed following preferred reporting items for systematic review and meta-analysis guidelines. RESULTS: Although not all studies found consistent results, the weight of the evidence suggests that high intakes and/or circulatory levels of magnesium, as well as vitamin D and the vitamin B group, may be associated with lower carotid IMT or reduced progression of carotid IMT. The majority of studies did not find any significant association between vitamin E and C and carotid IMT. Less evidence was available for associations of retinol, zinc, and iron with carotid IMT. CONCLUSIONS: In general, the current evidence concerning micronutrient intake and carotid IMT is largely inconclusive. Pragmatic clinical trials are required to determine whether dietary or supplemental intake of specific micronutrients alters carotid IMT, which is a surrogate measure of cardiovascular risk.
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Biomarcadores/sangre , Grosor Intima-Media Carotídeo , Micronutrientes/administración & dosificación , Micronutrientes/sangre , Estado Nutricional , Antioxidantes/administración & dosificación , Ácido Ascórbico/administración & dosificación , Ácido Ascórbico/sangre , Enfermedades Cardiovasculares/epidemiología , Bases de Datos Factuales , Progresión de la Enfermedad , Humanos , Hierro/administración & dosificación , Hierro/sangre , Magnesio/administración & dosificación , Magnesio/sangre , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Vitamina A/administración & dosificación , Vitamina A/sangre , Complejo Vitamínico B/administración & dosificación , Complejo Vitamínico B/sangre , Vitamina D/administración & dosificación , Vitamina D/sangre , Vitamina E/administración & dosificación , Vitamina E/sangre , Zinc/administración & dosificación , Zinc/sangreRESUMEN
Although the renin-angiotensin system (RAS) is counter-balanced by a salt-sensitive mechanism in the hypertensive state, both are reported to be up-regulated in chronic kidney disease (CKD) patients. We conducted this study to evaluate the associations among the RAS, renal function, hypertension, and atherosclerosis, as well as to identify markers for salt-sensitivity. A total of 213 pre-dialysis CKD patients with preserved cardiac function (EF >50 %) were enrolled. Their renal and cardiac biochemical markers and plasma renin activity (PRA) were measured, and echocardiography and carotid artery ultrasound were performed. Their salt intake was estimated by the NaCl excretion from a 24-h collected urine sample. The PRA was higher in patients with hypertension (p = 0.018), and had a significant negative correlation with the eGFR (r = -0.23, p = 0.0067). Importantly, the PRA had a strong negative correlation with the brain natriuretic peptide (BNP) level (r = -0.28, p = 0.017) regardless of whether the patients were being treated with RAS inhibitors. The BNP level was related to the renal functions (eGFR: p = 0.001, ACR: p = 0.009). There was a significant positive correlation between the BNP level and carotid intima-media thickness (p < 0.001). A multivariate analysis revealed that older age and an excess of NaCl excretion were independent predictors of BNP elevation (p = 0.02 and 0.003, respectively). Our analysis revealed details of the counterbalance between BNP and PRA, as well as identifying that excess salt intake is a predictor of BNP elevation. These results indicate that the BNP could be a possible valuable marker for salt sensitivity, and that high salt sensitivity could facilitate atherosclerosis in CKD patients.
Asunto(s)
Aterosclerosis/sangre , Hipertensión/sangre , Péptido Natriurético Encefálico/sangre , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/complicaciones , Sodio en la Dieta/efectos adversos , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Presión Sanguínea , Grosor Intima-Media Carotídeo , Ecocardiografía , Femenino , Tasa de Filtración Glomerular , Humanos , Japón , Riñón/metabolismo , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Renina/sangre , Sistema Renina-AngiotensinaRESUMEN
BACKGROUND: Type 2 diabetes mellitus is associated strongly with an increased risk of micro- and macro-vascular complications, leading to impaired quality of life and shortened life expectancy. In addition to appropriate glycemic control, multi-factorial intervention for a wide range of risk factors, such as hypertension and dyslipidemia, is crucial for management of diabetes. A recent cardiovascular outcome trial in diabetes patients with higher cardiovascular risk demonstrated that a SGLT2 inhibitor markedly reduced mortality, but not macro-vascular events. However, to date there is no clinical evidence regarding the therapeutic effects of SGLT2 inhibitors on arteriosclerosis. The ongoing PROTECT trial was designed to assess whether the SGLT2 inhibitors, ipragliflozin, prevented progression of carotid intima-media thickness in Japanese patients with type 2 diabetes mellitus. METHODS: A total of 480 participants with type 2 diabetes mellitus with a HbA1c between 6 and 10 % despite receiving diet/exercise therapy and/or standard anti-diabetic agents for at least 3 months, will be randomized systematically (1:1) into either ipragliflozin or control (continuation of conventional therapy) groups. After randomization, ipragliflozin (50-100 mg once daily) will be added on to the background therapy in participants assigned to the ipragliflozin group. The primary endpoint of the study is the change in mean intima-media thickness of the common carotid artery from baseline to 24 months. Images of carotid intima-media thickness will be analyzed at a central core laboratory in a blinded manner. The key secondary endpoints include the change from baseline in other parameters of carotid intima-media thickness, various metabolic parameters, and renal function. Other cardiovascular functional tests are also planned for several sub-studies. DISCUSSION: The PROTECT study is the first to assess the preventive effect of ipragliflozin on progression of carotid atherosclerosis using carotid intima-media thickness as a surrogate marker. The study has potential to clarify the protective effects of ipragliflozin on atherosclerosis. Trial registration Unique Trial Number, JPRN/UMIN000018440 ( https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000021348 ).