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Medicina (Kaunas, Lithuania) Oct 2023: Coronary angiography is the gold standard for diagnosing coronary artery disease (CAD). In the case of borderline changes, patients require further diagnosis through...
: Coronary angiography is the gold standard for diagnosing coronary artery disease (CAD). In the case of borderline changes, patients require further diagnosis through ischemia assessment via one of the recommended methods of invasive evaluation. This study aimed to assess whether clinical factors influence the risk of a positive result in invasive myocardial ischemia assessment and if these potential factors change with the patient's age and the consistency of ischemia assessment. : Data were collected retrospectively on all consecutive patients hospitalized in the University Hospital in Krakow between 2020 and 2021, on whom physiological assessments of coronary circulation were performed. Patients were divided into two groups: patients aged 60 or younger and patients older than 60. : Despite the older patients having more risk factors for CAD, their physiological assessment results of borderline lesions were similar to those of the younger patients. Positive fractional flow reserve (FFR) assessments were obtained from almost 50% of vessels. In the younger patients, cigarette use and type 2 diabetes mellitus increased the risk of a positive FFR result by 3.5 and 2.5 times, respectively. In the older patients, male gender and peripheral vascular disease significantly increased the risk of a positive FFR by 2.5 and 2 times, respectively. : Clinical characteristics of patients undergoing physiological assessment of borderline coronary stenosis varied significantly by age. Refining the definition of borderline lesions to include age, gender, and other factors may improve the identification of patients who would benefit from physiological assessment and coronary revascularization.
Topics: Humans; Male; Fractional Flow Reserve, Myocardial; Retrospective Studies; Diabetes Mellitus, Type 2; Coronary Stenosis; Coronary Artery Disease; Coronary Angiography; Ischemia; Coronary Vessels; Predictive Value of Tests; Severity of Illness Index
PubMed: 37893581
DOI: 10.3390/medicina59101863 -
Annals of Surgery Aug 2023The aim was to analyze the risk of progression to chronic limb-threatening ischemia (CLTI), amputation and subsequent interventions after revascularization versus...
OBJECTIVE
The aim was to analyze the risk of progression to chronic limb-threatening ischemia (CLTI), amputation and subsequent interventions after revascularization versus noninvasive therapy in patients with intermittent claudication (IC).
BACKGROUND
Conflicting evidence exists regarding adverse limb outcomes after each treatment strategy.
METHODS
Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. MEDLINE, Web of Science, and Google Scholar were searched aided by a health sciences librarian through August 16, 2022. Randomized control trials (RCTs) comparing invasive (endovascular or surgical revascularization) and noninvasive treatment (exercise and/or medical treatment) were included. PROSPERO registration was completed (CRD42022352831).
RESULTS
A total of 9 RCTs comprising 1477 patients (invasive, 765 patients; noninvasive, 712 patients) were eligible. During a mean of 3.6-year follow-up, progression to CLTI after invasive [5 (2-8) per 1000 person-years] and noninvasive treatment [6 (3-10) per 1000 person-years] were not statistically different [rate ratio (RR): 0.77; 95% CI, 0.35-1.69; P =0.51, I2 =0%]. Incidence of amputation (RR: 1.69; 95% CI, 0.54-5.26; P =0.36, I2 =0%) and all-cause mortality (hazard ratio: 1.26; 95% CI, 0.91-1.74; P =0.16, I2 =0%) also did not differ between the groups. However, the invasive treatment group underwent significantly more revascularizations (RR: 4.15; 95% CI, 2.80-6.16; P <0.00001, I2 =83%). The results were not changed by fixed effect or random-effects models, nor by sensitivity analysis.
CONCLUSIONS
Although there is equivalent risk of progression to CLTI, major amputation and all-cause mortality compared with noninvasive treatment, invasive treatment for patients with IC led to significantly more revascularization procedures and should be used selectively in patients with major lifestyle limitation. Guideline recommendation of noninvasive treatment for first-line IC therapy is supported.
