The Imperative of Primary Stroke Prevention: First Things First
Pub Date: Thursday, Dec. 2, 2010
Author: Natalia Rost, MD
CitationGoldstein 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.
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  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, 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. 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. 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.
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. 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, 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, 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." 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  and asymptomatic carotid stenosis ); therefore, the focus of primary stroke prevention in these new guidelines remains rightfully on the maximizing the "major offenders" (including the mandatory lifestyle changes)  in the patients with a mix of vascular risk factors as part of the current, state-of-the-art "best medical treatment" approach.
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. 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. 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. 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. 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%.
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.
- 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.
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-- The opinions expressed in this commentary are not necessarily those of the editors or of the American Heart Association