On the importance of LDL particle size and antibodies against oxidized LDL for early atherosclerosis development. Ultrasound studies in patients with hypercholesterolemia

Abstract

The main aim of the study was to test the hypothesis that small LDL particle size or high antibody titers against Ox-LDL were related to atherosclerosis development as measured by ultrasound in the carotid artery. Before these studies began the value of intima-media thickness as a surrogate variable for coronary atherosclerosis was evaluated by investigating the relationship between coronary atherosclerosis and ultrasound measurement of intima-media thickness in three different segments of the carotid- and femoral arteries. Furthermore, a new computerized method for a thorough evaluation of LDL particle size was developed.Results of the methodological development and evaluation showed a significant correlation between the ultrasound measurement of intima-media thickness of the carotid bulb and diameter stenosis in the coronary arteries and of carotid plaques and diameter stenosis. The evaluation of the computerized LDL particle size method showed that the method was easy to work with, the reproducibility was satisfactory with an excellent precision in the measurement of LDL peak particle size and other characteristics of the LDL particle size distribution. There were no significant differences in antibody titers against Ox-LDL or MDA-LDL between the group of patients with familial hypercholesterolemia and the controls. No significant associations were observed between intima-media thickness of the carotid or femoral arteries and antibody titers against Ox-LDL or between plaque occurrence and these titers. An unexpected finding was that patients with a history of myocardial infarction had significantly lower IgM titers against Ox-LDL compared with patients without a history of myocardial infarction, and also compared to controls. In the group of patients with primary hypercholesterolemia and signs of early atherosclerotic changes in the carotid artery, patients had significantly smaller LDL particles compared to healthy controls. However, the difference in LDL peak particle size between patients and controls disappeared when adjusting for serum triglycerides. There was no association between increasing intima-media thickness of the carotid bulb and decreasing LDL peak particle size or between the occurrence of moderate to large plaques in the carotid artery and small LDL peak particle size. In conclusion, the results of this study showed that atherosclerosis in the carotid artery bulb, as measured by ultrasound, is significantly associated with coronary atherosclerosis, as measured by quantitative angiography. The lack of correlation between carotid atherosclerosis and high antibody titers against Ox-LDL, and also the finding that patients with a history of previous myocardial infarction had lower IgM titers against Ox-LDL than patients with a negative history of myocardial infarction indicate that the relationship between the autoimmune response to Ox-LDL and the extent of atherosclerosis is more complex than previously anticipated. There was no association between atherosclerosis development in the carotid artery and small LDL peak particle size in patients with hypercholesterolemia. These data do not support the hypothesis that small LDL particles are of importance for atherosclerosis development in primary hypercholesterolemia.