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1.
Pharm Res ; 39(1): 41-56, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35044591

RESUMEN

PURPOSE: This study establishes a multiphysics simulation platform for both conventional and targeted thrombolysis using tissue plasminogen activator (tPA). Based on our computational results, the effects of therapeutic parameters on the dynamics of thrombolysis and the risk of side effects are investigated. METHODS: The model extends our previously developed one-dimensional(1D) mathematical models for fibrinolysis by incorporating targeted thrombolysis. It consists of two parts: (i) a coupled mathematical model of systemic pharmacokinetics (PK) and pharmacodynamics (PD) and local PD in a 1D occluded artery, and (ii) a mechanistic model for a targeted thrombolytic system via activated platelet-targeted tPA-loaded nanovesicles (tPA-NV), with model parameters derived from our in vitro experiments. A total of 16 therapeutic scenarios are simulated by varying the clot location and composition as well as the dosing regimen with free tPA or tPA-NV. RESULTS: Our simulation results indicate that tPA-NV offers several advantages over free tPA for thrombolysis. It reduces systemic exposure of tPA, thereby minimising the risk of bleeding complications. Simulations with different tPA-NV doses reveal that tPA-NV at 10% of the recommended dose can be as effective as the standard regimen with the full recommended dose of free tPA, demonstrating the potential of our tPA-NV as a new thrombolytic strategy with a reduced tPA dose. Moreover, faster recanalisation can be achieved with tPA-NV, especially for platelet-rich(or fibrin-poor) clots. CONCLUSIONS: Our simulation platform for thrombolysis with well-tuned model parameters can be used to evaluate and optimise treatment regimens of existing and new thrombolytic therapies via benefit/risk assessment under various therapeutic scenarios.


Asunto(s)
Fibrinólisis , Activador de Tejido Plasminógeno , Fibrinolíticos/farmacología , Nanomedicina , Terapia Trombolítica/métodos , Activador de Tejido Plasminógeno/farmacología , Activador de Tejido Plasminógeno/uso terapéutico
2.
Stroke ; 47(11): 2862-2864, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27729577

RESUMEN

BACKGROUND AND PURPOSE: Abnormalities of the retinal circulation may be associated with cerebrovascular disease. We investigated associations between retinal microvascular abnormalities and (1) strokes and subclinical cerebral infarcts and (2) cerebral white matter lesions in a UK-based triethnic population-based cohort. METHODS: A total of 1185 participants (age, 68.8±6.1 years; 77% men) underwent retinal imaging and cerebral magnetic resonance imaging. Cerebral infarcts and white matter hyperintensities were identified on magnetic resonance imaging, retinopathy was graded, and retinal vessels were measured. RESULTS: Higher retinopathy grade (odds ratio [OR], 1.40 [95% confidence interval (95% CI), 1.16-1.70]), narrower arteriolar diameter (OR, 0.98 [95% CI, 0.97-0.99]), fewer symmetrical arteriolar bifurcations (OR, 0.84 [95% CI, 0.75-0.95]), higher arteriolar optimality deviation (OR, 1.16 [95% CI, 1.00-1.34]), and more tortuous venules (OR, 1.20 [95% CI, 1.09-1.32]) were associated with strokes/infarcts and white matter hyperintensities. Associations with quantitative retinal microvascular measures were independent of retinopathy. CONCLUSIONS: Abnormalities of the retinal microvasculature are independently associated with stroke, cerebral infarcts, and white matter lesions.


Asunto(s)
Infarto Cerebral/diagnóstico por imagen , Leucoaraiosis/diagnóstico por imagen , Enfermedades de la Retina/diagnóstico por imagen , Vasos Retinianos/diagnóstico por imagen , Accidente Cerebrovascular/diagnóstico por imagen , Anciano , Arteriolas/diagnóstico por imagen , Infarto Cerebral/epidemiología , Comorbilidad , Femenino , Humanos , Leucoaraiosis/epidemiología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Enfermedades de la Retina/epidemiología , Accidente Cerebrovascular/epidemiología
3.
Microcirculation ; 22(2): 146-55, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25559612

RESUMEN

OBJECTIVE: The present study examined the impact of BP from childhood to mid-adulthood on retinal microvascular architecture. METHODS: The Cardiovascular Risk in Young Finns Study included children aged 3-18 years, from five Finnish University cities, with participants chosen randomly from the national population registrar from those areas. The age of participants included in the current analyses in childhood (1980) ranged from three to nine years and in mid-adulthood (2011) ranged from 34 to 40 years (complete data n = 657). Measures of retinal microvasculature architecture measured in adulthood included diameters, tortuosity, lengths, and LDR. RESULTS: Regression analysis showed a strong negative association between childhood systolic BP and adult arteriolar diameter (standardized regression coefficient [ß] -0.300; p < 0.001) and with change in systolic BP from childhood to adulthood (ß = -0.249; p < 0.001). For arteriolar tortuosity, there was a strong positive association between childhood systolic BP and adult arteriolar tortuosity (ß = 0.154; p < 0.001) and no association with change in systolic BP from childhood to adulthood (ß = 0.072; p = 0.110). CONCLUSIONS: High BP in childhood and increased BP from childhood to adulthood impacts on retinal microvascular architecture in mid-adulthood.


