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1.
J Sci Med Sport ; 19(12): 1039-1042, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27131837

RESUMEN

OBJECTIVES: Exaggerated exercise blood pressure (EEBP) recorded during exercise testing at moderate-intensity is independently associated with cardiovascular mortality. It is hypothesized that EEBP may be indicative of underlying hypertension unnoticed by standard clinic (resting) BP measures (thus explaining increased mortality risk), but this has never been confirmed by association with hypertension defined using ambulatory BP monitoring, which was the aim of this study. DESIGN: Cross-sectional study. METHODS: 100 consecutive patients free from coronary artery disease (aged 56±9 years, 72% male) underwent clinically indicated exercise stress testing. Exercise BP was recorded at each stage of the Bruce protocol. Presence of hypertension was defined as 24-hour systolic BP ≥130mmHg or daytime systolic BP ≥135mmHg. RESULTS: Exercise systolic BP at stage 1 and 2 of the test was significantly associated with the presence of hypertension (P<0.05), with the strongest association observed between stage 1 exercise systolic BP and 24-h systolic BP >130mmHg (AUC=0.752, 95% CI's 0.649-0.846, P<0.001). 79% of participants achieving systolic BP ≥150mmHg at stage 1 of the test were classified as having hypertension, with systolic BP >150mmHg predicting hypertension independently of age, sex and in-clinic hypertension status (OR=4.83, 95% CI's 1.62-14.39, P=0.005). CONCLUSIONS: Irrespective of resting BP, systolic BP ≥150mmHg during early stages of the Bruce exercise stress test is associated with presence of hypertension. EEBP should be a warning signal to health/exercise professionals on the presence of hypertension and the need to provide follow up care to reduce cardiovascular risk.


Asunto(s)
Presión Sanguínea/fisiología , Prueba de Esfuerzo , Ejercicio Físico/fisiología , Hipertensión/fisiopatología , Anciano , Enfermedades Cardiovasculares/prevención & control , Estudios Transversales , Femenino , Humanos , Hipertensión/mortalidad , Masculino , Persona de Mediana Edad , Curva ROC , Factores de Riesgo
2.
Acta Diabetol ; 53(3): 367-75, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26338006

RESUMEN

AIMS: People with type 2 diabetes mellitus (T2DM) have abnormal peripheral and central haemodynamics at rest and during exercise, probably due to metabolic perturbations, but mechanisms are unknown. We used untargeted metabolomics to determine the relationships between metabolic perturbations and haemodynamics (peripheral and central) measured at rest and during exercise. METHODS: Serum samples from 39 participants with T2DM (62 ± 9 years; 46 % male) and 39 controls (52 ± 10 years; 51 % male) were analysed by liquid chromatography-mass spectrometry, nuclear magnetic resonance spectroscopy and principal component analysis. Scores on principal components (PC) were used to assess relationships with haemodynamics including peripheral and central BP, central augmentation index (AIx) and central augmentation pressure (AP). RESULTS: Participants with T2DM had higher resting and exercise haemodynamics (peripheral and central BP, central AIx and central AP) compared to controls (p < 0.05). PC that comprised of a signature metabolic pattern of T2DM was independently associated with resting and exercise central AIx and central AP (p < 0.05). CONCLUSIONS: Serum metabolic profile was associated with central, but not peripheral, haemodynamics in T2DM participants, suggesting that metabolic irregularities may explain abnormal central haemodynamics in T2DM patients.


Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Ejercicio Físico , Hemodinámica , Metaboloma , Anciano , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad
3.
Eur J Appl Physiol ; 115(5): 1057-65, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25539599

