Harrisonkjeldgaard7450

ecision support tool for use in clinical settings.

Endothelial cell (EC) dysfunction is a well-established response to cardiovascular disease risk factors, such as smoking and obesity. Risk factor exposure can modify EC signaling and behavior, leading to arterial and venous disease development. Here, we aimed to identify biomarker panels for the assessment of EC dysfunction, which could be useful for risk stratification or to monitor treatment response. Approach and Results We used affinity proteomics to identify EC proteins circulating in plasma that were associated with cardiovascular disease risk factor exposure. Two hundred sixteen proteins, which we previously predicted to be EC-enriched across vascular beds, were measured in plasma samples (n=1005) from the population-based SCAPIS (Swedish Cardiopulmonary Bioimage Study) pilot. Thirty-eight of these proteins were associated with body mass index, total cholesterol, low-density lipoprotein, smoking, hypertension, or diabetes. Sex-specific analysis revealed that associations predominantly observed in female- or male-only samples were most frequently with the risk factors body mass index, or total cholesterol and smoking, respectively. We show a relationship between individual cardiovascular disease risk, calculated with the Framingham risk score, and the corresponding biomarker profiles.

EC proteins in plasma could reflect vascular health status.

EC proteins in plasma could reflect vascular health status.

To determine whether baseline aortic stiffness, measured by aortic pulse wave velocity (PWV), relates to longitudinal cerebral gray or white matter changes among older adults. Baseline cardiac magnetic resonance imaging will be used to assess aortic PWV while brain magnetic resonance imaging will be used to assess gray matter and white matter hyperintensity (WMH) volumes at baseline, 18 months, 3 years, 5 years, and 7 years. Approach and Results Aortic PWV (m/s) was quantified from cardiac magnetic resonance. Multimodal 3T brain magnetic resonance imaging included



-weighted imaging for quantifying gray matter volumes and



-weighted fluid-attenuated inversion recovery imaging for quantifying WMHs. Mixed-effects regression models related baseline aortic PWV to longitudinal gray matter volumes (total, frontal, parietal, temporal, occipital, hippocampal, and inferior lateral ventricle) and WMH volumes (total, frontal, parietal, temporal, and occipital) adjusting for age, sex, race/ethnicity, education, clts, higher baseline aortic PWV related to greater decrease in gray matter volume and greater increase in WMHs over time. Because of unmet cerebral metabolic demands and microvascular remodeling, arterial stiffening may preferentially affect certain highly active brain regions like the temporal lobes. These same regions are affected early in the course of Alzheimer disease.

In older adults, higher baseline aortic PWV related to greater decrease in gray matter volume and greater increase in WMHs over time. Because of unmet cerebral metabolic demands and microvascular remodeling, arterial stiffening may preferentially affect certain highly active brain regions like the temporal lobes. These same regions are affected early in the course of Alzheimer disease.

Gestational hypercholesterolemia concomitantly with a highly oxidative environment is associated with higher atherosclerosis in human and animal offspring. This work aimed to determine whether perinatal administration of a C-phycocyanin concentrate, a powerful antioxidant, can protect against atherosclerosis development in genetically hypercholesterolemic mice in adult life. Approach and Results C-Phycocyanin was administered during gestation solely or gestation and lactation to apolipoprotein E-deficient mice. Male and female offspring were studied until 25 weeks old. Progenies born to supplemented mothers displayed significantly less atherosclerotic root lesions than control group in all groups excepted in male supplemented during gestation and lactation. Female born to supplemented mothers had a greater gallbladder total bile acid pool, lower secondary hydrophobic bile acid levels such as lithocholic acid, associated with less plasma trimethylamine

-oxide at 16 weeks old compared with control mice. Regarding male born to C-Phycocyanin administrated mothers, they expressed a higher high-density lipoprotein cholesterol level, more soluble bile acids such as β-muricholic acids, and a decreased plasma trimethylamine at 16 weeks old. Liver reduced-to-oxidized glutathione ratio were increased and liver gene expression of superoxide dismutase and glutathione peroxidase were significantly decreased in male born to gestational supplemented mothers. No difference in the composition of cecal microbiota was found between groups, regardless of sex.

Our findings suggest a protective effect of perinatal antioxidant administration on atherosclerosis development in apolipoprotein E-deficient mice involving sex-specific mechanisms.

Our findings suggest a protective effect of perinatal antioxidant administration on atherosclerosis development in apolipoprotein E-deficient mice involving sex-specific mechanisms.

