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High levels of lipoprotein(a) [Lp(a)], an apoB100-containing lipoprotein, are an independent and causal risk factor for atherosclerotic cardiovascular diseases through mechanisms associated with increased atherogenesis, inflammation, and thrombosis. Lp(a) is predominantly a monogenic cardiovascular risk determinant, with ≈70% to ≥90% of interindividual heterogeneity in levels being genetically determined. The 2 major protein components of Lp(a) particles are apoB100 and apolipoprotein(a). Lp(a) remains a risk factor for cardiovascular disease development even in the setting of effective reduction of plasma low-density lipoprotein cholesterol and apoB100. Despite its demonstrated contribution to atherosclerotic cardiovascular disease burden, we presently lack standardization and harmonization of assays, universal guidelines for diagnosing and providing risk assessment, and targeted treatments to lower Lp(a). There is a clinical need to understand the genetic and biological basis for variation in Lp(a) levels and its relationship to disease in different ancestry groups. This scientific statement capitalizes on the expertise of a diverse basic science and clinical workgroup to highlight the history, biology, pathophysiology, and emerging clinical evidence in the Lp(a) field. Herein, we address key knowledge gaps and future directions required to mitigate the atherosclerotic cardiovascular disease risk attributable to elevated Lp(a) levels.

The value of an international experience--especially for students of business--continues to be an area of focus at colleges and universities. Students across all disciplines within the business curriculum: accounting, economics, finance, management, marketing, or sport management are expected by employers to possess knowledge of, and appreciation for, other cultures. Using as a backdrop two unique study abroad programs that immerse students into an intercultural business experience and have them interacting with--and learning from--the local residents as well, the survey research in this study measures student attitudes before and after they study abroad and it notes the changes that students report in their personal and professional knowledge, skills, and abilities. The findings of this research can reshape the way in which colleges and universities market these important international experiences. Through this research, we found that factors that prohibit students from studying abroad have more to do with individual social anxiety (i.e. doing something without their friends) than anxiety based on intercultural factors (i.e. language, culture, and distance from home)

Abstract Background Chronic inflammation may contribute to insulin resistance (IR), metabolic syndrome and atherosclerosis although evidence of causality is lacking in humans. We hypothesized that very low-dose experimental endotoxemia would induce adipose tissue inflammation and systemic IR during a low-grade but asymptomatic inflammatory response and thus provide an experimental model for future tests of pharmacologic and genomic modulation of cardio-metabolic traits in humans. Methods Ten healthy, human volunteers (50% male, 90% Caucasian, mean age 22.7 ± 3.8) were randomized in a double-masked, placebo-controlled, crossover study to separate 36-hour inpatient visits (placebo versus intravenous-LPS 0.6 ng/kg). We measured clinical symptoms via the McGill pain questionnaire and serial vital signs. Plasma and serum were collected for measurement of cytokines, C-reactive protein, insulin and glucose, serial whole blood & subcutaneous adipose tissue mRNA expression were measured by real-time PCR. HOMA-IR, a well-validated measure of IR was calculated to estimate insulin resistance, and frequently sampled intravenous glucose tolerance testing (FSIGTT) was performed to confirm an insulin resistant state. We performed ANOVA and within subject ANOVA to understand the differences in cytokines, adipose tissue inflammation and IR before and after LPS or placebo. Results There was no significant difference between placebo and LPS in clinical responses of symptom scores, body temperature or heart rate. However, low-dose endotoxemia induced a rapid and transient 25-fold induction of plasma TNF-alpha and 100-fold increase in plasma IL-6 (Figure 1B) (p p p = 0.01) increased with MCP-1 (peak 10-fold, F = 5.6, p p p p Conclusions We present a low dose human endotoxemia model of inflammation which induces adipose tissue inflammation and systemic insulin resistance in the absence of overt clinical response. Such a model has the potential for broad and safe application in the study of novel therapeutics and genomic influences in cardio-metabolic disease.

