Many anthropometric, clinical, and biochemical factors can infl uence the composition and size of lipoprotein subpopulations. It has been demonstrated that the prevalence of small dense LDL particles increases cardiovascular (CV) risk ( 1-3 ) and that the distribution of differently sized particles in HDL infl uences its anti-atherogenic effects ( 4-8 ).In the HDL-Atherosclerosis Treatment Study (HATS), in which patients with coronary disease and low HDL-cholesterol (HDL-C) were treated with a combinations of simvastatin, niacin, and antioxidants, the therapy had a selective effect on composition of lipoprotein subpopulations and therefore on consequent changes in the coronary artery stenosis ( 9 ). Although the composition of lipoprotein subpopulations contributes substantially to plasma atherogenicity, it is impractical to measure its variations as the assays have not been standardized and are expensive and thus not suitable for routine use.We have established that two markers of CV risk, namely cholesterol esterifi cation rate in apolipoprotein Abstract We examined the association between rate of cholesterol esterifi cation in plasma depleted of apolipoprotein B-containing lipoproteins (FER HDL ), atherogenic index of plasma (AIP) [(log (TG/HDL-C)], concentrations, and size of lipoproteins and changes in coronary artery stenosis in participants in the HDL-Atherosclerosis Treatment Study. A total of 160 patients was treated with simvastatin (S), niacin (N), antioxidants (A) and placebo (P) in four regimens. FER HDL was measured using a radioassay; the size and concentration of lipoprotein subclasses were determined by nuclear magnetic resonance spectroscopy. The S+N and S+N+A therapy decreased AIP and FER HDL , reduced total VLDL (mostly the large and medium size particles), decreased total LDL particles (mostly the small size), and increased total HDL particles (mostly the large size). FER HDL and AIP correlated negatively with particle sizes of HDL and LDL, positively with VLDL particle size, and closely with each other ( r = 0.729). Changes in the proportions of small and large lipoprotein particles, which were refl ected by FER HDL and AIP, corresponded with fi ndings on coronary angiography. Logistic regression analysis of the changes in the coronary stenosis showed that probability of progression was best explained by FER HDL ( P = 0.005). FER HDL and AIP refl ect the actual composition of the lipoprotein spectrum and thus predict both the cardiovascular risk and effectiveness of therapy. AIP is already available for use in clinical practice as it can be readily calculated from the routine lipid profi le. -Dobiášová, M., J. Frohlich, M. Šedová, M. C. Cheung, and B. G. Brown. Cholesterol esterifi cationThe study was supported by HDL-C, HDL-cholesterol; log(TG/HDL-C), logarithmically transformed ratio of molar concentrations of triglyceride and HDL-cholesterol; N, niacin; P, placebo; S, simvastatin; TC, total cholesterol; TG, triglyceride .

Purpose Dysregulation of the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is seen in 40–60% of colorectal cancer (CRC) patients. Everolimus, an oral inhibitor of mTOR, demonstrated efficacy in metastatic CRC (mCRC) patients in phase I studies. Experimental Design In sequential phase II studies assessing 2 dosing schedules, mCRC patients refractory to bevacizumab-, fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimens received everolimus 70 mg/week (N=99) or 10 mg/d (N=100). Primary endpoints were disease control rate (DCR) and objective response rate; secondary endpoints included progression-free survival (PFS), overall survival (OS), and duration of response or stable disease (SD). Tumor tissue was collected from all patients for predefined exploratory biomarker analyses. Results 71 patients were included in the per protocol set for each cohort. DCRs of 31.0% and 32.4% (all SD) were seen in the weekly and daily schedules, respectively. Median duration of SD was 3.9 months in each cohort. Median PFS and OS were 1.8 months and 4.9 months and 1.8 months and 5.9 months, respectively, for the weekly and daily schedules. Among patients receiving daily everolimus, those with a KRAS mutation experienced significantly shorter median OS (P = .008) and lower DCR (P = .035) compared with those with wild-type KRAS in exploratory biomarker analyses. Conclusions Everolimus 70 mg/week or 10 mg/day was well tolerated but did not confer meaningful efficacy in heavily pretreated mCRC patients. Future studies may consider evaluating everolimus in combination with other agents or in patients with dysregulation of the PI3K/Akt/mTOR pathway.