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BACKGROUND: Precisely defining the delay in onset of dementia is a particular challenge for early diagnosis. Brain [18F] fluoro-2-deoxy-2-D-glucose (18F-FDG) Positron Emission Tomography (PET) is a particularly interesting tool for the early diagnosis of neurodegenerative diseases, through the measurement of the cerebral glucose metabolic rate. There is currently a lack of longitudinal studies under real-life conditions, with sufficient patients, to accurately evaluate the predictive values of brain 18F-FDG PET scans. Here, we aimed to estimate the value of brain 18F-FDG PET for predicting the risk of dementia conversion and the risk of occurrence of a neurodegenerative pathology. METHODS: Longitudinal data for a cohort of patients with no diagnosis of dementia at the time of recruitment referred by a tertiary memory clinic for brain 18F-FDG PET were matched with (Prince M, Wimo A, Guerchet Maëlenn, Ali G-C, Wu Y-T et al. World Alzheimer Report 2015. The Global Impact of Dementia: An analysis of prevalence, incidence, cost and trends. [Research Report] Alzheimer's Disease International. 2015. 2015.) data from the French National Health Data System (NHDS), (Jack CR, Bennett DA, Blennow K, Carrillo MC, Dunn B, Haeberlein SB, et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018;14(4):535-62.) data from the National Alzheimer Bank (NAB), and (Davis M, O`Connell T, Johnson S, Cline S, Merikle E, Martenyi F, et al. Estimating Alzheimer's Disease Progression Rates from Normal Cognition Through Mild Cognitive Impairment and Stages of Dementia. CAR. 2018;15(8):777-88.) lumbar puncture (LP) biomarker data. The criteria for dementia conversion were the designation, within the three years after the brain 18F-FDG PET scan, of a long-term condition for dementia in the NHDS and a dementia stage of cognitive impairment in the NAB. The criterion for the identification of a neurodegenerative disease in the medical records was the determination of LP biomarker levels. RESULTS: Among the 403 patients (69.9 ± 11.4 years old, 177 women) from the initial cohort with data matched with the NHDS data, 137 were matched with the NAB data, and 61 were matched with LP biomarker data. Within three years of the scan, a 18F-FDG PET had negative predictive values of 85% for dementia conversion (according to the NHDS and NAB datasets) and 95% for the presence of LP neurodegeneration biomarkers. CONCLUSION: A normal brain 18F-FDG PET scan can help rule out the risk of dementia conversion and the presence of cerebrospinal fluid (CSF) biomarker of neurodegeneration early with high certainty, allowing modifications to patient management regimens in the short term. TRIAL REGISTRATION: Clinical Trials database (NCT04804722). March 18, 2021. Retrospectively registered.
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Biomarcadores , Demencia , Fluorodesoxiglucosa F18 , Tomografía de Emisión de Positrones , Humanos , Tomografía de Emisión de Positrones/métodos , Femenino , Masculino , Anciano , Demencia/diagnóstico por imagen , Demencia/líquido cefalorraquídeo , Biomarcadores/líquido cefalorraquídeo , Estudios Longitudinales , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Persona de Mediana Edad , Péptidos beta-Amiloides/líquido cefalorraquídeo , Péptidos beta-Amiloides/metabolismo , Progresión de la Enfermedad , Anciano de 80 o más Años , Diagnóstico Precoz , Enfermedades Neurodegenerativas/diagnóstico por imagen , Enfermedades Neurodegenerativas/líquido cefalorraquídeo , Proteínas tau/líquido cefalorraquídeo , Estudios de CohortesRESUMEN
BACKGROUND Cardiovascular (CV) mortality remains high despite the improvement of kidney function after kidney transplantation. In heart failure (HF), high concentrations of biomarkers of fibrosis, related to cardiac and/or vascular impairment, are associated with CV outcomes, but their significance in kidney transplantation is still unclear. Our aim was to investigate the association of procollagen type I C-terminal pro-peptide (PICP) and galectin-3 (Gal-3), markers of fibrosis, with arterial stiffness measured by pulse wave velocity (PWV) and CV morbi-mortality in kidney transplantation recipients from the prospective monocenter TRANSARTE study (Transplantation and Arteries), which compared the evolution of arterial stiffness in transplanted patients and patients remained on dialysis. MATERIAL AND METHODS PICP and Gal-3 were measured at 2 years after transplantation in 44 kidney transplantation patients. Spearman's rank-order correlation analysis was conducted to assess the relationship between biomarkers and PWV. Association of biomarkers with CV morbi-mortality was evaluated using Cox regression analysis adjusted for age, renal function, and PWV. RESULTS There was no significant correlation between PWV and PICP (r=-0.16, P=0.3) or Gal-3 (r=0.03, P=0.85). Gal-3, after adjusting for key prognostic factors, including PWV, was significantly associated with CV morbi-mortality [HR (95% CI)=4.30 (1.01-18.22), P=0.048], whereas PICP was not significantly associated with outcome. CONCLUSIONS In multivariable adjusted analysis, elevated Gal-3 concentrations were associated with CV morbi-mortality in kidney transplantation patients, whereas PICP was not. As Gal-3 was not related to PWV, other sources of fibrosis (eg, cardiac fibrosis) may be underlying the prognostic value of Gal-3 in kidney transplantation.
