D-dimer as a marker for cardiovascular and arterial thrombotic events in patients with peripheral arterial disease

SummaryPeripheral artery disease (PAD) is associated with an increased risk for cardiovascular events. D-dimers are a marker for hypercoagulability and are linked with thrombotic events in patients with venous as well as arterial thrombosis. The predictive value of plasma D-dimer levels in relation to cardiovascular events in patients with PAD is not unambiguously established. It was our objective to gather evidence evaluating the value of D-dimer as a predictor of arterial thrombotic events patients with PAD. The Pubmed, Embase, and Cochrane databases were searched (January 1980-November 2012), and 65 abstracts were found. The strategy was supplemented with manual review of reference lists. Case-control, cohort or prospective cohort studies that measured fibrin D-dimer in patients with PAD, were included. Studies were excluded if there was no follow-up for arterial thrombotic events or when no specific information on D-dimer was available. The search yielded 10 studies for our analysis, comprising 2,420 patients with PAD, with a total of 1,036 cardiovascular events in 10,599 patient-years. Two studies with a follow-up of one year showed that fibrin D-dimer predicts both deterioration of PAD and subsequent thrombotic events. Five out of six studies with a median follow-up of 2–4 years revealed that an increased D-dimer is predictive of various arterial thrombotic events including mortality. Two studies with a longer follow-up (over 6 years) did not show an independent association between increased D-dimer levels, arterial thrombotic events and CVD mortality. In conclusion, an increased D-dimer appeared to be independently associated with a two times increased risk of near-term cardiovascular events (relative risk 2.30, 95% confidence interval 1.43–3.68). However formal meta-analysis was only feasible for four out of 10 included studies. Due to the extended heterogeneity of the included studies cautious interpretation of these data is warranted.

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Is aspirin still the drug of choice for management of patients with peripheral arterial disease?

VASA ◽

10.1024/0301-1526/a000251 ◽

2013 ◽

Vol 42 (2) ◽

pp. 88-95 ◽

Cited By ~ 8

Author(s):

Pavel Poredos ◽

Mateja K. Jezovnik

Keyword(s):

Cardiovascular Events ◽

Meta Analysis ◽

Ankle Brachial Index ◽

Arterial Disease ◽

Antiplatelet Drugs ◽

Antiplatelet Drug ◽

Diabetic Patients ◽

Vascular Events ◽

Artery Disease ◽

Peripheral Arterial

Antiplatelet drugs represent one of the basic options for management of patients with different atherosclerotic diseases. Aspirin is the oldest and most often prescribed antiplatelet drug. The efficacy of aspirin depends on the clinical characteristics of the treated population and probably also on the type or location of atherosclerotic disease. It seems that it is most effective in coronary patients with clinically unstable disease, less effective in prevention of cerebrovascular incidents, and its efficacy is uncertain in peripheral artery disease (PAD) patients. One of the first meta-analyses (Antithrombotic Trialists Collaboration - ATC) indicated that antiplatelet drugs also significantly reduce cardiovascular events in patients with PAD. However, only one third of the PAD patients included were treated with aspirin, while the rest received other anti-platelet drugs. The latest ATC meta-analysis of randomized control trials of aspirin therapy involving patients with diabetes and PAD demonstrated no benefit of aspirin in reducing cardiovascular events. Also in patients with preclinical PAD (pathological ankle brachial index) aspirin did not result in a significant reduction of vascular events. The new anti-platelet drugs prasugrel, ticagrelor and picotamide seem to be more effective than aspirin in PAD patients, particularly in diabetic patients with PAD. In conclusion, antiplatelet drugs are effective in prevention of cardiovascular events in different atherosclerotic diseases, including PAD. However, recent studies indicated that in PAD patients aspirin is less effective than in coronary artery disease. New anti-platelet drugs showed marginal superiority over aspirin without definite advantages. Aspirin thus remains the first line of antiplatelet drug for secondary prevention of cardiovascular events in PAD patients and clopidogrel as its effective alternative. Further, new studies on PAD patients are necessary to better define the role of anti-platelet agents in these patients and one of the promising ways of access to anti-platelet treatment would be personalized anti-platelet therapy.

