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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been reported that both the DD genotype of the angiotensin converting enzyme (ACE) gene and the presence of cerebral white matter lesions (WML) may represent risk factors for the development of stroke. The present study investigates a possible association between 3 different genetic polymorphisms of the renin-angiotensin system and the presence of WML in 60 never-treated essential hypertensive patients (36 men, 24 women), aged 50 to 60 years, without clinical evidence of target organ damage. All patients underwent brain magnetic resonance imaging to establish the presence or absence of WML. The insertion/deletion (I/D) ACE gene, the M235T angiotensinogen (AGT) gene, and the A1166C angiotensin II type 1 receptor gene polymorphisms were determined by standard polymerase chain reaction. Twenty-five hypertensive patients (41.6%) were found to have WML on brain magnetic resonance imaging. No significant association between the M235T angiotensinogen or A1166C angiotensin II type 1 receptor genotypes and the presence of WML was found. However, the frequency of the DD genotype in patients with WML (64%) was significantly higher than that observed in patients without WML (28.6%; P=0.022). The DD genotype odds ratio for the presence of WML was 4.44 (95% confidence interval: 1.48 to 13.3). Likewise, the proportion of the D allele in patients with WML (74%) was significantly higher (P=0.014) than that observed in patients without WML (51.4%). We conclude that the presence of the DD genotype and/or the D allele of the ACE gene may be a predisposing factor for developing WML in essential hypertensive patients. However, because of the small sample size, these results require confirmation in a larger study.
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PMID:Renin-angiotensin system genetic polymorphisms and cerebral white matter lesions in essential hypertension. 1188 70

A 3-year follow-up of 273 participants (mean age 60 years) of the Austrian Stroke Prevention Study provides first information on the rate, clinical predictors and cognitive consequences of MRI white matter lesions (WML) in elderly individuals without neuropsychiatric disease. Lesion progression was found in 17.9% of individuals over a time period of 3 years. Diastolic blood pressure and early confluent or confluent white matter hyperintensities at baseline were the only significant predictors of white matter hyperintensity progression. Genetic association studies in the setting of the Austrian Stroke Prevention Study provide first evidence for genetic susceptibility factors for progression of WML. We observed associations with the paraoxonase Leu-->Met 54 polymorphism and with the M235T polymorphism of the angiotensinogen gene. Lesion progression had no influence on the course of neuropsychologic test performance over the observational period, but the statistical power of this analysis was low.
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PMID:Evolution of white matter lesions. 1190 Dec 38

Genetic polymorphisms/mutations associated with venous thrombosis have largely been confined to the genes that encode for proteins in either the coagulant or the anticoagulant pathway. Although genetic alterations in the renin-angiotensin system have been reported to have a role in myocardial infarction and hypertension, there is recent evidence to suggest that there may also be an association with venous thrombosis. To extend our earlier observation of an association between the ACE DD genotype in African-American males and venous thrombosis, other genes in the renin-angiotensin pathway were investigated for possible disease association and were compared with African-Americans with myocardial infarction. African-American patients with a documented history of venous thrombosis or a history of myocardial infarction were eligible for participation as cases in the study. Control subjects were African-American outpatients attending a clinical laboratory for routine blood tests who had comparable age and gender distributions to the cases. Persons with a history of myocardial infarction, stroke, or thrombosis were excluded. Genes that were analyzed for known polymorphisms included angiotensinogen, angiotensin-converting enzyme (ACE), and the angiotensin II type I receptor. Our results showed that the ACE DD genotype was also associated with MI in African-American males but not in females. Racial/ethnic and sex differences were also found with respect to the genotype distribution of the ACE 4656(CT)(2/3) polymorphism. It was observed that the 2/2 genotype had a protective effective in males for myocardial infarction and venous thrombosis. The data also demonstrated that the allele frequencies of the A1166C variant of the angiotensin II type I receptor were different in African-Americans as compared to Caucasians.
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PMID:Relationship of venous thromboembolism and myocardial infarction with the renin-angiotensin system in African-Americans. 1199 75

