WITHDRAWING ASPIRIN CAN TRIPLE THE RISK OF STROKE OR TIA

 

Recent data suggest that aspirin discontinuation can result in thromboembolic complications within 4 weeks after interruption of therapy.

In a case-control study, investigators enrolled 309 patients with ischemic stroke (IS) or transient ischemic attack (TIA) undergoing long-term aspirin treatment before their index event, and 309 control subjects who had not had an IS in the previous six months. Both these groups were matched for age, sex, and antiplatelet therapy. The investigators compared the frequency of aspirin therapy discontinuation during the four weeks before a cerebral ischemic event in patients and during the four weeks before interview in control subjects.

Both groups had a similar frequency of risk factors, except for coronary heart disease (CHD), which was more prevalent in IS or TIA patients (36% vs 18%; P < .001). Thirteen IS or TIA patients and four control subjects had discontinued aspirin. After adjustment in a multivariable model, aspirin interruption yielded an odds ratio for IS or TIA of 3.4 ( P < .005).

These results highlight the importance of aspirin therapy compliance and give an estimate of the risk associated with the discontinuation of aspirin therapy in patients at risk for IS, particularly those with coronary heart disease. The discontinuation of aspirin therapy could increase the risk of IS in patients with multiple cardiovascular risk factors, mainly in those with CHD and one should be aware of the indications, adverse effects, and potential complications of stopping aspirin use.

Arch Neurol 2005;62: 1217-20

AGGRESSIVE LIPID LOWERING REDUCES THE RISK OF STROKE IN PATIENTS OF CORONARY ARTERY DISEASE BY ONE-FOURTH

 

Aggressive lipid lowering with 80 mg of atorvastatin reduced the risk of fatal and nonfatal cerebrovascular events and stroke compared with those treated with lower doses, researchers reported at the American Heart Association 2005 Scientific Sessions.

The study involved a post-hoc analysis of cerebrovascular events in the Treating to New Targets (TNT) trial. 10,001 patients with stable coronary artery disease were randomized to treatment with 80 mg or 10 mg of atorvastatin and then followed for almost 5 years. Clinical end points included time to first cerebrovascular event, time to first stroke, and time to first TIA. Cerebrovascular events, strokes of any etiology, and hemorrhagic strokes were stratified and compared by quintile of achieved low-density lipoprotein cholesterol (LDL-C) levels.

The study showed that in patients given 80 mg atorvastatin LDL-C levels were lowered to 77 mg/dl (v/s 101 mg/dl with 10-mg atorvastatin) and there was a significant 25% reduction in the risk of stroke and 23% reduction in the risk of fatal and nonfatal cerebrovascular events. Also, there was a non-significant reduction in the risk of transient ischemic attacks (TIA) in patients given 80 mg atorvastatin.

LDL-C treatment at 3 months was the predictor of cerebrovascular events with each 1 mg/dl change associated with a 0.6% change in cerebrovascular event rate.

The study included various categories of stroke- ischemic, embolic, hemorrhagic, and unknown - and for each type of stroke, the incidence was lower in the 80-mg arm .

The researchers concluded that reduction in cerebrovascular events should be considered in addition to the reduction in coronary events when treating patients with stable coronary disease and the present study shows that lower is also better for cerebrovascular events in patients with coronary heart disease, thereby providing additional support for more aggressive approach .

AHA 2005 Scientific Sessions: Abstract 2019. Presented Nov. 14, 2005

NEGATIVE EMOTIONS MAY TRIGGER ISCHEMIC STROKE

 

Negative emotions, anger, and sudden changes in posture are independent triggers for ischemic stroke, according to the results of a case-crossover study done by researchers from Israel .

Although a lot is known about risk factors that predispose people to have a stroke, such as smoking and hypertension, there is no information regarding the reasons for a stroke to occur at a particular time

In this study, 200 consecutive patients hospitalized with an ischemic stroke or a transient ischemic attack were interviewed one to four days after stroke onset using a validated questionnaire. Reported exposure to potential triggers, such as negative and positive emotions, anger, sudden postural changes in response to a startling event, strenuous physical exertion, heavy eating, and sudden temperature changes during a two-hour period prior to stroke onset were compared with the same period during the preceding day and to average exposures in the previous year. Anger and other negative emotions were rated on a seven-point scale and were said to be present if the score was 5 or higher.

The average age of the patients was 68 years. During the two hours before the stroke, 76 patients (38%) experienced at least one of the study triggers. The odds ratio (OR) was 8.4 for all triggers combined; 14.0 for negative emotions; 14.0 for anger; and 24.0 for sudden changes in body posture in response to a startling event. The authors however stress that the reported ORs should be interpreted as estimates of a short-term two-hour period relative risk and not as cumulative risks.

