Vascular Pathological Changes Research Articles

Ultrasonic assessment of abnormal umbilical cord and its circulation

AbstractSince an abnormal umbilical cord such as excessive twisting/torsion, cord compression, coiling at the fetal neck are fetal life threatening or restrict fetal growth, it is diagnosed in detail by real time B-mode ultrasound, color Doppler flow mapping, pulsed Doppler flow velocity wave form, ultrasonic fetal monitor and actocardiogram. Abnormality is evaluated by its location, size, twisting and its pitch of the cord, the grade of variable deceleration (VD), non-invasive stress CTG test in maternal movement, RI and PI, absent or reverse flow of end diastole (ARED) of umbilical arterial blood flow velocity wave form, and particularly pulsating blood flow wave of the umbilical vein related to blood stagnation in the vein and pathological vascular changes of the placental villi, fetal and neonatal blood vessels. Its treatment is maternal position change in mild cord compression, while bed rest and total tocolysis is required when the compression signs are heavy in early pregnancy. The fetus is rescued...

Morphological changes in the Royal College of Surgeons rat retina during photoreceptor degeneration and after cell‐based therapy

There are concomitant morphological and functional changes in the inner retina during the course of photoreceptor degeneration in a range of animal models of retina degeneration and in humans with eye disease. One concern that has been raised is that the changes occurring in the inner retina might compromise attempts to rescue or restore visual input by various interventional approaches. It is known that cell-based therapy can preserve significant visual capability for many months. In this study, we examine the overall changes in the Royal College of Surgeons (RCS) rat during degeneration and the effects of cell transplantation by means of immunohistochemistry and confocal microscopy. The degenerative changes are complex, and they progress with age. They involve the neurons with which both rods and cones interconnect--retinal second- and third-order neurons underwent dramatic modification, including sprouting, retraction as photoreceptor loss progressed--as well as Müller glia and secondary vascular changes, which were associated at later times with neuronal migration. The pathological vascular changes led to major disruption of inner retina. After introducing a retinal pigment epithelial cell line to the subretinal space early in the progress of photoreceptor degeneration, most inner retinal changes were held in abeyance for up to at least 10 months of age. Given the concern that has been raised regarding whether inner retinal changes might compromise any graft-related benefit, this is an encouraging finding.

Association study of the vascular endothelial growth factor gene with the risk of developing Alzheimer's disease

Numerous observations indicate that cerebrovascular dysfunction contributes to cognitive decline and neurodegeneration in AD. Converging evidence points to a pivotal role for vascular endothelial growth factor (VEGF) in neuronal protection, and the lack of activity of this in neurodegenerative disorders. The VEGF gene is located at 6p21.3, a site several studies have shown to have significant linkage with AD, and a functional polymorphism within the VEGF promoter may alter the risk of developing AD. We assessed the potential impact of this polymorphism on the risk of developing AD in a large French case-control population, and investigated its association with the severity of brain vascular lesions (arteriosclerosis, white matter loss and cerebral amyloid angiopathy) in several brain regions (frontal, temporal, parietal and occipital cortex) in AD. No association of the VEGF promoter polymorphism with the risk of developing AD was observed. No relationship between this polymorphism and vascular pathological changes in AD was detected. Our data indicate that although this polymorphism is functional, it does not confer greater risk for AD, nor modulate the extent of vascular pathology.

