High Risk Of Cerebral Hemorrhage Research Articles

Probucol will become a New Model for Treating Cerebral Infarction with a High Risk of Hemorrhage.

Antiplatelet, antihypertensive, and lipid-lowering agents are the three foundational agents for secondary prevention of ischemic stroke, among which lipid-lowering is one of the most important cornerstones. Probucol is a potent antioxidative lipid-lowering drug used to prevent and treat atherosclerotic cardiovascular diseases and xanthomas. However, it has faded from Western markets by lowering LDL-C and HDL-C levels. Probucol alleviates atherosclerosis improving high-density lipoprotein function, and does not increase the risk of cardiovascular events. Probucol-induced pharmacological changes in HDL-C may not be a reliable prognostic marker for cardiovascular risk. Q-T interval prolongation is a rare adverse reaction as described in the manufacturer's instructions, but prolonged Q-T interval may only be an intermediate pharmacological phenomenon of electrophysiological changes, and as a result, probucol has a strong benefit for secondary prevention of cardiovascular events and can reduce mortality without increasing the risk of cardiovascular and cerebrovascular adverse events. The new mechanism is that probucol penetrates the core of lowdensity lipoprotein particles, enhancing the activity of plasma cholesteryl ester transfer protein and liver scavenger receptor type I activity, thereby reducing LDH; at the same time, increasing the activity of paraoxonase 1, strengthened the antioxidant function of HDL, and reduced the serum HDL-C. If clinical or imaging findings suggest a high risk of recurrence of cerebral ischemia with a high risk of cerebral hemorrhage, probucol may be selected for prevention. This article focuses on basic research and clinical evidence and provides new insights into the low bioavailability.

Elevated Pulse Pressure and Recurrent Hemorrhagic Stroke Risk in Stroke With Cerebral Microbleeds or Intracerebral Hemorrhage.

Background Which type of recurrent stroke is associated with pulse pressure (PP) remains uncertain in ischemic stroke with cerebral microbleeds or intracerebral hemorrhage. Methods and Results The PICASSO (Prevention of Cardiovascular Events in Ischemic Stroke Patients With High Risk of Cerebral Hemorrhage) database involving 1454 subjects was analyzed. Subjects were stratified into quartiles according to the distribution of mean PP (mmHg) during follow-up (mean, 1.9years): <47 (first quartile), 48 to 53 (second quartile), 54 to 59 (third quartile), and ≥60mmHg (fourth quartile). The primary end point was hemorrhagic stroke, and the secondary end points were ischemic stroke, stroke of any type, and major adverse cardiovascular events. Adjusted time-dependent area under the receiver operating characteristic curve analysis was performed to assess the prediction accuracy of mean PP. The mean frequency of visit for blood pressure checkup was 9.4±5.5 times. The stroke incidence rate per 100 person-years was 3.14, 2.24, 5.52, and 6.22, respectively in increasing quartile of mean PP, and the rate of major adverse cardiovascular events was 3.82, 2.84, 6.37, and 7.14, respectively. In the presence of mean arterial pressure, hemorrhagic stroke risk was higher in the highest quartile (adjusted hazard ratio, 6.03; 95% CI, 1.04-34.99) versus the lowest quartile, which was evident at higher mean systolic blood pressure. Higher mean PP as a continuous variable was also a predictor of hemorrhagic stroke (1.09, 1.03-1.15). The time-dependent area under the receiver operating characteristic curve for hemorrhagic stroke was 0.79. Conclusions Long-term elevated PP with higher systolic blood pressure confers a greater risk of subsequent hemorrhagic stroke among stroke patients with cerebral microbleeds or intracerebral hemorrhage. Registration URL: https://www.clinicaltrials.gov; Unique identifier, NCT01013532.