Asunto(s)
Envejecimiento , Presión Sanguínea , Microcirculación , Vasos Retinianos/fisiopatología , Adolescente , Adulto , Arteriolas/anatomía & histología , Arteriolas/fisiopatología , Niño , Preescolar , Femenino , Finlandia , Humanos , Masculino , Vasos Retinianos/anatomía & histología
4.
R Soc Open Sci ; 10(6): 230065, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37351500

RESUMEN

This study investigated the possibility of using low-cost, handheld, retinal imaging devices for the automatic extraction of quantifiable measures of retinal blood vessels. Initially, the available handheld devices were compared using a Zeiss model eye incorporating a USAF resolution test chart to assess their optical properties. The only suitable camera of the five evaluated was the Horus DEC 200. This device was then subjected to a detailed evaluation in which images in human eyes taken from the handheld camera were compared in a quantitative analysis with those of the same eye from a Canon CR-DGi retinal desktop camera. We found that the Horus DEC 200 exhibited shortcomings in capturing images of human eyes by comparison with the Canon. More images were rejected as being unevaluable or suffering failures in automatic segmentation than with the Canon, and even after exclusion of affected images, the Horus yielded lower measurements of vessel density than the Canon. A number of issues affecting handheld cameras in general and some features of the Horus in particular have been identified that might contribute to the observed differences in performance. Some potential mitigations are discussed which might yield improvements in performance, thus potentially facilitating use of handheld retinal imaging devices for quantitative retinal microvascular measurements.

5.
Eur Heart J ; 31(6): 747-52, 2010 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19942604

RESUMEN

AIMS: Patients with controlled hypertension are at risk of future cardiac events, but predicting first events remains difficult. We hypothesized that modern echocardiographic measures of left ventricular diastolic function may be more sensitive than traditional echocardiographic methods of risk prediction and set out to test this in a cohort of patients with well-controlled hypertension. METHODS AND RESULTS: Conventional and tissue Doppler echocardiography was performed on 980 participants in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). All subjects had hypertension, but no known cardiac disease. Cardiac events were defined as fatal and non-fatal myocardial infarction (including silent myocardial infarction), coronary revascularization procedures, new-onset angina (stable or unstable), fatal and non-fatal heart failure, and life-threatening arrhythmias. Analysis was performed by a single, blinded observer. There were 56 primary cardiac events during 4.2 +/- 0.7 years follow-up. The ratio of transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity (E/E') was the strongest predictor of first cardiac events in Cox-proportional hazards models. Following adjustment for covariates, a unit rise in the E/E' ratio was associated with a 17% increment in risk of a cardiac event (HR 1.17, CI 1.05-1.29; P = 0.003). CONCLUSION: Tissue Doppler E/E', a non-invasive estimate of left atrial filling pressure, independently predicts primary cardiac events in a hypertensive population and out-performed traditional echocardiographic measures in this moderately sized, well-treated hypertensive population. E/E' represents a simple, effective tool for assessing cardiac risk in a hypertensive population.


Asunto(s)
Ecocardiografía Doppler/métodos , Cardiopatías/diagnóstico por imagen , Hipertensión/complicaciones , Adulto , Anciano , Antihipertensivos/uso terapéutico , Diagnóstico Precoz , Femenino , Cardiopatías/etiología , Humanos , Hipertensión/tratamiento farmacológico , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Medición de Riesgo
6.
Microcirculation ; 16(2): 159-66, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19206002

RESUMEN

BACKGROUND: Recent studies have shown that changes in the retinal microvasculature predict cardiovascular disease (CVD); however, little is known regarding influences on the retinal microvasculature in healthy people without overt cardiovascular or metabolic disease. METHODS: We used a semiautomated computerized technique to analyze digitized retinal photographs from a total of 167 healthy people (age range, 45-75 years; 83 female), without clinical CVD, diabetes, or hypertension, randomly sampled from the population-based Beaver Dam Eye Study. We assessed arteriolar and venular narrowing, arteriolar optimality deviation, and other quantitative aspects of the retinal microvasculature. RESULTS: Arterioles were significantly narrower and longer, had wider branching angles, and were more tortuous than venules. Increased arteriolar length to diameter ratio (an index of ratio arteriolar narrowing) was positively and independently associated with older age and elevated systolic blood pressure. Arteriolar optimality deviation (an index of microvascular endothelial dysfunction) increased with greater body mass index. Current smoking and increased white blood cell (WBC) count was associated with wider venules. After controlling for smoking, WBC was no longer a significant predictor of venular diameter. CONCLUSIONS: CVD risk factors are associated with retinal microvascular changes in healthy individuals without evidence of CVD, diabetes, or hypertension. CVD risk factors have different influences on the arteriolar and venular bed.