Hypoxia and angiogenesis in rheumatoid arthritis

Angiogenesis is a prominent feature of rheumatoid synovitis. Although new blood vessels deliver oxygen to the augmented inflammatory cell mass, the neovascular network is dysfunctional and fails to restore tissue oxygen homeostasis, so that the rheumatoid joint remains a markedly hypoxic environment. The purpose of this review is to discuss the role of hypoxia and angiogenesis in the pathogenesis of rheumatoid arthritis. Vascular pathologic change, in the form of angiogenesis, is important in the perpetuation of rheumatoid arthritis and, in the form of endothelial dysfunction, contributes to associated cardiovascular comorbidity. Recent data suggest that tumor necrosis factor-alpha blockade may modify the vascular pathologic changes in rheumatoid arthritis. Angiogenesis is a prominent feature of rheumatoid synovitis. Emerging evidence based on ultrasonographic vascular imaging and angiogenic biomarkers implicates angiogenesis in the active phase of erosive disease. Many factors contribute to the profoundly hypoxic environment that can arise within the joint affected by rheumatoid arthritis. At a cellular level, hypoxia is detected by a mechanism that regulates cytoplasmic concentrations of hypoxia-inducible factor-1alpha. After translocation to the nucleus, hypoxia-inducible factor-1alpha binds its partner hypoxia-inducible factor-1beta to form a heterodimeric, functional transcription factor, hypoxia-inducible factor-1, which activates a gene program associated with angiogenesis, glycolysis, and adaptation to pH. Despite the luxuriant vasculature associated with rheumatoid arthritis synovitis, the joint affected by rheumatoid arthritis is hypoxic. Repetitive cycles of hypoxia and reoxygenation together with oxidants produced by phagocytic cells promote chronic oxidative stress within the microenvironment of the affected joint, leading to the generation of reactive oxygen species with the potential to contribute to tissue damage.

A Single Local Injection of Recombinant VEGF Receptor 2 But Not of Tie2 Inhibits Retinal Neovascularization in the Mouse

Purpose: The purpose of this study was to develop pharmacological therapeutic alternatives for ischemia-induced proliferative retinopathy. Methods: C57BL/6J mice were placed in 76% oxygen on postnatal day 7 (P7) for 5 days. On P12 recombinant, chimeric vascular endothelial growth factor (sVEGF-R2) or sTie2 was injected intravitreally in one eye. The fellow eye received a control injection. On P17, retinal wholemounts were prepared after perfusion with fluorescein-dextran to quantify the retinopathy. Results: A single intravitreal injection of sVEGF-R2 reduced pathologic vascular changes significantly (p = 0.02). No significant effect was observed after intravitreal application of sTie2 (p = 0.07), although Ang-2 was upregulated in control animals without treatment as neovascularization developed and Ang-1 was constantly transcribed (ratio PCR). Conclusions: sVEGF-R2 interferes with VEGF signaling via VEGF-R2 receptor. Thus, local application of soluble receptors for angiogenic factors is a possible therapy for proliferative retinopathy. Receptors with a wide range of ligands might prove more useful for local application than those binding few or antagonistic ligands.

CADASIL: what component of the vessel wall is really a target for Notch 3 gene mutations?

Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary cerebrovascular disease leading to cognitive decline, dementia and recurrent strokes. The underlying angiopathy of the small vessels is characterized by basophilic degeneration of the media, Notch 3 protein accumulation in vessel wall and a unique type of ultrastructural deposits located nearby the basal lamina. In some cases of CADASIL, morphological changes similar to those observed in panarteritis nodosa (PAN) were found. PAN-like changes manifested as fibrinoid necrosis of the tunica media and perivascular inflammatory infiltrates were found in arteries not only in the central nervous system but also in internal organs. Presence of PAN-like changes indicates that some autoimmunological mechanisms can participate in the CADASIL process. Although vascular smooth muscle cells seem to be a primary target of the pathogenic process triggered by mutations in Notch 3 gene they are probably not the only target. This article gives a brief overview on the morphologic spectrum of the vascular pathological changes in CADASIL and discusses some of the relevant mechanisms that lead from Notch 3 mutations to ischemic infarcts.

