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1.
Relation of Plasma Renin Activity to Subclinical Peripheral and Coronary Artery Disease (from the Multiethnic Study of Atherosclerosis).
Unkart, JT, Allison, MA, Abdelmalek, JA, Jenny, NS, McClelland, RL, Budoff, M, Ix, JH, Rifkin, DE
The American journal of cardiology. 2020;(12):1794-1800
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Abstract
Experimental studies support a link between activation of the renin-angiotensin-aldosterone system and cardiovascular disease (CVD). The relationship with subclinical atherosclerosis is uncertain. Among 1,699 individuals without prevalent CVD from the Multiethnic Study of Atherosclerosis, we measured plasma renin activity (PRA) and aldosterone. Using multivariable logistic regression with restricted cubic splines, we assessed continuous log-transformed PRA and aldosterone associations with the ankle-brachial index (ABI) and coronary artery calcium (CAC) scores (Agatston) with adjustment for cardiovascular disease (CVD) risk factors, kidney function, and inflammatory biomarkers. In fully adjusted models mutually adjusting for PRA and aldosterone, higher PRA was associated with an ABI <1.0 (p overall <0.001, p nonlinear = 0.02) and CAC Agatston score >300 (p overall = 0.02, p nonlinear = 0.22), while aldosterone was not associated with either outcome. For example, compared to the 10th percentile (0.16 ng/ml/hr) of PRA, the 90th percentile (2.68 ng/ml/hr) had 3.6 times (OR 3.62; 95% CI: 2.13 to 6.13) and 1.7 times higher odds (odds ratio 1.67; 95% confidence interval: 1.13 to 2.48) of ABI <1.0 and CAC >300, respectively. These associations persisted after adjustment for levels of C-reactive protein, Interleukin-6, and Tumor Necrosis Factor-alpha. There were no significant differences in these associations by race/ethnicity or antihypertensive medication status. In conclusion, in a multiethnic cohort of community-living adults without prevalent clinical CVD, PRA was associated with greater burden of subclinical peripheral artery and coronary artery disease. These findings provide additional evidence that PRA may have deleterious effects on cardiovascular health through an atherosclerotic pathway.
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The Current Status of Lithoplasty in Vascular Calcifications: A Systematic Review.
Khan, S, Li, B, Salata, K, Aljabri, BA, Hussain, MA, Khan, M, de Mestral, C, Verma, S, Al-Omran, M
Surgical innovation. 2019;(5):588-598
Abstract
Background. Lithoplasty is a method of alleviating vessel stenosis by using localized high-speed pressure waves to disrupt calcium deposits. A systematic review of the literature was performed to summarize the early outcomes of lithoplasty in peripheral and coronary artery disease. Methods. We searched EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials from database inception to July 2018 for original studies describing the use of lithoplasty. Study selection and data extraction were performed in duplicate, with a third author resolving discrepancies. Results. A total of 9 records were included from the 201 studies eligible for screening. In total, 211 patients with vascular calcification lesions underwent lithoplasty. The patients on average had an age of 73.2 years and had a maximum follow-up period of 5.5 months. Most lesions (72%, 152/212) were in peripheral artery beds, with the remainder occurring in coronary vessels. Lesioned vessels typically had severe calcium burden 62.6% (131/210), with an average initial stenosis of 76.6% (range, 68.1%-77.8%). After treatment, the average residual stenosis was 21.0% (range, 13.3%-26.2%), with a mean acute gain of vessel diameter of 2.5 mm. A limited number of type D dissections occurred, with a total of 2.4% (5/211) of patients requiring stent implantation. Conclusions. Recent studies suggest that lithoplasty is a promising intervention to decrease vessel stenosis in both peripheral artery disease and coronary artery disease, with minimal occurrence of major adverse events. Further research studies, with more rigorous study designs, are needed to determine the effectiveness of lithoplasty in vascular calcifications.
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Prostanoids for critical limb ischaemia.
