FAQ - Frequently Asked Questions on Stroke
Stroke Prevention by the Practitioner
Epidemiology of Stroke
Questions:
What Are the New Features of Epidemiology of Stroke in 1998?
Which Are the Common Types of Stroke?
Which Are the Risk Factors for Stroke?
Which Are the Modifiable Risk Factors for Stroke?
Is the Risk Factor Profile Similar for Ischemic and Hemorrhagic Stroke?
Is the Risk Factor Profile Similar for Stroke and Coronary Artery Disease?
What Is the Best Evidence for Stroke Prevention?
What Is the Morbidity due to Stroke?
What Is the Mortality due to Stroke?
Is There Any Secular Trend in Stroke and in Death-Related Stroke?
What Are the Costs of Stroke?
What Are the New Features of Epidemiology of Stroke in 1998?
Stroke is a huge public health concern because of its high morbidity and disability, partly as a consequence of its decreased mortality. Recent data have shown that about 72-86% of strokes are ischemic, 9-18% are due to hemorrhage (intracerebral or subarachnoid) and the rest are undefined. For hemorrhagic strokes, the main risk factors are hypertension and excessive alcohol consumption. Smoking is an important risk factor with an overall relative risk (RR) of 3.5 for stroke. In women smoking is a dominant risk factor for subarachnoid hemorrhage with a dose-response relationship. Heavy alcohol consumption is clearly associated with an increase risk in stroke but this association is less clear for moderate and light dose (see question 2). Risk factors for ischemic strokes are multiple and combined (age, hypertension, hyperlipidemia, diabetes mellitus, atrial fibrillation, valvular disorders, coagulation disorders, smoking). Whereas hypertension (RR 4.0) and age (RR per decade 1.6) are other important risk factors for stroke, new data have shown that a family history of stroke might also increase the risk of stroke. However, further studies are needed to confirm this. Other risk factors recently related to stroke include high cholesterol, use of oral contraceptives, physical inactivity, obesity, hypercysteinemia, increased fibrinogen, coagulation disturbance (protein C or protein S deficiency, antiphospholipid anti-bodies). Chronic atrial fibrillation, transient ischemic at-tacks, carotid bruits, patent foramen ovale, aortic arch atheroma are cardiovascular conditions associated with an increased risk of stroke. The risk of stroke is increased in patients with diabetes mellitus (RR 1.5-3.0) [but there is still no evidence that treatment reduces the risk of stroke]. Another novelty is that stroke is no more considered as unavoidable and untreatlable. It is now a clear consensus that stroke is an emergency and that specialized units and teams improve outcome and may lower costs.
Which Are the Common Types of Stroke?
The usual mode of expression of cerebrovascular diseases is the stroke, denned as a sudden, nonconvulsive and focal neurological deficit. Strokes are generally classified into two groups. The most frequent type of stroke results from cerebral infarction (ischemic stroke) whereas in 15-20% of cases, stroke is due to intracranial parenchymatous hemorrhage. Approximately 30% of cerebral infarctions result from atherothrombosis in the aortic arch and in extracranial arteries [Bogousslavsky ct al., 1988]. Strokes resulting from embolism of cardiac origin (cardioembolic stroke) account for 20 25% of ischemic strokes. In these cases, the most common causes of intracardiac thrombus are a myocardial infarction or atrial fibrillation. Another cardiac condition frequently associated with stroke is valvular disease, whether it is due to a defect in native valves or associated with prosthetic valves. The so-called lacunar strokes account for 15-20%i of cerebral infarctions. Lacunar strokes are usually associated with hypertension of long duration and result from changes in small intracerebral arteries. The remaining 30% of ischemic strokes are due to less common conditions (vasculitis, paradoxical embolism through a patent foramen ovale) or of unknown origin (fig.).
Fig. Frequency of different types of strokes.
Reference
Bogousslavsky J, Van Melle G, Regli F: The Lausanne Stroke Registry: Analysis of 1,000 consecutive patients with first stroke. Stroke 1988,19:1083–1092.
Which Are the Risk Factors for Stroke?
