Associations Among Serum Lipoprotein(a) Levels, Apolipoprotein(a) Phenotypes, and Myocardial Infarction in Patients With Extremely Low and High Levels of Serum Lipoprotein(a)

Abstract

ipoprotein(a) [Lp(a)] is a heterogeneous lipoprotein 1 that incorporates a low-density lipoprotein (LDL) particle and highly polymorphic apolipoprotein (a) [apo(a)], which is covalently linked to the apolipoprotein B moiety of the LDL by a single disulfide bridge. 2,3 Apo(a) is highly homologous to plasminogen and affects the human coagulation system. 4,5 The apo(a) gene locus is the major gene that controls plasma Lp(a) concentrations. 6,7 The alleles at this locus determine the size polymorphism of apo(a), which is the result of a variable number of expressed Japanese Circulation Journal Vol.63, September 1999 kringle IV repeats, 6-8 and is assessed by apo(a) genotyping. 7 Utermann et al first reported a size polymorphism of 6 apo(a) isoforms with different molecular weights, 8 and other researchers have detected additional apo(a) isoforms using different detection methods. 9,10 We recently detected 26 different apo(a) alleles, including a null allele, at the apo(a) locus by a sensitive high-resolution technique using sodium dodecyl sulfate (SDS)-agrose/gradient polyacrylamide gel electrophoresis (PAGE). 11 Approximately 75% of the subjects had a double band of apo(a), and the remaining subjects had a single band. An inverse relationship has been demonstrated between plasma Lp(a) concentrations and the size of apo(a), 8,11 and a smaller Lp(a) band was well correlated with Lp(a) levels in double-banded phenotypes. [11][12][13] High plasma levels of Lp(a) have been shown to be associated with myocardial infarction (MI), 14-17 although this association was not confirmed by 2 prospective studies. 18,19 Apo(a) size polymorphism has been shown to be inversely associated with the risk of coronary heart disease (CHD) in Jpn Circ J 1999; 63: 659 -665 (Received April 2, 1999; revised manuscript received May 24, 1999; accepted May 27, 1999 , age: 62±10 y) and control subjects (n=92, M/F: 53/39, age: 58±14 y) were classified into quintile groups (Groups I to V) according to Lp(a) levels. Apo(a) isoform phenotyping was performed by a sensitive, high-resolution technique using sodium dodecyl sulfate-agarose/gradient polyacrylamide gel electrophoresis (3-6%), which identified 26 different apo(a) phenotypes, including a null type. Groups with higher Lp(a) levels (Groups II, III, and V) had higher percentages of MI patients than that with the lowest Lp(a) levels (Group I) (54%, 56%, or 75% vs. 32%, p<0.05). Groups with different Lp(a) levels had different frequency distributions of apo(a) isoprotein phenotypes: Groups II, III, IV, and V, which had increasing Lp(a) levels, had increasingly higher percentages of smaller isoforms (A1-A4, A5-A9) and decreasingly lower percentages of large isoforms (A10-A20, A21-A25) compared to Group I. An apparent inverse relationship existed between Lp(a) and the apo(a) phenotype. Subjects with the highest Lp(a) levels (Group V) had significantly (p<0.05) higher serum levels of total cholesterol, apo B, and Lp(a). Patients with MI and the controls had different distributions of apo(a) phenot...

Large Scale Cohort Study of the Relationship Between Serum Cholesterol Concentration and Coronary Events With Low-Dose Simvastatin Therapy in Japanese Patients With Hypercholesterolemia. Primary Prevention Cohort Study of the Japan Lipid Intervention Trial (J-LIT).

“…Coronary events did not occur in any of the 871 patients (4,633 patient-years) whose baseline HDL-C concentration was ≥90 mg/dl, and an increase in the HDL-C concentration as a result of statin treatment may prevent CHD. 27,28 We observed an average reduction of LDL-C concentration of 48 mg/dl below baseline during 6 years of simvastatin treatment, and an increase in HDL-C concentration by 5.2 mg/dl. Using these combined changes in lipid concentrations and previously calculated rate of reduction in coronary events of 15.8% per 10 mg/dl reduction in LDL-C and 37.5% per 10 mg/dl increase in HDL-C, 66% reduction in coronary events during the treatment was predicted.…”

Large Scale Cohort Study of the Relationship Between Serum Cholesterol Concentration and Coronary Events With Low-Dose Simvastatin Therapy in Japanese Patients With Hypercholesterolemia and Coronary Heart Disease. Secondary Prevention Cohort Study of the Japan Lipid Intervention Trial (J-LIT).

“…The observation in TC concentration may be the result of opposite effects on coronary events influenced by the 2 lipoprotein-cholesterol components of TC because it has been established that LDL-C is a risk factor and HDL-C is, inversely, a negative risk factor for CHD. 2,19,20 In our previous primary prevention cohort study, TG concentration was a risk factor for coronary events, although the association was not strong. In the present study, serum TG concentration was not a risk factor for coronary events.…”

Lipoprotein(a) Is an Independent Risk Factor for Peripheral Arterial Disease in Chinese Type 2 Diabetic Patients in Taiwan

“…Lp(a) might be higher in type 2 diabetic patients, but glycemic control seems to have no effect on serum Lp(a) (6). With few exceptions (7,8), Lp(a) has been shown to be a risk factor for atherosclerotic disease, such as ischemic heart disease (9,10), myocardial infarction (11,12), stroke (13), and peripheral arterial disease (PAD) (14,15).…”