Statins for Stroke Prevention

Abstract

Abstract-The occurrence of stroke increases with age, particularly affecting the older elderly, a population also at higher risk for coronary heart disease (CHD). Epidemiological and observational studies have not shown a clear association between cholesterol levels and all causes of stroke. Nonetheless, large, long-term statin trials in patients with established CHD or at high risk for CHD have shown that statins decrease stroke incidence in these populations. Combined data from 9 trials including 70 070 patients indicated relative and absolute risk reductions for stroke of 21% and 0.9%, respectively, with statins. Key Words: cardiovascular risk Ⅲ prevention Ⅲ statins Ⅲ stroke I n the past decade, the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or "statins," have been proven to significantly decrease coronary events in primary and secondary prevention of coronary heart disease (CHD). [1][2][3][4][5][6][7][8] In patients with known CHD 1-3,6 and high-risk patients (eg, those with hypertension 8 or diabetes mellitus 9 ), stroke, a secondary end point, was also reduced by statin treatment. The neutral effect on stroke in older patients in the recent 3-year Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) trial 7 may have related to the relatively short period of follow-up, but has led some experts to again question whether stroke reduction by statins results from reductions in cardiac events and, therefore, systemic thromboembolism rather than from a direct effect on the cerebral arteries. Cholesterol as a Risk Factor for StrokeWhether increased serum cholesterol levels are a risk factor for stroke remains controversial. A meta-analysis of 45 prospective cohorts that included 450 000 subjects (total of 7.3 million patient-years; average follow-up: 16 years) and 13 000 incident strokes found no association between total cholesterol levels and stroke. 10 The Multiple Risk Factor Intervention Trial (MRFIT), however, showed that the risk of death from nonhemorrhagic stroke increased with increasing serum cholesterol in 351 000 men aged 35 to 57 years. 11 Conversely, in the same study, there was a negative association with hemorrhagic stroke for cholesterol levels Ͻ5.2 mmol/L (Ͻ201 mg/dL): the lower the total cholesterol level, the higher the risk of hemorrhagic stroke, suggesting a possible U-shaped relationship between cholesterol and stroke. The association between low cholesterol levels and hemorrhagic stroke was notable particularly in men with hypertension. The link between low cholesterol concentration and hemorrhagic stroke also was shown in a meta-analysis of 13 Chinese and Japanese cohorts, including 125 000 subjects and 1800 strokes, in which there was a tendency for increased risk of hemorrhagic stroke and decreased risk of ischemic stroke as cholesterol levels decreased. 12 Finally, in the Copenhagen City Heart Study, total cholesterol was positively associated with risk of nonhemorrhagic stroke, but only for levels Ͼ8 mmol/L (Ͼ309 mg/dL), corresponding to levels ...

Risk Factors for Intracerebral Hemorrhage in a Pooled Prospective Study

“…Despite the link between low cholesterol and ICH, statin therapy has increased ICH risk in clinical trials, 38 but did not increase risk in other reports. 39 The relation between smoking and ICH tends to be weak and inconsistent in individual studies. In a meta-analysis, 3 the relative risk of ICH from current smoking versus never smoking was 1.31 (95% CI 1.09 to 1.58).…”

Cerebral Vascular Dysfunction During Hypercholesterolemia

“…Although hypercholesterolemia is associated with carotid arterial disease and coronary heart disease, its role in the pathogenesis of stroke is unclear. [1][2][3] Several cohort studies have shown little or no positive correlation between the incidence of stroke and increased levels of serum cholesterol. 4,5 Some 6 -9 but not all 10,11 intervention studies of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have indicated beneficial effects of lowering cholesterol levels in reducing the risk of stroke.…”

Most Important Outcomes Research Papers on Stroke and Transient Ischemic Attack

“…6,7 Similarly, higher cholesterol levels are associated with an increased risk of ischemic stroke, and treatment with statins leads to a RR reduction of approximately 20%. 42 Anticoagulation remains the mainstay of preventing risk of stroke and TIA in patients with AF. While warfarin is highly effective, the emergence of newer antithrombotic agents and left atrial appendage closure devices may offer alternative therapeutic strategies for stroke prevention in patients with AF without the need for regular monitoring.…”