scholarly journals Sortilin levels correlate with major cardiovascular events of diabetic patients with peripheral artery disease following revascularization: a prospective study

2020 ◽  
Author(s):  
Federico Biscetti ◽  
Elisabetta Nardella ◽  
Maria Margherita Rando ◽  
Andrea Leonardo Cecchini ◽  
Nicola Bonadia ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Cardiovascular Events ◽  
Vascular Complications ◽  
Diabetic Patients ◽  
Operating Characteristics ◽  
Peripheral Artery ◽  
Baseline Serum ◽  
Increased Risk ◽  
Artery Disease

Abstract Background: Peripheral artery disease (PAD) represents one of the most relevant vascular complications of type 2 diabetes mellitus (T2DM). Moreover, T2DM patients suffering from PAD have an increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Sortilin, a protein involved in apolipoproteins trafficking, is associated with lower limb PAD in T2DM patients.Objective: To evaluate the relationship between baseline serum levels of sortilin, MACE and MALE occurrence after revascularization of T2DM patients with PAD and chronic limb-threatening ischemia (CLTI).Research Design and Methods: We performed a prospective non-randomized study including 230 statin-free T2DM patients with PAD and CLTI. Sortilin levels were measured before the endovascular intervention and incident outcomes were assessed during a 12-month follow-up.Results: Sortilin levels were significantly increased in individuals with more aggressive PAD (2.25 ± 0.51 ng/mL vs 1.44 ± 0.47 ng/mL, p < 0.001). During follow-up, 83 MACE and 116 MALE occurred. In patients, who then developed MACE and MALE, sortilin was higher. In particular, 2.46 ± 0.53 ng/mL vs 1.55 ± 0.42 ng/mL, p < 0.001 for MACE and 2.10 ± 0.54 ng/mL vs 1.65 ± 0.65 ng/mL, p < 0.001 for MALE. After adjusting for traditional atherosclerosis risk factors, the association between sortilin and vascular outcomes remained significant in a multivariate analysis. In our receiver operating characteristics (ROC) curve analysis using sortilin levels the prediction of MACE incidence improved (area under the curve [AUC] = 0.94) and MALE (AUC = 0.72).Conclusions: This study demonstrates that sortilin correlates with incidence of MACE and MALE after endovascular revascularization in a diabetic population with PAD and CLTI.

scholarly journals Sortilin levels correlate with major cardiovascular events of diabetic patients with peripheral artery disease following revascularization: a prospective study

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Federico Biscetti ◽  
Elisabetta Nardella ◽  
Maria Margherita Rando ◽  
Andrea Leonardo Cecchini ◽  
Nicola Bonadia ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Cardiovascular Events ◽  
Vascular Complications ◽  
Diabetic Patients ◽  
Operating Characteristics ◽  
Peripheral Artery ◽  
Baseline Serum ◽  
Increased Risk ◽  
Artery Disease

Abstract Background Peripheral artery disease (PAD) represents one of the most relevant vascular complications of type 2 diabetes mellitus (T2DM). Moreover, T2DM patients suffering from PAD have an increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Sortilin, a protein involved in apolipoproteins trafficking, is associated with lower limb PAD in T2DM patients. Objective To evaluate the relationship between baseline serum levels of sortilin, MACE and MALE occurrence after revascularization of T2DM patients with PAD and chronic limb-threatening ischemia (CLTI). Research design and methods We performed a prospective non-randomized study including 230 statin-free T2DM patients with PAD and CLTI. Sortilin levels were measured before the endovascular intervention and incident outcomes were assessed during a 12 month follow-up. Results Sortilin levels were significantly increased in individuals with more aggressive PAD (2.25 ± 0.51 ng/mL vs 1.44 ± 0.47 ng/mL, p < 0.001). During follow-up, 83 MACE and 116 MALE occurred. In patients, who then developed MACE and MALE, sortilin was higher. In particular, 2.46 ± 0.53 ng/mL vs 1.55 ± 0.42 ng/mL, p < 0.001 for MACE and 2.10 ± 0.54 ng/mL vs 1.65 ± 0.65 ng/mL, p < 0.001 for MALE. After adjusting for traditional atherosclerosis risk factors, the association between sortilin and vascular outcomes remained significant in a multivariate analysis. In our receiver operating characteristics (ROC) curve analysis using sortilin levels the prediction of MACE incidence improved (area under the curve [AUC] = 0.94) and MALE (AUC = 0.72). Conclusions This study demonstrates that sortilin correlates with incidence of MACE and MALE after endovascular revascularization in a diabetic population with PAD and CLTI.

