The effects of antihypertensive therapy on carotid vascular structure in man.

OBJECTIVE: An increased carotid intima-media thickness (IMT) has been found to be associated with a number of cardiovascular risk factors such as age, hypertension, cigarette smoking, hypercholesterolaemia and left ventricular hypertrophy. Our objective was to assess whether carotid intima-media thickness in hypertensive patients could be reduced by antihypertensive therapy. METHODS: 13 hypertensive patients, 10 previously untreated, were examined using carotid ultrasonography and echocardiography at baseline and then at 8 weeks and 39 weeks after commencement of antihypertensive therapy with ramipril and the second-line addition of felodipine. RESULTS: By the end of the study significant regression of IMT (0.1(0.05-0.16) mm, F-value 10.2, P < 0.01) and left ventricular mass index had occurred (25(10.7-39.3) g/m2, F-value 9.7, P < 0.01). The reduction in IMT was significantly related to the reduction in mean arterial pressure, r = 0.55, P = 0.05). CONCLUSION: Antihypertensive therapy with ramipril and felodipine causes regression of IMT in hypertensive patients, probably chiefly through blood pressure reduction. Large prospective studies are required to assess whether a reduction in IMT results in a reduction in morbidity and mortality.

A method of quantifying retinal microvascular alterations associated with blood pressure and age.

OBJECTIVE: To find an objective, sensitive method for quantifying microvascular alterations associated with level of blood pressure and age. DESIGN: A prospective cross-sectional study. SUBJECTS AND METHODS: Seventy-four previously untreated hypertensive patients, referred to a hospital outpatients department, and 26 normotensive volunteers participated. Twenty-four-hour ambulatory blood pressure monitoring and bilateral fundal photography were performed. The fundal photographs were projected on a screen such that the optic disc filled a circle of radius 5 cm. Microvessels crossing the border of a concentric circle of radius 20 cm were identified as arteriolar or venular, counted and their luminal diameters measured. MAIN OUTCOME MEASURES: Arteriolar and venular numbers, mean diameters and vascularities (arteriolar and venular vascularities defined as the sum of arteriolar and venular diameters, respectively). RESULTS: The technique was reproducible. As blood pressure increased, arteriolar vascularity declined and venular vascularity increased. These associations resulted in a strong inverse correlation between blood pressure level and the ratio arteriolar vascularity: venular vascularity (r = 0.48, P < 0.001). Arteriolar number declined with increasing diastolic blood pressure (r = 0.22, P < 0.05). Mean arteriolar diameter appeared to have a U-shaped relationship with diastolic blood pressure levels (r = 0.27, P < 0.05). Venular dilation was associated with increasing blood pressure levels (r = 0.22, P < 0.05). Mean arteriolar and venular diameters declined significantly with age (r = 0.33 and 0.26, respectively; P < 0.01) and there was no association between arteriolar vascularity:venular vascularity ratio and age. CONCLUSIONS: The method detected disparate retinal microvascular alterations with age and blood pressure. The arteriolar vascularity:venular vascularity ratio shows promise as a non-invasive, prognostic and therapeutic guide in hypertension.

Vascular network changes in the retina with age and hypertension.

OBJECTIVE: To compare retinal arterial bifurcation geometry in normotensive and hypertensive subjects. DESIGN: A retrospective observational study. METHODS: Fluorescein angiograms of normotensive (n = 13) and hypertensive (n = 12) subjects aged 30-80 years with uni-ocular retinal pathology were compared. Quantification of diameters of the parent, larger daughter and smaller daughter vessels (d0, d1 and d2, respectively) and of bifurcation angles (the angle between the two daughter arterioles, omega) of arteriolar bifurcations was performed from digitized retinal angiograms of the uninvolved eye. The relative diameters of parent and daughter vessels at bifurcations were summarized by junction exponents (x) such that d1x + d2x = d0x. RESULTS: Junction exponents were similar for normotensives and hypertensives (means +/- SEM, 2.65 +/- 0.18 and 2.48 +/- 0.17), but analysis of covariance showed a parallel decrease in x in the two groups with age. A positive association was found between x and arteriolar microvascular density. Bifurcation angles were more acute in hypertensives (74 +/- 3 degrees) than in normotensives (84 +/- 3 degrees) and declined with increasing age in both groups. CONCLUSIONS: The present findings indicate that ageing and possibly hypertension are associated with disadvantageous branching geometry in the human retinal vasculature, implying increased power costs of blood transport, uneven distribution of shear forces throughout the vascular tree and microvascular rarefaction. The present findings may have important implications for our understanding of the pathogenesis of vascular disease in ageing and hypertension and offer the prospect of a novel sensitive diagnostic approach to the cardiovascular system.