RESUMEN

PURPOSE: A hypertensive response to moderate intensity exercise (HRE) is associated with increased cardiovascular risk. The mechanisms of an HRE are unclear, although previous studies suggest this may be due to haemostatic and/or haemodynamic factors. We investigated the relationships between an HRE with haemostatic and hemodynamic indices. METHODS: Sixty-four participants (57 ± 10 years, 71 % male) with indication for exercise stress testing underwent cardiovascular assessment at rest and during moderate intensity exercise, from which 20 participants developed an HRE (defined as moderate exercise systolic BP ≥ 170 mmHg/men and ≥ 160 mmHg/women). Rest, exercise and post-exercise blood samples were analysed for haemostatic markers, including von Willebrand factor (vWf), and haemodynamic measures of brachial and central blood pressure (BP), aortic stiffness and systemic vascular resistance index (SVRi). RESULTS: HRE participants had higher rest vWf compared with normotensive response to exercise (NRE) participants (1,927 mU/mL, 95 % CI 1,240-2,615, vs. 1,129 mU/mL, 95 % CI 871-1,386; p = 0.016). vWf levels significantly decreased from rest to post-exercise in HRE participants (p = 0.005), whereas vWf levels significantly increased from rest to exercise in NRE participants (p = 0.030). HRE participants also had increased triglycerides, rest BP, aortic stiffness and exercise SVRi (p < 0.05 for all). Rest vWf predicted exercise brachial systolic BP (ß = 0.220, p = 0.043; adjusted R (2) = 0.451, p < 0.001) independent of age, sex, body mass index, triglycerides, rest brachial systolic BP and aortic stiffness. CONCLUSIONS: Increased rest blood levels of vWf are independently associated with moderate intensity exercise systolic BP. These findings implicate abnormalities in haemostasis as a possible factor contributing to HRE at moderate intensity.


Asunto(s)
Presión Sanguínea/fisiología , Enfermedades Cardiovasculares/fisiopatología , Ejercicio Físico/fisiología , Hipertensión/sangre , Factor de von Willebrand/análisis , Anciano , Prueba de Esfuerzo , Femenino , Hemodinámica/fisiología , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo
4.
PLoS One ; 9(12): e116221, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25549083

RESUMEN

Liquid chromatography mass spectrometry has become one of the analytical platforms of choice for metabolomics studies. However, LC-MS metabolomics data can suffer from the effects of various systematic biases. These include batch effects, day-to-day variations in instrument performance, signal intensity loss due to time-dependent effects of the LC column performance, accumulation of contaminants in the MS ion source and MS sensitivity among others. In this study we aimed to test a singular value decomposition-based method, called EigenMS, for normalization of metabolomics data. We analyzed a clinical human dataset where LC-MS serum metabolomics data and physiological measurements were collected from thirty nine healthy subjects and forty with type 2 diabetes and applied EigenMS to detect and correct for any systematic bias. EigenMS works in several stages. First, EigenMS preserves the treatment group differences in the metabolomics data by estimating treatment effects with an ANOVA model (multiple fixed effects can be estimated). Singular value decomposition of the residuals matrix is then used to determine bias trends in the data. The number of bias trends is then estimated via a permutation test and the effects of the bias trends are eliminated. EigenMS removed bias of unknown complexity from the LC-MS metabolomics data, allowing for increased sensitivity in differential analysis. Moreover, normalized samples better correlated with both other normalized samples and corresponding physiological data, such as blood glucose level, glycated haemoglobin, exercise central augmentation pressure normalized to heart rate of 75, and total cholesterol. We were able to report 2578 discriminatory metabolite peaks in the normalized data (p<0.05) as compared to only 1840 metabolite signals in the raw data. Our results support the use of singular value decomposition-based normalization for metabolomics data.


Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/metabolismo , Metabolómica/métodos , Anciano , Cromatografía Liquida/métodos , Bases de Datos Factuales , Humanos , Espectrometría de Masas/métodos , Persona de Mediana Edad , Reproducibilidad de los Resultados , Programas Informáticos
5.
J Hypertens ; 32(6): 1159-69, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24675680

RESUMEN

Hypertension is the most prevalent chronic medical condition and a major risk factor for cardiovascular morbidity and mortality. In the majority of hypertensive cases, the underlying cause of hypertension cannot be easily identified because of the heterogeneous, polygenic and multi-factorial nature of hypertension. Metabolomics is a relatively new field of research that has been used to evaluate metabolic perturbations associated with disease, identify disease biomarkers and to both assess and predict drug safety and efficacy. Metabolomics has been increasingly used to characterize risk factors for cardiovascular disease, including hypertension, and it appears to have significant potential for uncovering mechanisms of this complex disease. This review details the analytical techniques, pre-analytical steps and study designs used in metabolomics studies, as well as the emerging role for metabolomics in gaining mechanistic insights into the development of hypertension. Suggestions as to the future direction for metabolomics research in the field of hypertension are also proposed.