Newly diagnosed diabetes has high risk for cardiovascular outcome in ischemic stroke patients

We investigated cardiovascular outcomes in ischemic stroke patients with newly diagnosed diabetes mellitus (DM) compared with those of patients with previously known DM and no DM using the glycosylated hemoglobin (HbA1c) criteria. The relationship between new DM diagnosis and cardiovascular risk remains unclear to date. We performed post hoc analysis using the data of participants from the Prevention of Cardiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage (PICASSO) trial. Newly diagnosed DM was defined as HbA1c of ≥ 6.5% without known DM history. The outcome was the incidence of composite cardiovascular events, including stroke (ischemic and hemorrhagic), myocardial infarction, and cardiovascular death. In total, 1306 patients were included; 38 patients (2.9%) had newly diagnosed DM; 438 patients (33.5%), known DM; and 830 patients (63.6%), no DM. In patients with newly diagnosed DM, known DM, and no DM, the incidence of ischemic stroke was 8.93, 3.79, and 2.64 per 100 person-years (log-rank test; p = 0.0092), while that of composite cardiovascular events was 8.93, 5.92, and 3.87 per 100 person-years (p = 0.025), respectively. Newly diagnosed DM was an important risk factor for ischemic stroke and composite cardiovascular events after ischemic stroke.Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01013532.

Post-stroke cognitive impairment as an independent predictor of ischemic stroke recurrence: PICASSO sub-study.

To devise appropriate preventive strategies after stroke, knowledge of the association between post-stroke cognitive impairment (PSCI) and prognosis of stroke patients is important. We investigated the association between PSCI and the vascular outcomes in patients with ischemic stroke with best medical care considering their risk factors and adherence to medications. Of the 1534 ischemic stroke patients who randomly assigned to aspirin or cilostazol treatment with best medical therapy by the PICASSO (PreventIon of CArdiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage) trial, 1240 with baseline mini-mental state examination (MMSE) scores were analysed retrospectively. The patients were classified into three groups based on MMSE scores. Recurrence of ischemic stroke, stroke of any type and composite of major vascular events were compared among them. Of the 1240 patients, 376 had MMSE scores of 28-30 (highest tertile), 419 had scores of 24-27 (middle tertile) and 445 had scores of 0-23 (lowest tertile). The average time from stroke onset to MMSE examination was 31.8days. By trend analysis, lower tertile of MMSE score was significantly associated with recurrent ischemic stroke (p = 0.0017), stroke of any type (p = 0.0053) and composite vascular outcome (p = 0.0122). After adjustment for covariates, PSCI was independently associated with risk of recurrent ischemic stroke (HR 2.40, 95% confidence interval 1.12-5.14). Cognitive impairment was associated with recurrence of ischemic stroke in high risk patients during adequate medical therapy including antiplatelet therapy. However, the other vascular events were not.

White matter hyperintensities and recurrent stroke risk in patients with stroke with small-vessel disease.

White matter hyperintensities (WMH) are a predictor of stroke among elderly individuals. This study aimed to evaluate the association between WMH severity and the risk of recurrent vascular events among Asian patients with ischaemic stroke with small-vessel disease (SVD) including micro/macrobleeds and lacunes. Data from participants (n=1454) in the PICASSO (PreventIon of CArdiovascular Events in iSchemic Stroke Patients with High Risk of Cerebral HemOrrhage) trial were reviewed. The severity of WMH in baseline brain magnetic resonance imaging scans was assessed using the Fazekas scale. The association between WMH severity and stroke (ischaemic or hemorrhagic) and major vascular events (MVEs) (a composite of stroke/myocardial infarction/vascular death) was assessed. Study patients had a significant burden of SVD: Fazekas score 0 (n=2), 1 (n=426), 2 (n=650) and 3 (n=376) [median Fazekas score 2 (mean follow-up, 1.9 ± 1.3 years)]. The stroke incidence rate per 100 personyears was 2.6 in the Fazekas 0-1 group, 3.6 in the Fazekas 2 group and 7.0 in the Fazekas 3 group, and the rates for MVEs were 3.3, 4.3 and 7.6, respectively. Compared with the Fazekas 0-1 group, the Fazekas 3 group was associated with a higher risk of stroke [adjusted hazard ratio (HR), 2.15; 95% confidence interval (CI), 1.19-3.88; P=0.011], ischaemic stroke (adjusted HR, 2.11; 95% CI, 1.07-4.15; P=0.031), hemorrhagic stroke (adjusted HR, 3.72; 95% CI, 1.09-12.70; P=0.036) and MVEs (adjusted HR, 2.09; 95% CI, 1.20-3.66; P=0.010). Advanced WMH in Asian patients with ischaemic stroke with SVD burden was associated with an increased risk of recurrent vascular events. It may exert an effect as a prognostic indicator in high risk of recurrent vascular events.

