Human low-density lipoproteins: oxidative modification and its relation to age, gender, menopausal status and cholesterol concentrations.

Abstract

Recently much evidence has accumulated indicating that oxidative modification of atherogenic lipoproteins plays an important role in atherogenesis. The goal of this study was to ascertain whether any association exists between this and the previously incriminated risk factors of atherosclerotic cardiovascular disease like age, gender and cholesterol concentration. Serum lipid profile, low-density lipoprotein (LDL) composition and indicators of LDL oxidation were examined in a cohort of healthy, predominantly middle aged men and women. LDL oxidation was assessed using the copper catalysis method, and monitored routinely by the increase in conjugated dienes over 4 to 24 hours. A more objective computer-aided technique was used to estimate the oxidative indices based on the sigmoidal fit to data. No marked differences between men and women were found with respect to mean age, total and LDL cholesterol, LDL protein and oxidation of LDL. The post-menopausal as compared to pre-menopausal status was associated with a greater extent of LDL oxidation, as well as with higher total serum cholesterol and its fractions, LDL cholesterol and LDL protein. No such differences were found in the data for men appropriately separated according to age. In a group with high risk LDL cholesterol, the total LDL oxidation was higher, as well as age and total cholesterol. Lag time and half-time of LDL oxidation were significantly shorter, while the oxidation rate of LDL was significantly faster when compared with data in the lower quartile. About six percent of participants had a considerably prolonged initial oxidation phase. These persons also showed low total and LDL cholesterol. High oxidation resistance was reversible and most probably caused by very low pre-existent oxidation products. Multiple regression analysis showed that the closest association among age, gender, lipid profiles and LDL oxidation indices existed between LDL cholesterol and conjugated diene production in both sexes (men: r = 0.93; women: r = 0.81). This association remained high even if adjusted for age. As in earlier epidemiological studies using logistic regression and showing age- and gender-related rising frequency of coronary heart disease, the present paper demonstrated age- and gender-related rising frequency of highly oxidized LDL. In both cases it was closely associated with an increasing LDL cholesterol concentration.