Increased Prevalence of Hyperhomocysteinemia in Cervical Artery Dissection Causing Stroke

Abstract

Background: Spontaneous cervical artery dissection (sCAD) is a nonatherosclerotic vascular disease of unknown etiology. Mild elevation of total plasma homocysteine (tHcy) levels may be a risk factor for sCAD, but the precise mechanism remains unknown. On the other hand, mild hyperhomocysteinemia is also associated with ischemic stroke related to atherothrombotic or small artery disease. We undertook a case-control study to compare the prevalence of mild hyperhomocysteinemia and tHcy levels between patients with a first ischemic stroke due to sCAD and healthy volunteers, as well as patients with a first ischemic stroke due to atherothrombotic or small artery disease. Methods: Fasting tHcy levels were determined in 346 consecutive patients with a first ischemic stroke due to sCAD (n = 86) and atherothrombotic or small artery disease (n = 260) within 24 h after the onset of symptoms, and in 100 healthy volunteers. Results: Mild hyperhomocysteinemia was more prevalent in patients with sCAD causing ischemic stroke (n = 33, 38%) than in healthy volunteers (n = 23, 23%; p = 0.034), and less prevalent than in patients with ischemic stroke due to atherothrombotic or small artery disease (n = 149, 57%; p = 0.001). Mean fasting tHcy levels of patients with ischemic stroke caused by sCAD showed a trend to be higher (11.4 ± 3.8 μmol/l) than those of healthy volunteers (10.2 ± 3.0 μmol/l, p = 0.61), but were lower than those of patients with stroke due to atherothrombotic or small artery disease (13.6 ± 6.6 μmol/l, p = 0.002). Conclusion: Our results suggest that mild hyperhomocysteinemia may be a risk factor for sCAD causing ischemic stroke, but further studies are needed to identify a possible mechanism. This study confirms the association of hyperhomocysteinemia with ischemic stroke due to atherothrombotic or small artery disease.

Hyperhomocysteinemia and Methylenetetrahydrofolate Reductase Polymorphism in Cervical Artery Dissection: A Meta-Analysis

“…But the association between HHcy and CAD is still an enigma. Recently, several case-control reports have suggested that even mildly elevated homocysteine is associated with CAD [23,25,26,27], but Benninger et al [28] suggested that the difference between plasma homocysteine concentrations of CAD patients and those of healthy controls is not significant. Nevertheless, these studies are limited in the number of participants included and in their lack of statistical power.…”

Management of Spontaneous Dissection of the Cervical Carotid Artery

“…Case-control and observational studies suggest that patients with sCAD have a mild elevation of total homocysteine (tHcy) levels, an increased prevalence of hyperhomocysteinemia, or both (Benninger et al 2009;Gallai et al 2001;Konrad et al 2004;Pezzini et al 2002). The tHcy levels in patients with sCAD (± ischemic stroke) are lower compared to those in patients with ischemic stroke not due to sCAD (Benninger et al 2009;Kelly et al 2002;Pezzini et al 2002;Soriente et al 1998).…”

“…Case-control and observational studies suggest that patients with sCAD have a mild elevation of total homocysteine (tHcy) levels, an increased prevalence of hyperhomocysteinemia, or both (Benninger et al 2009;Gallai et al 2001;Konrad et al 2004;Pezzini et al 2002). The tHcy levels in patients with sCAD (± ischemic stroke) are lower compared to those in patients with ischemic stroke not due to sCAD (Benninger et al 2009;Kelly et al 2002;Pezzini et al 2002;Soriente et al 1998). Hyperhomocysteinemia damages the endothelium according to in vitro and animal studies (Harker et al 1976;Harker et al 1974;Wall et al 1980), impairs endothelial-dependent and flow mediated vasodilation in humans (Woo et al 1997), and is associated with premature peripheral and cerebrovascular disease and atherosclerosis in case-control studies (Boers et al 1985;Clarke et al 1991).…”

“…Gallai et al (Gallai et al 2001) have suggested that tHcy levels slightly above normal predispose to the development of an intimal tear and sCAD without the occurrence of atherosclerosis, although the underlying mechanism remains elusive. Several arguments suggest that the small difference in tHcy levels between normals and patients with sCAD might be an artifact (Benninger et al 2009): (1) tHcy levels are not assessed before, but after the onset of stroke. Even though the tHcy samples are collected soon after the ischemic event, there is still time for them to be affected by the stroke.…”

“…Also, food deprivation increases the tHcy levels (Lindgren et al 1995;Nurk et al 2001). In acute stroke, patients are kept fasting, and tHcy may therefore increase independently of the ischemic process (Benninger et al 2009). …”