Vascular pathologic changes in the flexor tenosynovium (subsynovial connective tissue) in idiopathic carpal tunnel syndrome

We used the Verhoeff–van Gieson stain method to identify histopathology and to localize elastin in the subsynovial connective tissue of the tendon sheath (SSCT) of the middle finger flexor digitorum superficialis (FDS) within the carpal tunnel in 10 carpal tunnel syndrome (CTS) patients and 10 control cadaver specimens. Normal SSCT stained for elastin abundantly around blood vessels and within vessel walls. The typical pathologic findings of CTS patients SSCT included vascular proliferation, vascular hypertrophy, and vascular obstruction with wall thickening. There was a decreased amount of elastin in the blood vessel walls and around the vessels in the CTS patients as well. The changes in the carpal tunnel patients were particularly remarkable in that the patients were younger than the controls, yet showed findings more characteristic of chronic degeneration.

Tranilast attenuates vascular hypertrophy, matrix accumulation and growth factor overexpression in experimental diabetes

The growth factors transforming growth factor-B (TGF-B) and epidermal growth factor (EGF) have both been implicated in the hypertrophic structural changes in the vasculature that are characteristic features of both human and experimental diabetes. Recently, tranilast (N(3,4-dimethoxycinnamoyl)anthranilic acid), a drug used in the treatment of allergic and dermatological diseases, has also been reported to inhibit transforming growth factor-B (TGF-B)-mediated collagen formation. However, its effects on vascular hypertrophy in diabetes are unknown. The present study thus sought to determine the effects of tranilast on both TGF-B and EGF expression and mast cells in mediating the trophic vascular changes in experimental diabetes. Vessel morphology, growth factors and collagen gene expression and matrix deposition were examined in the mesenteric arteries of control rats treated with or without tranilast, and streptozotocin-induced diabetic Sprague-Dawley rats treated with or without tranilast (200 mg/kg/day) during a 3-week period. Compared with control animals, diabetic rats had significantly increased vessel weight, wall: lumen ratio, ECM accumulation, gene expression of TGF-B1, EGF, and both alpha1 (I) and alpha1 (IV) collagen. Tranilast treatment did not influence plasma glucose or systemic blood pressure. However, tranilast significantly reduced mesenteric weight, wall: lumen ratio and matrix deposition and also attenuated the overexpression of TGF-B1, EGF, and both alpha1 (I) and alpha1 (IV) collagen mRNA in diabetic rats. These findings indicate that tranilast ameliorates pathological vascular changes observed in experimental diabetes in association with reduced growth factor expression independent of blood glucose or systemic blood pressure.

The value of combining anterior segment fluorescein angiography with indocyanine green angiography in scleral inflammation

Purpose To determine the value of anterior segment indocyanine green (ICG) angiography combined with anterior segment fluorescein angiography in scleral inflammation. Design Comparative observational case series. Participants The study included 18 patients with various forms of scleral and episcleral disease and a single normal subject. Methods Anterior segment angiography using both ICG and fluorescein was performed to identify any vascular abnormalities and pathologic changes in the anterior segment. Main outcome measure The pathologic criteria for anterior segment fluorescein angiography described by Watson and Bovey (1995) were used to compare and contrast the results of the angiograms. Results Fluorescein angiography and ICG angiography provide different and complementary information. Both dyes have different leakage patterns caused by their difference in optical and chemical properties. Areas of slow flow are more readily determined with fluorescein angiography. ICG angiography determines damage to and patency of individual vessels. Conclusion Fluorescein angiography and ICG angiography detect areas of damage not clinically visible and can be useful in the differential diagnosis, the selection of appropriate medication, and monitoring and regulation of treatment in scleritis. To obtain the most information both investigations should be performed sequentially.

