Differing Risk Factor Profiles of Ischemic Stroke Subtypes

Abstract

Background and Purpose-Differences in risk factor profiles between lacunar and other ischemic stroke subtypes may provide evidence for a distinct lacunar arteriopathy, but existing studies have limitations. We overcame these by pooling individual data on 2875 patients with first-ever ischemic stroke from 5 collaborating prospective stroke registers that used similar, unbiased methods to define risk factors and classify stroke subtypes. Methods-We compared risk factors between lacunar and nonlacunar ischemic strokes, altering the comparison groups in sensitivity analyses, and incorporated these data into a meta-analysis of published studies. Results-Unadjusted and adjusted analyses gave similar results. We found a lower prevalence of cardioembolic source (adjusted odds ratio, 0.33; 95% CI, 0.24 to 0.46), ipsilateral carotid stenosis (odds ratio, 0.21; 95% CI, 0.14 to 0.30), and ischemic heart disease (odds ratio, 0.75; 95% CI, 0.58 to 0.97) in lacunar compared with nonlacunar patients but no difference for hypertension, diabetes, or any other risk factor studied. Results were robust to sensitivity analyses and largely confirmed in our meta-analysis. Conclusions-Hypertension and diabetes appear equally common in lacunar and nonlacunar ischemic stroke, but lacunar stroke is less likely to be caused by embolism from the heart or proximal arteries, and the lower prevalence of ischemic heart disease in lacunar stroke provides additional support for a nonatherosclerotic arteriopathy causing many lacunar ischemic strokes. Our findings have implications for how clinicians classify ischemic stroke subtypes and highlight the need for additional research into the specific causes of and treatments for lacunar stroke. Key Words: stroke Ⅲ lacunar Ⅲ risk factors Ⅲ stroke subtypes A bout one quarter of ischemic strokes are caused by lacunar infarcts 1 resulting from the occlusion or, perhaps, leakiness 2 of one of the small perforating arteries supplying the deep subcortical areas of the brain. The arterial pathology remains poorly understood, with proposed mechanisms including lipohyalinosis, arteriosclerosis, poor cerebral blood flow, vasospasm, or abnormal endothelial function. 3 Much of our current understanding is based on the clinicopathological studies of Miller Fisher et al in the 1960s and 1970s. Progress since then has been limited, but there is growing evidence to suggest that the lacunar arteriopathy may differ from the atherothromboembolic processes that lead to occlusion of large intracranial and extracranial arteries, causing most other ischemic strokes. [2][3][4] One indirect approach to better understanding the arterial pathology of lacunar ischemic stroke is to look for differences in the vascular risk factor profiles of lacunar versus nonlacunar ischemic stroke, which may reflect distinct underlying pathologies and causes. In a previous meta-analysis of published studies that used an unbiased method (independent of vascular risk factors) to classify ischemic stroke subtypes, we found no difference in the preva...

Risk factors for lacune subtypes in the Atherosclerosis Risk in Communities (ARIC) Study

“…Although treatment of hyperglycemia appears to more successfully reduce microvascular disease than disease due to large-artery atherosclerosis, 8 in a recent systematic review diabetes was equally associated with lacunar and nonlacunar ischemic stroke. 21 However, in all studies included in this review, lacunar infarction was defined clinically, requiring the presence of lacunar symptoms. Therefore, the lacunes studied tend to represent Fisher's microatheromatous lacunar subtype, which we believe is more similar than smaller lacunes to large-artery cerebral infarctions.…”

Distinct non-cerebrovascular risk factors for ischemic lacunar stroke and non-lacunar stroke: preliminary results

“…Hypertension and diabetes appeared equally common in LS and NLS. Atrial fibrillation and carotid stenosis were associated more with NLS than LS (Jackson et al, 2010).…”

“…However, in lacunar stroke, hyperglycemia was not associated with functional outcome. Jackson et al (2010) systematically reviewed studies comparing risk factors in patients with lacunar stroke versus non-lacunar stroke. They reported that 16 of 28 studies included risk factors in their ischemic stroke subtype definitions.…”

“…Vascular risk factors of LS and NLS relate directly to the underlying etiologies of the two subtypes (Kazui et al, 2000;Khan et al, 2012;Park et al, 2012). However, relatively little is known of the non-vascular risk factors contributing to ischemic stroke (Petty et al, 2000;Cokar et al, 2008;Prodan et al, 2008;Castilla-Guerra et al, 2009;Jackson et al, 2010;Zhang et al, 2011). Identifying the risk factors of ischemic stroke and the determinants of outcome (stroke recurrence and mortality) after onset of stroke is the basis for stroke prevention strategies.…”

Association Between Arterial Calcifications and Nonlacunar and Lacunar Ischemic Strokes

“…Jackson et al 1,2 found that cardiovascular risk factors, such as hypertension and diabetes mellitus, are equally common in nonlacunar and lacunar infarcts, but atrial fibrillation or cardiac valve disease and significant carotid artery stenosis were more frequent in nonlacunar infarcts compared with lacunar infarcts, supporting the notion of separate etiologies. Others have found a lower risk of early stroke recurrence and myocardial infarction in patients with lacunar versus nonlacunar infarcts.…”