Asunto(s)
Procesamiento de Imagen Asistido por Computador , Microcirculación/fisiología , Retina/fisiología , Vasos Retinianos/fisiología , Anciano , Arteriolas/anatomía & histología , Arteriolas/fisiología , Presión Sanguínea/fisiología , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/patología , Enfermedades Cardiovasculares/fisiopatología , Femenino , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Retina/anatomía & histología , Vasos Retinianos/anatomía & histología , Vénulas/anatomía & histología , Vénulas/fisiología
7.
Clin Sci (Lond) ; 117(6): 229-36, 2009 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-19173676

RESUMEN

Diabetes aggravates the impact of elevated BP (blood pressure) on the microcirculation, and people of African ancestry with diabetes are more susceptible to microvascular damage than Europeans. In the present study, we investigated possible differences in the retinal microcirculation in people of European and African-Caribbean ethnicity with diabetes that might account for this. A total of 51 subjects with Type 2 diabetes (age 40-65 years; 25 male; 29 African-Caribbean) were studied. Clinic and 24 h ambulatory BP, and fasting glucose, insulin and lipids were measured. Digital retinal images were analysed using custom-written semi-automatic software to determine: LDR (length/diameter ratio) and AVR (arteriolar/venular diameter ratio), branching angles, vessel tortuosity and NT (number of terminal vessel branches). Arterioles were narrower in European people with diabetes than in African-Caribbean people with diabetes [mean (S.D.) arteriolar diameter, 76 (7) compared with 82 (11) microm respectively (P=0.03); arteriolar LDR, 28.1 (8.5) compared with 23.7 (7.0) respectively (P=0.046); and AVR, 0.66 (0.21) compared with 0.90 (0.36) respectively (P=0.028)]. Ethnic differences in arteriolar LDR, arteriolar diameter and AVR were not explained by differences in BP, but were attenuated by adjustment for the duration of diabetes. There was no significant relationship between BP and arteriolar narrowing in the group as a whole, although the relationship between arteriolar LDR and systolic BP was stronger in Europeans than African-Caribbeans [beta=0.08 (0.07) compared with beta=0.03 (0.06); P=0.03]. In conclusion, in the presence of diabetes, a relationship between BP and retinal arteriolar diameter was not evident and implies impaired small artery remodelling in the presence of diabetes. African-Caribbean people with diabetes have wider retinal arterioles and this could contribute to enhanced microvascular damage in this ethnic group.


Asunto(s)
Población Negra , Diabetes Mellitus Tipo 2/etnología , Retinopatía Diabética/etnología , Vasos Retinianos/patología , Población Blanca , Adulto , Anciano , Arteriolas/patología , Presión Sanguínea/fisiología , Diabetes Mellitus Tipo 2/patología , Diabetes Mellitus Tipo 2/fisiopatología , Retinopatía Diabética/patología , Retinopatía Diabética/fisiopatología , Femenino , Humanos , Londres/epidemiología , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Factores de Riesgo , Vénulas/patología
8.
Hypertension ; 74(4): 921-928, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31446803

RESUMEN

Clustering of arterial blood pressure (BP) waveform parameters could summarize complex information into distinct elements, which could be used to investigate cumulative (nonredundant) associations. We investigated this hypothesis in a large, adult population-based study (ViDA trial [Vitamin D Assessment] trial). To interpret the clusters and evaluate their usefulness, we examined their predictors and associations with cardiovascular events. In 4253 adults (mean age 65 years; 55% male) without a prior cardiovascular event, suprasystolic oscillometry was performed, yielding aortic pressure waveforms and several hemodynamic parameters. Participants were followed up for 4.6 years (median), accruing 300 cardiovascular events. Principal component analysis reduced 14 arterial waveform parameters to 3 uncorrelated factors that together explained 90% of the variability of the original data. Factors 1, 2, and 3 appeared to represent BP pulsatility, mean BP, and wave reflection, respectively. Across 6 antihypertensive drug classes, there were no differences in brachial systolic (P=0.23) and diastolic (P=0.13) BP; but there were significant variations in factor 3 (P<0.0001), especially for ß-blocker use. The first and third factors were positively associated with cardiovascular events (multivariable-adjusted standardized hazard ratio [95% CI]=1.33 [1.18-1.50] and 1.15 [1.02-1.30], respectively), whereas the second factor had a J-shaped relationship, with a nadir corresponding to a brachial diastolic BP of ≈75 mm Hg. In conclusion, BP pulsatility, mean BP, and wave reflection are prognostically meaningful, distinct aspects of arterial function that can be used to summarize physiological variations in multiple arterial waveform parameters and identify truly cumulative associations when used as cardiovascular risk outcomes.