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Insuficiencia Cardíaca , Trasplante de Riñón , Rigidez Vascular , Humanos , Galectina 3 , Estudios Prospectivos , Análisis de la Onda del Pulso , Biomarcadores , FibrosisRESUMEN
Background: The stiffening of large elastic arteries is currently estimated in research and clinical practice by propagative and non-propagative models, as well as parameters derived from aortic pulse waveform analysis. Methods: Common carotid compliance and distensibility were measured by simultaneously recording the diameter and pressure changes during the cardiac cycle. The aortic and upper arm arterial distensibility was estimated by measuring carotid−femoral and carotid−radial pulse wave velocity (PWV), respectively. The augmentation index and blood pressure amplification were derived from the analysis of central pulse waveforms, recorded by applanation tonometry directly from the common carotid artery. Results: 75 volunteers were enrolled in this study (50 females, average age 53.5 years). A significant inverse correlation was found between carotid distensibility and carotid−femoral PWV (r = −0.75; p < 0.001), augmentation index (r = −0.63; p < 0.001) and central pulse pressure (r = −0.59; p < 0.001). A strong correlation was found also between the total slope of the diameter/pressure rate carotid curves and aortic distensibility, quantified from the inverse of the square of carotid−femoral PWV (r = 0.67). No correlation was found between carotid distensibility and carotid−radial PWV. Conclusions: This study showed a close correlation between carotid−femoral PWV, evaluating aortic stiffness by using the propagative method, and local carotid cross-sectional distensibility.
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(1) Background: Increased arterial stiffness is associated with cardiovascular (CV) diseases in end-stage renal disease (ESRD) patients, and CV mortality remains higher in kidney transplantation (KT) recipients compared to in the general population. KT is associated with an improvement in arterial stiffness in the early post-transplant period, followed by a potential re-worsening in the late period. In a cohort of KT patients, we evaluated the associations of pulse-wave velocity (PWV) measured at different time-points (pre-transplant, and early and late post-transplant periods) with CV morbi-mortality, as well as the evolution between these measurements with CV morbi-mortality. (2) Methods: Forty KT recipients with a 10-year follow-up were included. The association of PWV with CV events was assessed with multivariable cox analysis. Backward linear regressions were conducted to identify the determinants of PWV at 1 year and those of the long-term evolution of PWV after KT (delta PWV at 1 yearlatest PWV). (3) Results: The absence of arterial stiffening during the long-term follow-up after KT is associated with a lower CV outcome rate (HR for the delta PWV = 0.76 (0.58−0.98), p = 0.036). Age at KT is associated with the worsening of arterial stiffness in the late post-transplantation period (ß for the delta PWV = −0.104, p = 0.031). A high PWV at 1 year was associated with a potential for recovery during follow-up (ß = 0.744, p < 0.0001). (4) Conclusions: The absence of PWV worsening in the late post-transplantation period was significantly associated with a lower risk of CV events, whereas early changes in PWV were not. Finding an intervention capable of reducing long-term PWV could improve the prognosis of KT recipients.
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BACKGROUND: Hippocampal atrophy is associated with cognitive decline. Determining the clinical features associated with hippocampal volume (HV)/atrophy may help in tailoring preventive strategies. OBJECTIVE: This study was aimed to investigate the association between HV (at visit 2) and vascular status (both at visit 1 and visit 2) in a cohort of individuals aged 60+ with hypertension and without overt cognitive impairment at visit 1 (visit 1 and visit 2 were separated by approximately 8 years). METHODS: Hippocampal volume was estimated in brain MRIs as HV both clinically with the Scheltens' Medial Temporal Atrophy score, and automatically with the Free Surfer Software application. A detailed medical history, somatometric measurements, cognitive tests, leukoaraiosis severity (Fazekas score), vascular parameters including pulse wave velocity, central blood pressure, and carotid artery plaques, as well as several biochemical parameters were also measured. RESULTS: 113 hypertensive patients, 47% male, aged 75.1±5.6 years, participated in both visit 1 and visit 2 of the ADELAHYDE study. Age (ß=â-0.30) and hypertension duration (ß=â-0.20) at visit 1 were independently associated with smaller HV at visit 2 (pâ<â0.05 for all). In addition to these variables, low body mass index (ß=â0.18), high MRI Fazekas score (ß=â-0.20), and low Gröber-Buschke total recall (ß=â0.27) were associated with smaller HV at visit 2 (pâ<â0.05 for all). CONCLUSION: In a cohort of older individuals without cognitive impairment at baseline, we described several factors associated with lower HV, of which hypertension duration can potentially be modified.
