Treatment and Prevention of Cerebrovascular Disease

Stroke is the third leading cause of death among Americans and is the most prevalent cause of permanent disability in the Western world. Each year more than 500,000 Americans have a cerebrovascular accident.[1,2,3] There are two types of stroke: ischemic stroke, which occurs when a blood vessel supplying blood to the brain is obstructed, and hemorrhagic stroke, which occurs when a blood vessel ruptures.[4]

Given the 7- to 10-year delay between the onset and diagnosis of diabetes, stroke and transient ischemic attacks (TIA) are often present the first time an elevated glucose is recognized. Thus, the presentation of stroke or TIA may finally trigger a long-standing diagnosis of diabetes. Although A1C is not yet used for the diagnosis of diabetes, an elevated A1C in the face of an acute stroke or TIA, accompanied by hyperglycemia, indicates that there have been glucose elevations for months prior to the hospital presentation.

Treatment of stroke

Acute treatment

For the acute treatment of ischemic stroke, tissue plasminogen activators, or tPAs, can be used. In order to be effective, a tPA must be administered within 3 hours from symptom onset.[5] Although this treatment can be effective, it is not widely used, as only 3% to 5% of people who suffer a stroke receive treatment within the 3-hour time frame.[5]

Surgical intervention

Treatment for hemorrhagic stroke frequently involves surgical intervention. Surgical intervention of hemorrhagic stroke caused by an aneurysm may involve placing a metal clip at the base of the aneurysm. Alternatively, stroke caused by arteriovenous malformation (AVM) may be treated by removing the abnormal vessels.[5]

Prevention of stroke

ABCs of diabetes

The current ABCs of diabetes include an A1C of less than 6.5%,[6] Blood pressure goals of less than 130/80,[7] and a low-density lipoprotein Cholesterol of less than 100 mg/dL,[7] although a recent update from the National Cholesterol Education Program's Adult Treatment Panel III indicates that a goal of LDL less than 70 mg/dL is a therapeutic option for very high-risk patients with overt cardiovascular disease.[7.8] Each of these factors has important implications for the prevention of stroke and other diabetic complications.

In terms of glycemic control, hyperglycemia is highly correlated with ischemic stroke, with approximately two thirds of all ischemic stroke subtypes evidencing blood glucose levels greater than 108 mg/dL.[9] In terms of blood pressure control, the United Kingdom Prospective Diabetes Study (UKPDS) found that by lowering BP from 154/87 to 144/82, there was a 32% reduction in diabetes-related deaths and a 44% reduction in stroke.[10] Based upon data from the Lipid Research Clinics cohort and from the Scandinavian Simvastatin Survival Study, reduction of stroke has been seen with the use of lipid-lowering medications. Further, this method has been shown to be cost effective in both the short term and the long term.[11] For LDL lowering (either to a goal of <100 mg/dL or 30% to 40%), statins are the drugs of choice. Nicotinic acid, ezetimbe, bile acid sequestrants, and fenofibrate also lower LDL.[7] 

In spite of the evidence suggesting that glycemic control, blood pressure control, and lipid control can be beneficial in the prevention of stroke, only 7.3% of adults with diabetes between 1999 and 2000 attained recommended goals of A1C levels less than 7% (higher than the AACE/ACE guidelines of 6.5%), blood pressure less than 130/80 mm Hg, and total cholesterol level less than 200 mg/dL.[12] Thus, it is critical to address not only glycemic control, but also blood pressure and lipid control in order to optimally prevent or delay stroke.

Anticoagulants/antiplatelets

Aspirin therapy or anticoagulants such as warfarin can be used for stroke prevention.[5] The American Diabetes Association recommends aspirin therapy as both a primary preventive strategy (eg, for use by patients with diabetes who have not had a stroke but who have additional risk factors) and a secondary prevention strategy (eg, for use by patients who have a history of stroke or other macrovascular complication(s).[7] A 20% decrease in strokes has been associated with aspirin use in several trials and populations, including a large meta-analysis.[7]

For primary prevention, the American Diabetes Association recommends a dose of 75 mg to 162 mg/day for people over age 21 with type 2 diabetes and a history of myocardial infarction, vascular bypass procedure, stroke, transient ischemic attack, peripheral vascular disease, claudication or angina.[7] This same dose (75 mg to 162 mg/day) is recommended for primary prevention in people over 21 with type 1 or type 2 diabetes who are at increased cardiovascular risk-- over 40 years old or having additional risk factors (family history of cardiovascular 
disease, hypertension, smoking, dyslipidemia, or albinuria). People with bleeding problems or allergy to aspirin are not candidates for aspirin therapy, but may be able to tolerate other anti-platelet agents.[7] No studies of aspirin therapy have been conducted in people under 30 years old.[7]

Surgical prevention

Two surgical options are available for the prevention of stroke: carotid endarterectomy and stenting/angioplasty.[5] In carotid endarterectomy, blocked blood vessels can be surgically removed from the carotid artery. Stenting/angioplasty is a procedure in which  mechanical devices are used to remove fatty buildup clogging a vessel.

References

1. American Stroke Association. Impact of stroke. Available at: http://www.strokeassociation.org. Accessed May 2004.
2. Centers for Disease Control and Prevention. Surveillance Report on Stroke, Vol 6, 1994.
3. Kalache A, Aboderin L. Stroke: the global burden. Health Policy Plan. 1995; 10:1-21.
4. American Stroke Association. What are the types of stroke? Available at http://www.strokeassociation.org/presenter.jhtml?identifier=1014. Accessed May 2004.
5. American Stroke Association. Treatments. Available at http://www.strokeassociation.org/presenter.jhtml?identifier=2532. Accessed May 2004.
6. American Association of Clinical Endocrinologists, American College of Endocrinology. The American Association of Clinical Endocrinologists medical guidelines for the management of diabetes mellitus: the AACE system of intensive diabetes self-management—2002 update. Endocr Pract. 2002; 8(suppl 1):41-82.
7. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2005;28(Suppl 1):S4-S36.
8. Grundy SM, Cleeman JI, Merz NB, et al for the Coordinating Committee of the National Cholesterol Education Program. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004; 110:227-239.
9. Lindsberg PJ, Roine RO. Hyperglycemia and acute stroke. Stroke. 2004; 35:363-364.
10. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of microvascular and macrovascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998; 317:703-713.
11. Grover SA, Coupal L, Paquet S, Zowall H. Cost-effectiveness of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor in the secondary prevention of cardiovascular disease: forecasting the incremental benefits of preventing coronary and cerebrovascular events. Arch Intern Med. 1999; 159:593-600.
12. Saydah Sh, Fradkin J, Cowie CC. Poor control of risk factors for vascular disease among adults with previously diagnosed diabetes. JAMA. 2004; 291:335-342.