A large number of risk factors for stroke have been described, a reflection of the heterogeneity of the disease. Generally, risk factors for stroke can be classified as modifiable, potentially modifiable and nonmodifiable [Sacco et al., 1977]. Nonmodifiable risk factors for stroke are important to detect, even if no measure can be taken to eliminate them, because their presence helps identify individuals at higher risk and thus justifies the implementation of vigorous treatments to reduce modifiable risk factors.
Well-documented nonmodifiable risk factors for stroke include age, gender, family history and ethnicity (table). Age is the single most important risk factor for stroke. Indeed, for each 10 years after age 55, the stroke rate more than doubles for both men and women [Brown et al., 1966: Wolf et al., 1992]. In the Framingham study, parental history of stroke or coronary artery disease constituted a risk factor for stroke [Kiely et al., 1993]. Gener-ally, the incidence of stroke appears to be higher in non-Caucasians than in Caucasians [Sacco ct al., 1997].
Modifiable risk factors are discussed in question 4.
Table. Major nonmodifiable risk factors for stroke
1 Age
2 Gender
3 Ethnicity
4 Positive family history
References
Brown RD. Whisnant JP. Sicks RD. O'Fallon WM. Wieber.s DO: Stroke incidence. prevalence, and survival: Secular trends in Rochester, Minnesota, through 1989. Stroke 1996:27:373–380.
Kiely DK. Wolf PA. Cupples LA. Reiser AS, Myers RH: Familial aggregation of stroke; The Framingham Study. Stroke 1993:24:1366–1371.
Sacco RL. Benjamin h.l. Broderick .IP. Dykcn M. Easton JD. Feinberg WM, Goluslein LB. Gordick Pli. Howard G. Kitlner SJ. Manolio TA, Whisnant JP. Woll PA: American Heart Association Prevention Conference. IV. Prevention and Rehabilitation of Stroke. Risk factors. Stroke 1997:28:1366–1371.
Wolf PA. D'Agostino RB. O'Ncal MA. Sytkowski P. Kase CS. Belanger AJ, Kannel WB: Secular trends in stroke incidence and mortality: The Framingham Study. Stroke 1992,23:1551–1555.
Which Are the Modifiable Risk Factors for Stroke?
In middle and late adult life, hypertension is undoubtedly the strongest modifiable risk factor for both ischemic and hemorrhagic stroke. Hypertension is present in approximately 70% of stroke cases. The risk of stroke rises in proportion to blood pressure, for males as well as for females, and almost doubles for every 7.5 mm Hg increment in diastolic blood pressure (DBP) [Collins and McMahon, 1994]. However, the strength of the associ-ation between DBP and the risk of stroke is attenuated when age increases. In a recent meta-analysis [Prospective Studies Collaboration, 1995] the relative risk for developing stroke between the highest and the lowest quintiles in DBP was tenfold, fivefold and twofold for individuals aged at the time of screening <45, 45-64 and > 65 years, respectively. The relationship between systolic blood pres-sure, including 'isolated' systolic hypertension, may be even stronger than for DBP [Shaper et al., 1991; Keli et al., 1992].
Cigarette smoking also represents a major cause of ischemic and hemorrhagic stroke. In their meta-analysis, Shinton and Beevcrs [1989] estimated that the relative risk of stroke for smokers and former smokers, as compared to nonsmokers, was 1.5 and 1.17, respectively. The risk of stroke increased in proportion to the number of cigarettes smoked per day and was higher for women as compared to men. As is the case for blood pressure, the risk of developing stroke attributable to smoking decreased with advancing age.
Diabetes is associated with stroke, independently of the various cardiovascular risk factors which usually ac-company this disease (hypertension, dyslipidemia and obesity). Indeed, the relative risk of stroke of all types was 1.8 for diabetic men and 3.0 for diabetic women [Shinton and Beevers, 1989; Burchfield et al., 1994].
Whether hypercholesterolemia, a major risk factor for coronary heart disease, is associated with stroke is controversial, for reasons discussed in questions 5-8. In a large meta-analysis of 45 prospective cohorts including 13,000 strokes [Prospective Studies Collaboration. 1995], plasma total cholesterol levels were highly significantly associated with the risk of developing stroke, but only in the subset of individuals aged <45 at the time of screening. In contrast, no association was observed for older groups.