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Hipocampo/diagnóstico por imagen , Hipertensión/diagnóstico por imagen , Microvasos/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Atrofia , Presión Sanguínea , Índice de Masa Corporal , Disfunción Cognitiva/patología , Estudios de Cohortes , Femenino , Genotipo , Humanos , Hipertensión/genética , Hipertensión/psicología , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Recuerdo Mental , Persona de Mediana Edad , Pruebas Neuropsicológicas , Estudios Prospectivos , Sustancia Blanca/diagnóstico por imagenRESUMEN
BACKGROUND/OBJECTIVE: The aim of this study was to assess, in routine, the rates with which an amyloid deposition was documented by 18F-florbetaben PET in patients with suspected Alzheimer's disease (AD) but with isolated increases in cerebrospinal fluid (CSF) tau-protein concentrations, and the subsequent impact of these PET results on medical management. METHODS: This prospective study included 34 patients with mild neurocognitive disorders (MND) and suspected AD (73±9 years, 16 women) and with abnormal CSF concentrations in total-tau (T-tau) and/or phosphorylated-tau (P-tau) proteins but normal Aß42 concentration and Aß42/Aß40 ratio. These patients were referred to 8F-florbetaben PET from which the PET-related changes in the confidence for AD diagnosis (low, intermediate, or high) and treatments were reported. RESULTS: The PET examinations were positive for amyloid deposition (brain amyloid plaque load, BAPL score >1) in none of the 9 patients with an increase in only T-tau proteins and in 8 among the 25 (32%) with an increase in P-tau proteins (one BAPL score of 2 and seven BAPL scores of 3). Knowledge of the PET results was associated with subsequent changes in diagnostic confidence in 44% of patients (15/34) and in the intention-to-treat with a cholinesterase inhibitor drug in 18% (6/34). CONCLUSION: In patients with suspected AD and isolated increase in CSF tau protein concentrations, an amyloid deposition is documented by 18F-florbetaben PET in as much as one third of cases when the concentration of P-tau is abnormal, and PET results are associated with significant further changes in medical management.
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Enfermedad de Alzheimer/diagnóstico por imagen , Proteínas Amiloidogénicas/metabolismo , Proteínas tau/líquido cefalorraquídeo , Anciano , Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Compuestos de Anilina , Femenino , Radioisótopos de Flúor , Humanos , Masculino , Neuroimagen , Fragmentos de Péptidos/metabolismo , Tomografía de Emisión de Positrones , Estudios Prospectivos , EstilbenosRESUMEN
Mild cognitive impairment and Alzheimer's dementia involve a grey matter disease, quantifiable by 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET), but also white matter damage, evidenced by diffusion tensor magnetic resonance imaging (DTI), which may play an additional pathogenic role. This study aimed to determine whether such DTI and PET variations are also interrelated in a high-risk population of older hypertensive patients with only subjective memory complaints (SMC). Sixty older hypertensive patients (75 ± 5 years) with SMC were referred to DTI and FDG-PET brain imaging, executive and memory tests, as well as peripheral and central blood pressure (BP) measurements. Mean apparent diffusion coefficient (ADCmean) was determined in overall white matter and correlated with the grey matter distribution of the metabolic rate of glucose (CMRGlc) using whole-brain voxel-based analyses of FDG-PET images. ADCmean was variable between individuals, ranging from 0.82 to 1.01.10- 3 mm2 sec- 1, and mainly in relation with CMRGlc of areas involved in Alzheimer's disease such as internal temporal areas, posterior associative junctions, posterior cingulum but also insulo-opercular areas (global correlation coefficient: - 0.577, p < 0.001). Both the ADCmean and CMRGlc of the interrelated grey matter areas were additionally and concordantly linked to the results of executive and memory tests and to systolic central BP (all p < 0.05). Altogether, our findings show that cross-sectional variations in overall white brain matter are linked to the metabolism of Alzheimer-like cortical areas and to cognitive performance in older hypertensive patients with only subjective memory complaints. Additional relationships with central BP strengthen the hypothesis of a contributing pathogenic role of hypertension.