Asunto(s)
Hipertensión/metabolismo , Metabolómica , Animales , Biomarcadores/metabolismo , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/mortalidad , Ensayos Clínicos como Asunto , Humanos , Hipertensión/mortalidad , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Reproducibilidad de los Resultados , Factores de Riesgo
6.
J Lipid Res ; 53(9): 1979-86, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22715155

RESUMEN

Intralipid is a fat emulsion that is regularly infused into humans and animals. Despite its routine use, Intralipid infusion can cause serious adverse reactions, including immunosuppression. Intralipid is a complex mix of proteins, lipids, and other small molecules, and the effect of its infusion on the human plasma metabolome is unknown. We hypothesized that untargeted metabolomics of human plasma after an Intralipid infusion would reveal novel insights into its effects. We infused Intralipid and saline into 10 healthy men in a double-blind, placebo-controlled experiment and used GC/MS, LC/MS, and NMR to profile the small-molecule composition of their plasma before and after infusion. Multivariate statistical analysis of the 40 resulting plasma samples revealed that after Intralipid infusion, a less-well-characterized pathway of linoleic acid metabolism had resulted in the appearance of (9Z)-12,13-dihydroxyoctadec-9-enoic acid (12,13-DHOME, P < 10(-3)), a leukotoxin that has powerful physiological effects and is known to inhibit the neutrophil respiratory burst. Intralipid infusion caused increased plasma 12,13-DHOME. Given that 12,13-DHOME is known to directly affect neutrophil function, we conclude that untargeted metabolomics may have revealed a hitherto-unknown mechanism of intralipid-induced immunosuppression.


Asunto(s)
Metabolómica , Ácidos Oléicos/sangre , Fosfolípidos/administración & dosificación , Fosfolípidos/efectos adversos , Aceite de Soja/administración & dosificación , Aceite de Soja/efectos adversos , Emulsiones/administración & dosificación , Emulsiones/efectos adversos , Femenino , Humanos , Masculino , Ácidos Oléicos/metabolismo
7.
Am J Hypertens ; 25(4): 414-20, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22223041

RESUMEN

BACKGROUND: Noninvasive central blood pressure (BP) independently predicts mortality, but current methods are operator-dependent, requiring skill to obtain quality recordings. The aims of this study were first, to determine the validity of an automatic, upper arm oscillometric cuff method for estimating central BP (O(CBP)) by comparison with the noninvasive reference standard of radial tonometry (T(CBP)). Second, we determined the intratest and intertest reliability of O(CBP). METHODS: To assess validity, central BP was estimated by O(CBP) (Pulsecor R6.5B monitor) and compared with T(CBP) (SphygmoCor) in 47 participants free from cardiovascular disease (aged 57 ± 9 years) in supine, seated, and standing positions. Brachial mean arterial pressure (MAP) and diastolic BP (DBP) from the O(CBP) device were used to calibrate in both devices. Duplicate measures were recorded in each position on the same day to assess intratest reliability, and participants returned within 10 ± 7 days for repeat measurements to assess intertest reliability. RESULTS: There was a strong intraclass correlation (ICC = 0.987, P < 0.001) and small mean difference (1.2 ± 2.2 mm Hg) for central systolic BP (SBP) determined by O(CBP) compared with T(CBP). Ninety-six percent of all comparisons (n = 495 acceptable recordings) were within 5 mm Hg. With respect to reliability, there were strong correlations but higher limits of agreement for the intratest (ICC = 0.975, P < 0.001, mean difference 0.6 ± 4.5 mm Hg) and intertest (ICC = 0.895, P < 0.001, mean difference 4.3 ± 8.0 mm Hg) comparisons. CONCLUSIONS: Estimation of central SBP using cuff oscillometry is comparable to radial tonometry and has good reproducibility. As a noninvasive, relatively operator-independent method, O(CBP) may be as useful as T(CBP) for estimating central BP in clinical practice.


Asunto(s)
Determinación de la Presión Sanguínea/instrumentación , Presión Sanguínea , Oscilometría/instrumentación , Brazo , Determinación de la Presión Sanguínea/métodos , Arteria Braquial/fisiología , Femenino , Humanos , Masculino , Manometría/métodos , Persona de Mediana Edad , Reproducibilidad de los Resultados
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