Topics: Humans; Endovascular Procedures; Exercise Therapy; Intermittent Claudication; Ischemia; Peripheral Arterial Disease; Risk Factors; Treatment Outcome; Vascular Surgical Procedures; Randomized Controlled Trials as Topic
PubMed: 36728522
DOI: 10.1097/SLA.0000000000005793 -
FASEB Journal : Official Publication of... Aug 2023Inflammatory processes are activated following ischemic stroke that lead to increased tissue damage for weeks following the ischemic insult, but there are no approved...
Inflammatory processes are activated following ischemic stroke that lead to increased tissue damage for weeks following the ischemic insult, but there are no approved therapies that target this inflammation-induced secondary injury. Here, we report that SynB1-ELP-p50i, a novel protein inhibitor of the nuclear factor kappa B (NF-κB) inflammatory cascade bound to the drug carrier elastin-like polypeptide (ELP), decreases NF-κB induced inflammatory cytokine production in cultured macrophages, crosses the plasma membrane and accumulates in the cytoplasm of both neurons and microglia in vitro, and accumulates at the infarct site where the blood-brain barrier (BBB) is compromised following middle cerebral artery occlusion (MCAO) in rats. Additionally, SynB1-ELP-p50i treatment reduces infarct volume by 11.86% compared to saline-treated controls 24 h following MCAO. Longitudinally, SynB1-ELP-p50i treatment improves survival for 14 days following stroke with no effects of toxicity or peripheral organ dysfunction. These results show high potential for ELP-delivered biologics for therapy of ischemic stroke and other central nervous system disorders and further support targeting inflammation in ischemic stroke.
Topics: Rats; Animals; NF-kappa B; Ischemic Stroke; Elastin; Brain; Peptides; Stroke; Brain Ischemia; Anti-Inflammatory Agents; Infarction, Middle Cerebral Artery; Inflammation; Microglia
PubMed: 37402128
DOI: 10.1096/fj.202300309RR -
European Journal of Cardio-thoracic... Aug 2023The aim of this study was to evaluate the incidence and outcomes of ischaemic organ complications after thoracic endovascular aortic repair (TEVAR). (Observational Study)
Observational Study
OBJECTIVES
The aim of this study was to evaluate the incidence and outcomes of ischaemic organ complications after thoracic endovascular aortic repair (TEVAR).
METHODS
This is a multicentre, retrospective, observational cohort study. We analysed data from patients treated with TEVAR between 22 June 2001 and 10 December 2022. Primary outcomes were postoperative overall organ ischaemic complications and early (≤30 days) survival. Secondary outcomes were long-term survival and freedom from aorta-related mortality.
RESULTS
A total of 255 patients were included in this study. We performed 233 (91.4%) isolated TEVARs, 14 (5.5%) fenestrated or branched TEVARs and 8 (3.1%) TEVARs in combination with normal infrarenal stent graft. Overall, 31 organ ischaemic complications were detected in 29 (11.4%) cases, out of which 8 (3.1%) complications were cerebrovascular, 8 (3.1%) spinal cord, 6 (2.3%) visceral, 4 (1.6%) renal, 2 (0.8%) peripheral and 3 (1.2%) myocardial. Binary logistic regression analysis identified grade III-IV aortic arch atheroma [odds ratio (OR): 6.6, P = 0.001; 95% confidence interval: 2.9-14.9] and shaggy aorta (OR: 12.1, P = 0.003; 95% confidence interval: 2.3-64.1) to be associated with the development of organ ischaemic complications. In patients with organ ischaemia, we observed higher early (≤30 days) mortality (20.7% vs 6.2%; OR: 3.6, P = 0.016), prolonged hospitalization (P = 0.001) and inferior estimated survival (log-rank, P = 0.001).
CONCLUSIONS
Aortic arch atherosclerotic overload as well as the presence of shaggy aorta are predictors of organ ischaemic complications following TEVAR. They are neither uncommon nor negligible and are associated with perioperative mortality, prolonged hospitalization and a negative impact on long-term survival.
Topics: Humans; Endovascular Aneurysm Repair; Blood Vessel Prosthesis Implantation; Retrospective Studies; Endovascular Procedures; Aorta, Thoracic; Postoperative Complications; Ischemia; Aortic Aneurysm, Thoracic; Treatment Outcome; Risk Factors
PubMed: 37335859
DOI: 10.1093/ejcts/ezad238 -
The Journal of Surgical Research Aug 2023Mitochondrial dysfunction is implicated in the metabolic myopathy accompanying peripheral artery disease (PAD) and critical limb ischemia (CLI). Type-2 diabetes mellitus...