Other modifiable well-documented risk factors for stroke include heart disease like atrial fibrillation, a recent large myocardial infarction and valvular defects. A causative treatment, if available, is obviously the therapy of choice, but their discussion extends beyond the limits of this question [Warlow et al., 1996; Sacco et al., 1997; Mohr et al., 1997].
Other potentially modifiable risk factors, whose value is still controversial, include the use of oral contraceptives (containing large doses of estrogen). consumption of large amounts of alcohol, use of illicit drugs, physical inactivity, obesity, elevated hematocrit, insulin resistance, migraine hypercoagulable states and others [Warlow et al., 1996; Sacco et al., 1997; Mohr et al., 1997].
In conclusion, the major modifiable risk factors for stroke include hypertension, cigarette smoking and hypercholeslerolemia. For these three factors, the strength of their association to the risk of developing stroke declines when age increases.
References
Burchfiel CM. Curb JD. Rodriguz. BL. Abbott RD. Chin D. Yano K: Glucose intolerance and 22-year stroke incidence: The Honolulu Heart Program. Stroke 1994:25:951–957.
Collins R. McMahon S: Blood pressure, antihypertensive drug treatment and risks of stroke and of coronary heart disease. Br Mod Bull 1994:50:272–298.
Keli S. Bloemberg B, Kromhout D: Predictive value of repeated syslolic blood pressure measurements for stroke risk: The Zutphen Study. Stroke 1992; 23:347–351.
Mohr JP, Albers GW. Amarenco P. Babikian VL, Billcr J. Brcy RL. Coull B, Easton JD. Gomez CR. Helgason CM. Kase CS. Pullicino PM. Turpie AG: American Heart Association Prevention Conference. IV Prevention and Rehabilitation of Stroke. Etiology of Stroke. Stroke 1997,28:1501–1506.
Prospective Studies Collaboration: Cholesterol, diastolic blood pressure, and stroke: 13.000 strokes in 450.000 people in 45 prospective cohorts. Lancet 1995:346:1647–1653.
Sacco RL. Benjamin EJ. Broderick JP. Dyken M, Easton JD. Feinberg WM. Goldstein LB. Gorelick PB, Howard G. Kittner SJ, Manolio TA, Whisnant JP. Wolf PA: American Heart Association Prevention Conference. IV. Pre-vention and Rehabilitation of Stroke. Risk factors. Stroke 1997,28:1507–1517.
Shaper AG. Phillips AN. Pocock SJ. Walker M. Macfarlane PW: Risk factors for stroke in middle aged British men. Br Mod J 1991:302:1111-1115. Shinton R. Becvcrs G: Meta-analysis of relation between cigarette smoking and stroke. BMJ 1989:298:789–94.
Warlow CP. Dennis MS. Van Gijn .1, Sandercock PAG, Bamford JM. Wardlaw J: Stroke: A Practical Guide to Management. Oxford. Blackwell, 1996, pp 190–203.
Is the Risk Factor Profile Similar for Ischemic and Hemorrhagic Stroke?
Stroke is the common manifestation of pathophysiological processes as different as intraparenchymatous hemor-rhage or thromboembolism from cardiac origin. The clinical heterogeneity of the disease is reflected by the different risk factor profiles associated with each stroke subtype [Mohret al., 1997; Sacco et al., 1997; Warlow et al.. 1996].
As it contributes to the development of both hemorrhages and atherosclerosis, hypertension is a common risk factor for both hemorrhagic and ischemic strokes (fig.), and this has been confirmed in numerous epidemiological studies [Mohr et al., 1997; Sacco et al., 1997; Warlow et al., 1996]. Conversely, treatment of hypertension has led to a substantial decline in the incidence of both hemorrhagic and ischemic strokes [McMahon and Rodgers, 1994].
Fig. Risk factors for hemorrhagic and ischemic stroke.
