Multiple Vascular Risk Factors Research Articles

Should the MATCH Results Be Extrapolated to All Stroke Patients and Affect Ongoing Trials Evaluating Clopidogrel Plus Aspirin?

Aspirin alone reduces the risk of recurrent stroke, myocardial infarction (MI), and vascular death by only 13%.1 Clopidogrel was 8% better than aspirin in the CAPRIE trial and was safer with less gastrointestinal bleeding complications.2 For these reasons, clinicians anticipated that the combination of clopidogrel and aspirin would be more effective than either drug alone with the hypothesis that bleeding complications would be only modestly increased. Accordingly, many stroke patients were switched to this combination of therapy, mainly in case of recurrent stroke while on a single antiplatelet agent and in patients with high vascular risk. The results of trials showing the efficacy and tolerance of such an approach after percutaneous coronary intervention was reassuring.3 However, the long-term major bleeding complication rate was unknown except in patients with unstable angina and non-Q wave MI,4 and the net benefit in stroke patients was hypothetical.5 ### The MATCH Trial For this reason, the combination therapy had to be tested for safety and efficacy in a stroke population, and this was the purpose of the MATCH trial.6 MATCH was a secondary prevention trial in patients with ischemic stroke or brain infarction with transient ischemic attack within 3 months of randomization and with 1 of the following entry criteria: diabetes mellitus, past coronary heart disease, recurrent stroke on aspirin, peripheral arterial disease. Aspirin (A) was tested against placebo on the background of clopidogrel (C) in both arms. So it was C+A versus C. As a consequence of the entry criteria stipulating the presence of multiple vascular risk factors, the MATCH population included 70% diabetic subjects, 54% with lacunar stroke (small vessel disease) plus 10% strokes of unknown cause (both at low risk for recurrence). Only 30% of patients had large artery atherosclerotic disease. Few patients (5%) had a past history of coronary …

Dynamic body tilt in internuclear ophthalmoplegia and one-and-a-half syndrome

We report five patients presenting acutely because of diplopia and lateropulsion. Four had internuclear ophthalmoplegia and the fifth, one-and-a-half syndrome. In addition, they presented with a peculiar sign, called lateropulsion, which is a slow falling down to the side in a roll plane when sitting, standing, or walking. All five patients were adults, the first three having a history of multiple vascular risk factors. Brain CT showed a mesencephalic infarct in one patient and no pathology in the rest. Brain MRI in one patient did not show any lesion in the pontomesencephalic area. Clinically, the neuro-ophthalmological constellation of these patients pointed to tegmental medial pontomesencephalic lesions, which were associated with a dynamic lateral body tilt accompanying the oculomotor signs. In all five patients, the body tilt was contralateral (contraversive) to the clinical brainstem lesion. Their recovery was good in the short term, with improvement in the body tilt and eye movements. We suggest that body tilt in the lateral (coronal) plane could be due to a graviceptive dysfunction, occurring in the medial longitudinal fasciculus or in its surrounding structures. The body tilt observed in these patients is phenomenologically identical to that observed in acute unilateral peripheral vestibulopathy.

Multiple modifiable risk factors for first ischemic stroke: a population-based epidemiological study.

The aims of this epidemiological population-based cohort study were to examine the prevalence of the multiple modifiable vascular risk factors, their distribution patterns and outcomes among a Bulgarian urban population. A total of 500 volunteers, 200 men and 300 women, without clinical signs and symptoms of cerebrovascular disease, aged 50-79 years, were enrolled in the study. A structured questionnaire, physical examination, electrocardiogram records, a battery of laboratory tests and carotid duplex scanning were employed. Three or more modifiable vascular risk factors were detected in 52% (260/500) of the subjects. Dyslipidemias, hypertension, obesity, cigarette smoking and cardiac diseases were found to be the most prevalent single risk factors. Asymptomatic carotid stenosis (ACS) of 50% or greater was detected in 8.8% (23/260) of the volunteers examined. After a 2-year follow-up, 2.7% (7/260) of the persons with modifiable vascular risk factors reached the end point transient ischemic attacks (TIAs), ischemic stroke and myocardial infarction. The following combinations of risk factors among the subjects enrolled in the study were significantly associated with these outcomes: hypertension and cardiac diseases (OR = 6.82; 95% CI, 1.21-38.41), cardiac diseases and obesity (OR = 6.13; 95% CI, 1.27-29.72), ACS and high low-density lipoprotein (LDL) cholesterol levels (OR = 11.11; 95% CI, 1.58-78.29). The identification of subjects with multiple vascular risk factors may be important for primary medical or surgical stroke prevention.