Design and Rationale of the Intima-Medial Thickness Sub-Study of the PreventIon of CArdiovascular Events in iSchemic Stroke Patients with High Risk of Cerebral hemOrrhage (PICASSO-IMT) Study

Atherosclerosis is one of the main mechanisms of stroke and cardiovascular diseases and is associated with increased risk of recurrent stroke and cardiovascular events. Intima-medial thickness (IMT) is a well-known surrogate marker of atherosclerosis and has been used to predict stroke and cardiovascular events. However, the clinical significance of IMT and IMT change in stroke has not been investigated in well-designed studies. The PreventIon of CArdiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage-Intima-Media Thickness (PICASSO-IMT) sub-study is designed to investigate the effects of cilostazol, probucol, or both on IMT in patients with stroke. PICASSO-IMT is a prospective sub-study of the PICASSO study designed to measure IMT and plaque score at 1, 13, 25, 37, and 49 months after randomization. The primary outcome is the change in mean carotid IMT, which is defined as the mean of the far-wall IMTs of the right and left common carotid arteries, between baseline and 13 months after randomization. PICASSO-IMT will provide the largest IMT data set in a stroke population and will provide valuable information about the clinical significance of IMT in patients with ischemic stroke.

REDUCING COGNITIVE DECLINE WITH PROBUCOL IN ISCHEMIC STROKE PATIENTS WITH HIGH RISK OF CEREBRAL HEMORRHAGE: PICASSO-COG TRIAL

Multiple cerebral microbleeds (CMBs) and prior intracerebral hemorrhage (ICH) are associated with higher risk of cognitive decline after stroke. We aimed to investigate the efficacy of probucol, a lipid-lowering and anti-oxidative agent, to prevent cognitive decline in stroke patients with multiple CMBs or prior ICH. PICASSO-Cog study is a predefined substudy of a randomized controlled clinical trial, PreventIon of CArdiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage (PICASSO). Patients with non-cardioembolic ischemic stroke or transient ischemic attack within 180 days and with previous ICH or multiple CMBs on gradient echo imaging were randomized to probucol versus no probucol groups from 61 institutes of South Korea. Mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) was conducted at 4 (baseline), 13, 25, 37, and 49 months after index-stroke. Changes in MMSE and MoCA scores over time from baseline were analyzed using mixed effects model. A total 892 subjects were included in the analysis, with a median follow-up of 20.9 months. Mean age was 64.9 ± 10.8 years, median National Institute of Health Stroke Scale score 1 (IQR 0 - 3), and baseline MMSE score 25.0 ± 4.6. Mean changes of MMSE from baseline to each follow-up was 0.02±2.45 (1st, n=888), -0.15±2.65 (2nd, n=593), -0.24±3.11 (3rd, n=361), and -0.88±3.06 (4th, n=138). The MMSE scores over time showed a favorable trend for probucol treatment, but not significant. Among them, a total of 877 subjects underwent MoCA at least twice after randomization. Baseline MoCA score 19.3 ± 6.2, and mean changes of MoCA from baseline to each follow-up was 0.02 ± 2.83 (1st, n=871), -0.20 ± 3.17 (2nd, n=582), -0.09 ± 3.59 (3rd, n=354), and -0.52 ± 3.49 (4th, n=132). Probucol could significantly prevent cognitive decline in MoCA scores compared to placebo (p=0.01 for treatment effect). These effects were observed in the subgroups without diabetes mellitus, with concomitant lipid-lowering agent, baseline MMSE score > 24, and mild to moderate white matter hyperintensities.