Asunto(s)
Presión Arterial/fisiología , Arteria Braquial/fisiopatología , Hipertensión/fisiopatología , Anciano , Anciano de 80 o más Años , Antihipertensivos/farmacología , Antihipertensivos/uso terapéutico , Presión Arterial/efectos de los fármacos , Femenino , Hemodinámica , Humanos , Hipertensión/tratamiento farmacológico , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Análisis de la Onda del Pulso
9.
Contemp Clin Trials ; 28(1): 6-17, 2007 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17030155

RESUMEN

The ADVANCE Retinal Measurements (AdRem) Study is a large intervention study evaluating the effects of target driven intensive glucose control and placebo controlled blood pressure lowering on retinal vascular changes. AdRem is a sub-study of the ADVANCE Study (Action in Diabetes and Vascular disease), a 2x2 factorial randomized controlled trial with an ACE inhibitor-diuretic combination (perindopril-indapamide) and a gliclazide MR-based regimen in patients with type 2 diabetes mellitus. The AdRem study is based on seven-field stereoscopic retinal photographs of both eyes. These are taken within 3 months after randomization in ADVANCE (baseline), at the biennial and at the final visit. The primary outcome is progression of two or more steps in ETDRS classification. Secondary outcomes include progression of retinal vascular lesions and distortion of retinal vascular geometry. Retinal photographs are made on film and digitized at a central laboratory. The AdRem study uses fully digitized quality control and grading. Between August 2002 and January 2004 1978 patients were included in the AdRem study, from 39 centers in 14 countries. Approximately 85% comply with the strict AdRem quality requirements. Publication of the results is expected in early 2008. The AdRem study is designed to provide reliable evidence on the effects of intensive glucose control and blood pressure lowering on both diabetic retinopathy and abnormalities of retinal vasculature in patients with type 2 diabetes mellitus.


Asunto(s)
Ensayos Clínicos como Asunto/métodos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Retinopatía Diabética/prevención & control , Hipertensión/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Proyectos de Investigación , Antihipertensivos/uso terapéutico , Glucemia , Humanos , Hipoglucemiantes/uso terapéutico , Fotograbar/métodos , Vasos Retinianos/patología , Análisis Espectral/métodos
10.
J Am Heart Assoc ; 6(10)2017 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-29066444

RESUMEN

BACKGROUND: The effects of monthly, high-dose, long-term (≥1-year) vitamin D supplementation on central blood pressure (BP) parameters are unknown. METHODS AND RESULTS: A total of 517 adults (58% male, aged 50-84 years) were recruited into a double-blinded, placebo-controlled trial substudy and randomized to receive, for 1.1 years (median; range: 0.9-1.5 years), either (1) vitamin D3 200 000 IU (initial dose) followed 1 month later by monthly 100 000-IU doses (n=256) or (2) placebo monthly (n=261). At baseline (n=517) and follow-up (n=380), suprasystolic oscillometry was undertaken, yielding aortic BP waveforms and hemodynamic parameters. Mean deseasonalized 25-hydroxyvitamin D increased from 66 nmol/L (SD: 24) at baseline to 122 nmol/L (SD: 42) at follow-up in the vitamin D group, with no change in the placebo group. Despite small, nonsignificant changes in hemodynamic parameters in the total sample (primary outcome), we observed consistently favorable changes among the 150 participants with vitamin D deficiency (<50 nmol/L) at baseline. In this subgroup, mean changes in the vitamin D group (n=71) versus placebo group (n=79) were -5.3 mm Hg (95% confidence interval [CI], -11.8 to 1.3) for brachial systolic BP (P=0.11), -2.8 mm Hg (95% CI, -6.2 to 0.7) for brachial diastolic BP (P=0.12), -7.5 mm Hg (95% CI, -14.4 to -0.6) for aortic systolic BP (P=0.03), -5.7 mm Hg (95% CI, -10.8 to -0.6) for augmentation index (P=0.03), -0.3 m/s (95% CI, -0.6 to -0.1) for pulse wave velocity (P=0.02), -8.6 mm Hg (95% CI, -15.4 to -1.9) for peak reservoir pressure (P=0.01), and -3.6 mm Hg (95% CI, -6.3 to -0.8) for backward pressure amplitude (P=0.01). CONCLUSIONS: Monthly, high-dose, 1-year vitamin D supplementation lowered central BP parameters among adults with vitamin D deficiency but not in the total sample. CLINICAL TRIAL REGISTRATION: URL: http://www.anzctr.org.au. Unique identifier: ACTRN12611000402943.


