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A Haplotype Analysis of the Angiotensin Converting Enzyme Gene in Ischaemic Stroke

By Gary Jon Dennis

Abstract

Background: Epidemiological studies lend some support for a genetic predisposition to human stroke. There is a growing body of evidence to suggest a role for Angiotensin II (ANGII) in vascular disease. The levels of Angiotensin converting enzyme (ACE), which converts ANGI to ANGII, are known to be under a significant degree of genetic control. The D allele of the ACE I/D polymorphism is associated with higher serum ACE levels and this allele has also been associated with ischaemic stroke. Recent identification of numerous ACE single nucleotide polymorphisms has allowed for a more powerful case control haplotype analysis of ACE in ischaemic stroke. \ud Patients and Methods: The validity of the published structure of the common ACE haplotypes was investigated and supported using long range allele specific PCR and DNA sequencing of a random sample of UK caucasian subjects. Using restriction fragment length polymorphism (RFLP) analysis of selected polymorphisms we generated ACE haplotypes for 359 ischaemic stroke patients and 328 unrelated controls. \ud Results: Age, hypertension, smoking, diabetes and hypercholesterolaemia were identified as significant clinical risk factors for ischaemic stroke. D allele frequencies showed no significant differences between cases and controls (0.55 vs 0.53 respectively). However a low frequency D allele haplotype (H9) was found to be an independent risk factor for ischaemic stroke (odds ratio 2.05, p=0.004). \ud Conclusion: This study has provided allele specific data to support the haplotype structure of the common ACE haplotypes in a UK caucasian population. For the first time, in a case control analysis, we have identified a significant and independent genetic association of a low frequency ACE haplotype, H9, with human ischaemic stroke. This result suggests an important role for ACE in ischaemic stroke which will require further study in other populations using a variety of control groups

Publisher: University of Leicester
Year: 2008
OAI identifier: oai:lra.le.ac.uk:2381/8737

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  1. (2004). A call for accurate phenotype definition in the study of complex disorders.
  2. (1997). A community based stroke register in a high risk area for stroke in north west England.
  3. (2002). A comprehensive linkage analysis for myocardial infarction and its related risk factors. Nat Genet
  4. (1995). a cyclic AMP-selective phosphodiesterase inhibitor, reduces neuronal damage following cerebral ischemia in the gerbil.
  5. (1999). A dominant relationship between the ACE D allele and serum ACE levels in a Ghanaian population.
  6. (1989). A genetic polymorphism in the renin gene of Dahl rats cosegregates with blood pressure.
  7. (2004). A genetic variant of ACE increases cell survival: a new paradigm for biology and disease.
  8. (2001). A genome-wide scan for coronary heart disease suggests in Indo-Mauritians a susceptibility locus on chromosome 16p13 and replicates linkage with the metabolic syndrome on 3q27. Hum Mol Genet
  9. (2000). A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase.
  10. (1989). A lack of genetic linkage of renin gene restriction fragment length polymorphisms with human hypertension. Hypertension
  11. (1967). A lacunar stroke. The dysarthria-clumsy hand syndrome. Neurology
  12. (1999). A Pilot Study of Stroke Admission Rates to Leicester Royal Infirmary, Leciester General and Glenfield General Hospitals. Unpublished
  13. (1993). A potent genetic risk factor for restenosis. Nat Genet
  14. (1995). A prospective evaluation of an angiotensin-converting-enzyme gene polymorphism and the risk of ischemic heart disease.
  15. (1988). A prospective study of acute cerebrovascular disease in the community: the Oxfordshire Community Stroke Project 1981-86. 1. Methodology, demography and incident cases of first-ever stroke.
  16. (1992). A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. Jama
  17. (1995). A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. Jama
  18. (1992). A study of twins and stroke. Stroke
  19. (1997). A survey of atrial fibrillation in general practice: the West Birmingham Atrial Fibrillation Project. Br J Gen Pract
  20. (1996). A systematic review of physical activity promotion strategies.
  21. (1989). A widespread abnormality of renin gene expression in the spontaneously hypertensive rat: modulation in some tissues with the development of hypertension. Clin Sci (Lond)
  22. (1996). Absence of association or genetic linkage between the angiotensin-convertingenzyme gene and left ventricular mass.
  23. Absence of linkage between the angiotensin converting enzyme locus and human essential hypertension.
  24. (1983). Absence of renin-like activity in rat aorta and microvessels. Hypertension
  25. (1998). ACE I/D gene polymorphism: presence of the ACE D allele increases the risk of coronary artery disease in younger individuals. Atherosclerosis
  26. (1994). ACE in three tunicae of rat aorta: expression in smooth muscle and effect of renovascular hypertension.
  27. (2004). ACE1 polymorphism and progression of SARS.
  28. (1994). Activation of angiotensinogen and angiotensin-converting enzyme gene expression in the left ventricle of senescent rats. Circulation
  29. (1997). Activation of cAMP-PKA signaling in vivo inhibits smooth muscle cell proliferation induced by vascular injury. Nat Med
  30. (1997). Activation of the cardiac renin-angiotensin system by adenoviral gene delivery.
  31. (2007). Advances in QTL mapping in pigs.
  32. (2002). Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet
  33. (1986). Aggregation of multiple risk factors for stroke in siblings of patients with brain infarction and transient ischemic attacks. Stroke
  34. Alcohol consumption and mortality from all causes, coronary heart disease, and stroke: results from a prospective cohort study of scottish men with 21 years of follow up. Bmj 1999a;
  35. (2002). Alcohol consumption and risk of ischemic stroke: The Framingham Study. Stroke
  36. (1986). Alexander RW. Sustained diacylglycerol formation from inositol phospholipids in angiotensin II-stimulated vascular smooth muscle cells.
  37. (2006). Altered blood pressure responses and normal cardiac phenotype in ACE2-null mice.
  38. (2004). Alzheimer disease risk and genetic variation in ACE: a meta-analysis. Neurology
  39. (1991). An autopsy study of the incidence of lacunes in relation to age, hypertension, and arteriosclerosis. Stroke
  40. (1990). An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels.
  41. (2003). An Introduction to Stroke Genetics.
  42. (1913). Analysis of risk factors for stroke in a cohort of men born in
  43. (1995). Angiotensin converting enzyme as a genetic risk factor for coronary artery spasm. Implication in the pathogenesis of myocardial infarction.
  44. (1995). Angiotensin converting enzyme gene deletion allele is independently and strongly associated with coronary atherosclerosis and myocardial infarction. Br Heart J
  45. (2005). Angiotensin converting enzyme gene polymorphism and cardiovascular morbidity and mortality: the Rotterdam Study.