Left ventricular hypertrophy, blood pressure and ACE genotype in untreated hypertension.

It has been suggested that the deletion polymorphism of the angiotensin-converting enzyme (ACE) genotype may be important in the development of left ventricular hypertrophy (LVH). In order to test this hypothesis we investigated the interaction between blood pressure (BP), LVH and ACE genotype in 86 previously untreated hypertensive patients. Each underwent two-dimensional and Doppler echocardiography and ACE genotyping. There were no significant differences in BP, the parameters of left ventricular structure (including left ventricular mass index) or diastolic function between the three genotype groups. Additionally, there were no significant differences in the relationship between systolic BP and left ventricular mass index among the three genotype groups (II genotype, r = 0.46, P = 0.02; ID genotype, r = 0.42, P = 0.01; DD genotype, r = 0.34, P = 0.10; F = 0.38). In contrast to some previous studies, we have found in this group of previously untreated hypertensive subjects no evidence to suggest that the deletion polymorphism of the ACE genotype is important in the development of LVH.

Computer algorithms for the automated measurement of retinal arteriolar diameters.

AIMS: Quantification of retinal vascular change is difficult and manual measurements of vascular features are slow and subject to observer bias. These problems may be overcome using computer algorithms. Three automated methods and a manual method for measurement of arteriolar diameters from digitised red-free retinal photographs were compared. METHODS: 60 diameters (in pixels) measured by manual identification of vessel edges in red-free retinal images were compared with diameters measured by (1) fitting vessel intensity profiles to a double Gaussian function by non-linear regression, (2) a standard edge detection algorithm (Sobel), and (3) determination of points of maximum intensity variation by a sliding linear regression filter (SLRF). Method agreement was analysed using Bland-Altman plots and the repeatability of each method was assessed. RESULTS: Diameter estimations obtained using the SLRF method were the least scattered although diameters obtained were approximately 3 pixels greater than those measured manually. The SLRF method was the most repeatable and the Gaussian method less so. The Sobel method was the least consistent owing to frequent misinterpretation of the light reflex as the vessel edge. CONCLUSION: Of the three automated methods compared, the SLRF method was the most consistent (defined as the method producing diameter estimations with the least scatter) and the most repeatable in measurements of retinal arteriolar diameter. Application of automated methods of retinal vascular analysis may be useful in the assessment of cardiovascular and other diseases.

Blood flow and vessel mechanics in a physiologically realistic model of a human carotid arterial bifurcation.

The pulsatile flow in an anatomically realistic compliant human carotid bifurcation was simulated numerically. Pressure and mass flow waveforms in the carotid arteries were obtained from an individual subject using non-invasive techniques. The geometry of the computational model was reconstructed from magnetic resonance angiograms. Maps of time-average wall shear stress, contours of velocity in the flow field as well as wall movement and tensile stress on the arterial wall are all presented. Inconsistent with previous findings from idealised geometry models, flow in the carotid sinus is dominated by a strong helical flow accompanied by a single secondary vortex motion. This type of flow is induced primarily by the asymmetry and curvature of the in vivo geometry. Flow simulations have been carried out under the rigid wall assumption and for the compliant wall, respectively. Comparison of the results demonstrates the quantitative influence of the vessel wall motion. Generally there is a reduction in the magnitude of wall shear stress, with its degree depending on location and phase of the cardiac cycle. The region of slow or reversed flow was greater, in both spatial and temporal terms in the compliant model, but the global characteristics of the flow and stress patterns remain unchanged. The analysis of mechanical stresses on the vessel surface shows a complicated stress field. Stress concentration occurs at both the anterior and posterior aspects of the proximal internal bulb. These are also regions of low wall shear stress. The comparison of computed and measured wall movement generally shows good agreement.

Inter-individual variations in wall shear stress and mechanical stress distributions at the carotid artery bifurcation of healthy humans.

