Causal Effect of Plasminogen Activator Inhibitor Type 1 on Coronary Heart Disease

Song, Ci; Burgess, Stephen; Eicher, John D.; O’Donnell, Christopher J.; Johnson, Andrew D.

doi:10.1161/jaha.116.004918

Cited by 93 publications

(57 citation statements)

References 66 publications

(131 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…PAI-1, which plays a role in both thrombosis and fibrosis, is undetectable in normal kidneys, whereas plasma PAI-1 levels increase in CKD [10]. However, in a systematic review and meta-analysis, the highest quantile of blood PAI-1 level was associated with high coronary heart disease risk; therefore, this marker may not be a specific marker for kidney disease [31]. …”

Section: Discussionmentioning

confidence: 99%

Biomarkers of Inflammation, Fibrosis, and Acute Kidney Injury in Patients with Heart Failure with and without Left Ventricular Assist Device Implantation

et al. 2019

View full text Add to dashboard Cite

Background/Aims: Renal dysfunction or renal failure is a common complication in left ventricular assist device (LVAD) recipients and is associated with reduced survival. To date, serum creatinine and glomerular filtration rate (GFR) are used for the evaluation of kidney function. However, serum creatinine and GFR have limitations. The objective of our study is to assess the levels of kidney biomarkers in LVAD recipients compared to heart failure patients and healthy controls and to examine their association with conventional clinical biomarkers. Methods: The biomarkers neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), plasminogen activator inhibitor-1 (PAI-1), and adiponectin were assessed in 51 participants: 19 heart failure patients, 16 LVAD recipients, and 16 healthy controls. Linear regressions were performed to assess whether demographic and clinical variables predict the levels of biomarkers that are associated with acute kidney injury and the risk of chronic kidney disease. Results: The levels of NGAL and adiponectin were higher in LVAD recipients and patients with heart failure as compared with healthy controls. The levels of PAI-1 and KIM-1 were not elevated in LVAD recipients. The results of linear regression analysis indicated that when controlling for the effect of CRP and BNP, 40.1% of the variance in NGAL levels can be explained by GFR (R² = 0.401, F = 5.56, p = 0.005), while CRP can explain 35.3% of the variance in adiponectin levels (R² = 0.353, F = 4.55, p = 0.01), when controlling for the effect of BNP and GFR. Conclusions: The levels of NGAL and adiponectin were augmented in LVAD recipients, suggesting that renal functions were not restored with circulatory support. Larger studies should assess the predictability of these biomarkers of renal dysfunction in LVAD recipients.

show abstract

Section: Discussionmentioning

confidence: 99%

Biomarkers of Inflammation, Fibrosis, and Acute Kidney Injury in Patients with Heart Failure with and without Left Ventricular Assist Device Implantation

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Another marker for rupture with promising results is PAI‐1, a known marker for coronary heart disease that plays an essential role in fibrinolysis 92. Its levels were ≈4 times higher in 102 patients with a ruptured AAA than in asymptomatic patients.…”

Section: Discussionmentioning

confidence: 99%

Systematic Review of Circulating, Biomechanical, and Genetic Markers for the Prediction of Abdominal Aortic Aneurysm Growth and Rupture

Groeneveld

Meekel

Rubinstein

et al. 2018

JAHA

View full text Add to dashboard Cite

BackgroundThe natural course of abdominal aortic aneurysms (AAA) is growth and rupture if left untreated. Numerous markers have been investigated; however, none are broadly acknowledged. Our aim was to identify potential prognostic markers for AAA growth and rupture.Methods and ResultsPotential circulating, biomechanical, and genetic markers were studied. A comprehensive search was conducted in PubMed, Embase, and Cochrane Library in February 2017, following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Study selection, data extraction, and methodological quality assessment were conducted by 2 independent researchers. Plausibility of markers was based on the amount of publications regarding the marker (more than 3), pooled sample size (more than 100), bias risk and statistical significance of the studies. Eighty‐two studies were included, which examined circulating (n=40), biomechanical (n=27), and genetic markers (n=7) and combinations of markers (n=8). Factors with an increased expansion risk included: AAA diameter (9 studies; n=1938; low bias risk), chlamydophila pneumonia (4 studies; n=311; medium bias risk), S‐elastin peptides (3 studies; n=205; medium bias risk), fluorodeoxyglucose uptake (3 studies; n=104; medium bias risk), and intraluminal thrombus size (5 studies; n=758; medium bias risk). Factors with an increased rupture risk rupture included: peak wall stress (9 studies; n=579; medium bias risk) and AAA diameter (8 studies; n=354; medium bias risk). No meta‐analysis was conducted because of clinical and methodological heterogeneity.ConclusionsWe identified 5 potential markers with a prognostic value for AAA growth and 2 for rupture. While interpreting these data, one must realize that conclusions are based on small sample sizes and clinical and methodological heterogeneity. Prospective and methodological consonant studies are strongly urged to further study these potential markers.

show abstract

“…The association of elevated PAI‐1 with cardiovascular disease, metabolic syndrome, diabetes, obesity and senescence, and as a prognostic marker for several cancers, has long been investigated (e.g. ). Evidence for an influence on venous thrombosis may be weaker and mixed.…”

Section: Individual Protein Componentsmentioning

confidence: 99%

Measuring fibrinolysis: from research to routine diagnostic assays

Longstaff

2018

Journal of Thrombosis and Haemostasis

123

119

View full text Add to dashboard Cite

SummaryDevelopment and standardization of fibrinolysis methods have progressed more slowly than coagulation testing and routine high‐throughput screening tests for fibrinolysis are still lacking. In laboratory research, a variety of approaches are available and are applied to understand the regulation of fibrinolysis and its contribution to the hemostatic balance. Fibrinolysis in normal blood is slow to develop. For practical purposes plasminogen activators can be added to clotting plasma, or euglobulin prepared to reduce endogenous inhibitors, but results are complicated by these manipulations. Observational studies to identify a ‘fibrinolysis deficit’ have concluded that excess fibrinolysis inhibitors, plasminogen activator inhibitor 1 (PAI‐1) or thrombin‐activatable fibrinolysis inhibitor (TAFI), zymogen or active enzyme, may be associated with an increased risk of thrombosis. However, results are not always consistent and problems of adequate standardization are evident with these inhibitors and also for measurement of fibrin degradation products (D‐dimer). Few methods are available to investigate fibrinolysis under flow, or in whole blood, but viscoelastic methods (VMs) such as ROTEM and TEG do permit the contribution of cells, and importantly platelets, to be explored. VMs are used to diagnose clinical hyperfibrinolysis, which is associated with high mortality. There is a debate on the usefulness of VMs as a point‐of‐care test method, particularly in trauma. Despite the difficulties of many fibrinolysis methods, research on the fibrinolysis system, taking in wider interactions with hemostasis proteins, is progressing so that in future we may have more complete models and better diagnostic methods and therapeutics.

show abstract

Causal Effect of Plasminogen Activator Inhibitor Type 1 on Coronary Heart Disease

Cited by 93 publications

References 66 publications

Biomarkers of Inflammation, Fibrosis, and Acute Kidney Injury in Patients with Heart Failure with and without Left Ventricular Assist Device Implantation

Biomarkers of Inflammation, Fibrosis, and Acute Kidney Injury in Patients with Heart Failure with and without Left Ventricular Assist Device Implantation

Systematic Review of Circulating, Biomechanical, and Genetic Markers for the Prediction of Abdominal Aortic Aneurysm Growth and Rupture

Measuring fibrinolysis: from research to routine diagnostic assays

Contact Info

Product

Resources

About