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Coronary atherosclerosis results from the delicate interplay of genetic and exogenous risk factors, principally taking place in metabolic organs and the arterial wall. Here we show that 224 gene-regulatory coexpression networks (GRNs) identified by integrating genetic and clinical data from patients with (n = 600) and without (n = 250) coronary artery disease (CAD) with RNA-seq data from seven disease-relevant tissues in the Stockholm–Tartu Atherosclerosis Reverse Network Engineering Task (STARNET) study largely capture this delicate interplay, explaining >54% of CAD heritability. Within 89 cross-tissue GRNs associated with clinical severity of CAD, 374 endocrine factors facilitated inter-organ interactions, primarily along an axis from adipose tissue to the liver (n = 152). This axis was independently replicated in genetically diverse mouse strains and by injection of recombinant forms of adipose endocrine factors (EPDR1, FCN2, FSTL3 and LBP) that markedly altered blood lipid and glucose levels in mice. Altogether, the STARNET database and the associated GRN browser (http://starnet.mssm.edu) provide a multiorgan framework for exploration of the molecular interplay between cardiometabolic disorders and CAD.

Key Clinical Message Possible links between inflammatory stimuli and atherothrombotic disease in the context of gallbladder pathology are not well understood. Our case demonstrates that clinical suspicion of cardiac disease after a diagnosis of acute cholecystitis should remain high in light of the dire consequences of a missed diagnosis.

Background: Whereas statins are well-known to contribute to atheromatic plaque stability and regression of atherosclerosis burden, possible interactions with anti-retroviral therapy have led to sub-prescription in this cohort. However, exactly how statins affect the angiographic phenotype, coronary lesion characteristics and clinical outcomes in HIV patients undergoing PCI has not yet been investigated. Aim: To assess and describe the angiographic features and burden of Coronary Artery Disease (CAD) between HIV patients pre-treated with statins as compared to statin naïve patients undergoing Percutaneous Coronary Intervention (PCI). Methods: This is a retrospective, single-center study comparing pre-treated with statin to statin-naïve HIV patients who underwent PCI between 2003-2011. Quantitative coronary angiography (QCA) was performed for all treated lesions at baseline and following PCI in both groups. 1- Year clinical outcomes post-PCI were also analyzed and compared. Results: Statin pre-treated patients (n=47, 51%) had more frequently hyperlipidemia (95% vs. 50%, p Conclusion: While statin pre-treatment HIV patients were more likely to present with ACS and had worse cardiovascular risk profile, detailed coronary angiographic analysis reveals no significant differences in CAD burden and lesion characteristics. Statin use is associated with more favorable clinical outcomes at 1 year post-PCI suggesting the beneficial effects of statins in atherosclerosis progression in HIV patients.

Objective: To elucidate a proposed role of TACI, a tumor necrosis factor (TNF) family member of human B cells, in atherosclerosis. Whereas atherosclerosis has been characterized by inflammation, adaptive immunity, and specifically the role of B cells and their respective cytokine processes have not, and thus we focused on the role of a B cell homeostasis regulator, TACI. We chose TACI because it has been shown, in combination with immunoglobulins, to inhibit cells involved in the innate response, known to be the initial responders to atherosclerosis. Approach and Results: As there are two isoforms of TACI in mice, we needed to first confirm whether human B cells had one or two isoforms, before understanding preferential expression. To this end, we examined peripheral blood mononuclear cells (PBMCs), multiple myeloma cell lines and Hodgkin’s disease cells and found that both the longer and the shorter isoform of TACI are expressed. We did this by: stimulation of cell lines with IL-6, western blot analysis and densitometry, polymerase chain reaction. Student’s t-test, with the use of Statistical Analysis System (Cray, NC), for statistical analysis. Conclusion: Thus, based on our findings of the existence of both isoforms, functional analyses in cardiomyocytes would shed light on any proposed role of TACI in the context if coronary artery disease.

Whereas statins are well-known to contribute to atheromatic plaque stability and regression of atherosclerosis burden, possible interactions with anti-retroviral therapy have led to sub-prescription in this cohort. However, exactly how statins affect the angiographic phenotype, coronary lesion

Whereas the effects of stent thrombosis in bare metal stents and drug eluting stents on mortality and myocardial infarction have been well documented in the literature, there are currently no reports of the effects of scaffold thrombosis on these outcomes of the newest stents in ABSORB bioresorbable

Patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) are at high-risk for thromboembolic and bleeding events. However, the influence of left ventricular dysfunction (LVD) on PCI outcomes and the post-procedural anti-thrombotic strategy in AF patients remains

Percutaneous coronary intervention (PCI) of true bifurcation lesions (Medina classification 1, 1, 1; 1, 0, 1; or 0, 1, 1) is challenging and may involve either a 1-stent strategy with provisional side branch stenting, or a 2-stent strategy. Diabetes mellitus is associated with greater atherosclerotic burden and higher incidence of bifurcation lesions, and unfavorable outcomes after PCI. It is unknown whether use of newer everolimus-eluting stent (EES) implantation impacts relative outcomes of 1-stent and 2-stent strategies in patients with diabetes.We performed a retrospective analysis of consecutive patients with diabetes mellitus and complex true bifurcation lesions (side branch diameter2.0 mm) who underwent PCI with EES between February 2010 and December 2011. We grouped subjects based on initial treatment to a 1-stent (n = 81) or 2-stent (n = 54) strategy, and compared baseline characteristics, quantitative coronary angiography, and 1-year major adverse cardiovascular event (MACE) rates, defined as death, myocardial infarction, target lesion revascularization (TLR), or target vessel revascularization (TVR).Baseline characteristics were well matched. A 2-stent strategy was associated with larger side-branch reference vessel diameter at baseline and post PCI. In-hospital events included 1 periprocedural myocardial infarction in each group and no deaths. At 1 year, there was no significant difference between 1-stent and 2-stent strategies in TVR rates (6.2% vs 3.7%; P=.53), TLR (both 3.7%; P.99), or MACE (7.4% vs 3.7%; P=.37).In this series of diabetic patients undergoing complex bifurcation PCI using EES implantation, there was no difference between 1-stent and 2-stent strategies with respect to ischemic events at 1 year.

Cardiovascular risk in patients with advanced aortic stenosis (AS) remains substantial following treatment with balloon aortic valvuloplasty (BAV). While concomitant atrial fibrillation or flutter (AF/AFL) is frequent among patients with AS, the impact of AF/AFL on outcomes following BAV remains

In the drug-eluting stent era, in-stent restenosis (ISR) followed by a new ISR recurrence, is defined "resistant" ISR (R-ISR). This event represents a rare yet challenging clinical problem. To date there are no published studies that evaluated the best percutaneous treatment for these patients. We

Clinical trials in the United States tend to enroll racially homogenous cohorts, thereby limiting generalizability. We sought to identify correlates of clinical trial enrollment from a large and racially diverse PCI registry. We conducted a single-center study of patients undergoing PCI between 1/1

Percutaneous coronary intervention (PCI) of complex true coronary bifurcation lesions is challenging and whether to stent side branch dedicatedly is still debatable. To date there is no published study showing the safety and efficacy of the Everolimus-eluting stent (EES) in true bifurcation lesions