Asymmetric Dimethylarginine Predicts Major Adverse Cardiovascular Events in Patients With Advanced Peripheral Artery Disease

Patients with peripheral artery disease (PAD) are at heightened risk for ischemic events related to atherothrombosis. Antithrombotic therapies can reduce the risk of atherothrombotic events but increase bleeding. Importantly, there is growing appreciation of the heterogeneity in risk profile and effect of antithrombotic therapies in different populations, including those with PAD. Further, patients with PAD are at risk for not only major adverse cardiovascular events but also major adverse limb events, and the drivers of risk for each are different. Within PAD populations, data from trials may be difficult to interpret due to differences among the studies with regards to patient population, clinical settings, and outcomes examined. The acute setting of peripheral revascularization which involves plaque rupture and endothelial disruption confers very high risk of major adverse limb events early postprocedure. Among patients with chronic PAD for whom the goal of antithrombotic therapy is secondary prevention, concomitant coronary artery disease, particularly with prior myocardial infarction, is associated with greatest risk for major adverse cardiovascular events, while prior peripheral revascularization or amputation is associated with greatest risk for major adverse limb events. Understanding of the potential impact of clinical setting and patient risk profile is important to guide evidence-based decisions regarding antithrombotic therapy in patients with PAD. In this article, we provide a contemporary review of data supporting the use of antithrombotic therapy in PAD, as well as a clinical framework for analysis and translation of these data into practice, highlighting areas in need of further investigation.

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Control of modifiable risk factors and major adverse cardiovascular events in people with peripheral artery disease and diabetes

World Journal of Diabetes ◽

10.4239/wjd.v12.i6.883 ◽

2021 ◽

Vol 12 (6) ◽

pp. 883-892

Author(s):

Jonathan Golledge ◽

Aaron Drovandi ◽

Sophie Rowbotham ◽

Ramesh Velu ◽

Frank Quigley ◽

...

Keyword(s):

Risk Factors ◽

Peripheral Artery Disease ◽

Cardiovascular Events ◽

Major Adverse Cardiovascular Events ◽

Modifiable Risk Factors ◽

Peripheral Artery ◽

Artery Disease

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CYP2C19 status and risk of major adverse cardiovascular events in peripheral artery disease: Insights from the EUCLID Trial

American Heart Journal ◽

10.1016/j.ahj.2020.07.017 ◽

2020 ◽

Vol 229 ◽

pp. 118-120

Author(s):

J. Antonio Gutierrez ◽

Gretchen M. Heizer ◽

W. Schuyler Jones ◽

Frank W. Rockhold ◽

Kenneth W. Mahaffey ◽

...

Keyword(s):

Peripheral Artery Disease ◽

Cardiovascular Events ◽

Major Adverse Cardiovascular Events ◽

Peripheral Artery ◽

Artery Disease

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Association between Peripheral Artery Disease and Major Adverse Cardiovascular Events in Patients with Acute Coronary Syndrome: Findings from the Gulf COAST Registry

Medical Principles and Practice ◽

10.1159/000497790 ◽

2019 ◽

Vol 28 (5) ◽

pp. 410-417 ◽

Cited By ~ 1

Author(s):

Ibrahim Al-Zakwani ◽

Ekram Al Siyabi ◽

Najib Alrawahi ◽

Arif Al-Mulla ◽

Abdullah Alnaeemi ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Peripheral Artery Disease ◽

Cardiovascular Events ◽

Arabian Gulf ◽

Major Adverse Cardiovascular Events ◽

Peripheral Artery ◽

Coronary Syndrome ◽

Vascular Insufficiency ◽

All Cause Mortality ◽

Artery Disease

Objective: To evaluate the association between peripheral artery disease (PAD) and major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS) in the Arabian Gulf. Methods: Data from 4,044 consecutive patients diagnosed with ACS admitted to 29 hospitals in four Arabian Gulf countries from January 2012 to January 2013 were analyzed. PAD was defined as any of the following: claudication, amputation for arterial vascular insufficiency, vascular reconstruction, bypass surgery, or percutaneous intervention in the extremities, documented aortic aneurysm or an ankle brachial index of <0.8 in any of the legs. MACE included stroke/transient ischemic attack (TIA), myocardial infarction (MI), all-cause mortality, and readmissions for cardiac reasons diagnosed between hospital admission and at 1-year post discharge. Analyses were performed using univariate and multivariate statistical techniques. Results: The overall mean age of the cohort was 60 ± 13 years and 66% (n = 2,686) were males. A total of 3.3% (n = 132) of the patients had PAD. Patients with PAD were more likely to be associated with smoking, prior MI, hypertension, diabetes mellitus, and stroke/TIA. At the 1-year follow-up, patients with PAD were significantly more likely to have MACE (adjusted OR [aOR], 2.07; 95% confidence interval [CI]: 1.41–3.06; p< 0.001). The higher rates of events were also observed across all MACE components; stroke/TIA (aOR, 3.22; 95% CI: 1.80–5.75; p< 0.001), MI (aOR, 2.15; 95% CI: 1.29–3.59; p =0.003), all-cause mortality (aOR, 2.21; 95% CI: 1.33–3.69; p =0.002), and readmissions for cardiac reasons (aOR, 1.83; 95% CI: 1.24–2.70; p =0.003). Conclusions: PAD was significantly associated with MACE in ACS patients in the Arabian Gulf.