Other factors which participate in the occurrence of hemorrhagic stroke include rupture or malformation of intracerebral vessels, as well as certain deficiencies in the hemostatic processes including the use of anticoagulants, antiplatelet therapy or thrombolytic agents. In addition, heavy alcohol consumption has been shown to be an important contributor to hemorrhagic strokes [Mohr et al., 1996]. Some earlier studies have reported an association between low or reduced plasma cholesterol levels and an increased risk of hemorrhagic stroke [Rossouw et al., 1993; Law et al., 1994]. The validity of this association has been recently challenged, as discussed in question 6.
During these last years, atherosclerosis has emerged as a major player in the pathogenesis of ischemic stroke. Atherosclerosis may promote the development of ischemic stroke in two ways [Mohr ct al., 1997]. The deposition of plaques within the aortic arch and extracerebral arteries may lead to an impairment in blood flow to cerebral tissues by narrowing of these vessels or by embolism of plaque material into cerebral arteries. Atherosclerosis may also promote the development of coronary artery disease, thus leading to myocardial infarction or atrial fibrillation, two major causes of cardioembolic strokes. Indeed, numerous risk factors for atherosclerosis have also been associated with stroke: hypertension, cigarette smoking, diabetes mellitus and increased fibrinogen concentrations are established risk factors for stroke [Sacco et al., 1997]. Moreover, the role of lipids in the develop-ment of stroke has recently been (unexpectedly and surprisingly enough) demonstrated by the dramatic reduction in the incidence of stroke in hyperlipidemic subjects given statins, a powerful cholesterol-lowering agent [Crouse et al.. 1997].
In conclusion, hypertension is clearly associated with an increased risk of strokes, irrespective of the subtypes. Anatomic and hemostatic abnormalities are main contributors to hemorrhagic strokes, whereas ischemic strokes are much more related to the major risk factors of atherosclerosis.
References
Crouse JR. Byington RP, Hoen HM, Furberg CD: Reductase inhibitor mono-therapy and stroke prevention. Arch Intern Med 1997.157:305 1310.
Law MR. Thompson SG. Wald N.I: Assessing possible hazards of reducing serum cholesterol. Bi Mcd ,1 1994:308:373–379.
McMahon S. Rodgers A: The epidemiologic association between blood pressure and stroke: Implication for primary and secondary prevention. Hypertens Res 1994:17(suppl 1 ":S23–S32.
Mohr JP. Albers GW. Ainarcnco P. Babikian VL. Billcr J. Brcy RL. Coull B, Easton .11). Gome/ CR. Helpason CM. Kase C'S, Pullicino PM. Turpie AG; American Heart Association Prevention Conference. IV. Prevention and Rehabilitation ol'Stroke. Etiology ol'Strokc. Stroke 1997;28:1501–1506.
Rossouw JE. Gotto AM Jr: Docs low cholesterol cause death? Cardiovase Drugs Ther 1993:7:789–793.
Sacco RL. Benjamin EJ. Broderick .IP. Dyken M. F.aston JD. Fcinbcrg WM, Goldslein l.B. Gorelick PB. Howard G. Kitlncr S.I, Manolio 'I'A. Whisnant JP. Woll'PA: American Heart Association Prevention Conference. IV. Pre-vention and Rehabilitation of Stroke. Risk factors. Stroke 1997;28:1507–1517.
WarlowCP. Dennis MS. Van Gijn J. Sandcrcock PAG. Bamtbrd JM. Wardlaw J: A Practical Guide to Management. Oxford. Blackwell. 1996. pp 190–203.
Is the Risk Factor Profile Similar for Stroke and Coronary Artery Disease?
While one considers the prominent role that atherosclerosis plays in the development of both coronary artery disease (CAD) and ischemic stroke, one would anticipate the risk factor profiles to be similar for both diseases. Indeed, epidemiological studies support this view with regards to three major risk factors: hypertension, cigarette smoking and diabetes which all predispose to stroke and CAD [Collinsand McMahon, 1994; Prospective Studies Collaboration 1995; Sacco et al., 1997; Neaton et al., 1992].
There is one major exception, however, Hypercholesterolemia [Prospective Studies Collaboration, 1995] (table). Hyperrcholesterolemia, particularly elevated levels of low-density lipoprotein (LDL)-cholesterol has been unambiguously associated with the development of coronary artery disease, but not with stroke (fig.), at least in subjects aged 45 or older.
