Lp(a) Lipoprotein and Plasminogen Activity in Patients with Different Etiology of Ischemic Stroke

Abstract

Background and Purpose: Lp(a) lipoprotein plays an important part in atherothrombogenesis and is considered an independent risk factor for coronary heart disease. However, its role in cerebrovascular disease remains unclear, in particular because of the heterogeneous nature of strokes. We investigated whether elevated Lp(a) is more frequent in ischemic stroke related to atherothrombosis than in other etiologies of stroke. Because of the close structural homology between Lp(a) and plasminogen, we also studied the role of plasminogen in different stroke subtypes and whether there is a dependency on Lp(a) plasma levels. Methods: Lp(a) levels and plasminogen activity were measured in 253 consecutive patients with acute ischemic stroke and in 63 controls (CS). Subtypes of stroke were established according to the TOAST criteria. Results: Median Lp(a) levels were found to be higher in the total cerebral infarction group and in patients with large artery atherosclerosis (LAA) when compared with CS (20.9 and 22.0 mg/dl, respectively, vs. 16.0 mg/dl; p < 0.05). In addition, elevated Lp(a) levels >30 mg/dl were more frequent among the LAA subgroup than among CS (39.4 vs. 11.1%; p < 0.001). Mean plasminogen activity was lower in the total cerebral infarction group (110.8 vs. 120.3%; p < 0.001) and in patients with cardioembolic stroke (109.8 vs. 120.3%; p < 0.05) when compared with CS. There was no correlation between Lp(a) levels and plasminogen activity. Conclusions: Our results support the hypothesis that elevated Lp(a) is a risk factor for ischemic stroke and especially for strokes caused by LAA. Low plasminogen activity may play a role in the pathogenesis of cerebrovascular disease, especially for the development of cardioembolic stroke.

Increased Stroke Risk and Lipoprotein(a) in a Multiethnic Community: The Northern Manhattan Stroke Study

“…In the NOMASS, the atherosclerotic subtype has been documented in 17% of all cases [25]. Unlike other studies which suggest that elevated Lp(a) is a risk factor for IS caused by large-artery atherosclerosis, we did not find a major difference across infarct subtypes [32]. Our sample size may be inadequate to look for a differential effect across infarct subtypes.…”

Clinical and genetic features in a family with CADASIL and high lipoprotein (a) values

“…The second phenotype, the elevated Lp(a), is caused by a small number of KIVT2 repeats in apo(a) alleles, confirming previous findings which the plasma Lp(a) level is inversely related to the size polymorphisms of apo(a) [21]. An association of elevated Lp(a) with ischemic cerebrovascular disease was demonstrated in several studies [22,23]. Thus, whether the co-occurrence of the two disorders in one family is incidental or whether there is an interaction between both Notch3 and apo(a) genetic defects, is unclear.…”

Lipoprotein (a) as a risk factor for ischemic stroke: A meta-analysis

“…Stroke subtypes significantly contributed to heterogeneity assessed by meta-regression; stroke due to large artery atherosclerosis and stroke due to undetermined etiology reported significantly higher ORs (QM ¼ 6.89; p ¼ 0.03; beta ¼ 0.008; se ¼ 0.003). Four studies [47,48,54,56] dichotomized Lp(a) levels at 30 mg/dl (clinical cut-off) or 14 mg/dl, respectively, three studies [27,49,58] compared highest vs. lowest tertile or quartile, respectively, and three studies [45,55,57] reported risk differences for continuous increase in Lp(a), see eTable 6 in the supplement. Four studies reported sex-specific ORs [27,47,48,56].…”