  46. (1977). Angiotensin converting enzyme: induction by steroids in rabbit alveolar macrophages in culture. Science
  47. (1993). Angiotensin I-converting enzyme in human circulating mononuclear cells: genetic polymorphism of expression in T-lymphocytes.
  48. (1988). Angiotensin II induces hypertrophy, not hyperplasia, of cultured rat aortic smooth muscle cells. Circ Res
  49. (1995). Angiotensin II regulates the expression of plasminogen activator inhibitor-1 in cultured endothelial cells. A potential link between the renin-angiotensin system and thrombosis.
  50. (1991). Angiotensin II stimulates angiogenesis in the chorio-allantoic membrane of the chick embryo.
  51. (1990). Angiotensin II-forming pathways in normal and failing human hearts. Circ Res
  52. (1990). Angiotensin II-induced proliferation of aortic myocytes in spontaneously hypertensive rats.
  53. (1996). Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone.
  54. (1982). Angiotensin production and metabolism in sheep. Clin Exp Pharmacol Physiol Suppl
  55. (2002). Angiotensin-1-converting enzyme (ACE) plasma concentration is influenced by multiple ACE-linked quantitative trait nucleotides. Hum Mol Genet
  56. (2002). Angiotensin-converting enzyme 2--a new cardiac regulator.
  57. (1983). Angiotensin-converting enzyme activity in postmortem human tissues. Lab Invest
  58. (2003). Angiotensin-converting enzyme DD genotype is associated with worse perinatal cardiorespiratory adaptation in preterm infants.
  59. (1996). Angiotensin-converting enzyme gene and lacunar stroke. Stroke
  60. (1997). Angiotensin-converting enzyme gene I/D polymorphism and carotid plaques in Japanese. Hypertension
  61. (1996). Angiotensin-converting enzyme gene polymorphism is associated with carotid arterial wall thickness in non-insulin-dependent diabetic patients. Circulation
  62. (1999). Angiotensin-converting enzyme genotype is associated with Alzheimer disease in the Japanese population. Neurosci Lett
  63. (1995). Angiotensin-converting enzyme I/D polymorphism and arterial wall thickness in a general population. The Vobarno Study. Circulation
  64. (1996). Angiotensin-converting enzyme insertion/deletion polymorphism and cerebrovascular disease. Stroke
  65. (1990). Angiotensin-converting enzyme: Biochemistry and molecular biology.
  66. (1978). Angiotensin-converting enzyme: presence of high activity in choroid plexus of mammalian brain.
  67. (1991). Angiotensin-induced growth related metabolism is activated in cultured smooth muscle cells from spontaneously hypertensive rats and Wistar-Kyoto rats.
  68. (1995). Angiotensinconverting enzyme gene deletion polymorphism. A new risk factor for lacunar stroke but not carotid atheroma. Stroke
  69. (2000). Anticoagulation to prevent stroke in atrial fibrillation. It's still not clear whether results in secondary care translate to primary care. Bmj
  70. (1994). Antihypertensive drug therapy: effects on stroke and coronary heart disease.
  71. (1983). Antithrombin III deficiency in ischaemic stroke. Klin Wochenschr
  72. Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis. Ann Intern Med 1999b;
  73. (1999). Antithrombotic therapy.
  74. (1990). Aortic smooth muscle cells are able to convert angiotensin I to angiotensin II.
  75. (1986). Aphasia after stroke: natural history and associated deficits.
  76. (1997). Apolipoprotein E polymorphism and silent microangiopathy-related cerebral damage. Results of the Austrian Stroke Prevention Study. Stroke
  77. (1996). Apolipoprotein E polymorphism is associated with segment-specific extracranial carotid artery intima-media thickening. Stroke
  78. (1995). Apolipoprotein E4 phenotype is not an important risk factor for coronary heart disease or stroke in elderly subjects. Arterioscler Thromb Vasc Biol
  79. (1978). Arrhythmias and the "Holiday Heart": alcohol-associated cardiac rhythm disorders. Am Heart J
  80. (1997). Arterioscler Thromb Vasc Biol
  81. (2004). Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet
  82. (1997). Aspirin use in middle-aged men with cardiovascular disease: are opportunities being missed? Br J Gen Pract
  83. (1994). Association between a deletion polymorphism of the angiotensin-converting-enzyme gene and left ventricular hypertrophy.
  84. (1995). Association between plasma homocysteine concentrations and extracranial carotid-artery stenosis.
  85. (2005). Association between the gene encoding 5-lipoxygenase-activating protein and stroke replicated in a Scottish population.
  86. (1992). Association of a polymorphism of the angiotensin I-converting enzyme gene with essential hypertension.
  87. (1995). Association of ACE gene polymorphism and diabetic nephropathy? The Diabetic Nephropathy Study Group. Kidney Int
  88. (1997). Association of angiotensin-converting enzyme gene I/D polymorphism with change in left ventricular mass in response to physical training. Circulation
  89. (2002). Association of angiotensin-converting-enzyme gene polymorphism with the depressor response to mild exercise therapy in patients with mild to moderate essential hypertension. Clin Genet
  90. (1997). Association of angiotensinogen gene T235 variant with progression of immunoglobin A nephropathy in Caucasian patients.
  91. (1992). Atrial fibrillation and stroke: prevalence in different types of stroke and influence on early and long term prognosis (Oxfordshire community stroke project). Bmj
  92. (1994). Atrial fibrillation and stroke. Revisiting the dilemmas. Stroke
  93. (1992). Autoradiographic analysis of cyclic adenosine monophosphate phosphodiesterase using [3H]rolipram in the postischemic rat brain. Neurosci Lett
  94. (1991). Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators.
  95. (1998). Betafibrinogen gene polymorphism (C148-->T) is associated with carotid atherosclerosis: results of the Austrian Stroke Prevention Study. Arterioscler Thromb Vasc Biol
  96. (1996). Black Americans have an increased rate of angiotensin converting enzyme inhibitor-associated angioedema. Clin Pharmacol Ther
  97. (1990). Black-white differences in stroke incidence in a national sample. The contribution of hypertension and diabetes mellitus. Jama
  98. (1984). Blockade of N-methyl-D-aspartate receptors may protect against ischemic damage in the brain. Science
  99. (1979). Blood pressure aggregation in families.
  100. (1990). Blood pressure, stroke, and coronary heart disease. Part 1, Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet
  101. (1990). Blood pressure, stroke, and coronary heart disease. Part 2, Short-term reductions in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet
  102. (1990). Brief angiotensin converting enzyme inhibitor treatment in young spontaneously hypertensive rats reduces blood pressure long-term. Hypertension
  103. (1995). Can lowering homocysteine levels reduce cardiovascular risk?
  104. (1979). Capsular infarcts: the underlying vascular lesions.