INTRODUCTION
Mitochondrial dysfunction is implicated in the metabolic myopathy accompanying peripheral artery disease (PAD) and critical limb ischemia (CLI). Type-2 diabetes mellitus (T2DM) is a major risk factor for PAD development and progression to CLI and may also independently be related to mitochondrial dysfunction. We set out to determine the effect of T2DM in the relationship between CLI and muscle mitochondrial respiratory capacity and coupling control.
METHODS
We studied CLI patients undergoing revascularization procedures or amputation, and non-CLI patients with or without T2DM of similar age. Mitochondrial respiratory capacity and function were determined in lower limb permeabilized myofibers by high-resolution respirometry.
RESULTS
Fourteen CLI patients (65 ± 10y) were stratified into CLI patients with (n = 8) or without (n = 6) T2DM and were compared to non-CLI patients with (n = 18; 69 ± 5y) or without (n = 19; 71 ± 6y) T2DM. Presence of CLI but not T2DM had a marked impact on all mitochondrial respiratory states in skeletal muscle, adjusted for the effects of sex. Leak respiration (State 2, P < 0.025 and State 4, P < 0.01), phosphorylating respiration (P < 0.001), and maximal respiration in the uncoupled state (P < 0.001), were all suppressed in CLI patients, independent of T2DM. T2DM had no significant effect on mitochondrial respiratory capacity and function in adults without CLI.
CONCLUSIONS
Skeletal muscle mitochondrial respiratory capacity was blunted by ∼35% in patients with CLI. T2DM was not associated with muscle oxidative capacity and did not moderate the relationship between muscle mitochondrial respiratory capacity and CLI.
Topics: Adult; Humans; Chronic Limb-Threatening Ischemia; Muscle, Skeletal; Peripheral Arterial Disease; Risk Factors; Energy Metabolism; Ischemia; Treatment Outcome; Limb Salvage; Diabetes Mellitus
PubMed: 36963297
DOI: 10.1016/j.jss.2023.02.015 -
Clinical Journal of the American... Dec 2023Distal ischemia is a rare complication in patients undergoing placement of an arteriovenous (AV) fistula or AV graft. There are limited studies on its frequency, risk...
BACKGROUND
Distal ischemia is a rare complication in patients undergoing placement of an arteriovenous (AV) fistula or AV graft. There are limited studies on its frequency, risk factors, clinical consequences, or feasibility of subsequent access.
METHODS
A prospective vascular access database from a large academic medical center was queried retrospectively to identify 1498 patients (mean age 56±15 years, 48% female patients, 73% Black patients) undergoing placement of at least one vascular access from 2011 to 2020. For patients who developed access-related distal ischemia requiring surgical intervention, we determined the frequency of distal ischemia, clinical risk factors, and subsequent outcomes.
RESULTS
Severe access-related distal ischemia occurred in 28 patients (1.9%; 95% confidence interval, 1.3% to 2.7%). The frequency was 0.2% for forearm AV fistulas, 0.9% for upper arm AV fistulas, 2.4% for forearm AV grafts, 2.2% for upper arm AV grafts, and 2.8% for thigh AV grafts. Risk factors independently associated with distal ischemia included female sex (odds ratio [OR], 3.64 [95% confidence interval, 1.52 to 8.72]), peripheral vascular disease (OR, 6.28 [2.84 to 13.87]), and coronary artery disease (OR, 2.37 [1.08 to 5.23]). Surgical interventions included ligation, excision, plication (banding), and other surgical procedures. Five patients developed tissue necrosis. A subsequent AV graft was placed in 13 patients, of whom only one (8%) developed distal ischemia requiring intervention.
CONCLUSIONS
Access-related distal ischemia requiring intervention was rare in this study and more common in women and patients with peripheral vascular disease or coronary artery disease. In some cases, a subsequent vascular access could be placed with a low likelihood of recurrent distal ischemia.