Design and Rationale for a Cognitive Outcome Substudy in Ischemic Stroke Patients with High Risk of Cerebral Hemorrhage

Cognitive impairment and dementia are common disabilities after stroke and are associated with increased risks of mortality and recurrent stroke. The prevention of dementia and preserving cognitive function are also important in stroke patients, but its strategy is not established yet. This PICASSO-COG (PreventIon of CArdiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage for reducing COGnitive decline) substudy aims to assess the effects of cilostazol and/or probucol on cognitive function. The substudy aims to assess the reduction in cognitive decline of patients treated with cilostazol and/or probucol in the PICASSO trial. Patients will be assessed using the Korean version of mini-mental state examination and Montreal Cognitive Assessment at 4, 7, 10, 13, 25, 37, and 49 months after randomization. The primary outcome is the change in mini-mental status examination score, compared between treatment groups, with a modified intention-to-treat population using a restricted maximum likelihood-based mixed effects model repeat measurement. This will allow a within-subject correlation due to repeated cognitive tests as well as a different number of measurements among subjects at baseline and each follow-up period. PICASSO-COG is a novel study for assessing the effect on cognitive function of different antiplatelet regimens and the addition of a nonstatin lipid-lowering agent to the current standard statin therapy in patients who have a recent ischemic lesion and prior intracerebral macro- or microbleeds.

Successful Semi-Ambulatory Veno-Arterial Extracorporeal Membrane Oxygenation Bridge to Heart–Lung Transplantation in a Very Small Child

Lung transplantation (LTx) may be denied for children on extracorporeal membrane oxygenation (ECMO) due to high risk of cerebral hemorrhage. Rarely has successful LTx been reported in children over 10 years of age receiving awake or ambulatory veno-venous ECMO. LTx following support with ambulatory veno-arterial ECMO (VA ECMO) in children has never been reported to our knowledge. We present the case of a 4-year-old, 12-kg child with heritable pulmonary artery hypertension and refractory right ventricular failure. She was successfully bridged to heart-lung transplantation (HLTx) using ambulatory VA ECMO. Initial resuscitation with standard VA ECMO was converted to an ambulatory circuit using Berlin heart cannulae. She was extubated and ambulating around her bed while on VA ECMO for 40 days. She received an HLTx from an oversized marginal lung donor. Despite a cardiac arrest and Grade 3 primary graft dysfunction, she made a full recovery without neurological deficits. She achieved 104% force expiratory volume in 1 s 33 months post-HLTx. Ambulatory VA ECMO may be a useful strategy to bridge very young children to LTx or HLTx. Patient tailored ECMO cannulation, minimization of hemorrhage, and thrombosis risks while on ECMO contributed to a successful HLTx in our patient.

Rationale and design of the PreventIon of CArdiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage (PICASSO) study: A randomized controlled trial.

Prior intracerebral haemorrhage and cerebral microbleeds may increase the risk of haemorrhagic stroke. However, the optimal long-term antiplatelet therapy and lipid management in these patients remain unclear. PreventIon of CArdiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage was designed to compare cilostazol and aspirin and to assess the effect of adding probucol, a lipid-lowering and anti-oxidative agent, in patients at high risk of haemorrhagic stroke. The projected sample size is 1600 patients with at least 12 months of follow-up. PreventIon of CArdiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage is a randomized trial involving 67 institutes from 3 countries. Patients with non-cardioembolic ischemic stroke or transient ischemic attack within 180 days and with prior intracerebral haemorrhage or multiple cerebral microbleeds on gradient echo imaging are eligible. Enrolled patients are simultaneously randomized in a 2 × 2 factorial design: double-blind for cilostazol 200 mg/day vs. aspirin 100 mg/day, and an open-label, blind end-point evaluation for probucol 500 mg/day vs. non-probucol. The co-primary end-points are the safety end-point of haemorrhagic stroke and the efficacy end-point of a composite of stroke, myocardial infarction, or vascular death. Time-to-event will be analyzed separately for each intervention: superiority testing for the safety of cilostazol over aspirin as well as the efficacy of probucol over non-probucol, and non-inferiority testing for the efficacy of cilostazol to aspirin. PreventIon of CArdiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage is the largest secondary stroke prevention trial for informing antiplatelet therapy and lipid management in patients at high risk of haemorrhagic stroke.