Fluid shear stress and mechanical wall stress may play a role in the formation of early atherosclerotic lesions, but these quantities are difficult to measure in vivo. Our objective was to quantify these parameters in normal subjects in a clinical setting, and to define regions of low wall shear stress and high mechanical stress. The right carotid bifurcations of five healthy male volunteers were investigated using a novel non-invasive technique which integrates magnetic resonance angiography, ultrasonography, tonometry and state-of-the-art computational fluid dynamics and solid mechanics models. Significant inter-subject variations in patterns as well as magnitude of wall shear stress and mechanical stress were found. In spite of individual variabilities, this study revealed that some regions of the artery wall are exposed simultaneously to low wall shear stress and high mechanical stress and that these regions correspond to areas where atherosclerotic plaque develops. The coexistence of regions of low wall shear stress and high tensile stress may be an important determinant of the formation of atheroma in human arteries.

Flow in carotid bifurcations: effect of the superior thyroid artery.

The superior thyroid artery was ignored in previous fluid dynamics studies of carotid bifurcations. However, it is not clear to what extent the flow patterns within the carotid might be influenced by the presence of this outflow tract in reality. In this study, quantitative effects of the superior thyroid artery upon the flow patterns and wall shear stress in the carotid bifurcation were investigated in detail by a numerical simulation method. Comparisons of the maximum reversed flow velocities, flow patterns and wall shear stress were made between models with and without the superior thyroid artery. Results demonstrate that this small artery has only a marginal effect on the overall flow characteristics within the carotid sinus. However, it does have significant effects on flow patterns in the common-external side branch. An alternative approach is proposed to compensate for the absence of this small artery in numerical calculations.

Haemodynamics, wall mechanics and atheroma: a clinician's perspective.

Atherosclerosis, leading to myocardial infarction and stroke, is the major cause of death and morbidity in Western societies. Atheromatous lesions characteristically occur in regions of branching and marked curvature. Low shear stress and increased mural tensile stress may be major determinants underlying atheroma formation at these sites. Furthermore, the distribution of circumferential tensile stresses may play a critical role in where, why and when advanced atheromatous plaques rupture, leading to catastrophic ischaemic events. Recent advances in the application of computational modelling to in vivo vascular ultrasound and magnetic resonance imaging data should further elucidate the roles of haemodynamic factors and vessel wall mechanics in atherosclerosis. In future this is likely to lead to better use of currently available anti-atherosclerosis strategies. It may also facilitate the discovery, evaluation and development of novel treatments.

Acute effects of oxygen and carbon dioxide on retinal vascular network geometry in hypertensive and normotensive subjects.

The optimal design of vascular networks maximizes circulatory efficiency while minimizing power costs. We investigated the effects of acute changes in vascular tone on retinal arteriolar network geometry. Six hypertensive and six normotensive subjects each breathed air, 5% CO(2) (with 12% O(2)), and 100% O(2) for 5 min periods in random order. Retinal photographs were taken at the end of each test period. Bifurcation angles and arteriolar diameters were measured using operator-directed image analysis, and junction exponents were calculated. Arteriolar diameters narrowed on breathing O(2). The magnitude of this change was significantly greater in normotensive than in hypertensive subjects. Angles narrowed in normotensive subjects, but not significantly in hypertensive subjects. Arteriolar diameters increased significantly on breathing CO(2) in normotensive but not in hypertensive subjects, but there were no changes in angles. Despite changes in diameter, junction exponents did not change under any conditions. Vascular reactivity in the retinal arteriolar bed appears to be diminished in hypertensive subjects. The failure of junction exponents to change, despite alterations in diameter, suggests that arteriolar diameters at retinal bifurcations adhere to optimality principles when exposed to acute vasoactive stress. As vasoconstriction is associated with the narrowing of bifurcation angles, previous observations showing narrowed angles in hypertensive subjects could be explained by increased tone in the retinal arteriolar bed.

Reconstruction of blood flow patterns in a human carotid bifurcation: a combined CFD and MRI study.

The carotid bifurcation is a common site for clinically significant atherosclerosis, and the development of this disease may be influenced by the local hemodynamic environment. It has been shown that vessel geometry and pulsatile flow conditions are the predominant factors that determine the detailed blood flow patterns at the carotid bifurcation. This study was initiated to quantify the velocity profiles and wall shear stress (WSS) distributions in an anatomically true model of the human carotid bifurcation using data acquired from magnetic resonance (MR) imaging scans of an individual subject. A numerical simulation approach combining the image processing and computational fluid dynamics (CFD) techniques was developed. Individual vascular anatomy and pulsatile flow conditions were all incorporated into the computer model. It was found that the geometry of the carotid bifurcation was highly complex, involving helical curvature and out-of-plane branching. These geometrical features resulted in patterns of flow and wall shear stress significantly different from those found in simplified planar carotid bifurcation models. Comparisons between the predicted flow patterns and MR measurement demonstrated good quantitative agreement.