Asunto(s)
Presión Sanguínea/efectos de los fármacos , Arteria Braquial/efectos de los fármacos , Colecalciferol/administración & dosificación , Suplementos Dietéticos , Hipertensión/tratamiento farmacológico , Deficiencia de Vitamina D/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Antihipertensivos/uso terapéutico , Biomarcadores/sangre , Arteria Braquial/fisiopatología , Colecalciferol/efectos adversos , Colecalciferol/sangre , Suplementos Dietéticos/efectos adversos , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Hipertensión/sangre , Hipertensión/diagnóstico , Hipertensión/fisiopatología , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Nueva Zelanda , Análisis de la Onda del Pulso , Factores de Tiempo , Resultado del Tratamiento , Vitamina D/análogos & derivados , Vitamina D/sangre , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/diagnóstico , Deficiencia de Vitamina D/fisiopatología
11.
J Hypertens ; 24(5): 889-94, 2006 May.
Artículo en Inglés | MEDLINE | ID: mdl-16612251

RESUMEN

OBJECTIVE: Grading of hypertension severity by fundoscopic appearance is difficult and inaccurate. We investigated whether essential hypertension (EHT) and malignant phase hypertension (MHT) were associated with quantifiable abnormalities of the topology and architecture of the retinal circulation. METHODS: The topology and architecture of the retinal microvasculature were compared in images from 20 normotensive subjects, 20 patients with EHT and 20 patients with MHT. Digitized retinal photographs were analysed by a novel multiscale image analysis method using a semi-automated program to quantify geometrical and topological properties of arteriolar and venular trees. RESULTS: EHT was associated with an increase in the arteriolar length-to-diameter ratio (P < 0.01). There were also alterations in arteriolar topology indicative of rarefaction, including a marked reduction in the number of terminal branches in EHT (P < 0.01). These changes in the arteriolar network were exaggerated in MHT and there was also increased venular tortuosity and venular rarefaction in MHT compared with normotensive subjects. CONCLUSIONS: Hypertension is associated with marked topological alterations in the retinal vasculature, and quantification of these changes may be a useful novel approach to the assessment of target organ damage in hypertension.


Asunto(s)
Hipertensión Maligna/patología , Hipertensión/patología , Vasos Retinianos/patología , Adulto , Anciano , Estudios Transversales , Humanos , Masculino , Microcirculación , Persona de Mediana Edad
12.
IEEE Trans Med Imaging ; 24(4): 451-6, 2005 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15822803

RESUMEN

The association between vascular wall shear stress (WSS) and the local development of atherosclerotic plaque makes estimation of in vivo WSS of considerable interest. Three-dimensional ultrasound (3DUS) combined with computational fluid dynamics (CFD) provides a potentially valuable tool for acquiring subject-specific WSS, but the interoperator and intraoperator variability associated with WSS calculations using this method is not known. Here, the accuracy, reproducibility and operator dependence of 3DUS-based computational fluid dynamics were examined through a phantom and in vivo studies. A carotid phantom was scanned and reconstructed by two operators. In the in vivo study, four operators scanned a healthy subject a total of 11 times, and their scan data were processed by three individuals. The study showed that with some basic training, operators could acquire accurate carotid geometry for flow reconstructions. The variability of measured cross-sectional area and predicted shear stress was 8.17% and 0.193 N/m2 respectively for the in vivo study. It was shown that the variability of the examined parameters was more dependent on the scan operators than the image processing operator. The range of variability of geometrical and flow parameters reported here can be used as a reference for future in vivo studies using the 3DUS-based CFD approach.


Asunto(s)
Algoritmos , Arteria Carótida Común/diagnóstico por imagen , Arteria Carótida Común/fisiopatología , Ecocardiografía Tridimensional/métodos , Aumento de la Imagen/métodos , Interpretación de Imagen Asistida por Computador/métodos , Modelos Cardiovasculares , Adulto , Simulación por Computador , Ecocardiografía Tridimensional/instrumentación , Humanos , Masculino , Variaciones Dependientes del Observador , Fantasmas de Imagen , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Resistencia al Corte , Estrés Mecánico , Técnica de Sustracción
13.
J Hypertens ; 20(3): 539-43, 2002 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11875323

