Current and future concepts in stroke prevention

Abstract

STROKE IS A MAJOR CAUSE OF MORBIDITY and mortality in an aging population. The current understanding of the pathophysiology of atherosclerotic diseases, the most common cause of stroke, and the evidence for existing therapeutic interventions for the prevention of stroke are presented. Specifically, we review the evidence for antiplatelet agents, anticoagulants, antihypertensive medications, lipidlowering agents and carotid endarterectomy for stroke prevention. primary preventive measure, antiplatelet agents do not reduce the risk of ischemic stroke among patients without vascular disease. They are associated with an increased risk of intracranial hemorrhage (odds ratio [OR] 1.35, 95% confidence interval [CI] 0.88-2.10) 23 and major noncerebral hemorrhage (OR 1.73, 95% CI 1.14-2.63 ). 24 The benefits of ASA in the secondary prevention of stroke have been well documented in the period immediately after a stroke 25 (Table 1). Long-term antiplatelet treatment after stroke shows an even more impressive reduction of 25 nonfatal strokes and 36 serious vascular events per 1000 treated over a 29-month follow-up period. 25 There appears to be no difference in efficacy between low (50 mg) and higher doses (up to 1500 mg) of ASA. 29,30 The combination of dipyridamole and ASA has been shown to reduce the relative risk of recurrent stroke compared with ASA alone 26 (Table 1). Dipyridamole inhibits platelet aggregation by increasing levels of cyclic adenosine monophosphate and cyclic guanosine monophosphate. The limiting factor in the use of the ASAdipyridamole combination is the latter's potential effects on coronary perfusion. Dipyridamole can cause coronary vasodilation, which results in increased blood flow to nonstenosed coronary arteries. The result is that myocardial ischemia may be provoked during exercise. As such, the current American College of Cardiology/American Heart Association guidelines recommend that dipyridamole not be used in patients with chronic stable angina. 31 However, this recommendation was based on shortacting dipyridamole, which also reduced myocardial ischemia in a similar number of patients in the study quoted by these guidelines. 32 With the use of sustained-release dipyridamole, no increase in cardiac events was observed in subjects with prior coronary artery disease. 33 Thienopyridines block adenosine-diphosphate-mediated platelet aggregation. Ticlopidine was the first of this class of drug to be studied for stroke prevention. One clinical trial demonstrated that patients treated with ticlopidine had similar rates of stroke as those treated with ASA 28 (Table 1). However, serious granulocytopenia associated with ticlo- Leukocytes localize in the earliest atherosclerotic lesions, binding to vascular cell adhesion molecules (VCAM-1) on the vascular endothelium and migrating into the intima. This initiates and perpetuates a local inflammatory response. Monocytes mature into lipid-scavenging macrophages and subsequently foam cells. T-lymphocytes express inflammatory cytokines, which cont...

Mechanisms of anti-inflammatory and neuroprotective actions of PPAR-gamma agonists

“…In both SCI as well as cerebral ischemia models, PPAR-alpha agonists exert neuroprotection primarily when administered prior to the injury, mainly by increasing endothelial-dependent vasodilation, which is independent of eNOS, since fibrates have limited capability to cross the BBB (26,42). Fibrates prevent secondary neuronal death by oxidative stress by enhancing the expression of anti-oxidant enzyme, Cu/Zn-SOD and by decreasing VCAM-1 expression in CNS blood vessels, possibly by inhibiting the NF-kappaB pathway (42,108).…”

Associação entre fatores de risco cardiovascular e proteína C-reativa em mulheres idosas

“…Atualmente existem muitas evidências sobre o papel do processo inflamatório na fisiopatogenia da aterosclerose, sendo amplamente aceito que a inflamação em nível endotelial é o seu fator desencadeador (16,23) . Níveis plasmáticos de marcadores inflamatórios, particularmente a proteína C-reativa (PCR), mostram-se preditivos para angina instável, infarto do miocárdio e morte súbita em indivíduos adultos e idosos, com ou sem doença cardiovascular (DCV) estabelecida, com mais eficiência do que poderia ser estimado pelos fatores de risco tradicionais (5, 9 ,12, 14, 19, 24, 28) .…”

Stroke prevention

“…Care for stroke patients accounts for 2.1% of Canadian health care expenditures. 1 The burden of this devastating disease can be reduced through a combination of clinical interventions targeted at high-risk individuals and broader population-health initiatives to control chronic diseases. 2 The causes and mechanisms of stroke vary.…”

“…1 Some risk factors for stroke, such as age, gender, ethnicity and genetic factors, cannot be modified. Others, if moderated, can greatly reduce both the likelihood of stroke and the severity of its outcomes: physical inactivity, hypertension, smoking, dyslipidemia, atrial fibrillation, diabetes and heavy use of alcohol.…”