Cerebral amyloid angiopathy-associated intracerebral hemorrhage in the very elderly: clinical manifestations, diagnosis and treatment

Objective To analyze the clinical manifestations, diagnosis and treatment of cerebral amyloid angiopathy (CAA)-associated intracerebral hemorrhage. Methods The clinical manifestations, treatment and prognosis of CAA-associated intracerebral hemorrhage were analyzed in 4 patients who were identified as CAA-related hemorrhage (CAAH) by pathology. Results All of the 4 patients showed massive lobar intracranial hemorrhage, and underwent craniotomy evacuation of hematoma. One patient had postoperative hemorrhage, and 2 patients were treated with recombinant activated factor VII after operation. In the next 6 months, re-hemorrhage was found in 3 patients in whom one patient died due to massive hemorrhage. Conclusions CAAH has varied clinical manifestations with high risk of cerebral hemorrhage, and pathological diagnosis is necessary for a definite diagnosis. The very elderly patients with CAAH can benefit from the craniotomy evacuation of hematoma. Although surgery for massive hemorrhage has risks in very elderly patients, it is a better treatment to save their lives. Key words: Cerebral amyloid angiopathy; Cerebral hemorrhage

Assessment of Degree of Anticoagulation Control in Patients With Atrial Fibrillation in Primary Health Care in Galicia, Spain: ANFAGAL Study

Introduction and objectivesTo determine the degree of control of patients on anticoagulants in follow-up in primary care in Galicia and investigate whether time in therapeutic range as estimated using the number of acceptable controls is comparable with the estimation using the Rosendaal method. MethodsTransversal study that included patients older than 65 years, diagnosed with nonvalvular atrial fibrillation, on anticoagulants for at least 1 year. Control was considered good when the time in therapeutic range was greater than 65%, estimated by the Rosendaal method, or 60% estimated by the number of acceptable controls. ResultsWe enrolled 511 patients (53.0% women; mean [standard deviation] age, 77.8 [0.6] years). Overall, 41.5% of the patients were in therapeutic range at fewer than 60% of the controls and 42.7% spent less than 65% of follow-up in therapeutic range, as estimated with the Rosendaal method. In the group of patients with poor control, we observed more drugs (6.8 [0.4] vs 5.7 [0.3]; P<.0001), greater presence of kidney disease (24.3% vs 17.0%; P=.05), and higher HAS-BLED scores (3.8 [0.1] vs 2.5 [0.1]; P<.0001). The cutoff of 60% for number of acceptable controls had a sensitivity and specificity of 79.4% and 86.7%, respectively, with an area under the curve of 0.92 (95%CI, 0.87-0.97). ConclusionsMore than 40% of patients on anticoagulants do not reach the minimum time in therapeutic range to benefit from anticoagulation. The factors associated with worse control were kidney disease and high risk of cerebral hemorrhage. The 2 methods of estimation are comparable.

Evaluación del grado de anticoagulación de pacientes con fibrilación auricular en el ámbito de atención primaria de Galicia. Estudio ANFAGAL