RESUMEN

OBJECTIVES: Afro-Caribbean subjects have a higher prevalence of hypertension, a lower prevalence of ischaemic heart disease and a higher premature mortality compared to White Europeans. Left ventricular hypertrophy (LVH) is also more prevalent in Afro-Caribbeans even at similar levels of blood pressure. It is widely believed that carotid artery intima-media thickening (IMT) represents an early marker for the development of atheroma, and carotid IMT and LVH are associated in White populations. Whether the relationship between carotid IMT and LVH is similar in Black subjects is unknown. METHODS: Thirty-eight subjects were studied using carotid and femoral ultrasonography and echocardiography; 19 Afro-Caribbean and 19 White European subjects were matched for age, sex and mean 24 h systolic blood pressure. RESULTS: The Afro-Caribbean group had a significantly greater left ventricular mass index (LVMI) compared to the White European: 136.4 +/- 6.1 versus 112.4 +/- 6.2 g/m2, P < 0.01. However, carotid IMT, carotid diameter, femoral IMT and femoral diameter were similar between the groups: 0.75 +/- 0.02 versus 0.77 +/- 0.04 mm, 6.54 +/- 0.15 versus 6.56 +/- 0.16 mm, 0.66 +/- 0.03 versus 0.68 +/- 0.03 mm and 8.40 +/- 0.33 versus 8.25 +/- 0.23 mm, respectively. CONCLUSIONS: Afro-Caribbean subjects with similar blood pressures have similar mean carotid and femoral IMTs compared to White Europeans, in spite of marked differences in LVMI. Whether this reflects a discrepancy in the degree of cardiovascular risk for similar levels of LVMI or whether this is a reflection of an altered pattern of target organ damage associated with hypertension in Afro-Caribbean subjects is unclear.


Asunto(s)
Población Negra , Arterias Carótidas/diagnóstico por imagen , Ecocardiografía , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/etnología , Población Blanca , Adulto , Región del Caribe , Europa (Continente) , Femenino , Arteria Femoral/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Túnica Íntima/diagnóstico por imagen , Túnica Media/diagnóstico por imagen
14.
IEEE Trans Med Imaging ; 23(5): 567-83, 2004 May.
Artículo en Inglés | MEDLINE | ID: mdl-15147010

RESUMEN

Three-dimensional (3-D) ultrasound is a relatively new technique, which is well suited to imaging superficial blood vessels, and potentially provides a useful, noninvasive method for generating anatomically realistic 3-D models of the peripheral vasculature. Such models are essential for accurate simulation of blood flow using computational fluid dynamics (CFD), but may also be used to quantify atherosclerotic plaque more comprehensively than routine clinical methods. In this paper, we present a spline-based method for reconstructing the normal and diseased carotid artery bifurcation from images acquired using a freehand 3-D ultrasound system. The vessel wall (intima-media interface) and lumen surfaces are represented by a geometric model defined using smoothing splines. Using this coupled wall-lumen model, we demonstrate how plaque may be analyzed automatically to provide a comprehensive set of quantitative measures of size and shape, including established clinical measures, such as degree of (diameter) stenosis. The geometric accuracy of 3-D ultrasound reconstruction is assessed using pulsatile phantoms of the carotid bifurcation, and we conclude by demonstrating the in vivo application of the algorithms outlined to 3-D ultrasound scans from a series of patient carotid arteries.


Asunto(s)
Algoritmos , Arteria Carótida Interna/diagnóstico por imagen , Estenosis Carotídea/diagnóstico por imagen , Ecocardiografía Tridimensional/métodos , Interpretación de Imagen Asistida por Computador/métodos , Arteria Carótida Común/diagnóstico por imagen , Arteria Carótida Externa/diagnóstico por imagen , Ecocardiografía Tridimensional/instrumentación , Humanos , Fantasmas de Imagen , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
15.
Int J Cardiol ; 86(2-3): 233-8, 2002 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-12419561

RESUMEN

BACKGROUND: Patients with pathological left ventricular hypertrophy have depressed midwall systolic shortening in spite of normal indices of left ventricular chamber function and a reduced midwall function has been observed to be an independent predictor of cardiovascular risk. Whether midwall shortening is depressed in physiological hypertrophy is unknown. METHODS: Forty-two subjects, 27 athletes and 15 age- and sex-matched normal control subjects (group 1) were studied. The athletes were divided into those with eccentric hypertrophy (group 2) and those with concentric hypertrophy (group 3). Systolic left ventricular function was assessed at the midwall and endocardium using two-dimensional echocardiography in all subjects. RESULTS: Left ventricular mass index was significantly greater in both athletic groups than in controls (group 1, 101+/-5.8 g/m(2), group 2, 141+/-11.1*, group 3, 155+/-5.8*; *P<0.01 compared with group 1). Left ventricular systolic function assessed at the endocardium was similar among all three groups (ejection fraction: group 1, 66.2+/-2.38, group 2, 66.8+/-1.44, group 3, 63.7+/-1.66%; endocardial fractional shortening: group 1, 37.1+/-1.71, group 2, 37.6+/-1.13, group 3, 35.1+/-1.25%). However, fractional shortening at the midwall was reduced in the concentric hypertrophy athletes compared with the other two groups (midwall fractional shortening: group 1, 21.9+/-1.1, group 2, 21.9+/-0.86, group 3, 18.4+/-0.96*%; P<0.05 compared with groups 1 and 2). CONCLUSION: Subjects with physiological concentric hypertrophy have depressed midwall fractional shortening. This suggests that the observed discrepancy between midwall and endocardial shortening in patients with left ventricular hypertrophy is likely to be a function of the geometry and not necessarily a reflection of pathology within the myocardium.


