Correspondence
Primary Prevention of Stroke
N Engl J Med 1996; 334:1138-1139April 25, 1996
- Article
To the Editor:
In their comprehensive and extensive review of the primary prevention of stroke (Nov. 23 issue),1 Bronner et al. do not mention atrial fibrillation as a risk factor for ischemic stroke. Data from the Framingham Study2 indicate that nonrheumatic atrial fibrillation is associated with a nearly fivefold increase in the risk of ischemic stroke, and the risk increases at a rate of 5 to 7 percent per year. Cerebral infarction eventually occurs in up to 35 percent of patients with atrial fibrillation.
Four prospective studies of the primary prevention of stroke in patients with nonvalvular atrial fibrillation3-6 have confirmed that patients with atrial fibrillation should be considered seriously as candidates for antithrombotic treatment. In these studies there was a reduction of 45 to 86 percent in the risk of stroke when the patients were treated with warfarin or aspirin. It therefore appears that patients with nonrheumatic atrial fibrillation are at substantial risk for stroke and that antithrombotic treatment with either warfarin or aspirin (325 mg) is suitable for the primary prevention of stroke.
6 ReferencesAntonio Martinez-Riera, M.D.
Francisco Santolaria-Fernandez, M.D.
Emilio Gonzalez-Reimers, M.D.
Hospital Universitario de Canarias, Tenerife, Spain1
Bronner LL ,Kanter DS ,Manson JE . Primary prevention of stroke. N Engl J Med 1995;333:1392-1400
Full Text | Web of Science | Medline2
Wolf PA ,Dawber TR ,Thomas HE Jr ,Kannel WB . Epidemiologic assessment of chronic atrial fibrillation and risk of stroke: the Framingham study. Neurology 1978;28:973-977
Web of Science | Medline3
Petersen P ,Boysen G ,Godtfredsen J ,Andersen ED ,Andersen B . Placebo controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation: the Copenhagen AFASAK study. Lancet 1989;1:175-179
CrossRef | Web of Science | Medline4
Stroke Prevention in Atrial Fibrillation Study Group Investigators
Web of Science | Medline5
The Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators
Full Text | Web of Science | Medline6
Connolly SJ ,Laupacis A ,Gent M ,Roberts RS ,Cairns JA ,Joyner C . Canadian Atrial Fibrillation Anticoagulation (CAFA) Study. J Am Coll Cardiol 1991;18:349-355
CrossRef | Web of Science | Medline
To the Editor:
Bronner and colleagues present a broad and informative review of the primary prevention of stroke. However, their discussion of the role of dietary modification in preventing this condition lacks balance. In particular, the potential effects of reducing salt intake and increasing the consumption of fruits and vegetables need greater emphasis.
Given the preeminence of hypertension as a predictor of stroke, it would seem reasonable to allude to the substantial body of evidence from both observational and interventional studies that links high dietary intake of sodium with elevated blood pressure.1 Moreover, data from ecologic studies2 and experiments in animals3 suggest that a diet high in salt may be associated with an increased risk of stroke, through effects independent of blood pressure. Conversely, a high dietary intake of potassium may decrease the risk of stroke, independently of its effects on blood pressure. These hypotheses, which have direct and practical implications for the primary prevention of stroke, need to be addressed in longitudinal studies that provide data on both the urinary excretion of electrolytes and stroke end points.
The authors refer to a single study that has linked increased consumption of fruits and vegetables with a reduced risk of stroke. A brief discussion of the possible mechanisms would have been of interest. For instance, fruits and vegetables are important sources of dietary potassium and folic acid. Folic acid intake is relevant to the work linking moderately elevated blood homocysteine levels with stroke, a finding now supported by data from a prospective, population-based study of middle-aged British men.4 Homocysteine levels depend critically on the adequate dietary intake of nutritional cofactors required for homocysteine metabolism (folic acid, vitamin B12, and vitamin B6). Low dietary intake of folic acid is probably the chief contributor to hyperhomocysteinemia in most populations. Hence, hyperhomocysteinemia provides a plausible biologic mechanism for the reported association between the consumption of fruits and vegetables and the risk of stroke.
4 ReferencesIvan J. Perry, M.D.
Royal Free Hospital School of Medicine, London NW3 2PF, United Kingdom1
Law MR ,Frost CD ,Wald NJ . By how much does dietary salt reduction lower blood pressure? III. Analysis of data from trials of salt reduction. BMJ 1991;302:819-824
CrossRef | Web of Science | Medline2
Perry IJ ,Beevers DG . Salt intake and stroke: a possible direct effect. J Hum Hypertens 1992;6:23-25
Web of Science | Medline3
Tobian L ,Hanlon S . High sodium chloride diets injure arteries and raise mortality without changing blood pressure. Hypertension 1990;15:900-903
Web of Science | Medline4
Perry IJ ,Refsum H ,Morris RW ,Ebrahim SB ,Ueland PM ,Shaper AG . Prospective study of serum total homocysteine concentration and risk of stroke in middle-aged British men. Lancet 1995;346:1395-1398
CrossRef | Web of Science | Medline
To the Editor:
In their review of the primary prevention of stroke, Bronner et al. discuss a meta-analysis of data on the relation between stroke and lipid-lowering therapy with drugs or diet.1 This meta-analysis preceded more recent trials using 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. In the Scandinavian Simvastatin Survival Study, patients with ischemic heart disease and hypercholesterolemia were randomly assigned to receive simvastatin or placebo.2 In the six-year period after randomization, a post hoc analysis documented 98 cerebrovascular events in 2223 patients receiving placebo, as compared with 70 such events in 2221 patients receiving simvastatin, corresponding to a reduction in risk of 30 percent (P = 0.024).