scholarly journals Sortilin levels correlate with major cardiovascular events of diabetic patients with peripheral artery disease following revascularization: a prospective study

2020 ◽  
Author(s):  
Federico Biscetti ◽  
Elisabetta Nardella ◽  
Maria Margherita Rando ◽  
Andrea Leonardo Cecchini ◽  
Nicola Bonadia ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Cardiovascular Events ◽  
Vascular Complications ◽  
Major Adverse Cardiovascular Events ◽  
Diabetic Patients ◽  
Operating Characteristics ◽  
Peripheral Artery ◽  
Increased Risk ◽  
Artery Disease

Abstract Background: Peripheral artery disease (PAD) represents one of the most relevant vascular complications of type 2 diabetes mellitus (T2DM). Moreover, T2DM patients suffering from PAD have an increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Sortilin, a protein involved in apolipoproteins trafficking, is associated with lower limb PAD in T2DM patients.Objective: To evaluate the relationship between baseline level of Sortilin levels, MACE and MALE occurrence after revascularization of T2DM patients with PAD and chronic limb-threatening ischemia (CLTI).Research Design and Methods: We performed a prospective non-randomized study including 230 statin-free T2DM patients with PAD and CLTI. Sortilin serum levels were measured before the endovascular intervention and incident outcomes were assessed during a 12-month follow-up.Results: Sortilin levels were significantly increased in individuals with more aggressive PAD (2.25 ± 0.51 ng/mL vs 1.44 ± 0.47 ng/mL, p < 0.001). During follow-up, 83 MACE and 116 MALE occurred. In patients, who then developed MACE and MALE, Sortilin was higher. In particular, 2.46 ± 0.53 ng/mL vs 1.55 ± 0.42 ng/mL, p < 0.001 for MACE and 2.10 ± 0.54 ng/mL vs 1.65 ± 0.65 ng/mL, p < 0.001 for MALE. After adjusting for traditional atherosclerosis risk factors, the association between Sortilin and vascular outcomes remained significant in a multivariate analysis. In our receiver operating characteristics (ROC) curve analysis using Sortilin levels the prediction of MACE incidence improved [area under the curve (AUC) = 0.94] and MALE (AUC = 0.72).Conclusions: This study demonstrates that Sortilin correlates with incidence of MACE and MALE after endovascular revascularization in a diabetic population with PAD and CLTI.

scholarly journals Burden of hospitalization in clinically diagnosed peripheral artery disease: A community-based study

2017 ◽  
Vol 23 (1) ◽  
pp. 23-31 ◽  
Author(s):  
Adelaide M Arruda-Olson ◽  
Homam Moussa Pacha ◽  
Naveed Afzal ◽  
Sara Abram ◽  
Bradley R Lewis ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Ankle Brachial Index ◽  
Inception Cohort ◽  
Peripheral Artery ◽  
Community Based ◽  
Increased Risk ◽  
Artery Disease ◽  
Recurrent Hospitalization ◽  
Over Time

The burden and predictors of hospitalization over time in community-based patients with peripheral artery disease (PAD) have not been established. This study evaluates the frequency, reasons and predictors of hospitalization over time in community-based patients with PAD. We assembled an inception cohort of 1798 PAD cases from Olmsted County, MN, USA (mean age 71.2 years, 44% female) from 1 January 1998 through 31 December 2011 who were followed until 2014. Two age- and sex-matched controls ( n = 3596) were identified for each case. ICD-9 codes were used to ascertain the primary reasons for hospitalization. Patients were censored at death or last follow-up. The most frequent reasons for hospitalization were non-cardiovascular: 68% of 8706 hospitalizations in cases and 78% of 8005 hospitalizations in controls. A total of 1533 (85%) cases and 2286 (64%) controls ( p < 0.001) were hospitalized at least once; 1262 (70%) cases and 1588 (44%) controls ( p < 0.001) ≥ two times. In adjusted models, age, prior hospitalization and comorbid conditions were independently associated with increased risk of recurrent hospitalizations in both groups. In cases, severe PAD (ankle–brachial index < 0.5) (HR: 1.25; 95% CI: 1.15, 1.36) and poorly compressible arteries (HR: 1.26; 95% CI: 1.16, 1.38) were each associated with increased risk for recurrent hospitalization. We demonstrate an increased rate of hospitalization in community-based patients with PAD and identify predictors of recurrent hospitalizations. These observations may inform strategies to reduce the burden of hospitalization of PAD patients.