Compared with their average level of anger, negative emotions, or sudden changes in body position in the year before the stroke, patients were more likely to have experienced these triggers in the two hours preceding the stroke.

Although the mechanism of how these triggers precipitate stroke is still unknown, effects on circulation or an excessive response by the sympathetic nervous system may be involved.

It is possible that brief episodes of mental stress cause transient changes in blood clotting and in the function of cells lining blood vessels. Other factors, including positive emotions, strenuous physical exertion, and heavy meals, had no significant relationship to stroke onset.

In conclusion, the main modifiable risk factors for stroke are high blood pressure, smoking, diabetes, hyperlipidemia, and obesity. However, this study demonstrates that there are factors that may trigger the premature onset of stroke and this is an important area of potential intervention.

Neurology 2004;63:2006-10

Stroke in the young

 

Introduction
Stroke is the most common life-threatening or disabling neurological condition. Despite the fact that stroke is considered to be a disease of the older population, it is not uncommon among adolescents and young adults (18 to 45 years).

Young stroke patients constitute 15-30% of all stroke patients in India as opposed to 3-8.5% of all stroke patients in the West. This has relevant impact on the years of potential life lost and on socio-economic costs, considering the long life expectancy at these ages. This disparity in the prevalence could be due to the population structure with more people in the younger age groups.

Etiology
Like in older adults, in young individuals also, stroke is characterized as ischemic or hemorrhagic. Ischemic stroke is much more common than hemorrhagic. The spectrum of underlying causes and risk factors in young individuals differ significantly from their older counterparts. The causes are more varied and even after extensive investigations, they remain elusive in about 20-50% of the young patients. The important causes for stroke in young individuals are listed in table 1.

A recent study from Delhi focused on the incidence of stroke in patients between 15-40 years of age. This study revealed that ischemic stroke accounted for 85.8% of the young patients of young stroke, while 14.2% had spontaneous intracerebral hemorrhage. The major risk factors for stroke in these patients were hypertension, hypercholesterolemia, hypertriglyceridemia, and smoking. Oral contraceptives, alcohol, and illicit drug use were infrequent risk factors. An interesting fact which emerged was that etiologies like APLA, hyperhomocysteinemia, MELAS (mitochondrial encephalopathy, lactic acidosis and stroke like episodes), migraine and moyamoya, need to be considered in cases of cerebral infarction in young patients.

As reported in Western patients, the etiology of stroke remains undetermined even in 10-37% of our patients which can pose a therapeutic dilemma.

Diagnosis
The presence of a given stroke risk factor does not assure that it is causative. Many young patients have multiple risk factors. Detailed history and examination, oriented toward common and uncommon etiologies, are especially important. Stroke mimics in the young adult population include multiple sclerosis and malignancy. The physical examination should include neurologic, cardiovascular, ophthalmologic and dermatologic assessments.

Table 1. Causes for stroke in young individuals.

Ischemic

Premature atherosclerosis Cerebral venous thrombosis and pregnancy related strokes Cardioembolic causes: rheumatic heart disease, congenital heart diseases, arrhythmias, bacterial and non-bacterial endocarditis, mitral valve prolapse and patent foramen ovale Inflammatory arterial diseases : infections (neurocysticercosis, HIV, tuberculosis, fungal infection, and syphilis), primary and secondary angiitis of CNS, systemic lupus erythematosus and antiphospholipid antibody syndrome, Susac's syndrome (retinocochleocerebral vasculopathy) Haematological causes: sickle cell disease, polycythaemia, hypercoagulable states (antiphospholipid antibody syndromes, deficiency of antithrombin III or protein S or C, resistance to activated protein C, increased factor VIII) Vasculitis (collagen vascular diseases — systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, polyarteritis nodosa; Takayasu's disease, Wegener's syndrome, cryoglobulinemia, sarcoidosis, inflammatory bowel disease, isolated central nervous system angiitis) Dissection (spontaneous or traumatic) Inherited metabolic diseases (homocystinuria, Fabry's, pseudoxanthoma elasticum, MELAS syndrome) Fibromuscular dysplasia Moyamoya disease Radiation Toxic (illicit drugs — cocaine, heroin, phencyclidine; therapeutic drugs — L-asparaginase, cytosine arabinoside) Migraine

Hemorrhagic

Arteriovenous malformation Neoplasm: primary central nervous system, metastatic, leukemia Hematologic :sickle-cell disease, neoplasm, thrombocytopenia Moyamoya disease Drug use (warfarin, amphetamines, cocaine, phenypropanolamine) Iatrogenic (peri-procedural)

The initial work-up should be as expeditious as possible to allow consideration of acute therapies, such as tissue plasminogen activator (t-PA). The various investigations which may need to be conducted in different patients in the initial stages are listed in table 2.