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Encéfalo/patología , Sustancia Gris/diagnóstico por imagen , Hipertensión/complicaciones , Trastornos de la Memoria/etiología , Sustancia Blanca/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Presión Sanguínea/fisiología , Estudios Transversales , Imagen de Difusión por Resonancia Magnética , Femenino , Fluorodesoxiglucosa F18/metabolismo , Humanos , Imagenología Tridimensional , Masculino , Pruebas Neuropsicológicas , Tomografía de Emisión de PositronesRESUMEN
OBJECTIVES: The longitudinal ADELAHYDE-2 study aims to identify the factors associated with cognitive impairment/decline and white matter hyperintensities burden. METHODS: Longitudinal single-center study comprising two visits separated by approximately 7 years. A total of 131 patients completed the two visits. The primary outcome was global memory composite scale, while the secondary outcome was white matter hyperintensities (WMH/Fazekas scale) load. RESULTS: Global memory at visit 2 (V2) was largely influenced by age, smoking status, glycated hemoglobin, and history of stroke already present at visit 1 (V1). These variables accounted for â¼51% of the memory alterations at V2. WMH at V2 was likely influenced by age, left ventricular hypertrophy, diabetes mellitus, carotid intima-media thickness, and body mass index at V1. These findings accounted for â¼37% of the WMH changes at V2. Increase in pulse wave velocity from V1 to V2 showed a trend for association with memory deterioration (adjusted estimates = 0.06; P = .067), whereas smoking and increase in systolic blood pressure (trend) were associated with an increment in WMH (adjusted estimates = 0.49; P = .047 and adjusted estimates = 0.01; P = .08, respectively). On the other hand, angiotensin-converting enzyme inhibitor/angiotensin receptor blockers and statins (trend) were likely to be protective (adjusted estimates for angiotensin-converting enzyme inhibitor/angiotensin receptor blockers = -0.49; P = .049, and adjusted estimates for statins = -0.46; P = .055). CONCLUSIONS: Several readily identifiable factors are associated with memory deterioration and WMH, many of which are potentially modifiable. Interventions aimed to control these risk factors need to be tested prospectively in order to assess their cognitive protective value.
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Hipertensión/complicaciones , Trastornos de la Memoria/etiología , Sustancia Blanca/irrigación sanguínea , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Factores de Riesgo , Sustancia Blanca/diagnóstico por imagenRESUMEN
BACKGROUND: This study aimed at assessing the changes in brain metabolism related to white-matter magnetic resonance (MR) hyperintensities of presumed vascular origin, with a voxel-based quantitative analysis of (18F)-fluorodesoxyglucose positron emission tomography (FDG-PET) imaging. METHODS: Sixty older hypertensive patients with subjective memory complaints (75 ± 5 years, 34 women) were prospectively referred to FDG-PET and MRI brain imaging. The Statistical Parametric Mapping software was used to assess the correlation between brain distribution of FDG and white-matter hyperintensities assessed by the Fazekas score on MRI images. RESULTS: The Fazekas score was inversely related to FDG uptake, independently of age and gender, within 14 Brodmann areas located mainly in the frontal lobe but also in certain limbic, insular and temporal areas. This relationship was also found to be largely independent of the volume of grey matter expressed in percentage of cranial volume, an index of atrophy. CONCLUSIONS: White-matter MR hyperintensities of presumed vascular origin are cross-sectionally associated with a lower grey-matter metabolism, mainly but not only within frontal areas and independently of age, gender and grey-matter atrophy.
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Metabolismo Energético , Sustancia Gris/diagnóstico por imagen , Hipertensión/complicaciones , Leucoencefalopatías/diagnóstico por imagen , Imagen por Resonancia Magnética , Trastornos de la Memoria/etiología , Memoria , Tomografía de Emisión de Positrones , Sustancia Blanca/diagnóstico por imagen , Factores de Edad , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Fluorodesoxiglucosa F18/administración & dosificación , Sustancia Gris/metabolismo , Humanos , Hipertensión/diagnóstico , Leucoencefalopatías/etiología , Leucoencefalopatías/metabolismo , Masculino , Trastornos de la Memoria/diagnóstico , Trastornos de la Memoria/psicología , Persona de Mediana Edad , Proyectos Piloto , Valor Predictivo de las Pruebas , Pronóstico , Radiofármacos/administración & dosificación , Factores de Riesgo , Sustancia Blanca/metabolismoRESUMEN
OBJECTIVES: Several studies have highlighted a link between vascular alterations and cognitive decline. The PARTAGE study showed that arterial stiffness as evaluated by carotid-femoral pulse wave velocity (cfPWV) was associated with a more pronounced cognitive decline over a 1-year period in very old frail institutionalized individuals. The aim of the present analysis was to assess the role of hemodynamic parameters, such as blood pressure (BP), heart rate (HR), cfPWV, and central/peripheral pulse pressure amplification (PPA) on cognitive decline over 2 years in very old frail individuals. METHODS: A total of 682 individuals from the PARTAGE study cohort, aged older than 80 years (mean age at inclusion: 87.5 ± 5.0 years) and living in French and Italian nursing homes, were analyzed. Mini-Mental State Examination (MMSE) score was assessed at baseline (BL) and at the end of the first and second year of follow-up (2y-FU). Those with a decrease in MMSE of 3 or more points between BL and 2y-FU were considered as "decliners." The cfPWV and PPA at baseline were assessed with an arterial tonometer. RESULTS: After adjustment for baseline MMSE, HR, body mass index, age, education level, and activities of daily living (ADLs), cfPWV was higher and PPA lower in "decliners" compared with "nondecliners," whereas BP did not differ between the 2 groups. Logistic multivariate analysis also revealed that high cfPWV, low PPA, high HR, and low ADLs were all determinants of MMSE decline. CONCLUSION: This 2-year longitudinal study in very old institutionalized individuals shows that arterial stiffness and high HR enabled us to identify subjects at higher risk of cognitive decline, whereas BP alone did not appear to have a significant predictive value. These findings highlight the contribution of vascular determinants in cognitive decline even in this very old population.
