The Imperative of Primary Stroke Prevention: First Things First

Updated:May 27,2014

The Imperative of Primary Stroke Prevention: First Things First

Disclosure: NONE
Pub Date: Thursday, Dec. 2, 2010
Author: Natalia Rost, MD


Goldstein LB, Bushnell CD, Adams RJ, et al; on behalf of the American Heart Association Stroke Council, Council on Cardiovascular and stroke 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 2010: published online before print December 2, 2010, 10.1161/STR.0b013e3181fcb238.

Article Text

Despite the recent advances in medical science, the folk wisdom of "prevention is better than cure" remains unequivocally true for stroke and other cerebrovascular disease. In this issue of Stroke, the statement from the American Heart Association/American Stroke Association Council on Stroke [1] provides the background and a thorough analysis of data to reinforce what is already a concerted effort in the field: each stroke can be and should be prevented. Since its previous edition,[2] the Guidelines for the Primary Prevention of Stroke are both more robust, fortified by the array of current evidence, and more extensive, offering broader scope on stroke and equipped with the strategies to reduce risk of stroke that are more patient oriented and widely applicable than ever.

The new guidelines bear few surprises; rather, they strongly build onto the existing foundation of ongoing and ever-so-complex science of stroke prevention.[1] The motivation for advancing the primary prevention measures is stated quite clearly in the paper: despite reduction in stroke mortality rates over the past decade,[3,4] overall stroke incidence is unyielding, along with its health care and humanitarian costs as the leading cause of adult disability.[5] Preventive measures focused on risk factor control have been shown to work on a population scale, both in stroke and cardiovascular disease[6,7]; however, in the new guidelines, Goldstein et al. emphasize that an individual patient-oriented approach to stroke prevention may provide additional tools necessary to address the depth and the scope of issues in primary prevention of stroke.[1]

Risk factors that are generally thought to be non-modifiable identify the persons who are at higher risk for stroke and in whom methodical primary prevention through thorough control of other modifiable risk factors may be vital.[2] The contribution of age, sex, and racial and ethnic background on the risk of incident and recurrent stroke continues to vary across populations[8-10]; furthermore, the influence of these factors may potentially be mediated through a variety of complex hereditary mechanisms of disease specific to each of the demographic categories.[11,12] Unlike the effects of known monogenic disorders associated with stroke and other cerebrovascular disease (such as distinct hypercoagulability disorders, Fabry disease, or familial cerebral aneurysm syndromes etc.), the attributable risk of complex genetic traits is difficult to estimate.[13,14] Evidence of common genetic risk factors between stroke and other vascular disorders has now been convincingly demonstrated in recent large-scale genome-wide association studies [15-17] providing much needed clues to underlying biology of disease; nevertheless, the genetic architecture of stroke is yet to be fully uncovered.[16,18,19] In the future, genetic studies, including the pharmacogenetics and pharmacogenomics of stroke, may indeed offer hope of turning non-modifiable risk factors into potentially modifiable.[20-22

For the risk factors traditionally thought of as modifiable, the message remains loud and clear: They should and can be modified to contribute to lowering the risk of incident strokes, and we should be doing a better job with that.[23,24] Modifying the most important contributing risk factors for both ischemic and hemorrhagic stroke such as hypertension and cigarette smoking is supported by the strongest level of evidence [25-27] and, theoretically, should have an array of strategies proven to work in different subgroups of patients with equal success.[28-30] The benefit of hypertension treatment is clear even in patients with diabetes mellitus,[31] despite the fact that the evidence for tight glycemic control reducing the risk of incident stroke remains elusive in this subgroup.[32-34] Similarly, whereas benefits of statins for primary stroke prevention in patients with coronary heart disease or diabetes and dyslipidemia have been well demonstrated,[35] no further indications for statin use in primary stroke prevention have been supported to date.[36-38] Otherwise, the scope of recommendations varies significantly for various and multiple potentially modifiable risk factors, ranging from the strongest level of evidence supporting the use of adjusted-dose warfarin (target international normalized ratio 2.0-3.0)(Class I, Level A) to the much less decisive support for interventional treatment of asymptomatic carotid stenosis in the face of recently completed trials' data,[39-41] as well as the ever-changing and more rigorous than ever standards of the so-called "best medical therapy."[42] All things considered, however, the total attributable risk of stroke from the risk factors that are readily modifiable but notoriously difficult to modify due to lack of patient compliance (such as hypertension, smoking, physical inactivity, obesity, high-sodium/high-fat diets) is above and beyond the contribution of some of the other low-prevalence conditions of unclear significance (such as patent foramen ovale [43] and asymptomatic carotid stenosis [44]); therefore, the focus of primary stroke prevention in these new guidelines remains rightfully on the maximizing the "major offenders" (including the mandatory lifestyle changes) [45] in the patients with a mix of vascular risk factors as part of the current, state-of-the-art "best medical treatment" approach.[1]