  105. (1999). Cardiovascular risk factors, angiotensin-converting enzyme gene I/D polymorphism, and left ventricular mass in systemic hypertension.
  106. (1989). Carotid arteriosclerosis in identical twins discordant for cigarette smoking. Circulation
  107. (2000). Carotid endarterectomy for asymptomatic carotid stenosis. Cochrane Database Syst Rev
  108. (2000). Carotid endarterectomy for symptomatic carotid stenosis (Cochrane Review). In:
  109. (2000). Carotid endarterectomy revisited.
  110. (2001). causes, and prevention of ischaemic stroke in elderly patients with symptomatic internalcarotid-artery stenosis. Lancet
  111. (1989). Cell Genet
  112. (1990). Cerebrovascular disease in Hong Kong Chinese. Stroke
  113. (1958). Changes in the endothelium of the aorta and the behaviour of macrophages in experimental atheroma of rabbits.
  114. (2000). Changing concepts of atherogenesis.
  115. (1985). Characteristics and prognosis of lone atrial fibrillation. 30-year follow-up in the Framingham Study. Jama
  116. (1990). Characteristics of stroke victims associated with early cardiovascular mortality in their children.
  117. (1999). Characterization of different subsets of atrial fibrillation in general practice in France: the ALFA study. The College of French Cardiologists. Circulation
  118. (1997). Cholesterol lowering statin drugs, risk of stroke, and total mortality. JAMA
  119. (1995). Cholesterol-years, blood pressure-years, pack-years, and carotid stenosis. Circulation
  120. (1996). Chromosomal mapping of quantitative trait loci contributing to stroke in a rat model of complex human disease.
  121. (1988). Circulating versus local renin-angiotensin system in cardiovascular homeostasis. Circulation
  122. (1991). Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet
  123. (1993). Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial.
  124. (1990). Clinical implications of the molecular biology of the reninangiotensin system.
  125. (1987). Clinicoepidemiologic study of stroke in
  126. (1994). Collaborative overview of randomised trials of antiplatelet therapy--I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists' Collaboration. Bmj
  127. (1996). Common Data Set
  128. (2001). Common genetic mutations as possible aetiological factors in stroke. Eur Neurol
  129. (1997). Comparable studies of the incidence of stroke and its pathological types: results from an international collaboration. International Stroke Incidence Collaboration. Stroke
  130. (1993). Comparison of transthoracic and transesophageal echocardiography for detection of abnormalities of prosthetic and bioprosthetic valves in the mitral and aortic positions.
  131. (1971). Concentrations of angiotensin-converting enzyme in tissues of the rat. Biochim Biophys Acta
  132. (1991). Concordance of ischemic heart disease in the NHLBI twin study after 14-18 years of follow-up.
  133. (1980). Construction of a genetic linkage map in man using restriction fragment length polymorphisms.
  134. (1997). Contribution of genetic polymorphism in the renin-angiotensin system to the development of renal complications in insulin-dependent diabetes: Genetique de la Nephropathie Diabetique (GENEDIAB) study group.
  135. (1992). Converting-enzyme inhibitors increase converting-enzyme mRNA and activity in endothelial cells.
  136. (1990). Cosegregation of the renin allele of the spontaneously hypertensive rat with an increase in blood pressure.
  137. (1970). Cross sectional analysis of mortality by country of birth in England and Wales,
  138. (1997). D allele of the angiotensin I-converting enzyme is a major risk factor for restenosis after coronary stenting. Circulation
  139. (2001). dbSNP: the NCBI database of genetic variation.
  140. (1990). Deep cerebral infarcts in the People's Republic of China. Stroke
  141. (1996). Deletion polymorphism in the angiotensin-converting enzyme gene in patients with a history of ischemic stroke. Arterioscler Thromb Vasc Biol
  142. (1995). Departure from Hardy-Weinberg equilibrium should be systematically tested in studies of association between genetic markers and disease. Circulation
  143. (1963). Development of a strain of spontaneously hypertensive rats.
  144. (1979). Diabetes and cardiovascular risk factors: the Framingham study. Circulation
  145. Diagnosis and initial management of stroke and transient ischemic attack across UK health regions from 1992 to 1996: experience of a national primary care database.
  146. (1995). diastolic blood pressure, and stroke: 13,000 strokes in 450,000 people in 45 prospective cohorts. Prospective studies collaboration. Lancet
  147. (1987). Difference in response of vascular angiotensin converting enzyme activity to cilazapril in SHR. Clin Exp Hypertens A
  148. Different antiplatelet regimens in the prevention of vascular events among patients at high risk of stroke: new evidence from the antithrombotic trialists' collaboration. Cerebrovasc Dis 1998; 8(suppl 4): 8.
  149. (1994). Digenic retinitis pigmentosa due to mutations at the unlinked peripherin/RDS and ROM1 loci. Science
  150. (2005). Dose-related association of MTHFR 677T allele with risk of ischemic stroke: evidence from a cumulative meta-analysis. Stroke
  151. (1983). Drinking and its relation to smoking, BP, blood lipids, and uric acid. The Framingham study. Arch Intern Med
  152. (1972). Effect of angiotensin II
  153. (1994). Effect of genetic architecture on the power of human linkage studies to resolve the contribution of quantitative trait loci. Heredity
  154. (1994). Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group. Circulation
  155. (2004). Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet
  156. (1992). Effect of tobacco advertising on tobacco consumption: a discussion document reviewing the evidence.
  157. (2002). Effects of a phosphodiesterase IV inhibitor rolipram on microsphere embolism-induced defects in memory function and cerebral cyclic AMP signal transduction system in rats.
  158. (2000). Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs: results of prospectively designed overviews of randomised trials. Blood Pressure Lowering Treatment Trialists' Collaboration. Lancet
  159. (1997). Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. Jama
  160. (2000). Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators.
  161. (1980). Effects of captopril (SQ 14, 225) on the renin-angiotensin-aldosterone system in normal rats.
  162. (2001). Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation.
  163. (1989). Effects of cytokines on vascular endothelium: their role in vascular and immune injury. Kidney Int
  164. (2002). Effects of losartan on cardiovascular morbidity and mortality in patients with isolated systolic hypertension and left ventricular hypertrophy: a Losartan Intervention for Endpoint Reduction (LIFE) substudy. Jama
  165. (1987). Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study.
  166. (2001). Effects of ramipril and vitamin E on atherosclerosis: the study to evaluate carotid ultrasound changes in patients treated with ramipril and vitamin E (SECURE). Circulation
  167. (2001). Elevated midlife blood pressure increases stroke risk in elderly persons: the Framingham Study. Arch Intern Med
  168. (1984). Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis.