Topics: Humans; Female; Adult; Middle Aged; Aged; Male; Treatment Outcome; Coronary Artery Disease; Arteriovenous Shunt, Surgical; Retrospective Studies; Prospective Studies; Renal Dialysis; Risk Factors; Ischemia; Peripheral Vascular Diseases; Fistula; Vascular Patency
PubMed: 37707801
DOI: 10.2215/CJN.0000000000000310 -
The Medical Journal of Australia Nov 2023Diabetes-related foot disease (DFD) - foot ulcers, infection, ischaemia - is a leading cause of hospitalisation, disability, and health care costs in Australia. The...
INTRODUCTION
Diabetes-related foot disease (DFD) - foot ulcers, infection, ischaemia - is a leading cause of hospitalisation, disability, and health care costs in Australia. The previous 2011 Australian guideline for DFD was outdated. We developed new Australian evidence-based guidelines for DFD by systematically adapting suitable international guidelines to the Australian context using the ADAPTE and GRADE approaches recommended by the NHMRC.
MAIN RECOMMENDATIONS
This article summarises the most relevant of the 98 recommendations made across six new guidelines for the general medical audience, including: prevention - screening, education, self-care, footwear, and treatments to prevent DFD; classification - classifications systems for ulcers, infection, ischaemia and auditing; peripheral artery disease (PAD) - examinations and imaging for diagnosis, severity classification, and treatments; infection - examinations, cultures, imaging and inflammatory markers for diagnosis, severity classification, and treatments; offloading - pressure offloading treatments for different ulcer types and locations; and wound healing - debridement, wound dressing selection principles and wound treatments for non-healing ulcers.
CHANGES IN MANAGEMENT AS A RESULT OF THE GUIDELINE
For people without DFD, key changes include using a new risk stratification system for screening, categorising risk and managing people at increased risk of DFD. For those categorised at increased risk of DFD, more specific self-monitoring, footwear prescription, surgical treatments, and activity management practices to prevent DFD have been recommended. For people with DFD, key changes include using new ulcer, infection and PAD classification systems for assessing, documenting and communicating DFD severity. These systems also inform more specific PAD, infection, pressure offloading, and wound healing management recommendations to resolve DFD.
Topics: Humans; Diabetic Foot; Ulcer; Australia; Foot Diseases; Ischemia; Diabetes Mellitus
PubMed: 37872875
DOI: 10.5694/mja2.52136 -
Diabetes/metabolism Research and Reviews Mar 2024Diabetes is a key risk factor for ischaemic foot disease, which causes pain, tissue loss, hospital admission, and major amputation. Currently, treatment focuses on... (Review)
Review
Diabetes is a key risk factor for ischaemic foot disease, which causes pain, tissue loss, hospital admission, and major amputation. Currently, treatment focuses on revascularisation, but many patients are unsuitable for surgery and revascularisation is frequently unsuccessful. The authors describe recent research in animal models and clinical trials investigating novel medical targets for ischaemia, including theories about impaired wound healing, animal models for limb ischaemia and recent randomised controlled trials testing novel medical therapies. Novel targets identified in animal models included stimulating mobilisation of CD34+ progenitor cells through upregulating oncostatin M or microRNA-181, downregulating tumour necrosis factor superfamily member 14, or activating the Wingless pathway. Within the ischaemic limb vasculature, upregulation of apolipoprotein L domain containing 1, microRNA-130b or long noncoding RNA that enhances endothelial nitric oxide synthase expression promoted limb blood supply recovery, angiogenesis, and arteriogenesis. Similarly, administration of soluble guanylate cyclase stimulators riociguat or praliciguat or 3-ketoacyl-CoA thiolase inhibitor trimetazidine promoted blood flow recovery. Translating pre-clinical findings to patients has been challenging, mainly due to limitations in clinically translatable animal models of human disease. Promising results have been reported for administering plasmids encoding hepatocyte growth factor or intra-arterial injection of bone marrow derived cells in small clinical trials. It remains to be seen whether these high resource therapies can be developed to be widely applicable. In conclusion, an ever-expanding list of potential targets for medical revascularisation is being identified. It is hoped that through ongoing research and further larger clinical trials, these will translate into new broadly applicable therapies to improve outcomes.