scholarly journals Artificial-Intelligence-Assisted Discovery of Genetic Factors for Precision Medicine of Antiplatelet Therapy in Diabetic Peripheral Artery Disease

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 116
Author(s):  
Chi-Hsiao Yeh ◽  
Yi-Ju Chou ◽  
Tsung-Hsien Tsai ◽  
Paul Wei-Che Hsu ◽  
Chun-Hsien Li ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Precision Medicine ◽  
Antiplatelet Therapy ◽  
Peripheral Artery Disease ◽  
Cardiovascular Events ◽  
Genetic Factors ◽  
Genome Wide Association Study ◽  
Peripheral Artery ◽  
Increased Risk ◽  
Artery Disease

An increased risk of cardiovascular events was identified in patients with peripheral artery disease (PAD). Clopidogrel is one of the most widely used antiplatelet medications. However, there are heterogeneous outcomes when clopidogrel is used to prevent cardiovascular events in PAD patients. Here, we use an artificial intelligence (AI)-assisted methodology to identify genetic factors potentially involved in the clopidogrel-resistant mechanism, which is currently unclear. Several discoveries can be pinpointed. Firstly, a high proportion (>50%) of clopidogrel resistance was found among diabetic PAD patients in Taiwan. Interestingly, our result suggests that platelet function test-guided antiplatelet therapy appears to reduce the post-interventional occurrence of major adverse cerebrovascular and cardiac events in diabetic PAD patients. Secondly, AI-assisted genome-wide association study of a single-nucleotide polymorphism (SNP) database identified a SNP signature composed of 20 SNPs, which are mapped into 9 protein-coding genes (SLC37A2, IQSEC1, WASHC3, PSD3, BTBD7, GLIS3, PRDM11, LRBA1, and CNR1). Finally, analysis of the protein connectivity map revealed that LRBA, GLIS3, BTBD7, IQSEC1, and PSD3 appear to form a protein interaction network. Intriguingly, the genetic factors seem to pinpoint a pathway related to endocytosis and recycling of P2Y12 receptor, which is the drug target of clopidogrel. Our findings reveal that a combination of AI-assisted discovery of SNP signatures and clinical parameters has the potential to develop an ethnic-specific precision medicine for antiplatelet therapy in diabetic PAD patients.

scholarly journals Valvular calcification and risk of peripheral artery disease: the Multi-Ethnic Study of Atherosclerosis (MESA)

2019 ◽  
Vol 21 (10) ◽  
pp. 1152-1159 ◽  
Author(s):  
Parveen K Garg ◽  
Petra Buzkova ◽  
Zahra Meyghani ◽  
Matthew J Budoff ◽  
Joao Lima ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Cardiac Computed Tomography ◽  
Ankle Brachial Index ◽  
Cox Proportional Hazards ◽  
Peripheral Artery ◽  
Ethnic Study ◽  
Valvular Calcification ◽  
Increased Risk ◽  
Artery Disease

Abstract Aims The detection of cardiac valvular calcification on routine imaging may provide an opportunity to identify individuals at increased risk for peripheral artery disease (PAD). We investigated the associations of aortic valvular calcification (AVC) and mitral annular calcification (MAC) with risk of developing clinical PAD or a low ankle–brachial index (ABI). Methods and results AVC and MAC were measured on cardiac computed tomography in 6778 Multi-Ethnic Study of Atherosclerosis participants without baseline PAD between 2000 and 2002. Clinical PAD was ascertained through 2015. Incident low ABI, defined as ABI &lt;0.9 and decline of ≥0.15, was assessed among 5762 individuals who had an ABI &gt;0.9 at baseline and at least one follow-up ABI measurement 3–10 years later. Adjusted Cox proportional hazards and Poisson regression modelling were used to determine the association of valvular calcification with clinical PAD and low ABI, respectively. There were 117 clinical PAD and 198 low ABI events that occurred over a median follow-up of 14 years and 9.2 years, respectively. The presence of MAC was associated with an increased risk of clinical PAD [hazard ratio 1.79; 95% confidence interval (CI) 1.04–3.05] but not a low ABI (rate ratio 1.28; 95% CI 0.75–2.19). No significant associations were noted for the presence of AVC and risk of either clinical PAD. Conclusion MAC is associated with an increased risk of developing clinical PAD. Future studies are needed to corroborate our findings and better understand whether MAC holds any predictive value as a risk marker for PAD.

scholarly journals Association of Hypertension and Arterial Blood Pressure on Limb and Cardiovascular Outcomes in Symptomatic Peripheral Artery Disease