Vietto, V, Franco, JV, Saenz, V, Cytryn, D, Chas, J, Ciapponi, A
The Cochrane database of systematic reviews. 2018;(1):CD006544
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Abstract
BACKGROUND Peripheral arterial occlusive disease (PAOD) is a common cause of morbidity and mortality due to cardiovascular disease in the general population. Although numerous treatments have been adopted for patients at different disease stages, no option other than amputation is available for patients presenting with critical limb ischaemia (CLI) unsuitable for rescue or reconstructive intervention. In this regard, prostanoids have been proposed as a therapeutic alternative, with the aim of increasing blood supply to the limb with occluded arteries through their vasodilatory, antithrombotic, and anti-inflammatory effects. This is an update of a review first published in 2010. OBJECTIVES To determine the effectiveness and safety of prostanoids in patients with CLI unsuitable for rescue or reconstructive intervention. SEARCH METHODS For this update, the Cochrane Vascular Information Specialist searched the Specialised Register (January 2017) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 1). In addition, we searched trials registries (January 2017) and contacted pharmaceutical manufacturers, in our efforts to identify unpublished data and ongoing trials. SELECTION CRITERIA Randomised controlled trials describing the efficacy and safety of prostanoids compared with placebo or other pharmacological control treatments for patients presenting with CLI without chance of rescue or reconstructive intervention. DATA COLLECTION AND ANALYSIS Two review authors independently selected trials, assessed trials for eligibility and methodological quality, and extracted data. We resolved disagreements by consensus or by consultation with a third review author. MAIN RESULTS For this update, 15 additional studies fulfilled selection criteria. We included in this review 33 randomised controlled trials with 4477 participants; 21 compared different prostanoids versus placebo, seven compared prostanoids versus other agents, and five conducted head-to-head comparisons using two different prostanoids.We found low-quality evidence that suggests no clear difference in the incidence of cardiovascular mortality between patients receiving prostanoids and those given placebo (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.41 to 1.58). We found high-quality evidence showing that prostanoids have no effect on the incidence of total amputations when compared with placebo (RR 0.97, 95% CI 0.86 to 1.09). Adverse events were more frequent with prostanoids than with placebo (RR 2.11, 95% CI 1.79 to 2.50; moderate-quality evidence). The most commonly reported adverse events were headache, nausea, vomiting, diarrhoea, flushing, and hypotension. We found moderate-quality evidence showing that prostanoids reduced rest-pain (RR 1.30, 95% CI 1.06 to 1.59) and promoted ulcer healing (RR 1.24, 95% CI 1.04 to 1.48) when compared with placebo, although these small beneficial effects were diluted when we performed a sensitivity analysis that excluded studies at high risk of bias. Additionally, we found evidence of low to very low quality suggesting the effects of prostanoids versus other active agents or versus other prostanoids because studies conducting these comparisons were few and we judged them to be at high risk of bias. None of the included studies assessed quality of life. AUTHORS' CONCLUSIONS We found high-quality evidence showing that prostanoids have no effect on the incidence of total amputations when compared against placebo. Moderate-quality evidence showed small beneficial effects of prostanoids for rest-pain relief and ulcer healing when compared with placebo. Additionally, moderate-quality evidence showed a greater incidence of adverse effects with the use of prostanoids, and low-quality evidence suggests that prostanoids have no effect on cardiovascular mortality when compared with placebo. None of the included studies reported quality of life measurements. The balance between benefits and harms associated with use of prostanoids in patients with critical limb ischaemia with no chance of reconstructive intervention is uncertain; therefore careful assessment of therapeutic alternatives should be considered. Main reasons for downgrading the quality of evidence were high risk of attrition bias and imprecision of effect estimates.
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Associations Between Adding a Radial Artery Graft to Single and Bilateral Internal Thoracic Artery Grafts and Outcomes: Insights From the Arterial Revascularization Trial.
Taggart, DP, Altman, DG, Flather, M, Gerry, S, Gray, A, Lees, B, Benedetto, U, ,
Circulation. 2017;(5):454-463
Abstract
BACKGROUND Whether the use of the radial artery (RA) can improve clinical outcomes in coronary artery bypass graft surgery remains unclear. The ART (Arterial Revascularization Trial) was designed to compare survival after bilateral internal thoracic artery (BITA) over single left internal thoracic artery (SITA). In the ART, a large proportion of patients (≈20%) also received an RA graft instead of a saphenous vein graft (SVG). We aimed to investigate the associations between using the RA instead of an SVG to supplement SITA or BITA grafts and outcomes by performing a post hoc analysis of the ART. METHODS Patients enrolled in the ART (n=3102) were classified on the basis of conduits actually received (as treated). The analysis included 2737 patients who received an RA graft (RA group; n=632) or SVG only (SVG group; n=2105) in addition to SITA or BITA grafts. The primary end point was the composite of myocardial infarction, cardiovascular death, and repeat revascularization at 5 years. Propensity score matching and stratified Cox regression were used to compare the 2 strategies. RESULTS Myocardial infarction, cardiovascular death, and repeat revascularization cumulative incidence was 2.3% (95% confidence interval [CI], 1.1-3.4), 3.5% (95% CI, 2.1-5.0), and 4.4% (95% CI, 2.8-6.0) in the RA group and 3.4% (95% CI, 2.0-4.8), 4.0% (95% CI, 2.5-5.6), and 7.6% (95% CI, 5.5-9.7) in the SVG group, respectively. The composite end point was significantly lower in the RA group (8.8%; 95% CI, 6.5-11.0) compared with the SVG group (13.6%; 95% CI, 10.8-16.3; P=0.005). This association was present when an RA graft was used to supplement both SITA and BITA grafts (interaction P=0.62). CONCLUSIONS This post hoc ART analysis showed that an additional RA was associated with lower risk for midterm major adverse cardiac events when used to supplement SITA or BITA grafts. CLINICAL TRIAL REGISTRATION URL: https://www.situ.ox.ac.uk/surgical-trials/art. Unique identifier: ISRCTN46552265.