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Association of Heart Failure With Outcomes Among Patients With Peripheral Artery Disease: Insights From EUCLID

Journal of the American Heart Association ◽

10.1161/jaha.120.018684 ◽

2021 ◽

Author(s):

Marc D. Samsky ◽

Anne Hellkamp ◽

William R. Hiatt ◽

F. Gerry R. Fowkes ◽

Iris Baumgartner ◽

...

Keyword(s):

Risk Factors ◽

Heart Failure ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Peripheral Artery Disease ◽

Cardiovascular Events ◽

Major Adverse Cardiovascular Events ◽

Peripheral Artery ◽

Factors Associated ◽

Artery Disease

Background Peripheral artery disease (PAD) and heart failure (HF) are each independently associated with poor outcomes. Risk factors associated with new‐onset HF in patients with primary PAD are unknown. Furthermore, how the presence of HF is associated with outcomes in patients with PAD is unknown. Methods and Results This analysis examined risk relationships of HF on outcomes in patients with symptomatic PAD randomized to ticagrelor or clopidogrel as part of the EUCLID (Examining Use of Ticagrelor in Peripheral Arterial Disease) trial. Patients were stratified based on presence of HF at enrollment. Cox models were used to determine the association of HF with outcomes. A separate Cox model was used to identify risk factors associated with development of HF during follow‐up. Patients with PAD and HF had over twice the rate of concomitant coronary artery disease as those without HF. Patients with PAD and HF had significantly increased risk of major adverse cardiovascular events (hazard ratio [HR], 1.31; 95% CI, 1.13–1.51) and all‐cause mortality (HR, 1.39; 95% CI, 1.19–1.63). In patients with PAD, the presence of HF was associated with significantly less bleeding (HR, 0.65; 95% CI, 0.45–0.96). Characteristics associated with HF development included age ≥66 (HR, 1.29; 95% CI, 1.18–1.40 per 5 years), diabetes mellitus (HR, 1.85; 95% CI, 1.41–2.43), and weight (bidirectionally associated, ≥76 kg, HR, 0.77; 95% CI, 0.64–0.93; <76 kg, HR, 1.12; 95% CI, 1.07–1.16). Conclusions Patients with PAD and HF have a high rate of coronary artery disease with a high risk for major adverse cardiovascular events and death. These data support the possible need for aggressive treatment of (recurrent) atherosclerotic disease in PAD, especially patients with HF.

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The impact of peripheral artery disease on major adverse cardiovascular events following myocardial infarction

International Journal of Cardiology ◽

10.1016/j.ijcard.2021.08.053 ◽

2021 ◽

Vol 343 ◽

pp. 131-137 ◽

Cited By ~ 1

Author(s):

Patricia Andersen ◽

Kristian Kragholm ◽

Christian Torp-Pedersen ◽

Svend Eggert Jensen ◽

Rubina Attar

Keyword(s):

Myocardial Infarction ◽

Peripheral Artery Disease ◽

Cardiovascular Events ◽

Major Adverse Cardiovascular Events ◽

Peripheral Artery ◽

Artery Disease ◽

The Impact

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Polyvascular Disease and Risk of Major Adverse Cardiovascular Events in Peripheral Artery Disease

JAMA Network Open ◽

10.1001/jamanetworkopen.2018.5239 ◽

2018 ◽

Vol 1 (7) ◽

pp. e185239 ◽

Cited By ~ 11

Author(s):

J. Antonio Gutierrez ◽

Hillary Mulder ◽

W. Schuyler Jones ◽

Frank W. Rockhold ◽

Iris Baumgartner ◽

...

Keyword(s):

Peripheral Artery Disease ◽

Cardiovascular Events ◽

Major Adverse Cardiovascular Events ◽

Peripheral Artery ◽

Artery Disease

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

10.21203/rs.3.rs-31908/v1 ◽

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.

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