Left ventricular structure and function in previously untreated hypertensive patients: the importance of blood pressure, the nocturnal blood pressure dip and heart rate.

BACKGROUND: Cardiac assessment is an important part of risk stratification in hypertensive patients. Left ventricular hypertrophy in particular is a powerful predictor of subsequent cardiovascular morbidity and mortality. Previous studies assessing haemodynamic factors that may be responsible for cardiac changes in hypertensive patients have been performed in those previously treated for hypertension. To investigate more fully these haemodynamic relationships, a large group of previously untreated patients were studied. METHODS: Ninety-eight previously untreated hypertensive patients underwent electrocardiography, two-dimensional and Doppler echocardiography, 24 h ambulatory blood pressure monitoring and exercise stress testing. RESULTS: The left ventricular mass index (LVMI) was more closely related to mean 24 h than to clinic blood pressures (24 h systolic r = 0.48, P < 0.01; 24 h diastolic r = 0.49, P < 0.01; clinic systolic r = 0.28, P < 0.01; clinic diastolic r = 0.31, P < 0.01). In addition, the systolic nocturnal blood pressure dip was found to be inversely related to LVMI in men (r = -0.32, P < 0.01). Of the indices of left ventricular diastolic function, age (r = -0.64, P < 0.01), heart rate (r = -0.25, P = 0.02) and LVMI (r = -0.22, P = 0.02) were independently related to the E-A ratio. Age (r = 0.40, P < 0.01), blood pressure (systolic r = 0.39, P < 0.01; diastolic r = 0.43, P < 0.01), the nocturnal blood pressure dip (systolic r = -0.38, P < 0.01, diastolic r = -0.31, P < 0.01) and LVMI (r = 0.37, P < 0.01) were independently related to the isovolumic relaxation time. CONCLUSIONS: Blood pressure was the only independent determinant of LVMI; nocturnal blood pressure may be particularly important in men. Age and both haemodynamic and structural factors are independent determinants of parameters of left ventricular diastolic function in hypertensive patients.

Effects of blood pressure lowering with amlodipine or lisinopril on vascular structure of the common carotid artery.

Increased intima-media thickness of the common carotid artery predicts increased risk of myocardial infarction and stroke. Preliminary evidence suggests that a decrease in blood pressure (BP) is associated with diminished wall thickness. It is not known if all classes of anti-hypertensive agents have similar protective effects. In this double-blind parallel-group clinical trial, 69 previously untreated patients with hypertension were allocated randomly to 1 year of treatment with either amlodipine (5-10 mg daily) or lisinopril (5-20 mg daily). Doxazosin and bendrofluazide were added if required to achieve BP control. After 12 months of treatment, clinic BP, ambulatory BP and cardiac mass were reduced similarly by the two treatment regimens. Common carotid artery intima-media thickness decreased by 0.048 mm (95% confidence intervals -0.066, -0.031 mm) in the amlodipine-treated group, but decreased by only 0.027 mm (-0.046, -0.007 mm) in the lisinopril-treated group (P<0.05 for difference between treatments). Common carotid artery lumen diameter declined significantly only in patients treated with lisinopril [amlodipine, -0.02 mm (-0.14, 0.10 mm); lisinopril, -0.21 mm (-0.32, -0.11 mm); P<0.02], while intima-media area declined similarly in the two treatment groups [amlodipine -1.32 mm(2) (-1.91, -0.74 mm(2)), lisinopril -1.26 mm(2) (-1.80, -0.72 mm(2)); not significant]. The results confirm that a decrease in BP causes regression of structural changes in the carotid artery in hypertensive patients. The nature of the structural regression differed markedly between the two treatment regimens, in spite of similar decreases in BP. The calcium channel blocker induced greater regression of common carotid artery intima-media thickness than the angiotensin-converting enzyme inhibitor. However, carotid artery wall mass, as indicated by intima-media area, was reduced to a similar extent by the two treatments. It remains to be established whether such differences confer a prognostic advantage.