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Arterias/fisiología , Envejecimiento Cognitivo/fisiología , Hemodinámica , Casas de Salud , Rigidez Vascular/fisiología , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Francia , Humanos , Italia , MasculinoRESUMEN
Incidence and prevalence of abdominal obesity (AO) are growing exponentially. Subjects with AO are at higher risk of developing heart failure. The purpose of the study was to investigate early changes in cardiac and arterial structure and function and extracellular matrix biomarkers in normotensive healthy subjects with AO. Subjects with AO and age- and sex-matched controls underwent echocardiography, MRI (cardiac remodeling index), carotid intima-media thickness, pulse wave velocity, and blood fibrosis biomarkers measurements. We enrolled 87 subjects with AO and 53 controls. Although normotensive, subjects with AO had higher systolic blood pressure (BP; 122±11 versus 116±11 mm Hg; P=0.003), left ventricular mass (94±24 versus 84±21 g; P=0.034), and cardiac remodeling index (0.67±0.16 versus 0.60±0.10 g/mL; P=0.026) but unchanged carotid intima-media thickness and pulse wave velocity. Diastolic dysfunction (E' <10 cm/s) could be detected in 38% of subjects with AO (4% in controls). Left ventricular remodeling, as assessed by cardiac remodeling index, was positively and independently associated with higher BP (systolic BP and mean arterial pressure but not diastolic BP) and AO. Higher BP, AO, and procollagen-III-N-terminal peptide (≥2.4 ng/mL) concentrations (odds ratio, 4.15 [1.42-12.2]; P=0.01) were positively associated with diastolic dysfunction. Early cardiac structural remodeling, fibrosis, and diastolic dysfunction were detectable in healthy subjects with AO. Higher BP, procollagen-III-N-terminal peptide, and AO were independently associated with early cardiac structural and functional changes. It is to be investigated whether in subjects with AO, an early BP reduction, even if normotensive, combined with weight loss may avoid adverse cardiac remodeling and protect against progression to heart failure.
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Presión Sanguínea/fisiología , Hipertensión/epidemiología , Miocardio/patología , Obesidad Abdominal/complicaciones , Fragmentos de Péptidos/sangre , Procolágeno/sangre , Remodelación Ventricular/fisiología , Adulto , Anciano , Biomarcadores/sangre , Grosor Intima-Media Carotídeo , Estudios de Casos y Controles , Estudios Transversales , Ecocardiografía , Femenino , Fibrosis/epidemiología , Fibrosis/metabolismo , Fibrosis/patología , Humanos , Hipertensión/fisiopatología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Miocardio/metabolismo , Obesidad Abdominal/patología , Obesidad Abdominal/fisiopatología , PrevalenciaRESUMEN
OBJECTIVES: Several studies have shown lower carotid-femoral pulse wave velocity (cfPWV) levels in women compared to men, a difference that could partially explain the increased longevity in women. However, these studies have been performed in industrial countries while few data are available in emerging populations. We studied arterial stiffness, as evaluated by cfPWV, in elderly Algerian men and women. METHODS: cfPWV was studied in 321 Algerian men (81.2â±â5.3 years) and women (81.1â±â4.4 years). An age-matched and sex-matched cohort of European individuals (nâ=â321) was used as a control group. RESULTS: Comparatively to men, Algerian women exhibited higher BMI and heart rate (HR), higher prevalence of hypertension, and were more frequently treated for hypertension. cfPWV was not different between Algerian men (14.8â±â3.3âm/s) and women (14.9â±â3.4âm/s). By contrast, in Europeans, women had lower cfPWV (12.7â±â2.7âm/s) than men (14.0â±â3.3âm/s; Pâ<0.001). Comparatively to European women, Algerian women had a higher cfPWV (Pâ<0.01). In both ethnic groups, multivariate analyses revealed that age, mean blood pressure (BP), HR, and diabetes were positively associated with cfPWV, whereas female sex was associated with lower cfPWV only in Europeans. CONCLUSION: Elderly Algerian women exhibit arterial stiffness similar to men, whereas European women display lower arterial stiffness than men. This loss of 'arterial sex advantage' in Algerians may be explained by higher BP, HR, and a worse metabolic profile in Algerian women. Interventions in emerging populations, especially in women, should be a priority in order to address these risk factors by acting on current lifestyle.