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Anti-oxidative treatment with vitamin E improves peripheral vascular function in patients with diabetes mellitus and Haptoglobin 2-2 genotype: A double-blinded cross-over study.
Alshiek, JA, Dayan, L, Asleh, R, Blum, S, Levy, AP, Jacob, G
Diabetes research and clinical practice. 2017;:200-207
Abstract
Vascular dysfunction in both conduit arteries and small vessels is a major contributor to the development of cardiovascular disease (CVD) in diabetes mellitus (DM). In diabetes there is a process of systemic chronic inflammation accompanied by high oxidative stress causing a subsequent decrease in vascular reactivity and negatively affect the metabolic processes responsible for functioning of the microvasculature. Vitamin E is classified as an antioxidant due to its ability to scavenge lipid radicals and terminate oxidative chain reactions. We conducted a double-blinded cross-over study with vitamin E versus placebo in individuals with type 2DM and the Hp2-2 genotype and assessed different aspects of peripheral vascular function in these patients. Twenty patients completed the study with 10 individuals in each study cohort. We were able to show significant improvement of indirect indices of vascular function following 8weeks of treatment with vitamin E. This improvement was consistent for weeks even after stopping the vitamin E treatment. We concluded that a pharmacogenomic rationale utilizing the Hp genotype might potentially provide cardiovascular benefit with vitamin E.
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The Place of Nailfold Capillaroscopy Among Instrumental Methods for Assessment of Some Peripheral Ischaemic Syndromes in Rheumatology.
Lambova, SN
Folia medica. 2016;(2):77-88
Abstract
Micro- and macrovascular pathology is a frequent finding in a number of common rheumatic diseases. Secondary Raynaud's phenomenon (RP) is among the most common symptoms in systemic sclerosis and several other systemic autoimmune diseases including a broad differential diagnosis. It should be also differential from other peripheral vascular syndromes such as embolism, thrombosis, etc., some of which lead to clinical manifestation of the blue toe syndrome. The current review discusses the instrumental methods for vascular assessments. Nailfold capillaroscopy is the only method among the imaging techniques that can be used for morphological assessment of the nutritive capillaries in the nailfold area. Laser-Doppler flowmetry and laser-Doppler imaging are methods for functional assessment of microcirculation, while thermography and plethysmography reflect both blood flow in peripheral arteries and microcirculation. Doppler ultrasound and angiography visualize peripheral arteries. The choice of the appropriate instrumental method is guided by the clinical presentation. The main role of capillaroscopy is to provide differential diagnosis between primary and secondary RP. In rheumatology, capillaroscopic changes in systemic sclerosis have been recently defined as diagnostic. The appearance of abnormal capillaroscopic pattern inherits high positive predictive value for the development of a connective tissue disease that is higher than the predictive value of antinuclear antibodies. In cases of abrupt onset of peripheral ischaemia, clinical signs of critical ischaemia, unilateral or lower limb involvement, Doppler ultrasound and angiography are indicated. The most common causes for such clinical picture that may be referred to rheumatologic consultation are the antiphospholipid syndrome, mimickers of vasculitides such as atherosclerosis with cholesterol emboli, and neoplasms.
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Drug-coated balloons: what is the evidence?