Introduction and objectivesTo determine the degree of control of patients on anticoagulants in follow-up in primary care in Galicia and investigate whether time in therapeutic range as estimated using the number of acceptable controls is comparable with the estimation using the Rosendaal method. MethodsTransversal study that included patients older than 65 years, diagnosed with nonvalvular atrial fibrillation, on anticoagulants for at least 1 year. Control was considered good when the time in therapeutic range was greater than 65%, estimated by the Rosendaal method, or 60% estimated by the number of acceptable controls. ResultsWe enrolled 511 patients (53.0% women; mean [standard deviation] age, 77.8 [0.6] years). Overall, 41.5% of the patients were in therapeutic range at fewer than 60% of the controls and 42.7% spent less than 65% of follow-up in therapeutic range, as estimated with the Rosendaal method. In the group of patients with poor control, we observed more drugs (6.8 [0.4] vs 5.7 [0.3]; P<.0001), greater presence of kidney disease (24.3% vs 17.0%; P=.05), and higher HAS-BLED scores (3.8 [0.1] vs 2.5 [0.1]; P<.0001). The cutoff of 60% for number of acceptable controls had a sensitivity and specificity of 79.4% and 86.7%, respectively, with an area under the curve of 0.92 (95%CI, 0.87-0.97). ConclusionsMore than 40% of patients on anticoagulants do not reach the minimum time in therapeutic range to benefit from anticoagulation. The factors associated with worse control were kidney disease and high risk of cerebral hemorrhage. The 2 methods of estimation are comparable.Full English text available from:www.revespcardiol.org/en

Safety and Efficacy of Tirofiban in Stent-Assisted Coil Embolization of Intracranial Aneurysms

Thromboembolic complications are a major concern in stent-assisted coiling of intracranial aneurysms that may be prevented with adequate antiplatelet therapy. To assess the safety and efficacy of tirofiban in stent-assisted coiling. Two protocols were used. In the initial protocol, tirofiban was administered intravenously as a 0.4 μg/kg per min bolus for 30 minutes followed by 0.10 μg·kg min maintenance infusion. The revised protocol consisted of a 0.10 μg·kg min maintenance infusion alone. Sixty-seven patients received tirofiban, 16 under the initial protocol and 51 under the revised protocol. Thirty (44.8%) patients had sustained a subarachnoid hemorrhage (SAH). Tirofiban infusion was initiated after thromboembolic events in 9 (13.4%) patients and prophylactically in 58 (86.6%). Four (6.0%) intracranial hemorrhages were noted. Three (18.8%) intracranial hemorrhages occurred with the initial protocol in patients treated electively and were fatal in 2 (66.7%) cases. The only complication (1.9%) under the revised protocol was a subclinical worsening of the computed tomographic appearance of an SAH. There was no tirofiban-related morbidity or deaths with the revised protocol. Of 9 patients that received tirofiban as a rescue treatment, 7 (77.8%) had complete and 2 (22.2%) had partial arterial recanalization. No thromboembolic events occurred in patients receiving prophylactic tirofiban. A bolus followed by a maintenance dose of tirofiban appears to have a high risk of cerebral hemorrhage. A maintenance infusion without an initial bolus, however, has an exceedingly low risk of hemorrhage and appears to be very safe and effective, even in the setting of SAH.

Cerebral Microbleeds in Patients with Moyamoya-like Vessels Secondary to Atherosclerosis

Hemorrhagic risk is unknown in patients with moyamoya-like vessels associated with atherosclerotic intracranial cerebral artery occlusion. This study was undertaken to investigate the association between moyamoya-like vessels and cerebral microbleeds (CMBs) in patients with atherosclerotic steno-occlusive disease. The study population comprised 34 patients with steno-occlusive lesions in the intracranial cerebral artery caused by atherosclerosis. We evaluated the presence of moyamoya-like vessels at the base of the brain by cerebral angiography, and the presence of CMBs by T2*-weighted MRI. Patients were divided into 2 groups: those with and those without moyamoya-like vessels; clinical histories and the incidence of CMBs were compared between the groups. Sixteen patients had moyamoya-like vessels. Twelve of 16 patients with moyamoya-like vessels had a history of ischemic stroke or transient ischemic attack, whereas only 1 patient had a history of symptomatic cerebral hemorrhage. The incidence of CMBs did not differ between the 2 groups (31% vs. 28%, p=0.82). The location of CMBs varied and was not associated with the site of moyamoya-like vessels. CMBs were not associated with moyamoya-like vessels in patients with atherosclerotic cerebral artery occlusion. These patients may not have a high risk of cerebral hemorrhage.