  169. (1998). Elite endurance athletes and the ACE I allele--the role of genes in athletic performance. Hum Genet
  170. (1995). Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study. Jama
  171. (2001). Endarterectomy or angioplasty for treatment of carotid stenosis? Lancet
  172. (1988). Endopeptidase-24.11 is striosomally ordered in pig brain and, in contrast to aminopeptidase N and peptidyl dipeptidase A ('angiotensin converting enzyme'), is a marker for a set of striatal efferent fibres. Neuroscience
  173. (1999). Endothelial dysfunction in human disease.
  174. (2001). Endovascular versus surgical treatment in patients with carotid stenosis in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): a randomised trial. Lancet
  175. (1982). Enhanced angiotensin-mediated facilitation of adrenergic neurotransmission in spontaneously hypertensive rats. J Pharmacol Exp Ther
  176. (1995). Enhanced pressor response to angiotensin I in normotensive men with the deletion genotype (DD) for angiotensinconverting enzyme. Hypertension
  177. (1980). Epidemiology as a guide to clinical decisions. The association between triglyceride and coronary heart disease.
  178. (1998). Epidemiology of stroke. Lancet
  179. (1999). Ethnic differences in incidence of stroke: prospective study with stroke register. Bmj
  180. (1991). Ethnic differences in mortality from ischaemic heart disease and cerebrovascular disease in England and Wales. Bmj
  181. (1996). European Stroke Prevention Study. 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke.
  182. (1991). Evidence for a functional tissue renin-angiotensin system in the rat mesenteric vasculature and its involvement in regulating blood pressure. J Pharmacol Exp Ther
  183. (1994). Evidence for direct local effect of angiotensin in vascular hypertrophy. In vivo gene transfer of angiotensin converting enzyme.
  184. (1998). Evidence for genetic variance in white matter hyperintensity volume in normal elderly male twins. Stroke
  185. (1983). Evidence of an increasing prevalence of diagnosed diabetes mellitus in the Poole area from
  186. (1992). Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin Iconverting enzyme (ACE) gene controls plasma ACE levels.
  187. (1988). Evolution and testing of the lacunar hypothesis. Stroke
  188. (1996). Expression of angiotensin-converting enzyme in remaining viable myocytes of human ventricles after myocardial infarction. Circulation
  189. (1988). Expression of the renin gene in extra-renal tissues of the rat.
  190. (1980). Factors related to stroke incidence in Hawaii Japanese men. The Honolulu Heart Study. Stroke
  191. (1993). Familial aggregation of stroke. The Framingham Study. Stroke
  192. (1997). Familial history of stroke and stroke risk. The Family Heart Study. Stroke
  193. (1988). Familial resemblance of plasma angiotensin-converting enzyme level: the Nancy Study.
  194. (1986). Family history of stroke as an independent predictor of ischemic heart disease in men and stroke in women.
  195. (1986). Fanburg BL. Stimulation of bovine endothelial cell angiotensin-Iconverting enzyme activity by cyclic AMP-related agents.
  196. (1968). Fate of angiotensin I in the circulation. Nature
  197. (1994). Fernandez Cruz AF. High plasma levels of endothelin-1 and atrial natriuretic peptide in patients with acute ischemic stroke.
  198. (1994). Fibrinogen and factor VII in the prediction of coronary risk. Results from the PROCAM study in healthy men. Arterioscler Thromb
  199. (1991). Fibrinogen and lipid concentrations as risk factors for transient ischaemic attacks and minor ischaemic strokes. Bmj
  200. (1987). Fibrinogen and risk of cardiovascular disease. The Framingham Study. Jama
  201. (1984). Fibrinogen as a risk factor for stroke and myocardial infarction.
  202. Fibroblast growth factor stimulates angiotensin converting enzyme expression in vascular smooth muscle cells. Possible mediator of the response to vascular injury.
  203. (1999). Finemapping of an ancestral recombination breakpoint in DCP1. Nat Genet
  204. (1980). Frequency of alcohol consumption and morbidity and mortality: The Yugoslavia Cardiovascular Disease Study. Lancet
  205. (1997). Fruit and vegetables, and cardiovascular disease: a review.
  206. (1987). Functional abilities after stroke: measurement, natural history and prognosis.
  207. (1997). Gathering the evidence. The INDANA (INdividual Data ANalysis of Antihypertensive intervention trials) Project Collaborators. Stroke
  208. (1997). Gender-specific associations of the fibrinogen B beta 448 polymorphism, fibrinogen levels, and acute cerebrovascular disease. Arterioscler Thromb Vasc Biol
  209. (1993). Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science
  210. (2000). Gene mapping in isolated populations: new roles for old friends? Hum Hered
  211. (1999). Genes encoding atrial and brain natriuretic peptides as candidates for sensitivity to brain ischemia in stroke-prone hypertensive rats. Hypertension
  212. (1994). Genetic Approaches to Hypertension. In:
  213. (1996). Genetic basis of variation in carotid artery wall thickness. Stroke
  214. (1995). Genetic control of blood pressure and the angiotensinogen locus.
  215. (1989). Genetic heritability and common environmental components of resting and stressed blood pressures, lipids, and body mass index in Utah pedigrees and twins.
  216. (1995). Genetic linkage of the ACE gene to plasma angiotensin-converting enzyme activity but not to blood pressure. A quantitative trait locus confers identical complex phenotypes in human and rat hypertension. Circulation
  217. (1991). Genetic mapping of a gene causing hypertension in the stroke-prone spontaneously hypertensive rat. Cell
  218. (1998). Genetic risk factors and ischaemic cerebrovascular disease: role of common variation of the genes encoding apolipoproteins and angiotensin-converting enzyme. Ann Med
  219. (1996). Genetic risk for Stroke: a long term follow up study of the National Academy of Science/Veterans Administraion Twin Registry (abstract). Neurology
  220. (1997). Genetic susceptibility for human familial essential hypertension in a region of homology with blood pressure linkage on rat chromosome 10. Hum Mol Genet
  221. (1998). Genetic variation in the promoter region of the beta-fibrinogen gene is associated with ischemic stroke in a Japanese population. Blood Coagul Fibrinolysis
  222. (2001). Genetically increased angiotensin I-converting enzyme level and renal complications in the diabetic mouse.
  223. (2000). Genetics and ischaemic stroke.
  224. (1985). Genetics of coronary heart disease and its risk factors. Prog Clin Biol Res
  225. (2005). Genome-wide linkage analysis of age at onset of alcohol dependence: a comparison between microsatellites and singlenucleotide polymorphisms.
  226. (2002). Genome-wide linkage analysis of the acute coronary syndrome suggests a locus on chromosome 2. Arterioscler Thromb Vasc Biol
  227. (1990). Genomic DNA 5' to the mouse and human angiotensin-converting enzyme genes contains two distinct regions of conserved sequence.