PATHOPHYSIOLOGY OF HYPERTENSION AND ENDOTHELIAL DYSFUNCTION IN PATIENTS WITH DIABETES MELLITUS

There is compelling evidence for endothelial dysfunction in both type 1 and type 2 diabetics. This dysfunction is manifest as blunting of the biologic effect of a potent endothelium-derived vasodilator, nitric oxide, and increased production of vasoconstrictors such as angiotensin II, ET-1, and cyclooxygenase and lipoxygenase products of arachidonic acid metabolism. These agents and other cytokines and growth factors whose production they stimulate cause acute increases in vascular tone, resulting in increases in blood pressure, and vascular and cardiac remodeling that contributes to the microvascular, macrovascular, and renal complications in diabetes. Reactive oxygen species, overproduced in diabetics, serve as signaling molecules that mediate many of the cellular biochemical reactions that result in these deleterious effects. Adverse vascular consequences associated with endothelial dysfunction in diabetes mellitus are Decreased nitric oxide formation, release, and action Increased formation of reactive oxygen species Decreased prostacyclin formation and release Increased formation of vasoconstrictor prostanoid Increased formation and release of ET-1 Increased lipid oxidation Increased cytokine and growth factor production Increased adhesion molecule expression Hypertension Changes in heart and vessel wall structure Acceleration of the atherosclerotic process Treatment with antioxidants and with inhibitors of the renin-angiotensin system may reverse some of the pathologic vascular changes associated with endothelial dysfunction.

Post-tumoral distorted vascular images: Diagnostic problem of sonogram

Most sonographists have probably encountered cases of liver tumor in which vascular images were distorted or poorly defined when the scanning plane included a tumor in front of a vessel. This phenomenon was thought to results from sound refraction through the tumor. We analyzed this phenomenon first by using the results of clinical studies, then by using the results of basic studies with microcomputer simulation models. Results of clinical studies showed (1) a small notch in vessel walls (29/83, 34.9%) and poor definition of vessels (29/83, 34.9%) appearing behind the tumors, as well as (2) poor vessel definition, predominantly behind heterogenous tumors (28/29, 96.6%). Basic studies showed that vessels appearing behind tumors with homogenous internal structure has a smooth rotation, and that these vessels were visualized as combinations of multiple small fragments behind tumors with heterogeneous internal structure. Refraction of the US beam passing through a tumor, especially one with a heterogeneous internal structure, results in distortion of the US image of vessels located behind such tumors. Familiarity with the pattern of artifactually distorted vessel images can help in preventing misinterpretation of these findings as true pathologic vascular changes. This limitation of sonography necessitates the use of other diagnostic modalities for accurate observation of a vessel situated behind a tumor.

Pathological analysis of local delivery of paclitaxel via a polymer-coated stent.

Paclitaxel can inhibit vascular smooth muscle proliferation in vitro, and early studies suggest that paclitaxel may be useful in preventing restenosis. Early and late intimal growth and local vascular pathological changes associated with paclitaxel delivered via stents have not been fully explored. Localized drug delivery was accomplished with balloon-expandable stainless steel stents coated with a cross-linked biodegradable polymer, chondroitin sulfate and gelatin (CSG), containing various doses of paclitaxel. CSG-coated stents with paclitaxel (42.0, 20.2, 8.6, or 1.5 microgram of paclitaxel per stent), CSG-coated stents without paclitaxel, and uncoated stents (without paclitaxel or CSG) were deployed in the iliac arteries of New Zealand White rabbits, which were killed 28 days after implant. Mean neointimal thickness at stent strut sites was reduced 49% (P<0.0003) and 36% (P<0.007) with stents containing 42.0 and 20.2 microgram of paclitaxel per stent, respectively, versus CSG-coated stents without paclitaxel. However, histological findings suggested incomplete healing in the higher-dose (42.0 and 20.2 microgram) paclitaxel-containing stents consisting of persistent intimal fibrin deposition, intraintimal hemorrhage, and increased intimal and adventitial inflammation. Stents coated with CSG alone (without paclitaxel) had similar neointimal growth as uncoated stents. In a separate group of rabbits killed at 90 days, neointimal growth was no longer suppressed by CSG-coated stents containing 42.0 or 21.0 microgram of paclitaxel CSG coating appears to be a promising medium for localized drug delivery. Paclitaxel polymer-coated stents reduce neointima formation but are associated with evidence of incomplete healing at 28 days. However, neointimal suppression was not maintained at 90 days.