Asymptomatic occlusion of the main trunk of the middle cerebral artery

An asymptomatic occlusion of the main branch of the middle cerebral artery (MCA) was diagnosed in a 53-year-old man with multiple vascular risk factors on digital substraction angiography. Repeat digital substraction angiography 31 months later confirmed the occlusion. A lacunar infarct in the right pallidum was seen on MRI, while the occlusion remained clinically silent. To the best of our knowledge, this report constituted the first description of a clinically silent, probably atherosclerotic MCA main branch occlusion.

Abnormalities of cerebral white matter and stroke risk in the Framingham Offspring Study

P131 Background: MRI Abnormalities of cerebral white matter (WMH) are associated with multiple cerebral vascular risk factors, such as hypertension. The association between WMH and risk for stroke, however, has been investigated only in a limited fashion. The Framingham stroke risk profile (FSRP), based on information from the original Framingham Study Cohort (FHS), has been shown to estimate age- and gender specific probability of stroke in a number of populations. To test the utility of WMH to predict future stroke, we related the FSRP to WMH in 909 offspring of the original FHS (FHS o ) who were free of clinical stroke. Methods: Quantification of MRI WMH was performed in the years 1999–2000 on 919 individuals of the FHS o who had taken Exam 5 during 1991–95 when they were ages 35–74 (mean age 55 ±9 years). None were demented. Data from 10 individuals with prior stroke were excluded. FSRP was computed using Exam 5 risk factor data. Using linear regression, age-related differences in WMH volume, corrected for differences in head size, were computed. WMH volumes >1 sd above the age-predicted mean were considered large. Analyses employed T-test comparison according to WMH category (large vs normal) as well as multiple logistic regression analysis to predict category. Results: 43 individuals (4.7%) were identified as having large volumes of WMH. These individuals had significantly higher SBP (132 ±19 mmHg vs 124 ±18 mmHg; p=0.003) and significantly higher FSRP (0.070 ±0.057 versus 0.040 ±0.043; p=0.002) at Exam 5. Using logistic regression, the odds of having large WMH volumes increased by 1.26 (95% CL 1.08–1.48; p=0.004) for each 10mmHg increase of SBP and 1.09 (95% CL 1.05–1.14; p=0.001) for each 1% increase in FSRP. Analysis by gender showed a similar pattern although SBP did not reach statistical significance for WMH in women (128.4 +19.1 versus 121.7 +18.7, p=0.068). Conclusion: Large WMH are seen in men and women with previously measured, significantly increased predicted stroke risk. Further prospective evaluation will be important to determine if the extent of WMH is a predictor of risk for stroke as suggested by the increased values of FSRP amongst those with large WMH.

Activated Polymorphonuclear Leukocytes and Monocytes in the Peripheral Blood of Patients with Ischemic Heart and Brain Conditions Correspond to the Presence of Multiple Risk Factors for Atherothrombosis

Objective: Risk factors like hypertension, diabetes mellitus, dyslipidemia and smoking contribute to the pathogenesis of atherothrombosis. We investigated whether the multiplicity of risk factors for atherothrombosis is associated with leukocyte activation. Methods: We examined the availability of CD11b/CD18 antigen on the surface of peripheral blood polymorphonuclear leukocytes and monocytes in patients with acute ischemic heart and brain conditions. Results: There was a highly significant (p < 0.00001) increment in the availability of the CD11b/CD18 antigen on the surface of the polymorphonuclear leukocytes in patients with multiple (2 or more) vascular risk factors [mean fluorescence intensity (MFI) ± SD, 210 ± 102] as opposed to individuals with none or 1 risk factor for atherothrombosis (MFI 159 ± 73). Similar results were observed on the monocytes: 309 ± 151 and 235 ± 97, respectively (p < 0.00001). Conclusion: The multiplicity of risk factors for atherothrombosis is associated with the up-regulation of CD11b/CD18 antigen on the surface of peripheral blood polymorphonuclear leukocytes and monocytes, suggesting the presence of an increased inflammatory response and leukocyte activation in these individuals.

Angioplastia de arteria carótida interna intracraneal

Percutaneous transluminal angioplastia has in recent years become an alternative to surgery and increasingly used for revascularization of the extracranial arteries in patients with cerebral ischemia. However, intracranial angioplasty is a technique which is still not widely used since it is technically more difficult and until now endoprotheses (stents) have not been available specifically designed for intracranial territory. A 73 year old patient with extensive extracranial and intracranial atheromatous lesions, multiple vascular risk factors and cardiac ischemia which contraindicated surgical treatment which was treated consecutively by angioplasty and angioplasty with implantation of stents in both carotid bifurcations. Subsequently, he was treated by angioplasty for a stenosing lesion of 90% of the right carotid siphon with clinical and hemodynamic repercussions. Following the procedure, which was well-tolerated by the patient, there was clinical and angiographic improvement and return to normal of the hemodynamic parameters measured by transcranial Doppler. Angioplasty is a technique which may be used in intracranial stenosing atheromatous lesions. Even without perfect angiographic correction, adequate blood flow is established in the hemodynamically affected lesions. As far as we know this is the first case of intracranial angioplasty of a lesion of the carotid siphon reported in Spain.