Asunto(s)
Hipertrofia Ventricular Izquierda/patología , Hipertrofia Ventricular Izquierda/fisiopatología , Miocardio/patología , Deportes , Disfunción Ventricular Izquierda/patología , Disfunción Ventricular Izquierda/fisiopatología , Adulto , Ecocardiografía , Endocardio/patología , Endocardio/fisiopatología , Femenino , Hemodinámica/fisiología , Humanos , Hipertrofia Ventricular Izquierda/complicaciones , Masculino , Esfuerzo Físico/fisiología , Valor Predictivo de las Pruebas , Medición de Riesgo , Disfunción Ventricular Izquierda/etiología
16.
Artery Res ; 4(3): 75-80, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21072124

RESUMEN

Conventionally, the relationship between parent and daughter vessels at vascular bifurcations has been expressed by the junction exponent (x), and deviations of this parameter from the optimal conditions predicted by Murray's law (x = 3) have been shown to be associated with vascular disease. However, the junction exponent is normally calculated iteratively from diameter measurements, and Monte-Carlo simulation studies show the junction exponent to be biased in the presence of measurement noise.We present an alternative parameter, referred to as optimality ratio, that is simpler to compute and also more robust in the presence of noise.To demonstrate the sensitivity of the optimality ratio to alterations in topography of the retinal vascular network, we analysed the effect of inducing endothelial dysfunction by infusion of NG-monomethyl-l-arginine (l-NMMA), a nitric oxide synthase inhibitor, compared to placebo in a double-blind crossover study. The optimality ratio showed a significant increase (p = 0.03) during infusion of l-NMMA compared to placebo.We propose that a measure of the extent of departure of optimality ratio from its optimal value of 2(-1/3) may be a useful indicator of microvascular endothelial dysfunction in vivo.

17.
J Am Coll Cardiol ; 56(1): 24-30, 2010 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-20620713

RESUMEN

OBJECTIVES: This study investigated whether wave reflection measured by wave intensity analysis predicts future cardiovascular events in individuals with hypertension and sought to establish whether this relationship is independent of other cardiovascular risk factors and is associated with evidence of increased load on the left ventricle. BACKGROUND: Wave reflection may impose an additional load on the left ventricle, and augmentation index, a surrogate of wave reflection, has been reported to predict cardiovascular events in some, but not all studies. METHODS: Measurements of brachial and carotid blood pressure (BP) measurement, carotid ultrasound, echocardiography, and blood chemistry analyses were performed on 259 ASCOT (Anglo Scandinavian Cardiac Outcomes Trial) participants approximately 1 year after randomization, and wave intensity analysis was used to calculate wave reflection index (WRI), the ratio of peak forward to peak backward pressure (P(b)/P(f)), and carotid augmentation index (cAI(x)). All participants were followed up for a median period of 5.9 years, accruing 33 cardiovascular events. RESULTS: WRI, P(b)/P(f), and to a lesser extent, cAI(x), were correlated. WRI predicted cardiovascular events (hazard ratio: 2.10; 95% confidence interval: 1.10 to 3.99; p = 0.02) in an unadjusted model. Multivariate analysis showed that this association was independent of BP. P(b)/P(f) and cAI(x) did not significantly predict cardiovascular events. WRI was also positively associated with increased left ventricular mass index and elevated B-type natriuretic peptide adjusted for age and sex, and these associations were independent of BP or other cardiovascular risk factors. CONCLUSIONS: Higher wave reflection predicts future cardiovascular events independent of conventional risk factors in people with treated hypertension.


Asunto(s)
Presión Sanguínea/fisiología , Enfermedades Cardiovasculares/etiología , Hipertensión/complicaciones , Anciano , Femenino , Ventrículos Cardíacos/fisiopatología , Humanos , Hipertensión/fisiopatología , Masculino , Péptido Natriurético Encefálico/sangre , Factores de Riesgo
18.
Ann Biomed Eng ; 38(8): 2606-20, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20364324

RESUMEN

The aim of this study was to develop a fully subject-specific model of the right coronary artery (RCA), including dynamic vessel motion, for computational analysis to assess the effects of cardiac-induced motion on hemodynamics and resulting wall shear stress (WSS). Vascular geometries were acquired in the right coronary artery (RCA) of a healthy volunteer using a navigator-gated interleaved spiral sequence at 14 time points during the cardiac cycle. A high temporal resolution velocity waveform was also acquired in the proximal region. Cardiac-induced dynamic vessel motion was calculated by interpolating the geometries with an active contour model and a computational fluid dynamic (CFD) simulation with fully subject-specific information was carried out using this model. The results showed the expected variation of vessel radius and curvature throughout the cardiac cycle, and also revealed that dynamic motion of the right coronary artery consequent to cardiac motion had significant effects on instantaneous WSS and oscillatory shear index. Subject-specific MRI-based CFD is feasible and, if scan duration could be shortened, this method may have potential as a non-invasive tool to investigate the physiological and pathological role of hemodynamics in human coronary arteries.