Table 2. List of various investigations necessary in the initial work-up on a young stroke patient

Brain computed tomography (CT): initial imaging study of choice as it is readily available and is highly sensitive for acute hemorrhage. Complete blood count with differential and platelet count, prothrombin time (international normalized ratio), activated partial thromboplastin time, glucose, chemistries, electrolytes, serology for syphilis, and an erythrocyte sedimentation rate. Pregnancy testing, a chest roentgenogram, and an electrocardiogram High-quality brain magnetic resonance imaging (MRI) or MRI with diffusion-weighted imaging (DWI) and perfusion imaging (PI). Magnetic Resonance Angiography (MRA). 2-D echocardiography, transoesophageal echocardiography, and 24 hours Holter monitoring (since 1/3 rd to 1/5 th of young strokes occur due to cardioembolic phenomena). Anticardiolipin antibodies, lupus anticoagulants, protein S, protein C, activated protein C resistance, antithrombin III (in patients without a firmly identified cause of stroke or if the patient or family members have a history of thromboses). Conventional angiography of cerebral and neck vessels (patients in whom dissection is suspected or in whom no other cause is found). Toxicological studies (if drug toxicity suspected) Other blood tests - may include homocysteine, fibrinogen, antinuclear antibody, lipids, lipoprotein (a), serum protein electrophoresis, hemoglobin electrophoresis, and sickle-cell assay. Cerebrospinal fluid analysis (cases suspicious for infectious, vasculitic, or occult hemorrhage origins).

Management and outcome
General management of ischemic and hemorrhagic strokes is similar to that for older adults. The drug therapy should comprise anti-platelet agents (aspirin or clopidogrel monotherapy or combination of aspirin and clopidogrel), statins, anti-hypertensives (if the patient has hypertension). The only situation where oral anticoagulation is beneficial in prevention of recurrent stroke is in patients with atrial fibrillation. The outcome of stroke in young adults is better than that for older adults. As many as two-thirds of the cases have a favorable prognosis.

Recurrent strokes
Although not fatal, recurrence of stroke can cause severe disability in young patients. The rate of recurrence in quite varied and can be as high as 10-15% of young stroke cases. It is therefore of utmost importance to properly diagnose and manage any patient of young stroke similar to an older stroke patient.

As per a recent study, the risk factors for recurrent stroke in the young are diabetes mellitus, hypertension, hypercholesterolemia, smoking, myocardial infarction, angina pectoris and intermittent claudication. The study also showed that patients with no risk factors had a vascular rate of 2.1% whereas those with five risk factors had a rate of 67%.

Summary
Strokes in young adults make up a significant proportion of strokes in general. A thorough investigation is recommended, looking into a broad array of potential etiologies, common and uncommon. Management is similar overall to that for older adults, with some aspects of treatment dictated by specific causes found. Health care providers must stress prevention with all of their young adult patients, especially those with identifiable risk factors. The potential for devastation is great in any case of stroke but prognosis in this population is better than that for older adults.

Stroke is not uncommon among adolescents and young adults Young stroke patients constitute 15–30% of all stroke patients in India Causes are more varied and are elusive in about 20-50% of the patients Detailed history and examination, oriented toward common and uncommon etiologies, are especially important in the diagnosis of stroke Management of young strokes is similar to older patients, with a more favorable prognosis

 

References:

 

1. Med Sci Monit 2004;10:535-41
2. Natl Med J India 1997; 10:107-12
3. J Neurol Neurosurg Psychiatry 2005;76:191-5
4. CNI Review Fall 2000, Volume 11 no. 2 ( http://www.thecni.org/reviews/11-2-p03-marcoux.htm )
5. Can J Neurol Sci 2000;27:120-4
6. JIACM 2002;3:228-30
7. J Neurol Neurosurg Psychiatry 2001;70(suppl I):i17-i22
8. Neurology 2005;65:609-11

BLOOD PRESSURE LOWERING MAY REDUCE WHITE MATTER HYPERINTENSITIES IN STROKE PATIENTS

 

Blood pressure lowering in stroke patients slows or stops progression of white matter hyperintensities (WMH) detected on cerebral magnetic resonance imaging (MRI), according to the results of a substudy of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS).

The prevalence of WMHs detected on cerebral MRI is associated with hypertension, but it is not known whether blood pressure lowering can arrest their progression. In this substudy, 322 stroke patients were randomized, and 192 completed the trial involving cerebral MRI both at baseline and after a mean follow-up time of 36 ± 6.0 months after randomization, with or without indapamide, or placebo equivalent. Using a visual rating scale, the investigators graded the first MRI from A (no WMH) to D (severe WMH).

