[Age related decrease of high density lipoproteins (HDL) in women after menopause. Quantification of HDL with genetically determined HDL arylesterase in women with healthy coronary vessels and in women with angiographically verified coronary heart disease]. / Zur altersabhängigen Verminderung von Lipoproteinen hoher Dichte (HDL) bei Frauen nach der Menopause. Quantifizierung von HDL über die genetisch determinierte HDL-Arylesterase bei koronargesunden Frauen und bei Frauen mit angiographisch gesicherter koronarer Herzkrankheit.

ABSTRACT

BACKGROUND: The decline in the concentration of high density lipoproteins (HDL) observed in postmenopausal women is thought to contribute to the increasing incidence of coronary artery disease (CAD) after menopause. Human serum arylesterase (EC 3.1.1.2) is exclusively associated with HDL. We therefore investigated possible differences in the decline of HDL-levels and of HDL-subfractions HDL2 and HDL3 between postmenopausal women without and with angiographically documented CAD. PATIENTS AND METHODS: HDL-, HDL2-and-HDL3- concentrations were studied in postmenopausal women with angiographically documented CAD (n = 24; 51 to 72 years mean 62 years) and compared to HDL-parameters of women without CAD (n = 22; 51 to 81 years, mean 58 years). Arylesterase activities of HDL2-and HDL3-subfractions and HDL2-cholesterol concentrations were determined after differential precipitation with polyethylene glycol (4.7 mM PEG). Phenotyping of HDL-arylesterase was achieved in CAD patients and in women without CAD after determining hydrolysis of arylesterase substrates paraoxon (PO) and phenylacetate (PA) by calculating paraoxonase/arylesterase activity ratios R (R = [PO]/[PA] x 1000) phenotype A (n = 26) with R < 2.5, phenotype AB (n = 16) with 5.0 < R < 10.7, and phenotype B (n = 4) with R > 13.5. RESULTS: In postmenopausal women with documented CAD, as compared to women without CAD, HDL-cholesterol (55 +/- 3 mg/dl vs. 69 +/- 3 mg/dl HDL2-arylesterase (25 +/- 1 kU/l vs. 33 +/- 2 kU/l), and HDL3-arylesterase (89 +/- 4 kU/l vs. 106 +/- 5 kU/I) were found to be significantly reduced. Analysis of the correlation of lipid parameters and age revealed in CAD patients, but not in postmenopausal women without CAD, a significant increase of total cholesterol (r = 0.42), and significant reductions of both HDL2-arylesterase (r = -0.47) and HDL3-arylesterase (r = 0.74) with increasing age. In contrast, HDL-cholesterol (r = -0.14) and HDL2-cholesterol (r = -0.06) of CAD patients showed only slight and non-significant reductions with age. Since HDL3-arylesterase was found to be age-dependently reduced in women without CAD (r = 0.17), HDL2-arylesterase of postmenopausal women, among all lipid parameters showed the most pronounced differences between women without CAD and CAD patients. The age-dependent decrease of HDL2-arylesterase in postmenopausal women with CAD does not result from an increased frequency of B-allele carriers in the subgroup of CAD patients with an age above the median (64 years). CONCLUSION: Genetically determined serum HDL-arylesterase is well suited to quantify HDL in postmenopausal women without and with CAD. HDL2-arylesterase of postmenopausal women should be evaluated as a screening parameter for both primary and secondary CAD prevention.