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Lipids and Ischemic Stroke
New evidence links levels of certain blood lipids to ischemic stroke risk.
Although plasma lipid levels are closely related to coronary heart disease (CHD), no clear association with stroke has been found, despite decades of research. Prospective epidemiologic studies have consistently shown that CHD incidence has strong positive associations with levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C) as well as inverse relations with high-density lipoprotein cholesterol (HDL-C) and total cholesterol/HDL-C ratio. Stroke investigators have suspected that the absence of evidence associating stroke with these lipid factors is due to misclassification of stroke events — i.e., studies have not separated hemorrhagic from ischemic stroke (IS) or distinguished among IS subtypes.
Bhatia and colleagues assessed the relations between various lipid subfractions and IS risk in a cohort of 261 patients after TIA. During 10 years of follow-up, 45 patients experienced IS. (It is unclear whether imaging was obtained after the strokes to support the distinction between TIA and stroke.) Apolipoprotein B (Apo B) and Apo B/Apo A1 ratio were the only predictors of stroke. Other methodologic shortcomings prohibited drawing further conclusions.
In the multicenter GENIC Study, Amarenco and colleagues systematically classified 492 IS patients by stroke subtype and compared the patients’ lipid profiles with those of age-, sex-, and center-matched hospitalized patients without stroke. Lipid levels correlated strongly with IS generally, but there were no substantial lipid differences by stroke subtype. However, the authors note that a previous large HMO-based case-control study confirmed the positive association between total cholesterol and ischemic stroke, particularly with atherosclerotic and lacunar subtypes and in patients younger than 66 whose HDL-C was below 50 mg/dL (Neurology 2004; 63:1868).
Comment: Several large, prospective, population-based studies have found only weak and inconsistent associations between multiple lipid fractions and ischemic stroke. In these same populations, lipid levels were strongly related to incident CHD. Of all lipid measures, lower levels of HDL-C have been correlated most consistently with increased ischemic stroke risk (Stroke 2003; 34:623), but even this relationship is considerably weaker than for HDL-C and CHD. Case-control studies invariably show lipids to be related to stroke generally, to IS specifically, and to various IS subtypes. However, prospective epidemiologic studies provide the clearest picture of the associations between risk factors and cerebrovascular outcomes.
Statins reduce stroke incidence in both patients with CHD and those with stroke, although possibly via different mechanisms. From a practice standpoint, prescribing statins in these high-risk patients clearly reduces stroke risk.
— Philip A. Wolf, MD
Dr. Wolf is Professor of Neurology, Medicine and Public Health, Boston University School of Medicine, Boston. He is the Principal Investigator of the Framingham Heart Study.
Published in Journal Watch Neurology November 14, 2006
Citation(s):
Bhatia M et al. Apolipoproteins as predictors of ischaemic stroke in patients with a previous transient ischaemic attack. Cerebrovasc Dis 2006 May; 21:323-8.
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Amarenco P et al. Blood lipids in brain infarction subtypes. Cerebrovasc Dis 2006 Jul; 22:101-8.
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