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Association of Circulating Hepatocyte Growth Factor and Risk of Incident Peripheral Artery Disease: The Multi-Ethnic Study of Atherosclerosis

Angiology ◽

10.1177/0003319720912935 ◽

2020 ◽

Vol 71 (6) ◽

pp. 544-551

Author(s):

Parveen K. Garg ◽

Petra Buzkova ◽

Christina L. Wassell ◽

Matthew Allison ◽

Michael Criqui ◽

...

Keyword(s):

Growth Factor ◽

Hepatocyte Growth Factor ◽

Ankle Brachial Index ◽

Arterial Disease ◽

Ethnic Study ◽

Increased Risk ◽

Artery Disease ◽

Peripheral Arterial ◽

Hepatocyte Growth

Higher levels of hepatocyte growth factor (HGF) have been associated with the presence of peripheral arterial disease (PAD), but prospective associations are unknown. We examined the association of circulating HGF levels with incident PAD. Between 2000 and 2002, HGF was measured in 6742 Multi-Ethnic Study of Atherosclerosis participants without PAD. Incident clinical PAD, adjudicated on the basis of a positive history for the presence of disease-related symptoms or treatment, was ascertained through 2015. Incident low ankle-brachial index (ABI), defined as an ABI < 0.9 and a decline of ≥ 0.15, was assessed among 5736 individuals who had an ABI > 0.9 at baseline and ≥1 follow-up ABI measurement 3 to 10 years later. There were 116 clinical PAD and 197 low ABI events that occurred over a median follow-up of 14 and 9 years, respectively. After adjustment for demographic and clinical variables, a standard deviation increment of HGF (303 ng/L) was associated with an increased risk of clinical PAD (hazard ratio: 1.21; 95% confidence interval [CI]: 1.05-1.39) but not a low ABI (rate ratio: 1.03; 95% CI: 0.85-1.25). In conclusion, higher HGF levels were modestly associated with an increased risk of developing clinical PAD.

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Increased risk of developing peripheral artery disease in hemodialysis patients receiving statin treatments: a population-based cohort study in Taiwan

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfz251 ◽

2019 ◽

Vol 35 (10) ◽

pp. 1753-1760 ◽

Cited By ~ 1

Author(s):

Yueh-Han Hsu ◽

Fung-Chang Sung ◽

Chih-Hsin Muo ◽

Shao-Yuan Chuang ◽

Chun-Ming Chen ◽

...

Keyword(s):

Proportional Hazards ◽

Arterial Disease ◽

Statin Treatment ◽

Population Based ◽

Cox Proportional Hazards ◽

Moderate Intensity ◽

Increased Risk ◽

Artery Disease ◽

Peripheral Arterial

Abstract Background Few investigations have evaluated the influences on peripheral arterial disease (PAD) risk of statin treatment in hemodialysis (HD) subjects with hyperlipidemia (HL). Methods From the National Health Insurance Research Dataset, we identified 3658 HD patients with statin therapy for HL as the statin cohort, and then selected, by 1:1 propensity score matching, 3658 HD patients with HL but without statin use as the nonstatin cohort in 2000–07. The cohorts were followed through until the end of 2011. We used Cox proportional hazards regression analysis to assess the hazard ratio (HR) of PAD development. Results The average follow-up period was 4.18 years; the incident PAD risk was 1.35-fold greater in statin users than in nonusers (16.87 versus 12.46/1000 person-years), with an adjusted HR (aHR) of 1.34 for PAD [95% confidence interval (CI) 1.12–1.62]. The PAD risk increases were significant for patients receiving fluvastatin (aHR 1.88; 95% CI 1.12–3.14) and atorvastatin (aHR 1.60; 95% CI 1.24–2.08). The risk increased with higher annual average statin dosage (P for trend <0.0001); the risk was higher for those receiving moderate-intensity statin treatment. The sensitivity test revealed similar findings. Conclusions HD patients with HL on statin medication were at increased PAD risk, which increased with cumulative statin dosage. Thorough considerations are needed before prescribing statins to HD patients.

