Association Between Uric Acid and Worsening Peripheral Microangiopathy in Systemic Sclerosis

Objective: The key element in the pathogenesis of systemic sclerosis (SSc) is microcirculatory changes in several vascular beds. Uric acid is associated with endothelial dysfunction and therefore, microvascular damage. The aim of this study was to examine the association between uric acid (UA) and peripheral microvascular involvement in patients with SSc.Methods: We included consecutive, consenting patients with SSc. Serum UA, urea and creatinine were measured, and glomerular filtration rate (GFR) was calculated with CKD-EPI. All participants underwent nailfold video-capillaroscopy (NVC) to evaluate the microcirculation.Results: A total of 64 patients (95.3% women) were included in the study. UA levels were significantly associated with the number of avascular areas (r = 0.290; p = 0.020), whereas no correlation was shown for the GFR (r = −0.065; p = 0.609). A significant trend of UA in the three capillaroscopic patterns was shown (3.90 ± 1.52 vs. 4.15 ± 0.98 vs. 5.38 ± 2.26; for early, active, and late patterns respectively, p = 0.028). Multivariate analysis showed that male gender (β = 3.049; 95% CI = 0.997–5.101) and UA (β = 0.352; 95% CI = 0.117–0.588) were independently associated with the number of avascular areas.Conclusion: These data suggest that UA levels are significantly associated with the capillaroscopic patterns, reflecting a progressive microvasculopathy.

Effects of Hemorrhagic Shock and Resuscitation on Mesenteric Circulation

Vascular beds may be variably affected by hemorrhage, which may have implications for resuscitation. The vascular anatomy of swine has been described with focus on its use for vascular and endovascular research; however, current research has predominantly focused on anatomy. (1,2) There is a lack of research regarding the physiology of mesenteric circulation at baseline physiology, as well as during hemorrhagic shock and resuscitation. The aim of this study was to develop a large animal model to characterize the implications of hemorrhage on mesenteric circulation and reperfusion. We constructed a surgical protocol to measure intestinal perfusion, as well as pressure and flow data of the superior mesenteric artery (SMA), portal vein, inferior vena cava (IVC), and aorta.

Human Immunodeficiency Viruses and its effect on the Pulmonary Vascular bed

December. 1st 2021 is "World AIDS Day" reminding us that HIV infection is still widespread and that many of its long-term effects can be deadly. One of these complications is its effect on the pulmonary vascular beds, leading to an increase in the pulmonary pressure, causing the clinical manifestation of "pulmonary hypertension". Unfortunately, we are still far from fully understanding the prevalence, mechanics, and pathobiology of "HIV pulmonary hypertension", especially in Africa and other developing countries where HIV is still common. In addition, the impact of other factors like co-infection and illicit drugs can add and modify the effect on the pulmonary vascular bed, complicating the pathological and clinical effects of HIV. Thus, "World AIDS Day" can be an impetus to pursue further research in this area.

Effects of Arachidonic Acid Metabolites on Cardiovascular Health and Disease

Arachidonic acid (AA) is an essential fatty acid that is released by phospholipids in cell membranes and metabolized by cyclooxygenase (COX), cytochrome P450 (CYP) enzymes, and lipid oxygenase (LOX) pathways to regulate complex cardiovascular function under physiological and pathological conditions. Various AA metabolites include prostaglandins, prostacyclin, thromboxanes, hydroxyeicosatetraenoic acids, leukotrienes, lipoxins, and epoxyeicosatrienoic acids. The AA metabolites play important and differential roles in the modulation of vascular tone, and cardiovascular complications including atherosclerosis, hypertension, and myocardial infarction upon actions to different receptors and vascular beds. This article reviews the roles of AA metabolism in cardiovascular health and disease as well as their potential therapeutic implication.

Trends in Utilization and Outcomes of Orbital, Laser, and Excisional Atherectomy for Lower Extremity Revascularization