  228. (1995). Glucocorticoids induce angiotensin-converting enzyme expression in vascular smooth muscle. Hypertension
  229. (1988). Glutamate neurotoxicity and diseases of the nervous system. Neuron
  230. Haemostatic function and ischaemic heart disease. Lancet 1981; 2: 88. Meade
  231. (1971). Handicapped and impaired in Great Britain.
  232. (1987). Haplotype relative risks: an easy reliable way to construct a proper control sample for risk calculations. Ann Hum Genet
  233. (2004). Haplotypes of the alpha-1 antitrypsin gene in healthy controls and Z deficiency patients. Hum Mutat
  234. (2002). Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet
  235. (1998). High risk of cerebral-vein thrombosis in carriers of a prothrombin-gene mutation and in users of oral contraceptives.
  236. (2002). Homocysteine, MTHFR 677C-->T polymorphism, and risk of ischemic stroke: results of a meta-analysis. Neurology
  237. (1965). Homolateral Ataxia and Crural Paresis: A Vascular Syndrome.
  238. (1984). Hormonal influence on endothelial cell angiotensin-converting enzyme activity.
  239. (1997). How to read a paper. Statistics for the non-statistician. I: Different types of data need different statistical tests. Bmj
  240. (1998). Human gene for physical performance. Nature
  241. (1989). Hyperglycaemia and stroke.
  242. Identification of a highly specific chymase as the major angiotensin II-forming enzyme in the human heart.
  243. (1996). Identification of new polymorphisms of the angiotensin I-converting enzyme (ACE) gene, and study of their relationship to plasma ACE levels by two-QTL segregationlinkage analysis.
  244. (1980). Identifying the child at risk for coronary disease as an adult: A strategy for prevention.
  245. (1989). Impact of cardiovascular risk factors on coronary heart disease and mortality among middle aged diabetic men: a general population study. Bmj
  246. (1998). Impaired vasorelaxant responses to natriuretic peptides in the stroke-prone phenotype of spontaneously hypertensive rats.
  247. (1974). Importance of genetic factors in stroke: an evidence obtained by selective breeding of stroke-prone and -resistant SHR. Jpn Circ J
  248. (2002). Incidence and case fatality rates of stroke subtypes in a multiethnic population: the South London Stroke Register.
  249. (1997). Incidence of and risk factors for atrial fibrillation in older adults. Circulation
  250. (1985). Incidence of transient ischemic attack in
  251. (1996). Incidence of transient ischemic attacks and minor ischemic strokes in
  252. (1989). Incidence of transient ischemic attacks in Oxfordshire,
  253. (1998). incidence, prognosis, and predisposing conditions for atrial fibrillation: population-based estimates.
  254. (1992). Increase of angiotensin converting enzyme gene expression in the hypertensive aorta. Hypertension
  255. (1990). Increased cardiac angiotensin-converting enzyme in rats with chronic heart failure. Clin Exp Pharmacol Physiol
  256. (1990). Increased rat cardiac angiotensin converting enzyme activity and mRNA expression in pressure overload left ventricular hypertrophy. Effects on coronary resistance, contractility, and relaxation.
  257. (2004). Increases in brain and cardiac AT1 receptor and ACE densities after myocardial infarct in rats.
  258. (1978). Induction of angiotensin converting enzyme in human monocytes in culture.
  259. (1980). Induction of angiotensin Iconverting enzyme rat lung with Captopril
  260. (1997). Induction of chymase that forms angiotensin II in the monkey atherosclerotic aorta. FEBS Lett
  261. (1986). Inflammatory infiltrates in human coronary atherosclerosis. Atherosclerosis
  262. (1987). Influence of blood pressure on development of aortic medial smooth muscle hypertrophy in spontaneously hypertensive rats. Hypertension
  263. (1989). Inhibitors of angiotensin-converting enzyme prevent myointimal proliferation after vascular injury. Science
  264. (1993). Insertion/deletion (I/D) polymorphism at the locus for angiotensin I-converting enzyme and myocardial infarction. Clin Genet
  265. Insertion/deletion (I/D) polymorphism at the locus for angiotensin I-converting enzyme and parental history of myocardial infarction.
  266. (1994). Insertion/deletion polymorphism of the angiotensin-converting enzyme gene is strongly associated with coronary heart disease in non-insulin-dependent diabetes mellitus.
  267. (1998). Interaction of genetic deficiency of endothelial nitric oxide, gender, and pregnancy in vascular response to injury in mice.
  268. (2000). Intercollegiate Working Party for Stroke. National Clinical Guidelines for Stroke. London: Royal College of Physicians,
  269. (2002). Interdependent effect of angiotensin-converting enzyme and platelet-activating factor acetylhydrolase gene polymorphisms on the progression of immunoglobulin A nephropathy. Clin Genet
  270. (1990). Intermittent claudication, heart disease risk factors, and mortality. The Whitehall Study. Circulation
  271. (1968). International trends in mortality from stroke,
  272. (1991). Involvement of second messenger systems in stimulation of angiotensin converting enzyme of bovine endothelial cells.
  273. (1984). Involvement of the vascular renin-angiotensin system in beta adrenergic receptor-mediated facilitation of vascular neurotransmission in spontaneously hypertensive rats. J Pharmacol Exp Ther
  274. (1987). Ionic dependence of glutamate neurotoxicity.
  275. Ischemic stroke risk with oral contraceptives: A meta-analysis. Jama 2000; 284: 72-8. Glazier AM, Nadeau JH, Aitman TJ. Finding genes that underlie complex traits.
  276. (1985). Its relation to the size and the location of the infarct and to the underlying vascular lesion. Stroke
  277. Lack of association between angiotensin converting enzyme gene insertion/deletion polymorphism and stroke.
  278. (1995). Lack of relationship between an insertion/deletion polymorphism in the angiotensin Iconverting enzyme gene and diabetic nephropathy and proliferative retinopathy in IDDM patients. Diabetes
  279. (1991). Lacunar infarctions due to cholesterol emboli. Stroke
  280. (1991). Lacunar infarcts: A Review. Cerebrovascular diseases
  281. (1986). Lacunar infarcts. Clin Neurol Neurosurg
  282. (1982). Lacunar strokes and infarcts: a review. Neurology
  283. (1991). Lacunar transient ischaemic attacks: a clinically useful concept? Lancet
  284. (2000). Largescale test of hypothesised associations between the angiotensin-convertingenzyme insertion/deletion polymorphism and myocardial infarction in about 5000 cases and 6000 controls.
  285. (2001). Lesser response to angiotensinconverting-enzyme inhibitor therapy in black as compared with white patients with left ventricular dysfunction.
  286. (2001). Linkage disequilibrium between microsatellite markers extends beyond 1 cM on chromosome 20 in Finns. Genome Res
  287. (1990). Linkage of early-onset familial breast cancer to chromosome 17q21. Science
  288. (1991). Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage.
