Prof. Guido Grassi
Based on the role exerted by the various risk factors in the pathophysiology of stroke, the 2011 stroke guidelines of the American Heart Association/American Stroke Association make a series of recommendations, which can schematically be summarised as follows :
Optimal stroke prevention and management is a major public health challenge. The World Health Organisation estimates that approximately 5.5 million stroke-related deaths occurred in 2002 with, however, a reduction in stroke-related fatal events by about 1/3 in recent years. This decline has enabled a greater number of patients to survive acute cerebrovascular events but many of which, in turn, present in our daily practice with serious long-term physical and mental disabilities. In addition, there is growing evidence that stroke incidence on the other hand, as assessed by stroke hospitalisation, has increased in recent years (1). Taken together these epidemiological findings emphasise the need for reduction of stroke occurrence, through improvement of both the primary and secondary prevention of cerebrovascular disease, and more generally, prevention of cardiovascular disease as a whole.
The 2011 guidelines for primary prevention (2), offer an updated revision of the 2006 document (3). The focus is not only on ischaemic stroke but also on haemorragic stroke. The document examines the “old” and the “new” risk factors of the disease and underlines strategies of intervention for reducing the burden of cerebrovascular disease. The new document develops its recommendations in regards to the risk factors of stroke, based on lifestyle modifications and drug treatment according to strength of supporting documentation. Among non-modifiable risk factors are age, sex, ethnicity as well as birth weight and genetic predisposition. It emphasises the need to improve our knowledge regarding the influence of low birth weight and genetic factors, which are the factors largely responsible for fetal malnutrition, in the view that improved specific gene therapies and socio-economic conditions will become available in the near future.
Table 1 summarises the modifiable risk factors of stroke, the relative risk of each condition as well as reversibility by treatment. Hypertension is the most important risk factor of stroke. Indeed, elevated blood pressure values are thought to be responsible for around 2/3 of haemorragic and ischaemic stroke events. Detailed analyses of the results of large scale observational studies have indicated that stroke incidence is
In reviewing the possible strategies for the choice of the most appropriate antihypertensive drug treatment for the individual patient, guidelines emphasise that at present there is no evidence that one drug class provides superior cerebrovascular protection to another, whether from reduction of elevated blood pressure values or specific additive favorable effects on the brain. This means that blood pressure reduction and optimal blood pressure control are the leading strategies for primary prevention of stroke. Unfortunately though, blood pressure control in various populations remains clearly unsatisfactory, and this finding may in a large part explain why the incidence of stroke has remained elevated in the last decades.
Beyond blood pressure, diabetes mellitus deserves to be addressed in detail, given the results of recent interventional trials (5). No doubt exists that the diabetic state is an important risk factor for stroke. In diabetic hypertensives, the administration of ACE-inhibitors or angiotensin II receptor blockers is effective in reducing the stroke risk by about 20 to 30% according to the results of the various studies performed thus far. However, there is no evidence that intensive glycaemic control reduces the risk of stroke in diabetic patients, as the results of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and The Action in Diabetes and Vascular Disease: PreterAx and DiamacroN MR Controlled Evaluation (ADVANCE) trial clearly suggest (6,7). In contrast, stroke risk can be favorably affected by statin treatment in diabetic patients, as suggested by the positive results of the Justification for the Use of statin in prevention: an Intervention Trial Evaluating Rosuvastatin (Jupiter) study (8).
Relatively “new” stroke risk factors are overweight and obesity, metabolic syndrome, obstructive sleep apnea, hyperhomocysteinemia, elevated circulating plasma levels of lipoprotein a and acquired or hereditary forms of hypercoagulation. A potential risk factor that will deserve greater attention in the future, when the data of ongoing studies will become available, is the inflammatory process, the link with stroke would be that inflammation affects the atherosclerotic plaque in its different sequential steps.
While there is overwhelming evidence that in high risk patients, aspirin is indicated for cardiovascular and cerebrovascular prevention, there is at present no data supporting the use of aspirin in stroke prevention in low-risk or in diabetic patients, even in cases where peripheral artery disease is concomitantly detected.
Several stroke risk scales have been developed over the years to collect information on the probability of the individual subject to develop in a ten-year life span a stroke event, but not one can be regarded as gold-standard. A widely used scale is the Framingham Stroke profile (9), which takes into account independent risk predictors such as age, systolic blood pressure, hypertension, diabetes mellitus, cigarette smoking, established cardiovascular disease, atrial fibrillation and left ventricular hypertrophy. An updated version of the Framingham stroke risk chart has recently included the use of antihypertensive drug treatment among risk factors.
Table 1. Relative risk (RR) and risk reduction with treatment of a number of risk factors for stroke. (Modified from Ref. 2)
1. Lloyd-Jones D, Adams RJ, Brown TM, et al. Heart disease and stroke statistics—2010 update: a report from the American Heart Association. Circulation. 2010;121:e46–e215. 2. Goldstein LB, Bushnell CD, Adams RJ, et al.; on behalf of the American Heart Association Stroke Council; Council on Cardiovascular Nursing; Council on Epidemiology and Prevention; Council for High Blood Pressure Research; Council on Peripheral Vascular Disease, and Interdisciplinary Council on Quality of Care and Outcomes Research. Guidelines for the Primary Prevention of Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2011;42:517-584 3. Goldstein LB, Adams R, Alberts MJ, Appel LJ, et al. Primary prevention of ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council: cosponsored by the Atherosclerotic Peripheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group. Stroke. 2006;37:1583–1633. 4. Mancia G, De Backer G, Dominiczak A, et al. Management of Arterial Hypertension of the European Society of Hypertension; European Society of Cardiology. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2007;25:1105-1187. 5. Patel A, MacMahon S, Chalmers J, et al. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomized controlled trial. Lancet. 2007;370:829–840. 6. Gerstein HC, Miller ME, Byington RP, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545–2559. 7. Patel A, MacMahon S, Chalmers J, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358:2560 –2572. 8. Ridker PM, Danielson E, Fonseca FAH, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. NEJM. 2008;359:2195–2207. 9. Wang TJ, Massaro JM, Levy D, et al. A risk score for predicting stroke or death in individuals with new-onset atrial fibrillation in the community: the Framingham Heart Study. JAMA. 2003;290:1049 –1056.
Clinica Medica, Università Milano Bicocca, Milan, Italy
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