Monitoring diabetic retinopathy in children with insulin-dependent diabetes mellitus

A total of 185 children (93 boys and 92 girls) aged 6 months to 15 years and disease duration of 1 to 13 years, residents of different regions of Russia, were examined. Pathological changes of the retina caused by diabetes were detected on the fundus oculi of 56 (30.3%) children. In 42 (22.7%)) of these, the initial changes (solitary retinal hemorrhages, microaneurysms) and in 14 (7.6%)) more pronounced micro- vascular pathological changes typical of nonproliferative diabetic retinopathy were detected, in 2 patients - the proliferative stage. Later argon coagulation of the retina was carried out in 10 patients with nonproliferative diabetic retinopathy and in 2 with proliferative diabetic retinopathy. The initial stages of nonproliferative and proliferative diabetic retinopathy are an indication for laser coagulation in children. The status of 6 (50%) children improved in remote periods (6-24 months) after laser coagulation: hemorrhages resolved and microaneurysms decreased; in 4 (33.3%) children the process was stabilized. Deterioration was observed in 2 (16. 7%o) children with nonproliferative and proliferative diabetic retinopathy.

Magnetic resonance (MR) imaging of the chest: state-of-the-art.

To date, magnetic resonance (MR) is established as an imaging modality in the diagnosis of chest diseases. Because of its excellent distinction of vessels and soft tissue, MR can be performed as the primary imaging procedure before computed tomography in patients with suspected vascular lesions, mediastinal masses, hilar lesions, and pathological changes of the pleura and the chest wall. In these cases, MR is able to provide all the necessary diagnostic information. In other patients, a limited number of MR images may be helpful in cases of equivocal or confusing CT or clinical findings. More detailed information can be obtained, using surface coils or special imaging sequences, i.e. high resolution MR images of the pleura or angiographic images of mediastinal and pulmonary vasculature. From a clinical viewpoint, the most important task for thoracic magnetic resonance nowadays is the pretherapeutic evaluation of intrathoracic masses, the differential diagnosis of benign versus malignant lesions, and the accurate documentation of tumour extent in malignancies including three-dimensional-display to improve surgical or radiation planning. Future directions in thoracic magnetic resonance will be predominantly influenced by postprocessing approaches, specialized imaging techniques, and magnetic resonance-guided interventional applications.

The effect of thalidomide treatment on vascular pathology and hyperalgesia caused by chronic constriction injury of rat nerve

Tumor necrosis factor alpha (TNF) may be involved in the pathogenic mechanisms of neuropathic pain by affecting endothelial cells and by upregulation of receptor sensitivity in afferent nerve fibers. To test the hypothesis that TNF plays a role in the vascular changes and the pain-related behavior in an experimental painful neuropathy in rats produced by tying loosely constrictive ligatures around one sciatic nerve, we investigated the effect of thalidomide, a selective blocker of TNF-production in activated macrophages. In rats in which treatment with thalidomide was started preoperatively, there was diminished mechanical allodynia and thermal hyperalgesia during the early stage of the disease. TNF immunohistochemistry revealed reduced endoneurial immunoreactivity on day 5 post surgery as compared to sham-treated animals. The pathologic vascular changes were also reduced in thalidomide-treated rats. Starting treatment with thalidomide at a time point when hyperalgesia was already present did not alter the course of the pain-related behavior. We conclude that preemptive treatment with a substance that blocks production of TNF reduces pain-related symptoms and pathologic vascular changes in the chronic constriction injury model of neuropathic pain.