  289. (1992). Lipoprotein and apolipoprotein profile in men with ischemic stroke. Role of lipoprotein(a), triglyceride-rich lipoproteins, and apolipoprotein E polymorphism. Stroke
  290. (1984). Local generation of angiotensin II as a mechanism of regulation of peripheral vascular tone in the rat.
  291. (2002). Localization of a susceptibility gene for common forms of stroke to 5q12.
  292. (1999). London: The Stationary Office,
  293. (1996). London: The Stroke Association,
  294. (1999). Lone atrial fibrillation in elderly persons: a marker for cardiovascular risk. Arch Intern Med
  295. (1994). Long-term risk of recurrent stroke after a first-ever stroke. The Oxfordshire Community Stroke Project. Stroke
  296. (1983). Manifestations of coronary disease predisposing to stroke. The Framingham study. Jama
  297. (1989). Mapping mendelian factors underlying quantitative traits using RFLP linkage maps. Genetics
  298. (2002). Mechanisms of acute cerebral infarctions in patients with middle cerebral artery stenosis: a diffusion-weighted imaging and microemboli monitoring study. Ann Neurol
  299. (1987). Mendelian etiologies of stroke.
  300. (2004). Meta-analysis of genetic studies in ischemic stroke: thirty-two genes involving approximately 18,000 cases and 58,000 controls. Arch Neurol
  301. (1989). Meta-analysis of relation between cigarette smoking and stroke. Bmj
  302. (1998). Meta-analysis of the ACE gene in ischaemic stroke.
  303. (1981). Metabolic studies in unaffected co-twins of non-insulin-dependent diabetics.
  304. (1992). Metabolism of angiotensin I by different tissues in the intact animal.
  305. (1994). Molecular approach to assessing the genetic risk of cerebral infarction: deletion polymorphism in the gene encoding angiotensin 1-converting enzyme.
  306. (1996). Molecular biology and genetics of the angiotensin-I-converting enzyme: potential implications in cardiovascular diseases. Cardiovasc Res
  307. (1991). Molecular biology of the renin-angiotensin system: implications for hypertension and beyond.
  308. (1993). Molecular biology of the reninangiotensin system. Circulation
  309. (1996). Molecular dissection of a major gene effect on a quantitative trait: the level of alcohol dehydrogenase expression in Drosophila melanogaster. Genetics
  310. (1983). Mortality from coronary heart disease and stroke in relation to degree of glycaemia: the Whitehall study.
  311. (1994). Mortality in relation to consumption of alcohol: 13 years' observations on male British doctors. Bmj
  312. (1999). Mortality Statistics: Cause. Review of the Registrar General on deaths by cause, sex and age, in England and Wales,
  313. (1991). MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (70-99%) or with mild (0-29%) carotid stenosis. European Carotid Surgery Trialists' Collaborative Group. Lancet
  314. (1995). Multiple significance tests: the Bonferroni method. Bmj
  315. (1983). Multivariate logistic analysis of risk factors for stroke in Tilburg, The Netherlands. Am J Epidemiol
  316. (2003). Mutation of MEF2A in an inherited disorder with features of coronary artery disease. Science
  317. (2004). Mutation screen of the glutamate decarboxylase-67 gene and haplotype association to unipolar depression.
  318. (2005). Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis. Nat Genet
  319. (1996). National patterns of warfarin use in atrial fibrillation. Arch Intern Med
  320. (2001). National Service Framework for Older People.
  321. (1998). Natriuretic peptides.
  322. (1998). Neurology and the blood: haematological abnormalities in ischaemic stroke.
  323. (1991). Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures.
  324. (1994). No effect of insertion/deletion polymorphism at the ACE locus on normal blood pressure level or variability. Clin Genet
  325. (1988). Office for Health Economics,
  326. (1985). Outlook after an acute stroke: urinary incontinence and loss of consciousness compared in 532 patients.
  327. (1997). Parental history of cardiovascular disease and risk of stroke. A prospective follow-up of 14371 middle-aged men and women in Finland. Stroke
  328. (2002). Pathophysiologic and therapeutic importance of tissue ACE: a consensus report. Cardiovasc Drugs Ther
  329. (1991). Peroxynitrite oxidation of sulfhydryls. The cytotoxic potential of superoxide and nitric oxide.
  330. (2003). Phenotype modulators in myophosphorylase deficiency. Ann Neurol
  331. (2004). Physical activity and angiotensin-converting enzyme gene polymorphism in mild hypertensives.
  332. (1997). PIA1/A2 polymorphism of platelet glycoprotein IIIa and risks of myocardial infarction, stroke, and venous thrombosis. Lancet
  333. (1999). Plasma antithrombin III deficiency in ischaemic stroke in the young. Neurol India
  334. (2001). Plasma concentration of C-reactive protein and risk of ischemic stroke and transient ischemic attack: the Framingham study. Stroke
  335. (2005). Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. Jama
  336. (2003). Plasma lipid profile and incident ischemic stroke: the Atherosclerosis Risk
  337. (1998). Platelet GP IIIa PlA and GP Ib variable number tandem repeat polymorphisms and markers of platelet activation in acute stroke. Arterioscler Thromb Vasc Biol
  338. (1997). Polymorphism of angiotensin converting enzyme, angiotensinogen, and apolipoprotein E genes in a Japanese population with cerebrovascular disease.
  339. (1997). Polymorphism of the angiotensin-converting enzyme (ACE) gene in patients with thrombotic brain infarction. Atherosclerosis
  340. (1998). Polymorphisms of platelet membrane glycoprotein Ib associated with arterial thrombotic disease. Blood
  341. (1994). Polymorphisms of the angiotensin-converting-enzyme gene in subjects who die from coronary heart disease.
  342. (2002). Possible roles of angiotensin II-forming enzymes, angiotensin converting enzyme and chymase-like enzyme, in the human aneurysmal aorta. Hypertens Res
  343. (2004). Power for genetic association studies with random allele frequencies and genotype distributions.
  344. (1988). Precursors of essential hypertension: body weight, alcohol and salt use, and parental history of hypertension. Prev Med
  345. (1997). Precursors of extracranial carotid atherosclerosis in the Framingham Study.
  346. (1995). Predictors of major vascular events in patients with a transient ischemic attack or minor ischemic stroke and with nonrheumatic atrial fibrillation. European Atrial Fibrillation Trial (EAFT) Study Group. Stroke
  347. (1985). Pressor effects of alcohol in normotensive and hypertensive subjects. Lancet
  348. (1998). Prevalence of apolipoprotein E alleles in healthy subjects and survivors of ischemic stroke: an Italian Case-Control Study. Stroke
  349. (1993). Prevalence of apolipoprotein E phenotypes in ischemic cerebrovascular disease. A casecontrol study. Stroke
  350. (1998). Prevalence of atrial fibrillation and eligibility for anticoagulants in the community. Lancet
  351. (1996). Prevalence of self reported stroke in a population in northern England.