Purpose: The aim of this study is to analyze the utilization pattern of atherectomy modalities and compare their outcomes. Materials and Methods: All patients undergoing atherectomy in the 2010–2016 Vascular Quality Initiative Database were identified. Utilization of orbital, laser, or excisional atherectomy was obtained. Characteristics and outcomes of patients treated for isolated femoropopliteal and isolated tibial disease by different modalities were compared. Results: Atherectomy use increased from 10.3% to 18.3% of all peripheral interventions (n = 122 938). Orbital atherectomy was most commonly used and increased from 59.4% in 2010 to 63.2% of all atherectomies in 2016, while laser atherectomy decreased from 19.2% to 13.1%. Atherectomy was mostly used for treatment of isolated femoropopliteal disease (51.1%), followed by combined femoropopliteal and tibial disease (25.8%) and isolated tibial disease (11.7%). In isolated femoropopliteal revascularization, excisional atherectomy was associated with higher rate of perforation (1.2%) compared with laser (0.4%) and orbital atherectomy (0.5%). The technical success of orbital atherectomy (96.7%) was lower compared with excisional atherectomy (98.7%). Concomitant stenting was significantly higher with laser atherectomy (43.0%) compared with orbital (27.2%) and excisional (26.1%) atherectomy. Nevertheless, there was no difference in 1-year primary patency, reintervention, major amputation, improvement in ambulatory status, or mortality. Multivariable analysis also demonstrated no difference in 1-year primary patency and major ipsilateral amputation among the modalities. In isolated tibial revascularization, there were no differences in perioperative outcomes among the modalities. Excisional atherectomy was associated with the highest 1-year primary patency (88.1%). After adjusting for confounders, excisional atherectomy remained associated with superior 1-year primary patency compared with orbital atherectomy (odds ratio [OR] = 2.59, 95% confidence interval [CI] = [1.18–5.68]), and excisional atherectomy remained associated with a lower rate of 1-year major ipsilateral amputation compared with laser atherectomy (OR = 0.29, 95% CI = [0.09–0.95]). Conclusion: Atherectomy use has increased, driven primarily by orbital atherectomy. Despite significant variation in perioperative outcomes, there were no differences in 1-year outcomes among the different modalities when used for treating isolated femoropopliteal disease. In isolated tibial disease treatment, excisional atherectomy was associated with higher 1-year primary patency compared with orbital atherectomy and decreased major ipsilateral amputation rates compared with laser atherectomy. These differences warrant further investigation into the comparative effectiveness of atherectomy modalities in various vascular beds.

Atherosclerotic Renal Artery Stenosis: A Review

Renal artery stenosis (RAS) is associated with hypertension and renal impairment. Atherosclerosis is the leading etiologic factor which accounts for >90% of the cases. Those with atherosclerotic RAS (ARAS) tend to have concomitant atherosclerosis in other vascular beds, so they are at a high risk of adverse coronary and cerebrovascular events. Management of ARAS is controversial, with limited indications for revascularization. In this review, the author aims to discuss the pathophysiology, natural history, diagnosis, and management of ARAS.

Comparison of peripheral artery plaque characteristics between ACS patients with plaque rupture and plaque erosion in culprit coronary artery: an OCT and ultrasound study

Background Recent research has found that the characteristics of peripheral arterial plaque are related to the increased risk of cardiovascular disease, however, the relationship of plaque characteristics between peripheral artery and coronary is still unknown. Purpose To assess the correlation between coronary plaque characteristics assessed by optical coherence tomography (OCT) and peripheral artery plaque characteristics assessed by ultrasound. Methods 150 patients with acute coronary syndrome (ACS) underwent coronary angiography were prospectively enrolled. OCT imaging of culprit vessel were performed during the procedure and ultrasound examination of bilateral carotid, iliofemoral and popliteal arteries was performed during hospitalization after procedure. Panvascular disease was defined as the presence of observable plaques in two or more vascular beds. Patients were divided into plaque rupture (PR) group and plaque erosion (PE) group according to culprit plaque characteristics on OCT. Results There were 132 (88%) ACS patients had panvascular disease in which 36 (24%) with generalized atherosclerosis (4 sites) and the prevalence of panvascular atherosclerosis in PR group was significantly higher than in PE group especially in carotid arteries and iliofemoral arteries (Figure 1, Figure 2). Compared to PE group, PR group had higher carotid plaque score (p=0.001) which indicates more plaques and severer atherosclerosis. Moreover, there were larger intima-media thickness (IMT) of iliofemoral arteries (6.9±1.4mm vs. 6.5±1.1mm, p=0.036) and more calcified plaques in PR group. Conclusions Panvascular disease is highly prevalent in ACS patients especially in patients with plaque rupture in culprit vessel, in which more than half of the patients had plaques in more than 3 sites of vascular beds. In addition, patients with plaque rupture had thicker iliofemoral IMT and higher panvascular atherosclerosis burden, which indicates that characteristics of coronary plaques are the focal expression of plaques in the whole panvcascular system. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Key R&D Program of China Figure 1. Prevalence of panvascular disease in ACS Figure 2. Comparison of peripheral artery plaques