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Long-term outcomes of peripheral arterial disease patients with significant coronary artery disease undergoing percutaneous coronary intervention

PLoS ONE ◽

10.1371/journal.pone.0251542 ◽

2021 ◽

Vol 16 (5) ◽

pp. e0251542

Author(s):

Byoung Geol Choi ◽

Ji-Yeon Hong ◽

Seung-Woon Rha ◽

Cheol Ung Choi ◽

Michael S. Lee

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Peripheral Arterial Disease ◽

Significant Coronary Artery Disease ◽

Arterial Disease ◽

Term Survival ◽

Artery Disease ◽

Peripheral Arterial

Background Patients with peripheral arterial disease (PAD) have known to a high risk of cardiac mortality. However, the effectiveness of the routine evaluation of coronary arteries such as routine coronary angiography (CAG) in PAD patients receiving percutaneous transluminal angioplasty (PTA) is unclear. Methods A total of 765 consecutive PAD patients underwent successful PTA and 674 patients (88.1%) underwent routine CAG. Coronary artery disease (CAD) was defined as angiographic stenosis ≥70%. Patients were divided into three groups; 1) routine CAG and a presence of CAD (n = 413 patients), 2) routine CAG and no CAD group (n = 261 patients), and 3) no CAG group (n = 91 patients). To adjust for any potential confounders that could cause bias, multivariable Cox-proportional hazards regression and propensity score matching (PSM) analysis was performed. Clinical outcomes were evaluated by Kaplan-Meier curved analysis at 5-year follow-up. Results In this study, the 5-year survival rate of patients with PAD who underwent PTA was 88.5%. Survival rates were similar among the CAD group, the no CAD group, and the no CAG group, respectively (87.7% vs. 90.4% vs. 86.8% P = 0.241). After PSM analysis between the CAD group and the no CAD group, during the 5-year clinical follow-up, there were no differences in the incidence of death, myocardial infarction, strokes, peripheral revascularization, or target extremity surgeries between the two groups except for repeat PCI, which was higher in the CAD group than the non-CAD group (9.3% vs. 0.8%, P<0.001). Conclusion PAD patients with CAD were expected to have very poor long-term survival, but they are shown no different long-term prognosis such as mortality compared to PAD patients without CAD. These PAD patients with CAD had received PCI and/or optimal medication treatment after the CAG. Therefore a strategy of routine CAG and subsequent PCI, if required, appears to be a reasonable strategy for mortality risk reduction of PAD patients. Our results highlight the importance for evaluation for CAD in patients with PAD.

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Relation between Chronic Obstructive Pulmonary Disease and Peripheral Arterial Disease among Construction Workers

10.53350/pjmhs2115103473 ◽

2021 ◽

Vol 15 (10) ◽

pp. 3473-3475

Author(s):

U. Sivakumar ◽

Rinku Garg ◽

Sunita Nighute

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Peripheral Arterial Disease ◽

Pulmonary Disease ◽

Arterial Disease ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Risk Of Death ◽

Increased Risk ◽

Peripheral Arterial

Introduction: PAD was asymptomatic in a large proportion of COPD patients and was associated with more severe lung disease than in COPD subjects without PAD. Materials and Methods: This was a Cross-sectional study conducted at Department of Physiology, Santosh Medical College diagnosed with COPD using Spirometry was recruited for the study with a Sample size of 130 patients. Results: The characteristics of the population for follow-up (n=130) are presented in table 1. The mean Mean±SD was 51.73±6.1 years. The prevalence of never smokers was 21.5%, former smokers were 51.5% and current smokers were 26.9%. In total, 41 out of 130 individuals (31.5%) had PAD based on an ABI of less than 0.6. A statistically significant association was found between COPD and newly diagnosed PAD during follow-up. The association between COPD and incident PAD was stronger (adjusted OR 1.91, 95% CI 1.14–3.21). Stratified analysis by smoking status revealed that the overall association between COPD and newly developed PAD was driven by the ever smoker group. Conclusion: Subjects with COPD have a higher risk of developing PAD. People with both COPD and PAD have a substantially increased risk of death. Consequently, early detection of PAD and preventive actions in people with COPD should receive more attention in clinical respiratory care. Keywords: Peripheral Arterial Disease, Chronic Obstructive Pulmonary Disease, Ankle-brachial index.

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Impact of Kidney Disease on Peripheral Arterial Interventions: A Systematic Review and Meta-Analysis

American Journal of Nephrology ◽

10.1159/000508575 ◽

2020 ◽

Vol 51 (7) ◽

pp. 527-533

Author(s):

Mahesh Anantha-Narayanan ◽

Azfar Bilal Sheikh ◽

Sameer Nagpal ◽

Kim G. Smolderen ◽

Jeffrey Turner ◽

...