Evidence for high risk of cerebral hemorrhage in chronic dialysis patients

One-half of the total deaths in chronic dialysis patients are due to cardiovascular disease; however, the precise incidence and relative risk of those compared to normals are not known. Therefore, we sought to determine the annual incidence of cardiovascular disease and relative risk of those on chronic dialysis to the general population. Both the general population (1.2 million, Census 1990) and chronic dialysis patients (N = 1,609) in Okinawa, Japan were studied prospectively from April, 1988, to March, 1991. Diagnosis of stroke was made by symptoms and brain CT scan, and acute myocardial infarction was done by changes in electrocardiogram and serum enzymes. The relative risk (observed/expected ratio) was calculated by using the standardized morbidity rate obtained in both sexes and age-class every 10 years in the general population. Forty-one stroke (8 cerebral infarction, 31 cerebral hemorrhage, and 2 subarachnoid hemorrhage) and four acute myocardial infarction cases were registered during the study period in chronic dialysis patients. The incidence per 1,000 person-year was 11.5 in stroke, 2.2 in cerebral infarction, 8.7 in cerebral hemorrhage, 0.6 in subarachnoid hemorrhage, and 1.1 in acute myocardial infarction. The relative risk compared to normals was 5.2 in stroke, 2.0 in cerebral infarction, 10.7 in cerebral hemorrhage, 4.0 in subarachnoid hemorrhage, and 2.1 in acute myocardial infarction. Cerebral hemorrhage occurred at 10 years younger than that of the general population (P < 0.001) and was associated with high prevalence of hypertension and low levels of serum albumin and cholesterol. Our results confirm the importance of blood pressure control and nutritional status in chronic dialysis patients.

Arterial disease of the iris predicts visceral arterial necrosis in rabbits with acute one-kidney, one clip hypertension: comparisons with acute one-kidney, one wrapped hypertension

Tortuosity, dilations, aneurysms and satellite hemorrhages consistently develop in the circular arteries of the iris of rabbits with acute one-kidney, one clip (1K1C) malignant hypertension. These lesions are easily visualized, quantitated and monitored during life. Graded iridoarteriopathy correlates directly with visceral arterial necrosis (r15 = 0.843; P less than 0.001), final indirect blood pressure (r15 = 0.591; P less than 0.02) and cardiac hypertrophy (r15 = 0.565; P less than 0.02). Arterial necrosis in the irises and other viscera in acute 1K1C hypertension in rabbits is qualitatively similar to that occurring in rabbits with acute one-kidney, one wrapped (1K1W) hypertension with regard to both the histological features and organ distribution. However, over three times as many arterial lesions occur in rabbits with acute 1K1W hypertension as occur in those with acute 1K1C hypertension (P less than 0.001). Since blood pressure elevation does not correlate with graded iridoarteriopathy or with visceral arterial necrosis in 1K1W rabbits, factors other than blood pressure elevation appear to be especially important in the pathogenesis of arterial necrosis in the 1K1W model. On the other hand, the present study indicates that high grade iridoarteriopathy appears to be indicative of a high risk of cerebral hemorrhage in 1K1C rabbits, as earlier studies have shown for 1K1W rabbits.

Concurrence of iris aneurysms and cerebral hemorrhage in hypertensive rabbits.

The development of miliary aneurysms of the iris is associated with the high risk of cerebral hemorrhage in rabbits with renal hypertension. The high-risk group of hypertensive rabbits in this series was characterized by the formation of iris aneurysms, and this group developed a striking proportion of hemorrhagic strokes (42.5%). In the low-risk group of hypertensive rabbits that did not develop aneurysms of the iris, only a low proportion of cerebral hemorrhages were found (11%). The development of iris aneurysms in rabbits was directly proportional to increments in level of blood pressure, and their rate of formation was very rapid. The formation of miliary aneurysms of the circular artery of the iris in hypertensive rabbits is likely related to the common embryologic origin and the morphologic similarity between perforating arteries of the brain and the principal arterial vessel of the iris.