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Análisis de la Onda del Pulso , Factores Sexuales , Rigidez Vascular/fisiología , Factores de Edad , Anciano , Anciano de 80 o más Años , Argelia , Arterias/fisiopatología , Índice de Masa Corporal , Países en Desarrollo , Femenino , Frecuencia Cardíaca , Humanos , Masculino , Análisis por Apareamiento , Análisis Multivariante , Prevalencia , Factores de Riesgo , Población BlancaRESUMEN
The major challenge of vascular tissue engineering is to develop a small calibre vascular graft with a high patency rate. In native vessels, the thrombosis is prevented by the endothelium located at the luminal site of the vessel. The aim of this study was to develop a resistant endothelial lining on the inner surface of vascular graft using a polyelectrolyte multilayers (PEM) film. Umbilical arteries were de-endothelialized, coated with 3.5 bilayers of poly(styrene sulfonate) (PSS)/poly(allylamine hydrochloride) (PAH) and then cellularized with endothelial cells. The grafts were cultured for a week in static condition and preconditioned by exposure to a shear stress of at 1 Pa for three hours before implantation on the rabbit carotid site. Histological and confocal microscopy in vitro investigations showed that PEMs films improve cell adhesion and retention on the luminal surface after shear stress preconditioning. In vivo Doppler data showed that graft preconditioning is a crucial factor for graft patency. Indeed, preconditioned grafts remained over the whole experimental period, whereas unpreconditioned grafts were obstructed after only one week of implantation. These results open the route toward the development of a new generation of vascular substitutes having a long term patency.
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Prótesis Vascular , Endotelio Vascular/citología , Poliestirenos/química , Arterias Umbilicales/citología , Grado de Desobstrucción Vascular , Animales , Materiales Biocompatibles/química , Adhesión Celular , Células Cultivadas , Humanos , Masculino , Poliaminas/química , Conejos , Estrés MecánicoRESUMEN
OBJECTIVES: To determine, using a comprehensive MRI investigation, prevalence and vascular correlates of early left-ventricular concentric remodeling in middle-aged patients with abdominal obesity. Left-ventricular and vascular remodeling are commonly associated with hypertension, but little is known for abdominal obesity patients, a population with definite increase in cardiovascular risk and high rates of further developments of hypertension and of the metabolic syndrome. METHODS: Seventy middle-aged abdominal obesity patients (56â±â5 years, 49% women, 69% with body mass index > 30âkg/m), who had no additional cardiovascular risk factor except for untreated stage 1 hypertension (16%), and 40 controls underwent MRI for detecting concentric remodeling (increase in left-ventricular mass/end-diastolic volume ratio) and identifying potential determinants, including arterial compliance indexes [aortic pulse wave velocity and total arterial compliance (TAC)] and total peripheral vascular resistances (TPVRs). RESULTS: Twenty abdominal obesity patients (29%) had concentric remodeling (concentric remodeling+), whereas 50 did not (concentric remodeling-). Concentric remodeling+ patients were mostly men (85%), they frequently had stage 1 hypertension (45%) and few had left-ventricular hypertrophy (20%). When adjusted for sex, there was a step-by-step decline in TAC between controls (meanâ±âSEM: 2.10â±â0.06âml/mmHg), concentric remodeling- (1.82â±â0.06âml/mmHg) and concentric remodeling+ (1.42â±â0.09âml/mmHg, Pâ<â0.005 for inter-group comparisons) and TPVRs were lower than controls for concentric remodeling- (14.7â±â0.5 vs. 16.8â±â0.5âml/mmHg, Pâ=â0.005) but not for concentric remodeling+ (17.5â±â0.7âmmHg/min per l). CONCLUSIONS: Concentric remodeling is frequently documented by MRI in the middle-aged men with abdominal obesity and in association with a decrease in TAC no longer counter-balanced by a decrease in TPVR, suggesting a remodeling from proximal to peripheral vasculature.
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Vasos Sanguíneos/fisiopatología , Obesidad Abdominal/fisiopatología , Remodelación Ventricular , Estudios de Casos y Controles , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Volumen SistólicoRESUMEN
BACKGROUND: Increased arterial stiffness (AS) is a major determinant of cardiovascular complications in end-stage renal disease (ESRD) patients. Little is known about AS evolution after kidney transplantation. The aim of the study was to characterize the evolution of AS after kidney transplantation in a population of ESRD patients, in comparison to those remaining in dialysis. METHODS: Eighty-eight patients (age between 35 and 65) were recruited from the waiting list for kidney transplantation of the University Hospital of Nancy. Two vascular evaluations were performed at a 1-year interval. During this interval, 39 patients were transplanted and 49 remained in dialysis. RESULTS: At inclusion, median pulse-wave velocity (PWV) was similar in transplanted patients and transplantation-pending patients, respectively, 9.2 (7.9-11.9) and 9.8 (7.7-12.1) m/s. No difference between the two groups was found at the 1-year interval. Median of time after transplantation was 6.3 (3.8-10.1) months. Median of blood pressure (MBP) decreased only in the transplanted patients [99 (93-112) versus 96 (90-101) mmHg, P < 0.01] Multivariate analysis showed that PWV changes depend on changes in MBP and baseline PWV. CONCLUSION: Although no difference in the 1-year PWV evolution was found, the low MBP value in transplanted patients allow to expect a better long-term evolution of AS and a better cardiovascular prognosis after kidney transplantation than in transplantation-pending patients.