Vascular disease risk factors and findings in patients with Alzheimer's disease

Vascular risk factors and data of different examinations relating to extracerebral vascular conditions were analysed in demented patients. Data of demented patients subsequently admitted to the Memory Clinic of the National Institute of Psychiatry and Neurology between March 1995 and February 1996 were registered in a specially designed data sheet. Three vascular examinations (ECG, Doppler examination of main extracerebral arteries on the neck, ophthalmoneurological examination) were carried out. The risk factors and vascular alterations were condensed in two factors. Neither the descriptive data nor the two factors showed statistically significant differences in the main groups (probable Alzheimer's disease--n=24, vascular dementia--n=23, mixed forms--n=15). Based on our results: vascular risk factors and pathological changes can occur in probable form of Alzheimer's disease; they can be present in early onset form as well; the most marked changes are in the vascular dementia group; relevant findings lack any correlation with each other in the point of severity of vascular changes. The extremely high cardio-cerebrovascular morbidity in Hungary seems to be reflected in the results. The role of vascular risk factors and (subclinical) pathological findings seem worth exploring further in Alzheimer's disease.

Vascular wall thickness in hypertension: the perindopril regression of vascular thickening European community trial: Protect

A high prevalence of increased intima/media thickness of the arterial wall has been documented in hypertension. These alterations in vascular wall structure may be potent determinants for the promotion of the development of atherosclerosis. Direct histologic data from animal models of hypertension, and indirect data from hypertensive patients, have demonstrated a marked regression of increased intima/media thickness by angiotensinconverting enzyme (ACE) inhibition. Long-term effects of ACE inhibition on structural wall changes in humans have not been examined. Therefore, a multicenter, randomized, double-blind European trial was designed to compare the effects of the ACE inhibitor perindopril and the diuretic hydrochlorothiazide in slowing or reversing progression of increased intima/media thickness of carotid and femoral arteries in hypertensive patients. A total of 800 patients at 17 clinical centers in 7 European countries, aged 35–65 years, with hypertension and ultrasonographically proven intima/media thickness ≥0.8 mm of the common carotid artery will be randomly assigned to receive in a doubleblind fashion either perindopril or hydrochlorothiazide and will be followed for 24 months. High resolution duplex sonography will be used to quantify intima/media thickness at baseline and twice a year during follow-up. A change of 0.1 mm of intima/media thickness from baseline is considered to be detectable, and the standard deviations of the changes from baseline are expected not to be higher than 0.2 mm. The primary endpoint of the study is the comparison of changes in intima/media thickness of the common carotid artery. Secondary endpoints include comparison of the effectiveness of the two treatments on left ventricular mass, posterior wall thickness, intraventricular septal thickness, left ventricular end-diastolic diameter, and comparison of the 2 treatments on ultrasonographically determined thickness of the intima/media complex of the common femoral artery. Further analyses will assess the relation between intima/ media thickness changes and the changes of blood pressure, heart rate, low and high density lipoprotein cholesterol, triglycerides, and glucose. The study is designed to assess the impact of antihypertensive therapy on early pathological vascular wall changes and to clarify whether this is due to a drug-specific action or only dependent on the blood pressure lowering effect.

Determination of blood flow in the lower leg of patients with diabetes mellitus and the effects of treatment with the principle of vitalizing blood and solubilizing thrombus

This paper reports the determination of blood flow of the lower leg in 50 cases of non-insulin dependent diabetes mellitus (NIDDM) using an XLJ-2 Bipolar Rheoencephalometry Impedance Rheogram. In patients with leg pain (but without obvious vascular pathological changes, 85 legs) the blood flow was decreased. In male patients the blood flow of the left leg (9 legs) was 3.28 +/- 0.47 ml/100ml.tissue.min (mean +/- S), while that in the right leg (11 legs) was 3.88 +/- 0.80; in females, the blood flow of the left leg (32 legs) was 2.72 +/- 0.8; while that in the right leg (33 legs) was 2.94 +/- 0.66. These figures were significantly (P less than 0.01-0.001) lower than those obtained from normals. In diabetic feet (15 painful legs) the decrease of blood flow of the lower leg was more apparent: it averaged 1.87 +/- 0.79 for the left leg (7 legs) and 2.66 +/- 0.87 for the right leg (5 legs) in male patients. The values were significantly different when compared with those of normals (P less than 0.001) or with those of the diabetic patients with leg pain (P less than 0.05). These results demonstrated that determination of the blood flow of the lower leg of diabetic patients might aid in early discovery of the abnormal changes of blood supply to the lower legs in diabetes mellitus and judge the degree of ischemia. Of the 50 cases of diabetics 32 were Qi-Yin deficiency with blood stasis while the remaining 18 cases were deficiency of both Yin and Yang with blood stasis.(ABSTRACT TRUNCATED AT 250 WORDS)