Mechanisms explaining the relationship between obesity and cardiovascular disease (CVD) are needed. Despite growing recognition of the importance of the anucleate platelet transcriptome, low levels of RNA in platelets make assessment difficult. We sought to perform unbiased platelet RNA profiling in obesity by performing a prospective study of severe obesity and weight loss via bariatric surgery on platelet characteristics and mRNA profile in 26 pre-menopausal, non-diabetic women (31.6 ± 8.4 years; BMI 43.0 ± 6.5 kg/m2) who underwent sleeve gastrectomy. Totally, 10 women of similar age with normal BMI served as controls. Platelet activation via flow cytometry was assessed before and after surgery. RNA-sequencing (RNAseq) was performed on platelet isolates from a subset of 13 subjects (eight obese women and five normal-BMI subjects). Platelet count, size, and age did not differ between control and obese women. However, platelet surface P-selectin and CD40 were higher in obesity. RNAseq demonstrated 629 differentially abundant transcripts in obesity. Notably, S100A9 and AGER, established markers of cardiovascular risk, were two of the most highly upregulated transcripts (each > 2.5 fold). At 6 months post-operatively, subjects lost 26.1 ± 5.8% body weight and inducible platelet P-selectin expression was reduced. Expression of 170 transcripts was affected by surgery, but only a small fraction (46/629) were genes found altered in obesity. We demonstrate that obesity is associated with an altered platelet transcriptome and increased platelet activation, which is partly attenuated by bariatric surgery. These observations suggest that platelets may contribute to increased cardiovascular risk in obesity through a variety of mechanisms. [ABSTRACT FROM AUTHOR]

Chronic inflammation drives many obesity‐associated conditions including atherosclerosis. GlycA, a marker of systemic inflammation with lower intra‐individual variability than high sensitivity C‐reactive protein, is independently associated with incident cardiovascular events and mortality. Although GlycA is elevated in obesity, correlations with anthropometric measures are modest and the effect of body weight loss on GlycA is untested. Obese (body mass index [BMI] 44.6 ± 6.6 kg/m2), non‐diabetic women (33.7 ± 8.2 years) undergoing Roux‐en‐Y gastric bypass (n = 23) or sleeve gastrectomy (n = 31) were prospectively studied at baseline, 6 and 12 months postprocedure. Women with normal BMI (n = 14) served as controls. Bariatric surgery significantly reduced GlycA by 6 months (451 ± 47 μmol/L vs. 383 ± 50 μmol/L; P < 0.001) with further reduction at 12 months (348 ± 41 μmol/L; P < 0.001) and no difference between procedures. At 12 months, despite 41% of surgical subjects maintaining BMI >30 kg/m2, GlycA levels did not differ between surgical and control subjects (P = 0.13). Increased high density lipoprotein particle size was strongly associated with reduced GlycA (r = −0.49; P < 0.001) and was found to mediate up to 43% of its body weight‐loss‐associated fall. This is the first study to demonstrate that surgical body weight loss markedly reduces levels of GlycA. [ABSTRACT FROM AUTHOR]

Background: Patients undergoing cardiovascular (CV) procedures often have suboptimal CV risk factor control and may benefit from strategies targeting healthy lifestyle behaviors and education. Implementation of prevention strategies may be particularly effective at this point of heightened motivation.Methods: A prospective, randomized, pilot study was conducted in 400 patients undergoing a nonurgent CV procedure (cardiac catheterization ± revascularization) to evaluate the impact of different prevention strategies. Patients were randomized in a 1:1:1 fashion to usual care (UC; group A, n = 134), in-hospital CV prevention consult (PC; group B, n = 130), or PC plus behavioral intervention program (telephone-based motivational interviewing and optional tailored text messages) (group C, n = 133). The primary end point was the Δ change in non-high-density lipoprotein cholesterol (non-HDL-C) from baseline to 6 month.Results: The mean age was 64.6 ± 10.8 years, 23.7% were female, and 31.5% were nonwhite. After 6 months, the absolute difference in non-HDL-C for all participants was -19.8 mg/dL (95% CI -24.1 to -15.6, P < .001). There were no between-group differences in the primary end point for the combined PC groups (B and C) versus UC, with a Δ adjusted between group difference of -5.5 mg/dL (95% CI -13.1 to 2.1, P = .16). Patients in the PC groups were more likely to be on high-intensity statins at 6 months (52.9% vs 38.1%, P = .01). After excluding participants with baseline non-HDL-C <100 mg/dL (initial exclusion criterion), Δ non-HDL-C and Δ low-density lipoprotein cholesterol were improved in the PC groups compared to UC (non-HDL-C -8.13 mg/dL [-16.00 to -0.27], P = .04; low-density lipoprotein cholesterol -7.87mg/dL [-15.10 to -0.64], P = .03).Conclusions: Although non-HDL-C reduction at 6 months following a nonurgent CV procedure was not significant in the overall cohort, an increased uptake in high-potency statins may translate into improved long-term health outcomes and cost reductions. [ABSTRACT FROM AUTHOR]