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Arterias/patología , Fallo Renal Crónico/complicaciones , Trasplante de Riñón/efectos adversos , Diálisis Renal , Rigidez Vascular , Adulto , Anciano , Velocidad del Flujo Sanguíneo , Presión Sanguínea , Estudios Transversales , Femenino , Estudios de Seguimiento , Frecuencia Cardíaca , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Flujo Pulsátil , Listas de EsperaRESUMEN
OBJECTIVE: To investigate in women older than 60 whether aortic stiffness or pulse pressure (PP) is associated with selected procoagulant or anticoagulant factors and to examine whether pulsatile stretch influences these factors in human vascular smooth muscle cells (VSMCs) in vitro. METHODS AND RESULTS: Aortic pulse wave velocity (PWV) and carotid PP were studied in 123 apparently healthy postmenopausal women. PWV, PP, von Willebrand factor, and free tissue factor pathway inhibitor (TFPI), but not mean arterial pressure, increased with age. Free TFPI and PWV were positively correlated, even after adjustment for age and PP and other confounding parameters. In vitro, 5% or 10% pulsatile stretch (at 1 Hz) enhanced TFPI synthesis and secretion by VSMCs in a time-independent manner (1 to 48 hours) without changes in protein level of smooth muscle myosin heavy chain. Application of 5% static stretch had no effect. CONCLUSIONS: In postmenopausal women, free TFPI increases as vascular wall function deteriorates and PP increases. These findings are supported by the increase in TFPI synthesized by VSMCs in response to cyclic stress in vitro. They suggest that VSMCs require pulsatility to interfere with the coagulation process and highlight the relevance of plasma free TFPI levels to cardiovascular diseases.
Asunto(s)
Envejecimiento/sangre , Coagulación Sanguínea , Presión Sanguínea , Lipoproteínas/sangre , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Posmenopausia/sangre , Flujo Pulsátil , Factores de Edad , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Aorta/metabolismo , Aorta/fisiopatología , Biomarcadores/sangre , Arterias Carótidas/metabolismo , Arterias Carótidas/fisiopatología , Células Cultivadas , Estudios Transversales , Elasticidad , Células Endoteliales/metabolismo , Femenino , Humanos , Modelos Lineales , Mecanotransducción Celular , Persona de Mediana Edad , Músculo Liso Vascular/fisiopatología , Estrés Mecánico , Factores de TiempoRESUMEN
BACKGROUND: We have recently shown that vascular abnormalities are associated with cognitive impairment as well as with white matter hyperintensities (WMH) in elderly hypertensive patients presenting with subjective memory complaints (SMC), a population at high risk of developing dementia. The aim of the present study was to identify genetic variants associated with the degree of cognitive impairment and the severity of WMH in the same study population, focusing on genes involved in vascular alterations. METHODS: 50 gene polymorphisms known to be associated with vascular alterations (blood pressure regulation, lipid and homocysteine metabolism, thrombosis and inflammation) were genotyped using a multilocus genotyping assay in 369 elderly treated hypertensive patients >60 years of age and presenting with SMC but no dementia. The patients underwent a combination of neuropsychological tests and brain magnetic resonance imaging with semiquantification of WMH. RESULTS: None of the tested polymorphisms were found to be associated with age- and gender-adjusted memory score, visual capacity, body-mass-index-adjusted verbal fluency score or the age-adjusted WMH Fazekas score. CONCLUSION: Our results suggest that the associations between arterial factors and cognitive decline or WMH are not genetically driven by the genes we investigated, at least at this early stage of cognitive decline.
Asunto(s)
Vasos Sanguíneos/patología , Hipertensión/genética , Hipertensión/patología , Trastornos de la Memoria/genética , Trastornos de la Memoria/patología , Polimorfismo Genético/genética , Anciano , Anciano de 80 o más Años , Apolipoproteínas E/genética , Presión Sanguínea/genética , Presión Sanguínea/fisiología , Trastornos del Conocimiento/genética , Trastornos del Conocimiento/psicología , Estudios Transversales , Interpretación Estadística de Datos , Femenino , Estudios de Asociación Genética , Variación Genética , Genotipo , Homocisteína/metabolismo , Humanos , Hipertensión/psicología , Inflamación/genética , Metabolismo de los Lípidos/genética , Imagen por Resonancia Magnética , Masculino , Trastornos de la Memoria/psicología , Persona de Mediana Edad , Familia de Multigenes/genética , Trombosis/genéticaRESUMEN
BACKGROUND: Hypertension is strongly associated with cognitive decline and a promising target for dementia prevention. Our aim was to investigate the association between different antihypertensive treatments and cognitive performance in elderly hypertensive patients presenting with subjective memory complaints. PATIENTS AND METHODS: Three hundred and seventy-eight elderly hypertensive patients more than 60 years (mean age 70.4 ± 6.3 years) treated with at least one antihypertensive agent and presenting with subjective memory complaints but without dementia were prospectively recruited and underwent a combination of neuropsychological tests, brain magnetic resonance imaging with semiquantification of white matter hyperintensities, carotid echotracking, brachial endothelial function, and ambulatory blood pressure assessments. RESULTS: None of the three composite scores (memory score, verbal fluency, and visual memory capacity) was found associated with blood pressure levels. On the other hand, age-adjusted and sex-adjusted analyses showed a significant and positive association between memory score and use of calcium channel blockers (CCBs) (users: +0.14 ± 0.09 versus nonusers: -0.12 ± 0.06; P = 0.016). Multivariate analyses also revealed that CCB use was significantly associated with a better memory score, independently of age, male sex, white matter hyperintensities, and carotid wall cross-sectional area, all of which were associated with worse memory scores. CONCLUSION: In elderly hypertensive treated patients with subjective memory complaints, CCB use was associated with better memory performance independently of blood pressure level and macrovascular and microvascular alterations, suggesting a specific neuroprotective effect of this pharmacological class. Interventional controlled trials are required to confirm the specific protective effect of CCBs on cognitive decline.