Functional HDL (high-density lipoprotein) particles that facilitate cholesterol efflux may be cardioprotective. EL (endothelial lipase) hydrolyzes phospholipids promoting catabolism of HDL and subsequent renal excretion. MEDI5884 is a selective, humanized, monoclonal, EL-neutralizing antibody. We sought to determine the safety, pharmacokinetics, and pharmacodynamic effects of multiple doses of MEDI5884 in patients with stable coronary artery disease. Approach and Results LEGACY was a phase 2a, double-blind, placebo-controlled, parallel-design trial that randomized 132 patients with stable coronary artery disease receiving high-intensity statin therapy to 3 monthly doses of 1 of 5 dose levels of MEDI5884 (50, 100, 200, 350, or 500 mg SC) or matching placebo. The primary end point was the safety and tolerability of MEDI5884 through the end of the study (day 151). Additional end points included change in HDL cholesterol and cholesterol efflux from baseline to day 91, hepatic uptake of cholesterol at day 91, chn of EL by MEDI5884 increases the quantity and quality of functional HDL in patients with stable coronary artery disease on high-intensity statin therapy without an adverse safety signal at the likely dose to be used. These data support further clinical investigation. Registration URL https//www.clinicaltrials.gov; Unique identifier NCT03351738.Background Chronic kidney disease is associated with adverse outcomes among patients with established cardiovascular disease (CVD) or diabetes. Commonly used medications to treat CVD are less effective among patients with reduced kidney function. Methods The Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) was a multicenter, double-blind, placebo-controlled trial that randomized statin-treated patients with elevated triglycerides (135-499 mg/dL) who had CVD or diabetes and one additional risk factor to treatment with icosapent ethyl (4 grams daily) or placebo. Selleck Navitoclax Patients from REDUCE-IT were categorized by prespecified eGFR categories to analyze the effect of icosapent ethyl on the primary endpoint (composite of cardiovascular [CV] death, nonfatal myocardial infarction nonfatal stroke, coronary revascularization, or unstable angina) and key secondary endpoint (a composite of CV death, nonfatal myocardial infarction, or nonfatal stroke). Results Among the 8179 REDUCE-IT patieation/flutter (icosapent ethyl 4.2%; placebo 3.0%; HR 1.42, 95% CI 0.86-2.32, P=0.17) and serious bleeding (icosapent ethyl 5.4%; placebo 3.6%; HR 1.40, 95% CI 0.90-2.18, P=0.13), hazard ratios for atrial fibrillation/flutter and serious bleeding were similar across eGFR categories (P-interaction for atrial fibrillation/flutter = 0.92; P-interaction for serious bleeding = 0.76). Conclusions In REDUCE-IT, icosapent ethyl reduced fatal and nonfatal ischemic events across the broad range of baseline eGFR categories. Clinical Trial Registration URL https//clinicaltrials.gov Unique Identifier NCT01492361.

There are limited data on differences in angiographic distribution of peripheral artery disease and endovascular revascularization strategies in patients presenting with intermittent claudication (IC) and critical limb ischemia (CLI). We aimed to compare anatomic features, treatment strategies, and clinical outcomes between patients with IC and CLI undergoing endovascular revascularization.

We examined 3326 patients enrolled in the Excellence in Peripheral Artery Disease registry from 2006 to 2019 who were referred for endovascular intervention for IC (n=1983) or CLI (n=1343). The primary outcome was 1-year major adverse limb events, which included death, repeat target limb revascularization, or target limb amputation.

Patients with CLI were older and more likely to have diabetes and chronic kidney disease and less likely to receive optimal medical therapy compared with IC. Patients with IC had higher femoropopliteal artery interventions (IC 87% versus CLI 65%;

<0.001), while below the knee interventions were more frequent in CLI (CLI 47% versus IC 12%;

<0.001). Patients with CLI were more likely to have multilevel peripheral artery disease (CLI 32% versus IC 15%,

<0.001). Patients with IC were predominantly revascularized with stents (IC 48% versus CLI 37%;

<0.001) while balloon angioplasty was more frequent in CLI (CLI 37% versus IC 25%;

<0.001). All-cause mortality was higher in patients with CLI (CLI 4% versus IC 2%;

=0.014). Major adverse limb event rates for patients with IC and CLI were 16% and 26%, respectively (

<0.001) and remained higher in CLI after multivariable adjustment of baseline risk factors.

Patients with IC and CLI have significant anatomic, lesion, and treatment differences with significantly higher mortality and adverse limb outcomes in CLI.

URL https//www.clinicaltrials.gov; Unique identifier NCT01904851.

URL https//www.clinicaltrials.gov; Unique identifier NCT01904851.

High-power short-duration (HP-SD) radiofrequency ablation (RFA) has been proposed as a method for producing rapid and effective lesions for pulmonary vein isolation. The underlying hypothesis assumes an increased resistive heating phase and decreased conductive heating phase, potentially reducing the risk for esophageal thermal injury. The objective of this study was to compare the esophageal temperature dynamic profile between HP-SD and moderate-power moderate-duration (MP-MD) RFA ablation strategies.

In patients undergoing pulmonary vein isolation, RFA juxtaposed to the esophagus was delivered in an alternate sequence of HP-SD (50 W, 8-10 s) and MP-MD (25 W, 15-20 s) between adjacent applications (distance, ≤4 mm). Esophageal temperature was recorded using a multisensor probe (CIRCA S-CATH). Temperature data included magnitude of temperature rise, maximal temperature, time to maximal temperature, and time return to baseline. In swine, a similar experimental design compared the effect of HP-SD and MP-MD perature dynamics are similar between HP-SD and MP-MD RFA strategies and result in comparable esophageal tissue injury. Therefore, when using a HP-SD RFA strategy, the shorter application duration should not prompt shorter intervals between applications.