At the time of the second MRI, blood pressure reduction for treatment vs placebo was 11.2 and 4.3 mm Hg diastolic. At follow-up, 24 patients (12.5%) developed new WMHs. Compared with the placebo group, the active treatment group had a 43% reduction in the risk of new WMH (95% confidence interval, -7% to 89%; P = .17) and a lower mean total volume of new WMHs (0.4 ± 0.8 vs 2.0 ± 0.7 mm 3 ; P = .012). The latter difference was greatest for patients with severe WMH at entry (0.0 ± 0.0 vs 7.6 ± 1.0; P < .0001).

These results indicate that an active blood pressure–lowering regimen stopped or delayed the progression of WMHs in patients with cerebrovascular disease. They now need to be confirmed and extended in further clinical trials, such as in hypertensive patients free of cerebrovascular disease.

Circulation 2005;112:1644-50.

CERTAIN PREGNANCY COMPLICATIONS LINKED TO SUBSEQUENT RISK OF STROKE

 

Certain complications during pregnancy put women at increased risk for stroke in later years, according to investigators who presented their findings at the 130 th annual meeting of the American Neurological Association.

Prior research had shown that preeclampsia is associated with maternal cardiovascular disease later in life, but there are no definitive findings regarding stroke. Their case-control study used data from the Duke University Medical Center Perinatal and Health Services Outcomes Database which included all 42,263 women who had given birth between 1979 and 2005 at their facilities.

The complications that the researchers considered included abruption, preeclampsia, preterm birth, gestational diabetes, in utero fetal demise, small- and large-for-gestational-age size, oligohydramnios, postpartum hemorrhage, and stillbirth.

164 women who had had a stroke after the postpartum period were matched to 311 women by age and the date of delivery who had not had a stroke.

Strokes occurred an average of 13.5 years after delivery, and the women were an average of 40.1 years old. The women who had had strokes were 70% more likely to have had a pregnancy complication than control patients ( P = .0059). Among the complications considered, only preeclampsia and gestational diabetes were associated with stroke; these complications were associated with odds ratios of 2.06 and 2.44, respectively.

This study suggests that preeclampsia is perhaps an early signal of endothelial dysfunction, a risk of stroke later in life, and heart disease.

ANA 130th Annual Meeting: Abstract 222. Presented September 27, 2005.

NEW APPROVALS INTERNATIONALLY

 

US FDA approves atorvastatin to reduce risk of strokes and heart attacks in patients with Type 2 Diabetes and for reduction of the risk of stroke in people who are at a risk of developing heart disease

The U.S. Food and Drug Administration (FDA) has approved atorvastatin to reduce the risk of stroke and heart attack in people with type 2 diabetes without evidence of heart disease but with other risk factors. Atorvastatin was also approved for reducing the risk of stroke in people without evidence of heart disease but with multiple risk factors other than diabetes.

This decision was based on the findings of the Collaborative Atorvastatin Diabetes Study (CARDS)- a landmark trial of more than 2,800 patients with type 2 diabetes, near normal cholesterol, and at least one other risk factor, such as high blood pressure or smoking- which showed that patients on atorvastatin experienced nearly 50 percent fewer strokes than those on placebo.

The additional approval of atorvastatin to reduce the risk of stroke in patients with multiple risk factors reflects findings from the Anglo-Scandinavian Cardiac Outcomes Trial: Lipid-Lowering Arm (ASCOT-LLA) trial. The trial found that atorvastatin reduced the relative risk of stroke by 26% percent compared to placebo.

Patients with multiple risk factors, including diabetes, face a greater threat of heart attack and stroke, so reducing their risk is critical. The fact that one can reduce the risk of heart attack and stroke even in this high-risk population with atorvastatin assumes great importance.

www.medscape.com accessed on September 30 th 2005.

NEW GUIDELINES

• The American Heart Association (AHA)/ American Stroke Association (ASA) have released the Guidelines for Prevention of Stroke in Patients With Ischemic Stroke or Transient Ischemic Attack.
  
  Stroke 2006;37:577-617
  
• The American Heart Association (AHA)/ American Stroke Association (ASA) have updated the Guidelines for the Early Management of Patients With Ischemic Stroke published previously in 2003.This update is intended to reflect advances in the field since the publication of the previous guidelines.
  
  Stroke 2005; 36:916-21.
  
• The American Heart Association (AHA) and American Stroke Association (ASA) endorse stroke rehabilitation guidelines developed by the Veterans Administration (VA) Department of Defense.
  
  Stroke 2005; 36:e100-e143.

 Full text of these guidelines is available at:
http://www.cipladoc.com/html/neurology_update/treatmentguide.htm

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