Marques, L, Hopf-Jensen, S, Müller-Hülsbeck, S
The Journal of cardiovascular surgery. 2016;(1):12-7
Abstract
Having evolved at a rapid pace, the therapy options for percutaneous treatment of peripheral arterial disease in the lower limbs, especially percutaneous transluminal angioplasty in combination with stent-technology, are able to deliver a rate where at least 80% of the treated patients remain free from reintervention after the first years under ideal study conditions, meaning that defined and often restrict in- and exclusion criteria were fulfilled and mid-term dual platelet therapy is warranted. This is somewhat a huge leap when compared to the 50-60% in the 1980s and 1990s, but we now face an era of an increasingly demanding clientele, where the industry also strives to cover this final 20% with newer technologies. As recent studies with drug-eluting stents (DES) suggests, nowadays it is possible to achieve up to 90% patency in the short- and mid-term, but this comes accompanied by remarkably increased therapy costs, making it almost impossible to most centers to implant it as the standard therapy option. Trying to fill this gap between the low-patency of the plain old balloon angioplasty and the higher costs of the DES, drug-coated balloon technology has found its niche, knowing that reimbursement shows a broad variation across the countries and continents.
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Drug coated balloons below-the-knee: just too early?
Fanelli, F, Cannavale, A
The Journal of cardiovascular surgery. 2016;(1):18-22
Abstract
Patients with infrapopliteal arterial disease are generally considered challenging due to the usual presence of multivessel atherosclerotic disease. Several treatment options have been used by different authors but none of them can be considered ideal. In the last few years drug coated balloons have gained popularity especially due to the extraordinary results in the femoro-popliteal region. Following the great success, physicians started to use this promising device also in the below-the-knee (BTK) region. The initial enthusiasm correlated to some studies is not confirmed by the largest randomized trial, IN.PACT Deep, comparing In.Pact DCB to standard PTA. This trial failed completely to show the superiority of drug coated balloon (DCB). The negative outcome was mainly correlated to safety issues with an amputation rate higher for the drug coated balloon when compared to the conventional balloon (8.8% DCB vs.3.6% PTA, P=0.08). A thorough evaluation has been performed to justify these negative outcomes, given the good results reported by other studies. But nowadays it is still difficult to find a clear explanation. Especially for this negative outcome and for the big difference, in term of results, between the different studies in the BTK region and also between the above and below the knee regions more trials are mandatory.
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What are the potential limitations of drug coated balloons and possible ways to overcome.
Werk, M
The Journal of cardiovascular surgery. 2016;(1):23-8
Abstract
In several independent randomized clinical studies, it has been shown that drug-coated balloons (DCBs) cause persistent clinically meaningful and statistically significant inhibition of restenosis in femoropopliteal arteries in comparison to percutaneous transluminal angioplasty with uncoated balloon catheters. The potential benefits of delivering an antiproliferative drug into the vessel wall using a balloon as transporter are manifold: 1) widespread applicability: balloon angioplasty is suitable for use in a wide range of lesions. The use of DCBs is technically less demanding and offers greater flexibility compared with stenting techniques. 2) Maintaining options: minimizing the use of durable implants is providing more options for following and complementary revascularization procedures; 3) proven efficacy: consistent, positive outcomes across studies and key subgroups have been demonstrated from the first preclinical studies to ongoing clinical trials. Beside the enthusiasm carried along with this novel technique and questioning if DCBs will become standard-of-care-therapy for the superficial femoral artery, the potential limitations have to be discussed.
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Disease understanding in patients with intermittent claudication: A qualitative study.
Lokin, JL, Hengeveld, PJ, Conijn, AP, Nieuwkerk, PT, Koelemay, MJ
Journal of vascular nursing : official publication of the Society for Peripheral Vascular Nursing. 2015;(3):112-8
Abstract
The aim of our qualitative study was to investigate the understanding of patients with intermittent claudication (IC) regarding the etiology and atherosclerotic nature of their disease. Patients were recruited from participants of the SUPER study, a randomized trial comparing angioplasty and supervised exercise therapy for alleviation of IC owing to an iliac artery obstruction. Patients were submitted to explorative, semistructured, in-depth interviews that were fully transcribed, coded, and categorized. We interviewed 19 patients. The majority of respondents (79%) recognized smoking as a major risk factor contributing to the etiology of IC. However, nearly one-half (47%) underestimated the effects of unhealthy dietary and exercise patterns. In contrast, a substantial number of respondents (42%) overestimated the contribution of genetics to the etiology of their disease. Most respondents (79%) were unaware of the fact that IC implies systemic atherosclerosis.This study shows that the patients' interpretation of the etiology and nature of IC was mostly incorrect. Therefore, we suggest that health care providers enhance counseling about etiologic factors and the systemic nature of IC to optimize outcomes of lifestyle adjustments.