Does this mean that high cholesterol levels do not contribute to the development of stroke? Certainly not. Indeed, prospective studies and interventional studies [Crouse et al., 1997] using highly effective lipid-lowering agents show that reducing cholesterol levels in plasma significantly decreases the risk of stroke (see question 7). Numerous explanations can be provided to account for the lack of association in cross-sectional epidemiological studies between hypercholesterolemia and stroke, at least in the elderly:
- Stroke is a more heterogeneous condition than CAD. Obviously, CAD is mainly the result of the development of atherosclerotic lesions within the coronary arteries, whereas stroke is the common manifestation of various pathophysiological processes affecting the heart as well as extracranial or intracerebral vessels.
- Cholesterol may have divergent effects on hemorrhagic and ischemic stroke. Low cholesterol levels have been associated with an increased risk of hemorrhagic stroke (discussed in question 8) whereas on the other hand high cholesterol levels may promote the development of ischemic stroke.
- Plasma concentrations of cholesterol decline with advancing age, partly due to poor nutrition, changes in diet or associated diseases. The majority of strokes occur in the elderly, but the disease may have developed over decades and the hypercholesterolemic state which has contributed to the development of the disease in earlier years may no longer be noticeable when the disease be-comes clinically manifest.
In conclusion, the most striking difference between the risk factors profile for stroke of all types and coronary heart disease is characterized by a weaker predictive value of cholesterol levels, particularly when this lipid parameter is assessed in the elderly.
References
Collins R. McMahon S: Blood pressure, antihypertensive drug treatment and risks of stroke and of coronary heart disease. Br Mod Bull 1994.50:272–298.
Crouse JR. Byington RP. Hoen HM, Furberg CD: Reductase inhibitor monotherapy and stroke. Arch Intern Mod 1997;157:1305–1310.
Neaton JD. Blackburn H. Jacobs D. Kuller 1.. Lee DJ. Sherwin R. Shih J, Stamler J. Wenlworth I.: Serum cholesterol level and mortality findings for men screened in the Multiple Risk Factor Intervention Trial. Arch Intern Mod 1992:152:1490–1500.
Prospective Studies Collaboration: Cholesterol, diastolic blood pressure, and stroke: 13.000 strokes in 450,000 people in 45 prospective cohorts. Lancet 1995:346:1647–1653.
Sacco RL. Benjamin F., Broderick .IP, Dyken M. Easton JD, Feinherg WM, Goldslein LB.Gorelick PB. Howard G. KitlnerSJ. ManolioTA.Whisnant.IP, Wolf' PA: American Heart Association Prevention CoriCcrence. IV. Prevention and Rehabilitation of Stroke. Risk factors. Stroke 1997:28:1507–1517.
What Is the Best Evidence for Stroke Prevention?
The aim of primary prevention is to anticipate major adverse events to health. Risk of stroke is clearly influenced by lifestyle.
The aim of primary prevention could be reached first by population education, i.e. by attempting to suppress the development of risk factors. Modification of lifestyle is the first line of work, and the targets to modify are poor diet, alcohol drinking, smoking and lack of physical activity. Clear recommendations must be given for weight reduction, decreased salt and animal fat intake, smoking cessation, increased exercise and how to drink alcohol in a 'safe' way. The second step is an individual approach and aim to detect hypertension and atrial fibrillation and introduce specific treatment. Aspirin has not been shown to be beneficial in the primary prevention of stroke.
Secondary stroke prevention concerns patients with risk of stroke or transient ischemic attacks. Aspirin, ticlopidine, dipyridamole, and clopidogrel are the drugs which have proven efficacious for reducing stroke recurrence. Anticoagulation for atrial fibrillation with a therapeutic range of INR 2-3 has proven its efficiency with very low acceptable level of intracerebral hemorrhage (less than 1% per year). Carotid endarterectomy is beneficial to patients with recent transient ischemic attack or nondisabling stroke and ipsilateral high-grade stenosis (70-99%) of the internal carotid artery.
