Lipoprotein(a) serum concentration and apolipoprotein(a) phenotype correlate with severity and presence of ischemic cerebrovascular disease.

BACKGROUND AND
PURPOSE: Serum lipoprotein(a) [Lp(a)] levels are genetically determined and considered to be an independent risk factor for atherosclerosis. The aim of this study was to provide a complete analysis of Lp(a) serum levels, apolipoprotein(a) phenotypes, and other lipid parameters for different forms of severity of symptomatic ischemic cerebrovascular disorders as well as for different stages of carotid atherosclerosis.
METHODS: Lp(a) concentration, apolipoprotein(a) phenotype, triglyceride, low-density lipoprotein, high-density lipoprotein, and total cholesterol levels of blind-coded specimens as well as degree of carotid artery stenosis were assessed in a consecutive series of patients with ischemic cerebrovascular disease. We evaluated 265 male (34%) and female (66%) patients (mean age, 51 +/- 7.4 years) with transient ischemic attack (55.8%), prolonged reversible ischemic neurological deficits (28.3%), and cerebral infarction (15.9%) as well as 288 male (30%) and female (70%) control subjects (mean age, 51 +/- 7.1 years). All subjects were white.
RESULTS: Lp(a), total, and low-density lipoprotein cholesterol were statistically significantly elevated in all patients compared with control subjects. Lp(a) correlated with the severity of symptomatic cerebrovascular disease and the degree of carotid stenosis. Logistic regression analysis revealed Lp(a) as the best single marker for the presence of cerebrovascular disease (P < .001) followed by high-density lipoprotein cholesterol (P = .003) and triglycerides (P = .049). With a cutoff of 20 mg/dL of Lp(a), the odds ratio for a subject to have had ischemic stroke with elevated Lp(a) was 20.3 and 23.7 depending on the method of the Lp(a) estimation, whereas the odds ratio when the sonography score was > 0 was 15.4. The investigation of the distribution of the apo(a) phenotypes revealed that 16.73% of the control subjects had major isoforms < or = 580 kD molecular weight (B, F, S1, S2) versus 42.65% of the patients' group (P < .001). These isoforms were also present in 14.71% of all individuals with a sonography score of 0 but in 52.30% of all individuals with a sonography score > 0 (P < .001).
CONCLUSIONS: This case-control study shows that an elevated Lp(a) level is the primary factor associated with the presence of ischemic cerebrovascular disease and that the increased portion of the smaller-molecular-weight apo(a) isoforms in patients and individuals with a sonography score > 0 points toward an inherited predisposition for this disease.