2020 ◽  
Vol 13 (9) ◽  
Author(s):  
Marat Fudim ◽  
Charles W. Hopley ◽  
Zhen Huang ◽  
Sarah Kavanagh ◽  
Frank W. Rockhold ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Lower Extremity ◽  
Peripheral Artery Disease ◽  
Hazard Ratio ◽  
Peripheral Artery ◽  
Increased Risk ◽  
History Of ◽  
Artery Disease ◽  
Lower Extremity Revascularization

Background: Current guidelines recommend aggressive management of hypertension. Recent evidence suggested potential harm with low blood pressure targets in patients with peripheral artery disease. We investigated the association of a history of hypertension and office systolic blood pressure (SBP) with major adverse cardiovascular events (MACEs) and major adverse limb events (MALEs). Methods and Results: The EUCLID trial (Examining the Use of Ticagrelor in Peripheral Artery Disease) included 13 885 participants with symptomatic peripheral artery disease; median follow-up was 30 months. Cox proportional hazards regression was used to calculate hazard ratios (HRs) for any MACE, MALE, and MALE including lower extremity revascularization. A clinical history of arterial hypertension was present in 10 857 (78%) participants, and these participants were older and more likely to be female when compared with the 3026 (22%) patients without hypertension. In patients with a history of hypertension, the adjusted hazard ratio for MACE was 0.94, 95% CI, 0.82–1.08; P =0.39, and the adjusted hazard ratio for MALE was 1.08, 95% CI, 0.96–1.23; P =0.21. During follow-up, average SBP was 135 mm Hg (125–145). Every 10 mmHg increase in SBP>125 mmHg was associated with an increased risk of MACE (HR, 1.10 [95% CI, 1.06–1.14]; P <0.001), a marginally increased risk of MALE (HR, 1.07 [95% CI, 1.00–1.15]; P =0.062), and an increased risk of MALE/lower extremity revascularization (HR, 1.08 [95% CI, 1.04–1.11]; P <0.001). Every decrease in 10 mmHg SBP ≤125 mmHg was associated with an increased risk of MACE (HR, 1.19 [95% CI, 1.09–1.31]; P <0.001) but not MALE or MALE/lower extremity revascularization (HR, 1.02 [95% CI, 0.84–1.23], P =0.824; HR, 1.04 [95% CI, 0.95–1.13], P =0.392, respectively). Conclusions: History of hypertension was not associated with higher hazard for MACE or MALE in patients with peripheral artery disease. In contrast, there was a higher hazard of MACE in patients with out-of-target low and high SBP. High but not low SBP was associated with an increased risk of ischemic limb events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01732822.

scholarly journals Growth Factor Deregulation and Emerging Role of Phosphatases in Diabetic Peripheral Artery Disease

2021 ◽  
Vol 7 ◽  
Author(s):  
Clément Mercier ◽  
Marina Rousseau ◽  
Pedro Geraldes
Keyword(s):  
Growth Factor ◽  
Peripheral Artery Disease ◽  
Molecular Mechanisms ◽  
Diabetic Patients ◽  
Peripheral Artery ◽  
Protein Tyrosine ◽  
Collateral Arteries ◽  
Increased Risk ◽  
Artery Disease

Peripheral artery disease is caused by atherosclerosis of lower extremity arteries leading to the loss of blood perfusion and subsequent critical ischemia. The presence of diabetes mellitus is an important risk factor that greatly increases the incidence, the progression and the severity of the disease. In addition to accelerated disease progression, diabetic patients are also more susceptible to develop serious impairment of their walking abilities through an increased risk of lower limb amputation. Hyperglycemia is known to alter the physiological development of collateral arteries in response to ischemia. Deregulation in the production of several critical pro-angiogenic factors has been reported in diabetes along with vascular cell unresponsiveness in initiating angiogenic processes. Among the multiple molecular mechanisms involved in the angiogenic response, protein tyrosine phosphatases are potent regulators by dephosphorylating pro-angiogenic tyrosine kinase receptors. However, evidence has indicated that diabetes-induced deregulation of phosphatases contributes to the progression of several micro and macrovascular complications. This review provides an overview of growth factor alterations in the context of diabetes and peripheral artery disease, as well as a description of the role of phosphatases in the regulation of angiogenic pathways followed by an analysis of the effects of hyperglycemia on the modulation of protein tyrosine phosphatase expression and activity. Knowledge of the role of phosphatases in diabetic peripheral artery disease will help the development of future therapeutics to locally regulate phosphatases and improve angiogenesis.

