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Objective-LDLs include particle subclasses that have different mobilities on polyacrylamide gradient gels: LDL-I (27.2 to 28.5 nm), LDL-IIa (26.5 to 27.2 nm), LDL-IIb (25.6 to 26.5 nm), LDL-IIIa (24.7 to 25.6 nm), LDL-IIIb (24.2 to 24.7 nm), LDL-IVa (23.3 to 24.2 nm), and LDL-IVb (22.0 to 23.3 nm in diameter). We hypothesized that the association between smaller LDL particles and coronary artery disease (CAD) risk might involve specific LDL subclasses. Methods and Results-Average 4-year onstudy lipoprotein measurements were compared with annualized rates of stenosis change from baseline to 4 years in 117 men with CAD. uman plasma LDLs include multiple distinct subclasses of different particle size that are separable on nondenaturing polyacrylamide gradient gels. 1 Seven LDL subclasses have been identified: LDL-I (27.2 to 28.5 nm), LDL-IIa (26.5 to 27.2 nm), LDL-IIb (25.6 to 26.5 nm), LDL-IIIa (24.7 to 25.6 nm), LDL-IIIb (24.2 to 24.7 nm), LDL-IVa (23.3 to 24.2 nm), and LDL-IVb (22.0 to 23.3 nm in diameter). 1,2 Several case-control, nested case-control, and prospective studies have suggested that a predominance of smaller LDL particles (ie, LDL-III or LDL-IV) is associated with increased coronary heart disease (CHD) risk. [3][4][5][6][7][8][9][10] The contribution of individual subclasses within LDL-III and LDL-IV to CHD risk has not been determined.HDLs also include a heterogeneous mixture of particles of differing size that can be separated into at least 5 subclasses on nondenaturing polyacrylamide gradient gels. 11 These include HDL 3c (7.2 to 7.8 nm), HDL 3b (7.8 to 8.2 nm), HDL 3a (8.2 to 8.8 nm), HDL 2a (8.8 to 9.7 nm), and HDL 2b (9.7 to 12 nm). 11 Case-control and angiographic studies suggest that CHD risk may be increased when HDL 2b is reduced relative to HDL 3c and HDL 3b . [12][13][14] The rate at which coronary artery lesions progress is a risk factor for clinical coronary events. The rate of change in percent stenosis has been shown to be significantly predictive of myocardial infarctions and coronary deaths during 7-year 15 and 12-year 16 follow-up periods. The rate is also reflective of atherosclerosis elsewhere, eg, changes in carotid artery intima-media thickness. 17 Quantitative changes in coronary artery diameters and stenosis have been associated with plasma levels of total cholesterol, 18 LDL cholesterol,18,19 HDL cholesterol,20,21 24 The purpose of this study was to examine the relations of LDL and HDL subclasses to rates of CHD progression. Specifically, average onstudy measurements of lipoprotein subclasses were compared with annual rates of stenosis change of coronary lesions in men who remained under care of their usual physician when serving as controls in a randomized trial. 26 The analyses show that the annual rate of progression of coronary artery stenosis is related to the relative levels of specific LDL and HDL subclasses. Consistent with other reports, 22,27 we found preliminary evidence that effects of lipoproteins on atherosclerotic progression may be related to baseline lesi...