Topics: Animals; Humans; Ischemia; Risk Factors; Foot Diseases; MicroRNAs
PubMed: 37563926
DOI: 10.1002/dmrr.3703 -
European Journal of Preventive... Jan 2024To investigate the association between cumulative social disadvantage and cardiovascular burden and mortality in a large cohort of the general population.
AIMS
To investigate the association between cumulative social disadvantage and cardiovascular burden and mortality in a large cohort of the general population.
METHODS AND RESULTS
Cross-sectional (n = 15 010, aged 35 to 74 years, baseline investigation period 2007 to 2012) and longitudinal data (5- and 10-year follow-ups from 2012 to 2022) from the Gutenberg Health Study were used to investigate the association between individual socioeconomic status (SES, measured via a validated questionnaire) and cardiovascular disease (CVD, composite of atrial fibrillation, coronary artery disease, myocardial infarction, stroke, chronic heart failure, peripheral artery disease, and/or venous thromboembolism) risk and mortality. Subjects with prevalent CVD had a lower SES sum score, as well as lower education, occupation, and household net-income scores (all P < 0.0001). Logistic regression analysis showed that a low SES (vs. high, defined by validated cut-offs) was associated with 19% higher odds of prevalent CVD [odds ratio (OR) 1.19, 95% CI 1.01; 1.40] in the fully adjusted model. At 5-year follow-up, low SES was associated with both increased cardiovascular [hazard ratio (HR) 5.36, 2.24; 12.82] and all-cause mortality (HR 2.23, 1.51; 3.31). At 10-year follow-up, low SES was associated with a 68% higher risk of incident CVD (OR 1.68, 1.12; 2.47) as well as 86% higher all-cause mortality (HR 1.86, 1.55; 2.24). In general, the education and occupation scores were stronger related to risk of CVD and death than the household net-income score. Low SES was estimated to account for 451.45 disability-adjusted life years per 1000 people (years lived with disability 373.41/1000 and years of life lost 78.03/1000) and an incidence rate of 11 CVD cases and 3.47 CVD deaths per 1000 people per year. The population attributable fraction for CVD incidence after 5 years was 4% due to low SES.
CONCLUSION
Despite universal healthcare access, cumulative social disadvantage remains associated with higher risk of CVD and mortality. Dimensions of education and occupation, but not household net income, are associated with outcomes of interest.
Topics: Humans; Cardiovascular Diseases; Cross-Sectional Studies; Risk Factors; Social Class; Myocardial Infarction
PubMed: 37721449
DOI: 10.1093/eurjpc/zwad264 -
International Journal of Molecular... Jul 2023Melatonin is a circadian hormone with antioxidant properties that protects against myocardial ischemia-reperfusion injury. Genetic variations of the melatonin receptor...
Melatonin is a circadian hormone with antioxidant properties that protects against myocardial ischemia-reperfusion injury. Genetic variations of the melatonin receptor 1B gene () play an important role in the development of type 2 diabetes, a risk factor for cardiovascular diseases. Accordingly, polymorphisms are crucial in numerous disorders of the cardiovascular system. Therefore, the aim of the present study was to investigate a possible association of polymorphisms with chronotype and susceptibility to myocardial infarction. The present case-control study included 199 patients with myocardial infarction (MI) (57% men) and 198 control participants (52% men) without previous cardiovascular diseases who underwent genotyping for the polymorphisms rs10830963, rs1387153, and rs4753426 from peripheral blood samples. Chronotype was determined using the Morningness-Eveningness Questionnaire (MEQ). As estimated by the chi-square test, no significant association was found in the distribution of alleles and genotypes between myocardial infarction patients and controls. In addition, there was no association between polymorphisms and chronotype in MI patients. As some previous studies have shown, the present negative results do not exclude the role of the polymorphisms studied in the development of myocardial infarction. Rather, they may indicate that polymorphisms are a minor risk factor for myocardial infarction.
Topics: Female; Humans; Male; Case-Control Studies; Diabetes Mellitus, Type 2; Genetic Predisposition to Disease; Genotype; Myocardial Infarction; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Receptor, Melatonin, MT2; Risk Factors
PubMed: 37511203
DOI: 10.3390/ijms241411444