  352. (1998). Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group.
  353. (1991). Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension.
  354. (1992). Prevention of structural changes in the heart in hypertension by angiotensin converting enzyme inhibition. J Hypertens Suppl
  355. (2002). Primary prevention of ischemic stroke: A statement for healthcare professionals from the Stroke Council of the American Heart Association.
  356. (1998). Primatesta Pe. Health Survey for England:Cardiovascular disease
  357. (1991). Probability of stroke: a risk profile from the Framingham Study. Stroke
  358. (1990). Prognosis of transient ischemic attacks
  359. (1992). Programmed cell death: the paths to suicide. Trends Neurosci
  360. (1999). Prospective evaluation of the angiotensin-converting enzyme insertion/deletion polymorphism and the risk of stroke. Circulation
  361. (1998). Prospective study of coronary heart disease incidence in relation to fasting total homocysteine, related genetic polymorphisms, and B vitamins: the Atherosclerosis Risk in Communities (ARIC) study. Circulation
  362. (1995). Prospective study of serum total homocysteine concentration and risk of stroke in middleaged British men. Lancet
  363. (2003). Protein C deficiency manifesting as an acute myocardial infarction and ischaemic stroke. Heart
  364. (1994). Pure motor hemiparesis and sensorimotor stroke. Accuracy of very early clinical diagnosis of lacunar strokes. Stroke
  365. (1965). Pure Motor Hemiplegia of Vascular Origin. Arch Neurol
  366. (1965). Pure Sensory Stroke Involving Face, Arm, and Leg. Neurology
  367. (2002). Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme.
  368. (1990). Racial differences in the anterior circulation in cerebrovascular disease. How much can be explained by risk factors? Arch Neurol
  369. (2004). Racial' differences in genetic effects for complex diseases. Nat Genet
  370. (1997). Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Lancet
  371. (2001). Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack. Lancet
  372. (1998). Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST). Lancet
  373. (2005). Relation of C-reactive protein to stroke, cognitive disorders, and depression in the general population: systematic review and meta-analysis. Lancet Neurol
  374. (1992). Relationship of cardiac disease to stroke occurrence, recurrence, and mortality. Stroke
  375. (1968). Relationship of stroke to other cardiovascular disease. Circulation
  376. (1995). Relationship of the apolipoprotein E polymorphism with carotid artery atherosclerosis.
  377. (1997). Relative mutation rates at di-, tri-, and tetranucleotide microsatellite loci.
  378. (2004). Reply to "A call for accurate phenotype definition in the study of complex disorders"
  379. (1989). Risk factors and clinical manifestations of pathologically verified lacunar infarctions. Stroke
  380. (1994). Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials. Arch Intern Med
  381. (1991). Risk factors for stroke in middle aged British men. Bmj
  382. (1991). Risk factors for subarachnoid hemorrhage in a longitudinal population study.
  383. (1995). Role of the deletion of polymorphism of the angiotensin converting enzyme gene in the progression and therapeutic responsiveness of IgA nephropathy.
  384. (1998). Saltsensitive aortic aneurysm and rupture in hypertensive transgenic mice that overproduce angiotensin II. Lab Invest
  385. (1999). Saving Lives: Our healthier nation.
  386. (1997). Scottish Intercollegiate Guidelines Network. Management of patients with stroke 1: assessment, investigation, immediate management and secondary prevention.
  387. (1998). Screening for atrial fibrillation in primary care. Heart
  388. (2000). Searching for genetic determinants in the new millennium.
  389. (1993). Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke.
  390. (1995). Segregation and linkage analysis of serum angiotensin I-converting enzyme levels: evidence for two quantitative-trait loci.
  391. (1989). Selected cognitive losses after stroke. Frequency, recovery and prognostic importance. Int Disabil Stud
  392. (1987). Selfreported transient ischemic attack and stroke symptoms: methods and baseline prevalence.
  393. (1997). Sensitivity to cerebral ischaemic insult in a rat model of stroke is determined by a single genetic locus. Nat Genet
  394. (1977). Sensorimotor stroke due to thalamocapsular ischemia. Arch Neurol
  395. (1999). Sequence variation in the human angiotensin converting enzyme. Nat Genet
  396. (1989). Serum cholesterol levels and six-year mortality from stroke in 350,977 men screened for the multiple risk factor intervention trial.
  397. (1991). Serum lipids and lipoproteins are less powerful predictors of extracranial carotid artery atherosclerosis than are cigarette smoking and hypertension. Mayo Clin Proc
  398. (1999). Seven lessons from two candidate genes in human essential hypertension: angiotensinogen and epithelial sodium channel. Hypertension
  399. (2002). Severity of meningococcal disease in children and the angiotensin-converting enzyme insertion/deletion polymorphism. Am J Respir Crit Care Med
  400. (1981). Sex differences in the incidence of cerebrovascular disease.
  401. (1992). Sib pair linkage analysis of renin gene haplotypes in human essential hypertension. Hum Genet
  402. (1979). Sickle cell anemia as a syndrome: a review of diagnostic features.
  403. (1990). Similar frequencies of renin gene restriction fragment length polymorphisms in hypertensive and normotensive subjects. Hypertension
  404. (1989). Smoking as a risk factor for cerebral ischaemia. Lancet
  405. (1994). Stroke (acute cerebrovascular disease). In: Stevens A and
  406. (1986). Stroke and alcohol consumption.
  407. (1998). Stroke care: reducing the burden of disease. London: The Stroke Association,
  408. (1999). Stroke epidemiology, evidence and clinical practice.
  409. (1988). Stroke incidence and risk factors for stroke in Copenhagen, Denmark. Stroke
  410. (1995). Stroke incidence, case fatality, and mortality in the WHO MONICA project. World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease. Stroke
  411. (1990). Structural alterations of the renin gene in stroke-prone spontaneously hypertensive rats: examination of genotypephenotype correlations.
  412. (1994). Structural constraints of inhibitors for binding at two active sites on somatic angiotensin converting enzyme.
  413. (2003). Structure of human ACE gives new insights into inhibitor binding and design. Trends Pharmacol Sci
  414. (1991). Structure of the angiotensin I-converting enzyme gene. Two alternate promoters correspond to evolutionary steps of a duplicated gene.
  415. (1990). Substrate-dependent angiotensin II formation in the peripheral circulation. Life Sci
  416. (1993). Surveys ftOoPCa. Health Survey for England
  417. (1984). Synaptic release of excitatory amino acid neurotransmitter mediates anoxic neuronal death.