Acute arterial events across all vascular territories in the FOURIER trial

Background In the FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk) trial, adding the PCSK9 inhibitor evolocumab to statin therapy reduced low-density lipoprotein cholesterol (LDL-C) and cardiovascular risk. Although atherosclerotic coronary, cerebrovascular, and peripheral vascular events share a related pathobiology, the effect of aggressive LDL-C lowering with PCSK9 inhibition on the risk of acute arterial events across all three vascular beds is not well-described. Purpose To assess the efficacy of evolocumab on acute arterial events in all vascular territories including coronary, cerebral, and peripheral vascular beds. Methods In the FOURIER trial, patients (n=27,564) with stable atherosclerotic cardiovascular disease and LDL-C ≥70 mg/dL on a statin were randomly assigned to evolocumab versus placebo and followed for a median of 2.2 years (1.8–2.5). Acute arterial events were defined as a composite of coronary (coronary heart disease [CHD] death, myocardial infarction [MI], or urgent coronary revascularization), cerebrovascular (ischemic stroke, transient ischemic attack [TIA], or urgent cerebral revascularization), or peripheral vascular (acute limb ischemia, major amputation, or urgent peripheral revascularization) events. Cox proportional-hazard models were used to assess the efficacy of evolocumab on these outcomes. Landmark and total event analyses were also done. Results Of the 2,210 first acute arterial events occurring during follow-up, 74% were coronary, 22% were cerebrovascular, and 4% were peripheral vascular. Evolocumab reduced the risk of a first acute arterial event by 19% (HR 0.81, 95% CI 0.74–0.88; P<0.001), with significant individual reductions in acute coronary (HR 0.83; 95% CI 0.75–0.91; P<0.001), acute cerebrovascular (HR 0.77; 95% CI 0.65–0.92; P=0.004), and acute peripheral vascular (HR 0.58; 95% CI 0.38–0.88; P=0.01) events (Figure, top). The magnitude of the risk reduction with evolocumab tended to increase over time, with a 16% reduction (HR 0.84; 95% CI 0.75–0.96) in the first year followed by a 24% reduction (HR 0.76; 95% CI 0.67–0.85) thereafter (Figure, bottom). There were 3,780 total acute arterial events (first plus recurrent), with a 22% reduction with evolocumab (incidence rate ratio [RR] 0.78; 95% CI 0.70–0.87). Evolocumab prevented 496 total acute arterial events as compared to 222 first events. Conclusions The addition of the PCSK9 inhibitor evolocumab to statin therapy reduced the risk of acute arterial events across all vascular territories with a robust effect over time. These findings indicate a pan-vascular impact of aggressive lipid-lowering therapy on these acute and clinically meaningful events. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): The FOURIER trial was supported by Amgen.

Emerging techniques in atherosclerosis imaging

Atherosclerosis is a chronic immunomodulated disease that affects multiple vascular beds and results in a significant worldwide disease burden. Conventional imaging modalities focus on the morphological features of atherosclerotic disease such as the degree of stenosis caused by a lesion. Modern CT, MR and positron emission tomography scanners have seen significant improvements in the rapidity of image acquisition and spatial resolution. This has increased the scope for the clinical application of these modalities. Multimodality imaging can improve cardiovascular risk prediction by informing on the constituency and metabolic processes within the vessel wall. Specific disease processes can be targeted using novel biological tracers and smart contrast agents. These approaches have the potential to inform clinicians of the metabolic state of atherosclerotic plaque. This review will provide an overview of current imaging techniques for the imaging of atherosclerosis and how various modalities can provide information that enhances the depiction of basic morphology. This publication is the reprint with Russian translation from original: Syed MBJ, Fletcher AJ, Forsythe RO, Kaczynski J, Newby DE, Dweck MR, et al. Emerging techniques in atherosclerosis imaging. Br J Radiol 2019; 92: 20180309. DOI: https://doi.org/10.1259/bjr.20180309

The Transient Receptor Potential Vanilloid 4 Channel and Cardiovascular Disease Risk Factors

Vascular endothelial cells regulate arterial tone through the release of nitric oxide and other diffusible factors such as prostacyclin and endothelium derived hyperpolarizing factors. Alongside these diffusible factors, contact-mediated electrical propagation from endothelial cells to smooth muscle cells via myoendothelial gap junctions, termed endothelium-dependent hyperpolarization (EDH), plays a critical role in endothelium-dependent vasodilation in certain vascular beds. A rise in intracellular Ca2+ concentration in endothelial cells is a prerequisite for both the production of diffusible factors and the generation of EDH, and Ca2+ influx through the endothelial transient receptor potential vanilloid 4 (TRPV4) ion channel, a nonselective cation channel of the TRP family, plays a critical role in this process in various vascular beds. Emerging evidence suggests that the dysregulation of endothelial TRPV4 channels underpins endothelial dysfunction associated with cardiovascular disease (CVD) risk factors, including hypertension, obesity, diabetes, and aging. Because endothelial dysfunction is a precursor to CVD, a better understanding of the mechanisms underlying impaired TRPV4 channels could lead to novel therapeutic strategies for CVD prevention. In this mini review, we present the current knowledge of the pathophysiological changes in endothelial TRPV4 channels associated with CVD risk factors, and then explore the underlying mechanisms involved.