Abnormalities of cerebral white matter and stroke risk in the Framingham Offspring Study

P131 Background: MRI Abnormalities of cerebral white matter (WMH) are associated with multiple cerebral vascular risk factors, such as hypertension. The association between WMH and risk for stroke, however, has been investigated only in a limited fashion. The Framingham stroke risk profile (FSRP), based on information from the original Framingham Study Cohort (FHS), has been shown to estimate age- and gender specific probability of stroke in a number of populations. To test the utility of WMH to predict future stroke, we related the FSRP to WMH in 909 offspring of the original FHS (FHS o ) who were free of clinical stroke. Methods: Quantification of MRI WMH was performed in the years 1999–2000 on 919 individuals of the FHS o who had taken Exam 5 during 1991–95 when they were ages 35–74 (mean age 55 ±9 years). None were demented. Data from 10 individuals with prior stroke were excluded. FSRP was computed using Exam 5 risk factor data. Using linear regression, age-related differences in WMH volume, corrected for differences in head size, were computed. WMH volumes >1 sd above the age-predicted mean were considered large. Analyses employed T-test comparison according to WMH category (large vs normal) as well as multiple logistic regression analysis to predict category. Results: 43 individuals (4.7%) were identified as having large volumes of WMH. These individuals had significantly higher SBP (132 ±19 mmHg vs 124 ±18 mmHg; p=0.003) and significantly higher FSRP (0.070 ±0.057 versus 0.040 ±0.043; p=0.002) at Exam 5. Using logistic regression, the odds of having large WMH volumes increased by 1.26 (95% CL 1.08–1.48; p=0.004) for each 10mmHg increase of SBP and 1.09 (95% CL 1.05–1.14; p=0.001) for each 1% increase in FSRP. Analysis by gender showed a similar pattern although SBP did not reach statistical significance for WMH in women (128.4 +19.1 versus 121.7 +18.7, p=0.068). Conclusion: Large WMH are seen in men and women with previously measured, significantly increased predicted stroke risk. Further prospective evaluation will be important to determine if the extent of WMH is a predictor of risk for stroke as suggested by the increased values of FSRP amongst those with large WMH.

Duplex ultrasound risk stratification of percutaneous puncture of the brachial artery for diagnostic and interventional coronary angiography

Diagnostic and interventional heart catheterization in peripheral vascular disease often requires due to iliacal disease additional methods of arterial approach besides the Judkin's technique. The percutaneous catheterization of the brachial artery finds widespread use. A major complication linked with this method is an increased rate of thrombotic occlusions at the puncture site. Thus, we investigated in a prospective set-up the ability of duplex ultrasound to identify predictive risk factors for vascular complications. Over a period of 20 months, 8000 patients referred to heart catheterization were studied. Routine catheterization via the femoral route was contraindicated in 34 out of 8000 mostly due to severe peripheral vascular disease with multiple vascular risk factors (diabetes, hypertension, and smoking). 53 patients who had a comparable low risk-profile served as the control group. The brachial artery was examined by ultrasound duplex for vessel anatomy and diameter at the puncture site before coronary angiography. Both groups (patient and control group) showed in 15% a variable anatomy with a premature division of the brachial artery in 6% proximal of the elbow and in 9% already distal to the axillary artery. Because of reduced diameters of these variable vessels no procedure was carried out at these arms. In all cases the opposite arm was successfully used instead, because the variants were always located only at one arm. The diameter of the brachial artery measured in average 5.0 +/- 0.8 mm and 4.8 +/- 0.7 mm in patients and controls, respectively. Women had a significantly smaller vessel diameter than men, measuring a difference of 0.4 and 0.6 mm, respectively (p < 0.05). For coronary angiography 6F and 7F arterial sheats were used equally, and in 32% of all cases a coronary intervention was performed. 31 (91%) procedures were carried out without complications; there was a false aneurysm in 1 patient (3%) and an occlusion of the brachial artery at the puncture site in 2 patients (6%). The occluded vessels of two diabetic women had a reduced diameter at the level of 10% of the standard distribution and an unfavorable ratio of sheat-to-vessel-diameter which lead initially to an obstruction of nearly 50% of the vessel lumen during catheterization. Screening of the brachial artery by ultrasound duplex before a percutaneous catheterization for coronary angiography and intervention showed reproducibly the variable anatomy and differences in vessel diameter, which can be risk factors for thrombotic occlusion. Important details for the location of the puncture site and the possible size of the arterial sheat can be obtained, so that coronary interventions with 7F catheter systems are still practicable. This technique is a simple and efficient method to estimate the relative risk of arterial occlusion prior to percutaneous puncture of the brachial artery, especially in a group of patients with severe atherosclerosis and elevated vascular risk-factors.