We sought to determine whether the M235T angiotensinogen (AGT) polymorphism, either interacting with habitual physical activity (PA) levels or independently, was associated with cardiovascular (CV) hemodynamics during maximal and submaximal exercise. Sixty-one healthy postmenopausal women (16 sedentary, 21 physically active, and 24 endurance athletes) had heart rate (HR), blood pressure (BP), cardiac output, stroke volume (SV), total peripheral resistance (TPR), and arteriovenous O2 difference (a-vDO2) assessed during 40, 60, 80, and approximately 100% of VO2 max treadmill exercise. VO2 max did not differ among AGT genotype groups; however, maximal HR was 14 beats/min higher in AGT TT than MM genotype women (P < 0.05). AGT TT genotype women also had 19 beats/min higher HR during approximately 100% VO2 max exercise than AGT MM genotype women (P = 0.008). AGT genotype also interacted with habitual PA levels to associate with systolic BP and a-vDO2 during approximately 100% VO2 max exercise (both P < 0.01). AGT TT genotype women had 11 beats/min higher HR during submaximal exercise than MM genotype women (P < 0.05). AGT genotype interacted with habitual PA levels to associate with systolic BP during submaximal exercise (P = 0.009). AGT genotype, independently or interacting with habitual PA levels, did not associate significantly with diastolic BP, cardiac output, SV, or TPR during maximal or submaximal exercise. Thus this common genetic variant in the renin-angiotensin system appears to associate, both interactively with habitual PA levels and independently, with HR, systolic BP, and a-vDO2 responses to maximal and submaximal exercise in postmenopausal women.
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PMID:Angiotensinogen M235T polymorphism associates with exercise hemodynamics in postmenopausal women. 1218 60

The rate and extent of progression of white matter hyperintensities (WMH) over time in elderly subjects is yet unclear. These abnormalities may represent an early form of subcortical vascular dementia. As to whether such changes could be used, as a surrogate marker for this subtype of vascular dementia remains to be determined. So far there exists only a very limited number of studies determining the rate, clinical predictors and cognitive consequences of WMH evolution. There is evidence that these changes do progress over time, however the results of the different studies cannot be compared due to methodological differences. The Austrian Stroke Prevention Study reported that 17.9% of normal individuals show progression over time. The only published quantitative data demonstrated an absolute increase of 1.1 cm(3) over an observational period of 4 years in healthy subjects. Diastolic blood pressure, early confluent or confluent WMH at baseline and genetic variants in the angiotensinogen gene are so far the only known predictors of WMH progression. The Austrian Stroke Prevention Study did not find an association between the evolution of WMH and cognitive functioning but the statistical power of this analysis was small and the relationship needs to be further explored.
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PMID:The natural course of MRI white matter hyperintensities. 1241 93

A three year follow-up of 273 participants (mean age 60 years) of the Austrian Stroke Prevention Study provides first information on the rate and clinical predictors of progression of small vessel disease related cerebral abnormalities including white matter changes and lacunes. White matter hyperintensity progression was found in 17.9% of individuals over the 3 year period. New lacunes occurred in 2.2% of subjects. The overall frequency of progression of small vessel disease related brain changes was 19%. Diastolic blood pressure and early confluent or confluent white matter hyperintensities at baseline predicted lesion progression. Genetic association studies in the setting of the Austrian Stroke Prevention Study described that polymorphisms in the renin angiotensin system (RAS) increase the susceptibility for progression of cerebral small vessel disease. Homozygosity for the T allele of the M235T polymorphism of the angiotensinogen gene was associated with a 3.19-fold increased risk for lesion progression independently of arterial hypertension. These data suggest that drugs influencing the RAS system may allow to intervene with an unfavorable course of cerebral small vessel disease.
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PMID:Risk factors and progression of small vessel disease-related cerebral abnormalities. 1245 49

