Small dense LDL (sdLDL) has been reported to be more atherogenic than large buoyant LDL (lbLDL). We examined the metabolism and protein composition of sdLDL and lbLDL in six subjects with combined hyperlipidemia on placebo and rosuvastatin 40 mg/day. ApoB-100 kinetics in triglyceride-rich lipoproteins (TRLs), lbLDL (density [d] = 1.019-1.044 g/ml), and sdLDL (d = 1.044-1.063 g/ml) were determined in the fed state by using stable isotope tracers, mass spectrometry, and compartmental modeling. Compared with placebo, rosuvastatin decreased LDL cholesterol and apoB-100 levels in TRL, lbLDL, and sdLDL by significantly increasing the fractional catabolic rate of apoB-100 (TRL, +45%; lbLDL, +131%; and sdLDL, +97%), without a change in production. On placebo, 25% of TRL apoB-100 was catabolized directly, 37% was converted to lbLDL, and 38% went directly to sdLDL; rosuvastatin did not alter these distributions. During both phases, sdLDL apoB-100 was catabolized more slowly than lbLDL apoB-100 (P < 0.01). Proteomic analysis indicated that rosuvastatin decreased apoC-III and apoM content within the density range of lbLDL (P < 0.05). In our view, sdLDL is more atherogenic than lbLDL because of its longer plasma residence time, potentially resulting in more particle oxidation, modification, and reduction in size, with increased arterial wall uptake. Rosuvastatin enhances the catabolism of apoB-100 in both lbLDL and sdLDL.-Thongtang, N., M. R. Diffenderfer, E. M. M. Ooi, P. H. R. Barrett, S. M. Turner, N.-A. Le, W. V. Brown, and E. J. Schaefer. Metabolism and proteomics of large and small dense LDL in combined hyperlipidemia: effects of rosuvastatin. J. Lipid Res. 2017. 58: 1315-1324

Background: Peripheral arterial compliance is a measure of elasticity of the arteries that has been found to be a robust predictor of prevalent arteriosclerosis as well as incident stroke and myocardial infarction. Psychiatric diagnoses and second generation antipsychotics may contribute to cardiovascular risk and stroke, but effects on peripheral arterial compliance are unknown. This study compared peripheral arterial compliance in healthy male controls to male patients with psychiatric diagnoses who were treated with quetiapine or risperidone or off antipsychotics at time of testing. Methods: The groups consisted of 63 patients with mental illness taking quetiapine, risperidone, or no antipsychotics. There were 111 males in the control group. Mean thigh and calf arterial compliance among four groups were compared by ANCOVA, adjusting for body mass index and Framingham Risk Score. All patients were also compared to the control group. Compliance was measured with a computerized plethysmography device. Results: Patients (. n=. 63) had significantly lower arterial compliance in both thigh and calf than the controls. Arterial compliance in the calf was significantly lower in the subgroups of quetiapine (. n=. 16) and risperidone (. n=. 19) treated, and in unmedicated (. n=. 28) patients than in controls. In the thigh, patients taking either quetiapine or risperidone had significantly lower arterial compliance than controls. These subgroups did not differ from each other in arterial compliance. Conclusion: The presence of psychiatric diagnoses is associated with reduced arterial compliance. A large study may be required to measure any specific affects of antipsychotics such as quetiapine and risperidone on compliance compared to controls.