A new model of radiation-induced myelopathy: A comparison of the response of mature and immature pigs

Purpose : The development of an experimental model of radiation-induced myelopathy in the pig which would facilitate the study of the effects of clinically relevant treatment volumes. Methods and Materials : The effects of local spinal cord irradiation, to a standard 10 × 5 cm field, have been evaluated in mature (37–42.5 weeks) and immature (15.5–23 weeks) pigs. Irradiation was with single doses of 60Co γ-rays at a dose-rate of 0.21–0.65 Gy/min. The incidence of paralysis was used as an endpoint. Results : Irradiation of mature animals resulted in the development of frank paralysis with animals showing combined parenchymal and vascular pathologic changes in their white matter. These lesions, in common with those seen in patients, had a clear evidence of an inflammatory component. The latency for paralysis was short, 7.5–16.5 weeks, but within the wide range reported for patients. However, it was shorter than that reported in other large animal models. The ED 50 value (± SE) for paralysis was 27.02 ± 0.36 Gy, similar to that in rats taking into account doserate factors. The irradiation of immature pigs only resulted in transient neurological changes after doses comparable to those used in the mature animals, ED 50 value (± SE) 26.09 ± 0.37 Gy. The reasons for these transient neurological symptoms are uncertain. Conclusion : A reliable experimental model of radiation-induced myelopathy has been developed for mature pigs. This model is suitable for the study of clinically relevant volume effects.

Vascular wall thickness in hypertension

A high prevalence of increased intima/media thickness of the arterial wall has been documented in hypertension. These alterations in vascular wall structure may be potent determinants for the promotion of the development of atherosclerosis. Direct histologic data from animal models of hypertension, and indirect data from hypertensive patients, have demonstrated a marked regression of increased intima/media thickness by angiotensinconverting enzyme (ACE) inhibition. long-term effects of ACE inhibition on structural wall changes in humans have not been examined. Therefore, a multicenter, randomized, double-blind European trial was designed to compare the effects of the ACE inhibitor perindopril and the diuretic hydrochlorothiazide in slowing or reversing progression of increased intima/media thickness of carotid and femoral arteries in hypertensive patients. A total of 800 patients at 17 clinical centers in 7 European countries, aged 35-65 years, with hypertension and ultrasonographically proven intima/media thickness ~0.8 mm of the common carotid artery will be randomly assigned to receive in a doubleblind fashion either perindopril or hydrochlorothiazide and will be followed for 24 months. High resolution duplex sonography will be used to quantify intima/media thickness at baseline and twice a year during follow-up. A change of 0.1 mm of intima/media thickness from baseline is considered to be detectable, and the standard deviations of the changes from baseline are expected not to be higher than 0.2 mm. The primary endpoint of the study is the comparison of changes in intima/media thickness of the common carotid artery. Secondary endpoints include comparison of the effectiveness of the two treatments on left ventricular mass, posteriorwall thickness, intraventricular septal thickness, left ventricular end-diastolic diameter, and comparisonof the 2 treatments on ultrasonographitally determined thickness of the intima/media complex of the common femoral artery. Further analyses will assess the relation between intima/ media thickness changes and the changes of blood pressure, heart rate, low and high density lipoprotein cholesterol, triglycerides, and glucose. The study is designed to assess the impact of antihypertensive therapy on early pathological vascular wall changes and to clarify whether this is due to a drug-specific action or only dependent on the blood pressure lowering effect. (Am J Cardioll995; 7650E64E)