title: Heterozygous apolipoprotein (a) status and protein expression as a risk factor for premature coronary heart disease.
abstract: Exactly how apolipoprotein a [APO(a)] isoform size affects the degree of cardiovascular risk associated with high lipoprotein a [LP(a)] levels is not fully understood. Using a sodium dodecyl sulfate-agarose APO(a) & LP(a) phenotyping method, we assessed the role of APO(a) size heterogeneity according to the number of kringle 4 repeats and the differential APO(a) protein expression in 91 male Spanish patients with premature coronary heart disease (CHD) compared with 99 healthy Spanish men. CHD patients had significantly increased median plasma LP(a) levels (0.31 g/L) and a higher percentage of subjects with LP(a) levels of 0.30 g/L or greater (51%) than controls (0.15 g/L and 23%, respectively). Patients with the double-band phenotype had significantly higher plasma LP(a) levels (median 0.37 g/L) compared with those expressing a single-band phenotype (median 0.20 g/L; P =.018) and with their corresponding controls (median 0.15 g/L; P <.001). The double-band phenotype and LP(a) values of 0.30 g/L or greater had a significant association with CHD (odds ratio [OR] 6.47, 95% confidence interval [CI] 2.51-16.7), stronger than that observed for the entire group (OR 4.19, 95% CI 1.97-8.90). The adjusted OR for the APO(a) protein pattern that equally expressed both isoforms indicates an independent association with premature CHD (OR 3.33; 95% CI 1.08-10.3). These results suggest that APO(a) phenotyping might be used in subjects with hyperlipoproteinemia a as a powerful marker to assess the risk of premature CHD because heterozygous status, mainly when both isoforms are equally expressed, is associated with higher cardiovascular risk.
authors.affiliation: Unitat de Lípids i Epidemiologia Cardiovascular and Departament de Farmacologia, Institut Municipal d'Investigació Mèdica, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Martín
authors.forename: Juan
authors.initials: J
authors.lastname: Pedro-Botet
authors.forename: Jorge
authors.initials: J
authors.lastname: Joven
authors.forename: Josep M
authors.initials: JM
authors.lastname: Simó
authors.forename: Margarita G
authors.initials: MG
authors.lastname: Ladona
authors.forename: Marco
authors.initials: M
authors.lastname: Pavesi
authors.forename: Juan
authors.initials: J
authors.lastname: Rubiés-Prat
mesh_terms: D001054:Apolipoproteins A / Q000097:blood* / Q000737:chemistry / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003327:Coronary Disease / Q000097:blood*; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D006951:Hyperlipoproteinemias / Q000097:blood; D018082:Kringles; D017270:Lipoprotein(a) / Q000097:blood; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood; D016017:Odds Ratio; D010641:Phenotype; D020033:Protein Isoforms / Q000097:blood / Q000737:chemistry / Q000235:genetics; D020449:Repetitive Sequences, Amino Acid; D012307:Risk Factors; D013030:Spain; D014280:Triglycerides / Q000097:blood
chemical_list: D001054:Apolipoproteins A; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D017270:Lipoprotein(a); D020033:Protein Isoforms; D014280:Triglycerides; D002784:Cholesterol