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Bloqueadores de los Canales de Calcio/uso terapéutico , Trastornos del Conocimiento/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Anciano , Animales , Trastornos del Conocimiento/complicaciones , Trastornos del Conocimiento/patología , Estudios Transversales , Humanos , Hipertensión/complicaciones , Hipertensión/patología , Imagen por Resonancia Magnética , Persona de Mediana EdadRESUMEN
Carotid-femoral pulse wave velocity (PWV) is considered the gold-standard measurement of arterial stiffness. Obesity, however, can render inaccurate the measurement of PWV by external noninvasive devices. Phase-contrast MRI allows the determination of aortic PWV in multiple aortic locations with intra-arterial distance measurements, as well as the assessment of aortic mechanical properties. The purpose of this study was to assess the reliability of external carotid-femoral PWV values measured by well-validated external devices in comparison with MRI acquisitions of PWV and aortic mechanical properties in a population of obese subjects. PWV was measured with PulsePen and Complior II devices in 32 volunteers (18 men and 14 women), aged 46 to 65 years (mean: 55.7+/-5.1 years), presenting with isolated abdominal obesity, with a waist circumference >102 cm for men and >88 cm for women, and a body mass index between 27 and 35. These results were then compared with MRI PWV values and cross-sectional MRI thoracic aorta distensibility values. MRI PWV values were positively correlated with PWV measured by both PulsePen (r=0.47; P=0.005) and Complior (r=0.43; P=0.01). Aortic cross-sectional stiffness was positively correlated with PulsePen PWV (r=0.42; P=0.02). The same trend was also observed with Complior PWV (r=0.33; P=0.06). This is the first study comparing transcutaneous PWV measurements with MRI aortic elastic properties in obese subjects. Our results indicate that, for body mass index values < or =35 kg m(-2), PWV measured externally with Complior or PulsePen validly reflect values obtained directly in the thoracic aorta through MRI.
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Aorta Abdominal/patología , Imagen por Resonancia Magnética/métodos , Obesidad/diagnóstico , Flujo Pulsátil , Resistencia Vascular/fisiología , Pared Abdominal/irrigación sanguínea , Pared Abdominal/patología , Análisis de Varianza , Velocidad del Flujo Sanguíneo , Índice de Masa Corporal , Medios de Contraste , Elasticidad , Femenino , Hemodinámica/fisiología , Humanos , Masculino , Persona de Mediana Edad , Probabilidad , Estudios Prospectivos , Estadísticas no Paramétricas , Circunferencia de la CinturaRESUMEN
BACKGROUND AND PURPOSE: Arterial stiffening and thickening and endothelial dysfunction may be associated with cognitive decline or white matter hyperintensities (WMH) independently of blood pressure level. We aimed to investigate, using an integrative approach, the relative contributions of structural and functional vascular factors to the degree of cognitive impairment (primary outcome) and the severity of WMH (secondary outcome) in elderly hypertensive patients with subjective memory complaints, a group prone to dementia. METHODS: A prospective, dedicated, cross-sectional population of 198 elderly hypertensive patients (mean age 69.3+/-6.2 years) with subjective memory complaints underwent a full set of cognitive function assessments, brain MRI with semiquantification of WMH, carotid ultrasonography, carotid-femoral pulse wave velocity, brachial endothelial function, and plasma von Willebrand Factor measurements. RESULTS: After adjustment for the usual cardiovascular risk factors, increased arterial stiffness (as assessed by pulse wave velocity) was significantly and independently associated with memory impairment in men. The severity of WMH was independently associated with increased carotid intima media thickness and stiffness (as assessed by augmentation index) as well as with increased age and plasma levels of von Willebrand Factor, a biomarker of endothelial dysfunction. CONCLUSIONS: Our data suggest that vascular abnormalities, independently of blood pressure levels, may play a role in the setting of subjective memory complaints as well as of WMH in elderly hypertensive patients. Arterial thickness and stiffness as well as endothelial function should be assessed simultaneously and may represent additional targets for the prevention of subjective memory complaints and WMH.