Whereas, there is currently a plethora of targeted treatments for known vascular risk factors, the arsenal of specific treatments in primary prevention of stroke continues to be limited.[1] Prior attempts of lowering elevated serum homocysteine and lipoprotein (a) with vitamins to reduce the risk of incident stroke were inconclusive[46-48]; moreover, antibiotics in chronic inflammatory states and aspirin in those with persistently elevated antiphospholipid antibodies were proven ineffective, at best.[49] New in the current guidelines are the data extracted from the large, prospective studies of statins in primary prevention of cardiovascular events among patients with elevated levels of pro-inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP), notably the JUPITER trial.[50] Based on these data, the authors propose, at least, some level of support for considering statin use as part of primary stroke prevention in patients with elevated levels of hs-CRP, and with this, offering a new targeted treatment in primary prevention of stroke.[1] Alternatively, for those who prefer the "tried and true," low-dose aspirin use for cardiovascular (yet not specific to stroke except for women) prophylaxis remains the staple of primary prevention in a population with overall 10-year cardiovascular event risk of at least 6% to 10%.[51]

In summary, the new guidelines are robust and timely in getting their message across: (1) screen patients early for risk of incident stroke, (2) in those patients with higher risk of stroke from non-modifiable factors, focus in particular on rigorous control of their modifiable risk factors, (3) do a better job in modifying the lifestyle factors and the major treatable factors such as hypertension using all of the possible targeted treatments available with the goal of gaining control over them, (4) seize the opportunity to intervene early and at every occasion one may have, including the screening and counseling in the emergency departments for visits not necessarily related to cerebrovascular events, and finally, (5) do not retreat: we can and must systematically identify and manage the risk factors in order for a primary prevention program to work. The incidence rates of stroke in the United States do not yield - and neither should we.