scholarly journals High ankle brachial index predicts high risk of cardiovascular events amongst people with peripheral artery disease

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242228
Author(s):  
Jonathan Golledge ◽  
Joseph V. Moxon ◽  
Sophie Rowbotham ◽  
Jenna Pinchbeck ◽  
Frank Quigley ◽  
...  
Keyword(s):  
Risk Factors ◽  
Peripheral Artery Disease ◽  
Cardiovascular Events ◽  
Ankle Brachial Index ◽  
Cardiovascular Death ◽  
Peripheral Artery ◽  
Major Cardiovascular Events ◽  
Increased Risk ◽  
Traditional Risk Factors ◽  
Artery Disease

Ankle-brachial pressure index (ABPI) is commonly measured in people referred to vascular specialists. This study aimed to assess the association of high ABPI (≥ 1.4) with cardiovascular events in people with peripheral artery disease (PAD). 1533 participants with PAD diagnosed by a vascular specialist were prospectively recruited from four out-patient clinics in Australia. ABPI was measured at recruitment and the occurrence of myocardial infarction (MI), stroke or cardiovascular death (major cardiovascular events; MACE) and any amputation were recorded over a median (inter-quartile range) follow-up of 3.3 (1.0–7.1) years. The association of high, compared to normal, low (0.5–0.9) or very low (<0.5), ABPI with clinical events was estimated using Cox proportional hazard analyses, adjusting for traditional risk factors and reported as hazard ratio with 95% confidence intervals. 596 (38.9%), 676 (44.1%), 157 (10.2%) and 104 (6.8%) participants had normal, low, very low and high ABPI, respectively. Participants with high ABPI had increased risk of MACE, MI and death by comparison to those with either normal ABPI [1.69 (1.07, 2.65), 1.93 (1.07, 3.46) and 1.67 (1.09, 2.56)] or either low or very low ABPI [1.51 (1.02, 2.23), 1.92 (1.16, 3.19) and 1.47 (1.02, 2.14)] after adjusting for other risk factors. Findings were similar in a sensitivity analysis excluding people with ABPI only measured in one leg (n = 120). Participants with high ABPI also had an increased risk of MACE and MI compared to those with very low ABPI alone. High ABPI is a strong indicator of excess risk of cardiovascular events amongst people with PAD.

P4497Serum ceramides and type 2 diabetes are mutually independent predictors of cardiovascular events in patients with peripheral artery disease

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Leiherer ◽  
A Muendlein ◽  
C H Saely ◽  
R Laaksonen ◽  
M Laaperi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Peripheral Artery Disease ◽  
Cardiovascular Events ◽  
Atherosclerotic Plaques ◽  
Peripheral Artery ◽  
Event Risk ◽  
Artery Disease ◽  
Mutually Independent

Abstract Background Ceramides are enriched in atherosclerotic plaques, and a set of circulating ceramides including Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:1), and Cer(d18:1/24:0) has recently emerged as predictors of cardiovascular outcomes in coronary artery disease patients. Purpose The purpose of this study was to investigate their power to predict cardiovascular events in patients with peripheral artery disease (PAD). Methods We measured the serum concentrations of the above mentioned ceramides in a cohort of 380 patients with sonographically proven PAD, of whom 107 had type 2 diabetes (T2DM). Prospectively, we recorded 221 cardiovascular events over a mean follow-up time of 6.3±2.3 years. Results Cardiovascular event risk was higher in T2DM patients than in those who did not have diabetes (69 vs. 52%, p=0.001). The ceramides Cer(18:1/16:0) and Cer(18:1/24:1) and the respective ratios Cer(18:1/16:0) / Cer(18:1/24:0) and Cer(18:1/24:1) / Cer(18:1/24:0) were significant predictors of cardiovascular events both univariately and after multivariate adjustment including the presence of T2DM (figure). Conversely, T2DM predicted cardiovascular events independently from the investigated ceramides (adjusted HR 1.76 [1.31–2.35], p<0.001). Conclusion We conclude that the investigated ceramides and T2DM are mutually independent predictors of cardiovascular events in PAD patients.

Effectiveness of revascularization of the ulcerated foot in diabetic patients with peripheral artery disease for one year follow-up

2018 ◽  
Vol 13 (6) ◽  
pp. 458-463
Author(s):  
Mohammad Momen Gharibvand ◽  
Mina Mounesi ◽  
Arman Shahriari ◽  
Asghar Sharif Najafi ◽  
Azim Motamed far ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Diabetic Patients ◽  
Peripheral Artery ◽  
Artery Disease ◽  
One Year
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