More recently, data were pooled3 from four studies of the regression of atherosclerosis that evaluated pravastatin in double-blind, controlled trials. Although it was not part of the original study design to do so, this analysis revealed that 13 of 936 patients who received placebo had strokes (fatal or nonfatal), as compared with 5 of 953 pravastatin-treated patients. This difference corresponded to a reduction in risk of 62 percent, which approached statistical significance (P = 0.054).
These data suggest that patients with hypercholesterolemia and atherosclerotic vascular disease affecting their coronary arteries, who are therefore at increased risk for cerebrovascular events,4 may benefit from therapy with HMG-CoA reductase inhibitors for the primary prevention of stroke.
4 ReferencesR.E. Gilbert, M.D.
G. Jerums, M.D.
M.E. Cooper, Ph.D.
Austin and Repatriation Medical Centre, Heidelberg, Victoria, 3084, Australia1
Atkins D ,Psaty BM ,Koepsell TD ,Longstreth WT Jr ,Larson EB . Cholesterol reduction and the risk for stroke in men: a meta-analysis of randomized, controlled trials. Ann Intern Med 1993;119:136-145
Web of Science | Medline2
Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)
Web of Science | Medline3
Byington RP ,Jukema JW ,Salonen JT , et al. Reduction in cardiovascular events during pravastatin therapy: pooled analysis of clinical events of the Pravastatin Atherosclerosis Intervention Program. Circulation 1995;92:2419-2425
Web of Science | Medline4
Mitchell JRA ,Schwartz CJ . Relationship between arterial disease in different sites. BMJ 1962;1:1293-1301
CrossRef | Medline
Author/Editor Response
The authors reply:
To the Editor: Dr. Martinez-Riera and colleagues comment on our lack of discussion of atrial fibrillation. In the original version of our manuscript, we devoted a substantial amount of space to discussing the role of warfarin and aspirin in nonrheumatic atrial fibrillation, as well as to the potential benefits of carotid endarterectomy for symptomatic and asymptomatic carotid stenosis, but this material was removed because an article on medical and surgical therapy in the prevention of stroke had recently been published in the Journal. 1 Our article focused on modifiable risk factors and lifestyle factors in stroke prevention.
In response to Dr. Perry, space constraints limited our opportunity to discuss dietary predictors of stroke in greater detail. The dietary variables we chose to discuss (alcohol, fatty acids, and antioxidants) are those that have been studied most extensively and directly in relation to stroke. Although it is clear that dietary sodium intake has an important role in the development of hypertension, data are sparse on the role of sodium in the genesis of stroke. Analytic studies of the relation between dietary potassium and stroke are also limited. With respect to fruits and vegetables, we did mention that their increased consumption has been linked to a reduced risk of stroke. We agree that the mechanism of this apparent association remains unclear, but it could be related to a number of micronutrients and other dietary factors, including potassium, folic acid, vitamin B6, antioxidant vitamins, and fiber. Further research is needed to assess the role of these dietary factors, as well as that of homocysteine metabolism, in the pathogenesis of stroke.
Dr. Gilbert and colleagues point to promising recent data relating lipid-lowering therapy with HMG-CoA reductase inhibitors to the reduced occurrence of stroke. Although these initial studies are encouraging, a recent large study of pravastatin failed to demonstrate a significant reduction in stroke.2 Because of the rarity of stroke in these cohorts and because of differences in the populations studied, larger studies are needed to clarify the effects of HMG-CoA reductase inhibitors in the primary prevention of stroke. Given the complex associations between serum cholesterol concentrations and both ischemic and hemorrhagic stroke, the role of lipid-lowering therapy is likely to be less straightforward in the case of stroke than in that of coronary disease.
2 ReferencesLeslie L. Bronner, Dr.P.H.
Daniel S. Kanter, M.D.
JoAnn E. Manson, M.D., Dr.P.H.
Brigham and Women's Hospital, Boston, MA 021151
Barnett HJM ,Eliasziw M ,Meldrum HE . Drugs and surgery in the prevention of ischemic stroke. N Engl J Med 1995;332:238-248
Full Text | Web of Science | Medline2
Shepherd J ,Cobbe SM ,Ford I , et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995;333:1301-1307
Full Text | Web of Science | Medline