  1. 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 2010: published online before print December 2, 2010, 10.1161/STR.0b013e3181fcb238.
  2. Goldstein LB, Adams R, Alberts MJ, 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: The American Academy of Neurology affirms the value of this guideline. Stroke 2006;37:1583-1633.
  3. Schwamm L, Fayad P, Acker JE III, et al. Translating evidence into practice: a decade of efforts by the American Heart Association/American Stroke Association to reduce death and disability due to stroke: a presidential advisory from the American Heart Association/American Stroke Association. Stroke 2010;41(5):1051-65.
  4. Towfighi A, Ovbiagele B, Saver JL. Therapeutic milestone: stroke declines from the second to the third leading organ- and disease-specific cause of death in the United States. Stroke 2010;41:499-503.
  5. Lloyd-Jones D, Adams RJ, Brown TM, et al; on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Executive summary: heart disease and stroke statistics - 2010 update: a report from the American Heart Association. Circulation 2010;121:948-954.
  6. Pearson TA, Bazzarre TL, Daniels SR, et al. American Heart Association guide for improving cardiovascular health at the community level: a statement for public health practitioners, healthcare providers, and health policy makers from the American Heart Association Expert Panel on Population and Prevention Science. Circulation 2003;107:645-651.
  7. Goldstein LB, Rothwell PM. Advances in prevention and health services delivery 2009. Stroke 2009;41:e71-73.
  8. Petrea RE, Beiser AS, Seshadri S, et al. Gender differences in stroke incidence and poststroke disability in the Framingham heart study. Stroke 2009;40:1032-1037.
  9. van Asch CJ, Luitse MJ, Rinkel GJ, et al. Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis. Lancet Neurol 2010;9:167-76.
  10. Kleindorfer D. Sociodemographic groups at risk: Race/ethnicity. Stroke 2009;40:S75-78.
  11. Schulz UG, Flossmann E, Rothwell PM. Heritability of ischemic stroke in relation to age, vascular risk factors, and subtypes of incident stroke in population-based studies. Stroke 2004;35:819-824.
  12. Seshadri S, Beiser A, Pikula A, et al. Parental occurrence of stroke and risk of stroke in their children: the Framingham study. Circulation 2010;121:1304-1312.
  13. Dichgans M. Genetics of ischaemic stroke. Lancet Neurol 2007;6:149-61.
  14. de Bakker PI, Rosand J. In search of genes for stroke. Lancet Neurol 2007;6:383-4.
  15. Gschwendtner A, Bevan S, Cole JW, et al. Sequence variants on chromosome 9p21.3 confer risk for atherosclerotic stroke. Ann Neurol 2009;65:531-539.
  16. Gudbjartsson DF, Arnar DO, Helgadottir A, et al. Variants conferring risk of atrial fibrillation on chromosome 4q25. Nature 2007;448:353-7.
  17. Anderson CD, Biffi A, Rost NS, et al. Chromosome 9p21 in ischemic stroke: population structure and meta-analysis. Stroke 2010;41:1123-1131.
  18. Rost NS, Greenberg SM, Rosand J. The genetic architecture of intracerebral hemorrhage. Stroke 2008;39:2166-2173.
  19. Meschia JF. Stroke genome-wide association studies: the large numbers imperative. Stroke 2010;41:579-580.
  20. Ansell J, Hirsh J, Hylek E, et al. Pharmacology and management of the vitamin K antagonists. Chest 2008;133:160S-198S.
  21. Mega JL, Close SL, Wiviott SD, et al. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med 2009;360:354-362.
  22. SEARCH Collaborative Group, Link E, Parish S, et al. Slco1b1 variants and statin-induced myopathy - a genomewide study. N Engl J Med 2008;359:789-799.
  23. Kettani FZ, Dragomir A, Cote R, et al. Impact of a better adherence to antihypertensive agents on cerebrovascular disease for primary prevention. Stroke 2009;40:213-220.
  24. Bushnell C, Zimmer L, Schwamm L, et al. The Adherence eValuation After Ischemic Stroke Longitudinal (AVAIL) registry: design, rationale, and baseline patient characteristics. Am Heart J 2009;157:428-435.e422.
  25. Wolf PA, D'Agostino RB, Belanger AJ, Kannel WB. Probability of stroke: a risk profile from the Framingham study. Stroke. 1991;22:312-318.
  26. Feigin V, Parag V, Lawes CM, et al; on behalf of the Asia Pacific Cohort Studies Collaboration. Smoking and elevated blood pressure are the most important risk factors for subarachnoid hemorrhage in the Asia-Pacific region: an overview of 26 cohorts involving 306,620 participants. Stroke 2005;36:1360-1365.
  27. Feldmann E, Broderick JP, Kernan WN, et al. Major risk factors for intracerebral hemorrhage in the young are modifiable. Stroke 2005;36:1881-1885.
  28. Cahill K Stead LF, Lancaster T. Nicotine receptor partial agonists for smoking cessation. Cochrane Database Syst Rev 2008;3:CD006103.
  29. Counseling and interventions to prevent tobacco use and tobacco-caused disease in adults and pregnant women: U.S. Preventive Services Task Force reaffirmation recommendation statement. Ann Intern Med 2009;150:551-555.
  30. Wright JM, Musini VM. First-line drugs for hypertension. Cochrane Database Syst Rev 2009;3:CD001841.
  31. Holman RR, Paul SK, Bethel MA, et al. Long-term follow-up after tight control of blood pressure in type 2 diabetes. N Engl J Med 2008;359:1565-1576.
  32. The Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008;358:2545-2559.
  33. The ADVANCE Collaborative Group, Patel A, MacMahon S, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008;358:2560-2572.
  34. Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 2009;360:129-139.
  35. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002;106:3143-421.
  36. Goldstein LB, Suarez JI. The quest for the "Holy Grail" of ischemic stroke cytoprotection: statins may not be the answer. Neurology 2009;73:2058-2059.
  37. Kastelein JJ, Akdim F, Stroes ES, et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med 2008;358:1431-1443.
  38. Amarenco P, Labreuche J. Lipid management in the prevention of stroke: review and updated meta-analysis of statins for stroke prevention. Lancet Neurol 2009;8:453-63.
  39. Rothwell PM, Goldstein LB. Carotid endarterectomy for asymptomatic carotid stenosis: asymptomatic carotid surgery trial. Stroke 2004;35:2425-2427.
  40. Bain M, Moheet AM, Rasmussen P. Which patients benefit from carotid stenting? What recent trials show. Cleve Clin J Med 2008;75:714-720.
  41. Brott TG, Hobson RW II, Howard G, et al. Stenting versus endarterectomy for treatment of carotid-artery stenosis. N Engl J Med 2010;363(1):11-23.
  42. Marquardt L, Geraghty OC, Mehta Z, Rothwell PM. Low risk of ipsilateral stroke in patients with asymptomatic carotid stenosis on best medical treatment: a prospective, population-based study. Stroke 2010;41:e11-17.
  43. Mattle HP, Meier B, Nedeltchev K. Prevention of stroke in patients with patent foramen ovale. Int J Stroke 2010;5:92-102.
  44. Woo K, Garg J, Hye RJ, Dilley RB. Contemporary results of carotid endarterectomy for asymptomatic carotid stenosis. Stroke 2010;41:975-979.
  45. Lichtenstein AH, Appel LJ, Brands M, et al. Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee. Circulation 2006;114:82-96.
  46. Toole JF, Malinow MR, Chambless LE, et al. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: The vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA 2004;291:565-575.
  47. The Heart Outcomes Prevention Evaluation Investigators. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006;354:1567-1577.
  48. Smolders B, Lemmens R, Thijs V. Lipoprotein (a) and stroke: a meta-analysis of observational studies. Stroke 2007;38:1959-1966.
  49. Doruk E, Melanie JH, Roger L, et al. Aspirin for primary thrombosis prevention in the antiphospholipid syndrome: a randomized, double-blind, placebo-controlled trial in asymptomatic antiphospholipid antibody-positive individuals. Arthritis Rheum 2007;56:2382-2391.
  50. Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008;359:2195-2207.
  51. Pearson TA, Blair SN, Daniels SR, et al. AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002 Update: Consensus Panel Guide to Comprehensive Risk Reduction for Adult Patients Without Coronary or Other Atherosclerotic Vascular Diseases. Circulation 2002;106:38-391.

    -- The opinions expressed in this commentary are not necessarily those of the editors or of the American Heart Association

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