Tertiary prevention consists in patient rehabilitation after stroke, in order to recover partial or complete independence and to improve quality of life. Recovery from stroke is seldom complete and it is estimated that 40% of patients living at home after stroke need help in daily living. Probably it will be a challenge in the future to improve hospital and community rehabilitation programs in the way to give to patients a maximum independence and diminish the cost of hospitalization and disability.
What Is the Morbidity due to Stroke?
Two weeks after stroke up to 60% of patients require some assistance in daily activity. The frequency of deficits are hemiparesis (70-80%), ambulation problems (70-80%), visual perception deficits (60-75%), dysarthria (55%), depression (40%), aphasia (20 35%), dysphagia (15-35%), alteration of recent memory (10-20%).
The prognosis for functional recovery after a stroke is influenced by various clinical and medical factors.
The main predictors of stroke evolution or localization and type of stroke as well as the time from the onset of its first manifestations to the arrival at hospital, and the type of medical care, including stroke unit, stroke team, stroke pathway. It has been shown that a well-determined clinical pathway for patients with nonhemorrhagic stroke improved the quality of care and functional recovery.
Social support also seems to be associated with faster and more extensive recovery of functional disability after stroke. Socially isolated patients may be at a particular risk for poor outcome. The other factors which determine functional recovery and duration of hospital are age, sex, severity of the initial deficit, etiology and localization of stroke. A majority of first ischemic stroke survivors having access to a rehabilitation service return home (84%), but only a few return to work.
What Is the Mortality due to Stroke?
Stroke is the second most common cause of mortality, after cardiovascular disease. The crude death rates range from 63.5/100.000 (males Switzerland 1992) to 273.4/ 100.000 (females Russia 1991). The underlying stroke etiology influences the 30-day mortality: 8-15% for cerebral infarction, 42 46% for subarachnoid hemorrhage and 48-82% for intracerebral hemorrhage. The causes of 180-day mortality following acute stroke are mainly due to comorbid diseases: heart disease in 35% of the cases, acute and recurrent stroke in 25%, pneumonia in 15%, pulmonary embolism in 10% and other causes in 15%. The age-specific mortality rates increase exponentially with age. doubling every 5 years after 45 years.
A trend of reduction in death rate is observed in many European countries as well as North America. This de-crease is probably multifactorial. The detection and more effective treatment for hypertension may play an important factor, as well as improved acute medical care and improvement in diagnostic procedures.
Is There Any Secular Trend in Stroke and in Death-Related Stroke?
The annual overall incidence of stroke is estimated at 127,000 in Germany, 112,000 in Italy, 101,000 in UK, 89,000 in Spain and 78,000 in France.
In Japan which had the highest stroke rate in the 1970s, there has been a dramatic decline in stroke incidence during these last years (7%/year).
Death related to stroke is declining in many countries (Finland, Sweden, France, Spain) and in both sexes. The Scandinavian countries (Norway, Sweden, Denmark).
The Netherlands and Switzerland have the lowest rates (38/100.000/year to 47/100.000/year). However, in eastern European countries (Russia, Bulgaria, Hungary, etc.) the rate of stroke mortality is still high (176/100,000/year to 249/1,000,000/year) and may even be currently increasing.
What Are the Costs of Stroke?
Stroke is mainly a disease of the elderly, although 15% of the patients may be younger than 45-50 years. With an aging population, the costs of stroke will increase in the future. It has been estimated that approximately 50% of the costs of the first years are due to hospital stay. Two studies have estimated the costs of the first stroke. A Swedish study showed that the lifetime costs directly related from first stroke to death in 1991 were USD 30,000 per patient. The indirect annual costs were estimated to USD 405 million, which represented 24% of the costs of stroke. It should be pointed out that the indirect costs are difficult to evaluate, so this result must be interpreted with caution. A Dutch study showed that the direct lifetime cost per patient, from first stroke to death, was USD 43,990 for women and USD 37,630 for men in 1991. The difference between women and men was due to the higher risk for women to be discharged to a nursing home, which was the major cost component for the lifetime costs. Stroke accounted for 4% of the total healthcare in the Netherlands.