Asunto(s)
Aorta/fisiología , Vasos Coronarios/fisiología , Movimiento (Física) , Adulto , Vasos Sanguíneos/fisiología , Corazón/fisiología , Hemodinámica/fisiología , Humanos , Angiografía por Resonancia Magnética/métodos , Masculino , Estrés Mecánico
19.
J Am Coll Cardiol ; 55(17): 1875-81, 2010 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-20413040

RESUMEN

OBJECTIVES: We hypothesized that an amlodipine-based regimen would have more favorable effects on left ventricular (LV) diastolic function. BACKGROUND: Different antihypertensive therapies may vary in their effect on LV diastolic function. METHODS: The HACVD (Hypertension Associated Cardiovascular Disease) substudy of ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) collected detailed cardiovascular phenotypic data on a subset of 1,006 participants recruited from 2 centers (St. Mary's Hospital, London, and Beaumont Hospital, Dublin). Conventional and tissue Doppler echocardiography and measurement of plasma B-type natriuretic peptide (BNP) were performed approximately 1 year after randomization to atenolol-based or amlodipine-based antihypertensive treatment to assess LV diastolic function. RESULTS: On-treatment blood pressure (BP) (mean +/- SD) was similar in both groups: atenolol-based regimen, systolic BP of 137 +/- 17 mm Hg, diastolic BP of 82 +/- 9 mm Hg; amlodipine-based regimen, systolic BP of 136 +/- 15 mm Hg, diastolic BP of 80 +/- 9 mm Hg. Ejection fraction did not differ between groups, but early diastolic mitral annular velocity (E'), a measure of diastolic relaxation, was lower in patients on the atenolol-based regimen: atenolol-based regimen, 7.9 +/- 1.8; amlodipine-based regimen, 8.8 +/- 2.0. A measure of left ventricular filling pressure, E/E', and BNP were significantly higher in patients on the atenolol-based regimen. Differences in E', E/E', and BNP remained significant after adjustment for age and sex. Further adjustment for systolic BP, LV mass index, and heart rate had no impact on differences in mean E' or BNP. The difference in E/E' was attenuated. CONCLUSIONS: Patients receiving treatment with an amlodipine-based regimen had better diastolic function than patients treated with the atenolol-based regimen. Treatment-related differences in diastolic function were independent of BP reduction and other factors that are known to affect diastolic function.


Asunto(s)
Amlodipino/farmacología , Antihipertensivos/farmacología , Atenolol/farmacología , Función Ventricular Izquierda/efectos de los fármacos , Amlodipino/uso terapéutico , Antihipertensivos/uso terapéutico , Atenolol/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Diástole/efectos de los fármacos , Ecocardiografía Doppler , Femenino , Humanos , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre
20.
J Am Soc Echocardiogr ; 22(2): 177-82, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19022622

RESUMEN

BACKGROUND: The aim of this study was to determine the impact of percutaneous coronary intervention (PCI) on myocardial function assessed by tissue Doppler echocardiography. METHODS: Myocardial tissue peak velocities were recorded at the lateral, septal, posterior, and inferior angles of the mitral annulus as well as at the lateral tricuspid annulus by pulsed-wave tissue Doppler echocardiography before PCI, as well as 1 day and 6 weeks after intervention. RESULTS: Twenty-four consecutive patients with chronic stable angina and preserved systolic left ventricular function (20 men; mean age, 64 +/- 9 years) undergoing PCI were studied. Compared with preinterventional values, early diastolic velocities improved at all sites (P < .05 for each). The most pronounced improvement occurred in the septal area. Similarly, systolic peak velocity improved in the septal, lateral, inferior, and right ventricular areas (P < .04 for each). CONCLUSIONS: Tissue Doppler parameters of diastolic and systolic function improve early after successful PCI, and this effect persists to 6 weeks after intervention.


Asunto(s)
Angina de Pecho/diagnóstico por imagen , Angina de Pecho/cirugía , Angioplastia Coronaria con Balón , Ecocardiografía Doppler/métodos , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/cirugía , Angina de Pecho/complicaciones , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Resultado del Tratamiento , Disfunción Ventricular Izquierda/complicaciones
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