Keyword(s):

Systematic Review ◽

Lower Extremity ◽

Meta Analysis ◽

Limb Ischemia ◽

Arterial Disease ◽

Major Amputation ◽

Early Mortality ◽

Comorbid Condition ◽

Increased Risk ◽

Peripheral Arterial

Background: There are limited data on outcomes of patients undergoing peripheral arterial disease (PAD) interventions who have comorbid CKD/ESRD versus those who do not have such comorbid condition. We performed a systematic review and meta-analysis to analyze outcomes in this patient population. Methods: Five databases were searched for studies comparing outcomes of lower extremity PAD interventions for claudication and critical limb ischemia (CLI) in patients with CKD/ESRD versus non-CKD/non-ESRD from January 2000 to June 2019. Results: Our study included 16 observational studies with 44,138 patients. Mean follow-up was 48.9 ± 27.4 months. Major amputation was higher with CKD/ESRD compared with non-CKD/non-ESRD (odds ratio [OR 1.97] [95% confidence interval [CI] 1.39–2.80], p = 0.001). Higher major amputations with CKD/ESRD versus non-CKD/non-ESRD were only observed when indication for procedure was CLI (OR 2.27 [95% CI 1.53–3.36], p < 0.0001) but were similar for claudication (OR 1.15 [95% CI 0.53–2.49], p = 0.72). The risk of early mortality was high with CKD/ESRD patients undergoing PAD interventions compared with non-CKD/non-ESRD (OR 2.55 [95% CI 1.65–3.96], p < 0.0001), which when stratified based on indication, remained higher with CLI (OR 3.14 [95% CI 1.80–5.48], p < 0.0001) but was similar with claudication (OR 1.83 [95% CI 0.90–3.72], p = 0.1). Funnel plot of included studies showed moderate bias. Conclusions: Patients undergoing lower extremity PAD interventions for CLI who also have comorbid CKD/ESRD have an increased risk of experiencing major amputations and early mortality. Randomized trials to understand outcomes of PAD interventions in this at-risk population are essential.

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Marine and plant-based n-3 PUFA and atherosclerotic cardiovascular disease

Proceedings of The Nutrition Society ◽

10.1017/s0029665119000582 ◽

2019 ◽

Vol 79 (1) ◽

pp. 22-29 ◽

Cited By ~ 2

Author(s):

Christian S. Bork ◽

Stine K. Venø ◽

Anne N. Lasota ◽

Søren Lundbye-Christensen ◽

Erik B. Schmidt

Keyword(s):

Ischaemic Stroke ◽

Arterial Disease ◽

Atherosclerotic Cardiovascular Disease ◽

Peripheral Artery ◽

Ascvd Risk ◽

Artery Disease ◽

Atherosclerotic Process ◽

Peripheral Arterial

n-3 PUFA may exert favourable effects on several processes that may inhibit the atherosclerotic process. However, the role of n-3 PUFA in lowering the risk of atherosclerotic CVD (ASCVD) has been fiercely debated. In the present paper, we summarise the main findings from previous follow-up studies of intake and studies using adipose tissue as an objective biomarker to investigate exposure to n-3 PUFA in relation to ASCVD risk and discuss some perspectives for further research. The majority of previous studies investigating intake of marine- and plant-based n-3 PUFA have focused on CHD while other ASCVD such as ischaemic stroke and peripheral artery disease have been less studied. However, recent data from Danish Diet, Cancer and Health cohort suggest that marine n-3 PUFA may be inversely associated with risk of myocardial infarction, ischaemic stroke and peripheral arterial disease caused by atherosclerosis. The effect of the plant-derived n-3 PUFA α-linolenic acid on ASCVD is less clear and several gaps in the literature remain to be explored.

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Anticoagulation in Patients with Ischaemic Heart Disease and Peripheral Arterial Disease: Clinical Implications of COMPASS Study

European Cardiology Review ◽

10.15420/ecr.2018.12.2 ◽

2018 ◽

Vol 13 (2) ◽

pp. 115 ◽

Cited By ~ 1

Author(s):

Josep Gradolí ◽

Verónica Vidal ◽

Adrian JB Brady ◽

Lorenzo Facila ◽

◽

...