Dementia after stroke increases the risk of long-term stroke recurrence.

Although risk factors for first stroke have been identified, the predictors of long-term stroke recurrence are less well understood. We performed the present study to determine whether dementia diagnosed three months after stroke onset is an independent risk factor for long-term stroke recurrence. We examined 242 patients (age = 72.0 +/- 8.7 years) hospitalized with acute ischemic stroke who had survived the first three months without recurrence and followed them to identify predictors of long-term stroke recurrence. We diagnosed dementia three months after stroke using modified DSM-III-R criteria based on neuropsychological and functional assessments. The effects of conventional stroke risk factors and dementia status on survival free of recurrence were estimated using Kaplan-Meier analyses, and the relative risks (RR) of recurrence were calculated using Cox proportional hazards models. Dementia (RR = 2.71, 95% CI = 1.36 to 5.42); cardiac disease (RR = 2.18, CI = 1.15 to 4.12); and sex, with women at higher risk (RR = 2.03, CI = 1.01 to 4.10), were significant independent predictors of recurrence, while education (RR = 1.90, CI = 0.77 to 4.68), admission systolic blood pressure >160 mm Hg (RR = 1.80, CI = 0.94 to 3.44) and alcohol intake exceeding 160 grams per week (RR = 1.86, CI = 0.79 to 4.38) were weakly related. Our results suggest that dementia significantly increases the risk of long-term stroke recurrence, with additional independent contributions by cardiac disease and sex. Cognitive impairment may be a surrogate marker for multiple vascular risk factors and larger infarct volume that may serve to increase the risk of recurrence. Alternatively, less aggressive medical management of stroke patients with cognitive impairment or noncompliance of such patients with medical therapy may be bases for an increased rate of stroke recurrence.

Insulin sensitivity and regular alcohol consumption: large, prospective, cross sectional population study (Bruneck study)

To assess the relation between regular alcohol consumption and insulin sensitivity, and to estimate the importance of insulin in the association of alcohol with multiple vascular risk factors and cardiovascular disease. Prospective and cross sectional study of a large randomly selected population sample. Part of the Bruneck study 1990-5 (Bolzano province, Italy). 820 health, non-diabetic women and men aged 40-79 years. Concentrations of fasting and post-glucose insulin, cholesterol, apolipoproteins, triglycerides, Lp(a) lipoprotein glucose, fibrinogen, and antithrombin III; blood pressure; insulin resistance estimated by the homeostasis model assessment. Fasting insulin concentrations in those who did not drink alcohol and subjects reporting low (1-50 g/day), moderate (51-99 g/day), and heavy (> or = 100 g/day) alcohol intake were 12.4, 10.0, 8.7, and 7.1 mU/l (P < 0.001). Likewise, post-glucose insulin concentrations and estimates for insulin resistance assessed by the homeostasis model assessment decreased significantly with increasing amounts of regular alcohol consumption. These trends were independent of sex, body mass index, physical activity, cigarette smoking, medication, and diet (P < 0.001). Regular alcohol intake predicted multiple changes in vascular risk factors over a five year period including increased concentrations of high density lipoprotein cholesterol and apolipoprotein A I; higher blood pressure; and decreased concentration of antithrombin III. These associations were in part attributable to the decrease in insulin concentrations observed among alcohol consumers. Low to moderate amounts of alcohol, when taken on a regular basis, improve insulin sensitivity. Insulin is a potential intermediate component in the association between alcohol consumption and vascular risk factors (metabolic syndrome).

Retroperitoneal Fibrosis and Chronic Periaortitis: A New Hypothesis

The etiology of retroperitoneal fibrosis (Ormond's disease) has still not been clarified. A new hypothesis postulates chronic fibrosing periaortitis. Atherosclerosis of the abdominal aorta and plaque rupture lead to the liberation of oxidized lipoproteins through the adventitia into the periaortic fatty tissue. This results in a chronic inflammatory process. In support of the periaortitis hypothesis is our finding that 9 of 14 consecutively studied patients with retroperitoneal fibrosis had either proven atherosclerosis of the abdominal aorta or a high probability of this in view of multiple vascular risk factors. No patients had received previous methysergide medication.