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ATP-binding cassette hetero-dimeric transporters G5 and G8 (ABCG5/G8) have been postulated to mediate intestinal cholesterol efflux, whereas Niemann-Pick C1 Like 1 (NPC1L1) protein is believed to be essential for intestinal cholesterol influx. The individual or combined genetic markers, such as single nuclear polymorphisms (SNPs), of these two transporter genes may explain inter-individual variations in plasma cholesterol response following plant sterol (PS) intervention. The present study was aimed at investigating the association between ABCG5/G8 and NPC1L1 genotype SNPs with sterol absorption and corresponding plasma concentrations. The study used a 4-week crossover design with 82 hypercholesterolemic men characterized by high vs. low basal plasma PS concentrations consuming spreads with or without 2 g/day of PS. For the ABCG8 1289 C > A (T400 K) polymorphism, the A allele carriers with high basal plasma PS concentrations demonstrated a 3.9-fold greater reduction (p < 0.05) in serum low density lipoprotein cholesterol (LDL-C) than their low basal plasma PS counterparts. For the NPC1L1 haplotype of 872 C > G (L272L) and 3929 G > A (Y1291Y), individuals carrying mutant alleles showed a 2.4-fold greater (p < 0.05) reduction in LDL-C levels, compared to wild type counterparts. Results suggest that genetic and metabolic biomarkers together may predict inter-individual lipid level responsiveness to PS-intervention, and thus could be useful in devising individualized cholesterol lowering strategies.

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Background/Objectives: Plant sterol (PS) consumption lowers serum cholesterol levels, while modestly increasing plasma PS concentrations. Plasma PS concentrations may reflect sterol absorption, thus individuals with high plasma plant sterol (HPS) concentrations may show greater changes in circulating cholesterol and PS than individuals with low plasma plant sterol (LPS) concentrations. The objective of this study was to examine whether HPS and LPS concentrations are related to subsequent changes in plasma PS, serum lipid and C-reactive protein (CRP) concentrations, following dietary PS intake in otherwise healthy hypercholesterolemic men. Subjects/Methods: This single-blinded, randomized, diet-controlled study consisted of two 4-week phases, separated by a 4-week washout, where a diet with a placebo or the 2.0 g per day PS-enriched spread was consumed during the phases. Results: At baseline, men with HPS possessed higher (Po0.01) mean serum cholesterol concentration, while those with LPS had higher (Po0.05) body mass index. Following PS intake, plasma sum of campesterol plus sitosterol concentrations were elevated from 34.6±4.2 to 46.2±3.3 mmol l À1 (mean±SE) and 16.5±0.9 to 20.8±1.2 mmol l À1 after PS intake in men with HPS and LPS, respectively. Changes in plasma PS concentrations, however, were not different between individuals with either HPS or LPS baseline concentrations. Total cholesterol and low-density lipoprotein cholesterol levels were decreased (Po0.0001) by 6.3 and 7.8%, respectively, with PS consumption for all individuals. Changes in lipid parameters were not different between individuals with HPS or LPS baseline concentrations. No changes in CRP were apparent subsequent to PS intervention. Conclusions: Baseline plasma PS concentrations are not associated or predictive of changes in serum cholesterol or plasma PS concentrations after PS intervention. Thus, individuals with HPS show similar increases in PS concentrations as individuals with LPS following PS supplementation. Plasma PS remained in the range of previously reported concentrations.

In this article, we provide the rationale for the ELOPE (Evaluation of Long-term Outcomes after Pulmonary Embolism) Study, a prospective, observational, multicenter cohort study of patients with a newly diagnosed, first episode of pulmonary embolism (www.clinicaltrials.govNCT01174628) that aims to identify clinical, anatomic, physiologic and biomarker determinants of poor outcome after pulmonary embolism.Pulmonary embolism, the most serious form of venous thromboembolism (VTE), leads to the hospitalization or death of over 30,000 Canadians, 225,000 Americans and 300,000 Europeans each year, numbers that have risen over the past decade. Although numerous studies have evaluated optimal approaches to the diagnosis and treatment of pulmonary embolism, their focus has primarily been on short-term outcomes such as mortality and recurrent VTE in the days, weeks or months after pulmonary embolism diagnosis. However, it is increasingly recognized that pulmonary embolism may have long-lasting sequelae that impact on patients' health. The objective of this article was to review the available evidence on long-term clinical, functional, anatomic and physiologic outcomes after pulmonary embolism, and discuss avenues for research in this field, including the ELOPE Study. Residual pulmonary vascular abnormalities on follow-up imaging and echocardiogram are frequent in pulmonary embolism patients, but the clinical significance of these abnormalities is poorly understood. Whether initial and/or residual clot burden, recurrent pulmonary embolism, altered pulmonary artery or right ventricular hemodynamics or other prognostic factors such as biomarker levels contribute to long-term morbidity after pulmonary embolism is as yet unknown. The ELOPE Study will describe and identify the predictors of long-term outcomes after pulmonary embolism in the setting of a rigorous, multicenter cohort study in which long-term clinical, anatomic, physiologic and functional sequelae such as quality of life, return to work and loss of productivity after pulmonary embolism are systematically evaluated.

Blinding strategies used in our trial were successful overall and appeared to be most effective for site investigators and research coordinators. For patients, there may have been some degree of unblinding in the active stocking group. However, as the trial results were negative with active elastic compression stocking showing no benefit over placebo elastic compression stocking, this potential unblinding has minimal impact on the overall conclusions of the trial.

These data suggest that basal PS concentrations indicate not only sterol absorption efficiency but also the extent of PS-induced cholesterol reduction and thus might be clinically useful to predict the extent of cholesterol response to PS intervention within a given individual.