Microangiopathy-related cerebral damage (MARCD) is a common finding in the elderly. It may lead to cognitive impairment and gait disturbances. Arterial hypertension and age are the best accepted risk factors for MARCD. Genes involved in blood pressure regulation, like genes encoding the proteins of the renin-angiotensin system (RAS) therefore represents good candidate genes for MARCD. Plasma angiotensinogen level is a major determinant of the RAS activity. Positive correlation between angiotensinogen gene expression and RAS activity, as well as blood pressure were observed. Common mutations described in the AGT promoter were able to alter AGT expression in cell culture. We described that 4 frequent mutations at the AGT promoter are combined in 5 haplotypes coded as A (-6:g, -20:a, -152:g, -217:g), B (-6:a, -20:c, -152:g, -217:g), C (-6:a, -20:c, -152:a, -217:g), D (-6:a, -20:a, -152:g, -217:g), and E (-6:a, -20:a, -152:g, -217:a). The B haplotype was significantly associated with MARCD in the cohort of the Austrian Stroke Prevention Study (p = 0.005). The association was independent of hypertension, which pinpointed to a possible role of the local RAS in this relationship. Investigation of the promoter activity of the AGT gene in astrocytes suggests that expression of this gene may be modulated by the haplotype.
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PMID:Microangiopathy-related cerebral damage and angiotensinogen gene: from epidemiology to biology. 1245 50

Possible correlation of M/T polymorphism of angiotensinogen gene with risk of ischemic stroke and basic risk factors of cerebral pathology (levels of arterial pressure and blood cholesterol; presence of diabetes mellitus, coronary heart disease, or myocardial infarction in anamnesis; and stenosis of major cerebral arteries) was studied. It was shown that M/T polymorphic variants of angiotensinogen gene were factors determining neither clinical variant of cerebral ischemia development (acute ischemic stroke or chronic brain ischemia) nor formation of main risk factors of stroke.
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PMID:[Role of missense mutation (M235T) in the angiotensinogen gene in development of cerebral ischemia]. 1265 48

Polymorphic variants of genes for angiotensin-converting enzyme (ACE) and angiotensinogen (ATG) were studied in 110 patients with different types of brain ischemic disease--carotid atherothrombotic ischemic stroke (one of the pathogenic brain infarction variants) as well as in 119 their siblings with the main risk factors of cerebrovascular pathology development being taken into account. No association has been found between ACE and ATG genes polymorphisms and carotid atherothrombotic ischemic stroke. However, the presence of a homozigous DD ACE genotype was shown to be an independent risk factor for development of hemodynamically relevant stenosis of the major brain arteries. The absence of differences in genetic variants distribution in patients with acute ischemic stroke, comparing to those with prolonged chronic brain ischemic disease (without infarction formation) and the highest frequency of this polymorphism in "longevity" group (without lifetime stroke) imply a relatively independent character of the atherothrombogenic process, which may probably underlie a further development of pathological process.
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PMID:[The role of polymorphic variants of renin-angiotensin system genes in the development of ischemic stroke in Moscow population]. 1283 May 7

Hypertension is the major controllable risk factor associated with cardiovascular disease (CVD) events such as myocardial infarction, stroke, heart failure, and end-stage diabetes. A 5 mm Hg decrease in blood pressure has been equated with approximately 16% decrease in CVD. In the U.S. alone current annual antihypertensive drug costs are approximately dollars 15 billion. The renin-angiotensin-aldosterone system is a target for blood pressure control. Cleavage of angiotensinogen by renin produces angiotensin I which is subsequently hydrolyzed by angiotensin-I-converting enzyme (ACE) to angiotensin II (a potent vasoconstrictor). Various side effects are associated with the use of ACE inhibitory drugs in the control of blood pressure including hypotension, increased potassium levels, reduced renal function, cough, angioedema, skin rashes, and fetal abnormalities. Milk proteins, both caseins and whey proteins, are a rich source of ACE inhibitory peptides. Several studies in spontaneously hypertensive rats show that these casokinins and lactokinins can significantly reduce blood pressure. Furthermore, a limited number of human studies have associated milk protein-derived peptides with statistically significant hypotensive effects (i.e., lower systolic and diastolic pressures). The advent of effective milk protein based functional food ingredients/nutraceuticals for the prevention/control of blood pressure therefore has the potential to significantly reduce global healthcare cost.
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PMID:Hypotensive peptides from milk proteins. 1505 58


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