  418. (2001). Systematic review of long term anticoagulation or antiplatelet treatment in patients with non-rheumatic atrial fibrillation. Bmj
  419. (1995). Ten year cerebrovascular morbidity and mortality in 68 year old men with asymptomatic carotid stenosis. Bmj
  420. (1956). The amino acid composition of hypertensin II and its biochemical relationship to hypertensin I.
  421. The amino acid sequence of hypertensin.
  422. (1997). The apolipoprotein E and beta-fibrinogen G/A-455 gene polymorphisms are associated with ischemic stroke involving large-vessel disease. Arterioscler Thromb Vasc Biol
  423. (2000). The association between the Val34Leu polymorphism in the factor XIII gene and brain infarction. Blood
  424. (1993). The Atherosclerosis Risk in Communities Study. Circulation
  425. (1991). The cardiac renin-angiotensin system: a synopsis of current experimental and clinical data. Acta Cardiol
  426. (1948). The causation of acute arterial necrosis in hypertensive disease.
  427. (2000). The causes and risk of stroke in patients with asymptomatic internal-carotid-artery stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators.
  428. (1989). The contractile effects of porcine tetradecapeptide renin substrate in human resistance vessels: evidence of activation by vascular wall renin and serine proteases.
  429. (1999). The DD genotype of the ACE gene polymorphism is associated with progression of diabetic nephropathy to end stage renal failure in IDDM. Clin Nephrol
  430. (1994). The epidemiological association between blood pressure and stroke: implications for primary and secondary prevention. Hypertension Research
  431. (2004). The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke. Nat Genet
  432. (2003). The gene encoding phosphodiesterase 4D confers risk of ischemic stroke.
  433. (2003). The genetics of coronary heart disease: the contribution of twin studies. Twin Res
  434. (1998). The Greater Cincinnati/Northern Kentucky Stroke Study: preliminary first-ever and total incidence rates of stroke among blacks. Stroke
  435. (1986). The Health of the Nation: a strategy for health in England. Cm
  436. (1995). The Human Brain and Spinal Cord: Functional Neuroanatomy and Dissection Guide.
  437. (1993). The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell
  438. (1999). The impact of smoke-free workplaces on declining cigarette consumption in Australia and the United States.
  439. (1994). The importance of family history in cerebrovascular disease. Stroke
  440. (1991). The mRNAs encoding the two angiotensinconverting isozymes are transcribed from the same gene by a tissue-specific choice of alternative transcription initiation sites.
  441. (1987). The natural history of lacunar infarction: the Oxfordshire Community Stroke Project. Stroke
  442. (1985). The neurotoxicity of excitatory amino acids is produced by passive chloride influx.
  443. (1993). The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature
  444. (1990). The perils of obesity in middle-aged women.
  445. The preparation and function of the hypertensin-converting enzyme.
  446. (1999). The prevalence of stroke and associated disability.
  447. (1999). The protective effect of moderate alcohol consumption on ischemic stroke. Jama
  448. The purification of hypertensin II.
  449. (1996). The region responsible for stroke on chromosome 4 in the stroke-prone spontaneously hypertensive rat.
  450. (1990). The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death. Annu Rev Neurosci
  451. (1994). The role of lifestyle factors in the etiology of stroke. A population-based case-control study in Perth,
  452. (1998). The role of tissue angiotensin-converting enzyme (ACE): studies of ACE mutant mice.
  453. (1984). The study of human twins in medical research.
  454. (1957). The toxic effect of sodium L-glutamate on the inner layers of the retina.
  455. (2002). The World Health Report 2002; Reducing Risks, Promoting Healthy Life. Geneva: World Health Organisation,
  456. (1996). Thickening of the carotid wall. A marker for atherosclerosis in the elderly? Cardiovascular Health Study Collaborative Research Group. Stroke
  457. Thienopyridine derivatives (ticlopidine, clopidogrel) versus aspirin for preventing stroke and other serious vascular events in high vascular risk patients. Cochrane Database Syst Rev 2000a:
  458. (2000). Thienopyridines or aspirin to prevent stroke and other serious vascular events in patients at high risk of vascular disease? A systematic review of the evidence from randomized trials. Stroke
  459. (1981). Thresholds in cerebral ischemia - the ischemic penumbra. Stroke
  460. (1990). Tissue renin systems as a possible factor in hypertension. In:
  461. (1987). Tissue renin-angiotensin systems: focus on the heart. J Hypertens Suppl
  462. (1993). Tissue renin-angiotensin systems. Their role in cardiovascular disease. Circulation
  463. (1987). Tissue-specific regulation of renin expression in the mouse. Hypertension
  464. (1997). tobacco control policies and smoking among young adults.
  465. (1991). Transgenic mice demonstrate a testis-specific promoter for angiotensinconverting enzyme.
  466. (1989). Transient increase in the expression of cardiac angiotensinogen in a rat model of myocardial infarction and failure (abstract). Circulation
  467. (1991). Transient ischaemic attacks and small-vessel disease. Dutch TIA Study Group. Lancet
  468. (1997). Transient neurological attacks in the general population. Prevalence, risk factors, and clinical relevance. Stroke
  469. (1993). Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM).
  470. (2001). Tsongalis GJ. Correlation of polymorphisms to coagulation and biochemical risk factors for cardiovascular diseases.
  471. (1987). Twin studies of coronary heart disease and its risk factors. Acta Genet Med Gemellol (Roma)
  472. (2000). Two loci on chromosomes 2 and X for premature coronary heart disease identified in early- and late-settlement populations of Finland.
  473. (1988). Two putative active centers in human angiotensin I-converting enzyme revealed by molecular cloning.
  474. (1992). Type and extent of hemispheric brain infarctions and clinical outcome in early and delayed middle cerebral artery recanalization. Neurology
  475. (1992). Use of alternative polyadenylation sites for tissue-specific transcription of two angiotensinconverting enzyme mRNAs. Nucleic Acids Res
  476. (1995). Validation of a population screening questionnaire to assess prevalence of stroke. Stroke
  477. (1997). Variations on a theme: cataloging human DNA sequence variation. Science
  478. (1993). Vascular cell adhesion molecule-1 (VCAM-1) gene transcription and expression are regulated through an antioxidant-sensitive mechanism in human vascular endothelial cells.
  479. (1979). Vascular renin-like activity and blood pressure maintenance in the rat. Studies of the effect of changes in sodium balance, hypertension and nephrectomy. Hypertension
  480. (1997). Ventricular dysfunction and the risk of stroke after myocardial infarction.
  481. (1998). What's wrong with Bonferroni adjustments. Bmj
  482. (2004). Whole-genome scan, in a complex disease, using 11,245 single-nucleotide polymorphisms: comparison with microsatellites.

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