Keyword(s):

Cardiovascular Events ◽

Arterial Disease ◽

Platelet Inhibition ◽

Clinical Implications ◽

Peripheral Artery ◽

Everyday Clinical Practice ◽

Major Cardiovascular Events ◽

Novel Oral Anticoagulant ◽

Artery Disease ◽

Peripheral Arterial

Patients with established cardiovascular disease may suffer further cardiovascular events, despite receiving optimal medical treatment. Although platelet inhibition plays a central role in the prevention of new events, the use of anticoagulant therapies to reduce events in atheromatous disease has, until recently, been overlooked. The recent Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease (COMPASS) study showed an important reduction in cardiovascular events without increasing the risk of fatal and intracranial bleeding when using rivaroxaban, a novel oral anticoagulant, combined with aspirin. This article reviews the available evidence regarding the use of anticoagulant therapies for prevention of cardiovascular events, the results of the COMPASS study and how these results may affect patient management in everyday clinical practice.

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P1737Influence of peripheral arterial disease on prognosis in patients with left main coronary artery disease treated with percutaneous coronary intervention

European Heart Journal ◽

10.1093/eurheartj/ehz748.0491 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

A Martinez Leon ◽

A Adeba Garcia ◽

D Garcia Iglesias ◽

P Florez Llano ◽

A Flores Fuentes ◽

...

Keyword(s):

Coronary Artery Disease ◽

Multivariate Analysis ◽

Coronary Artery ◽

Coronary Intervention ◽

Arterial Disease ◽

Left Main ◽

Percutaneous Coronary ◽

Artery Disease ◽

Peripheral Arterial

Abstract Introduction Percutaneous coronary intervention (PCI) in patients with left main (LM) coronary artery disease is acquiring an important role in the last years as an alternative to coronary artery bypass grafting (CABG) in selected patients. The objective of the study was to evaluate predictors of mortality in patients with LM coronary artery disease treated with PCI. Methods Prospective and observational study of consecutive patients referred to our centre for coronary angiography, with LM coronary artery disease, whom PCI was decided in a “Heart team” as a strategy for revascularization between July 2015 and December 2017. Baseline clinical, analytical and coronary angiography data were collected. Follow-up was conducted in person or by telephone for a minimum of one year. We analysed the predictive variables of mortality by means of an uni and multivariate logistic regression model. In addition, a survival analysis was performed. Results A total of 191 patients were recruited. The average age was 72 years (±11.4), 79% males. 42% had previous documented coronary artery disease. PCI was performed in the context of acute coronary syndrome in 81% of them. The mean follow-up period was 17.9 months (± 8.3). After multivariate analysis, the following variables remained as independent predictors of mortality: the hemodynamic situation of the patient, assessed by the Killip-Kimball scale (OR 1.58, 95% CI 1.03–2.43; p=0.04) and the presence of peripheral arterial disease (PAD) (OR 2.61, 95% CI 1.03–6.67; p=0.04) (table 1). The ROC curve of the multivariate model showed an AUC of 0.796 (figure 1A). In the survival analysis, patients with PAD had a significantly lower survival, with a median survival of 6 months, compared to 13.9 months in those without PAD, with p=0.008 (figure 1B). Uni and multivariate analysis Univariate analysis Multivariate analysis OR (95% CI) p OR (95% CI) p Killip-Kimbal scale 1.94 (1.39–2.72) 0 1.58 (1.03–2.43) 0.04 LVEF 0.96 (0.93–0.99) 0.01 0.99 (0.95–1.03) 0.46 Mitral regurgitation 2.54 (1.12–5.63) 0.02 1.60 (0.55–4.56) 0.38 Number of affected vessels 1.96 (1.24–3.29) 0.01 1.78 (1.03–3.37) 0.05 PAD 2.54 (1.16–5.49) 0.02 2.61 (1.03–6.67) 0.,04 Figure 1 Conclusion Although PCI revascularization of LM coronary artery disease is an attractive alternative to CABG in selected patients, a word of caution should be raised in patients with PAD, as in the present study this variable was an important predictor of short-medium term mortality.

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