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Soluble urokinase plasminogen activation receptor and long-term outcomes in persons undergoing coronary angiography.

ABSTRACT: Soluble urokinase plasminogen activation receptor (suPAR) is risk factor for kidney disease and biomarker for cardiovascular outcomes but long term longitudinal analyses in a large European cohort have not been perfomed. To hus, we studied suPAR in participants of the Ludwigshafen Risk and Cardiovascular Health study over a very long follow-up time of nearly 10 years. We estimated overall risk of all-cause and cardiovascular death by Cox proportional hazards regression according to quartiles of suPAR, including age, sex, use of lipid-lowering drugs, body mass index, diabetes mellitus, hypertension, smoking, lipids, as well as glomerular filtration rate (eGFR), NT-proBNP, interleukin-6 and high-sensitive CRP as covariates. A total of 2940 participants (age 62.7?±?10.5years) having a median eGFR of 83.8?mL/min/1.73?m2 were included. The median suPAR concentration was 3010?pg/mL (interquartile range, 2250-3988?pg/mL). Using the lowest quartile of suPAR as the reference, crude hazard ratio for cardiovascular mortality were 1.58 (95% CI 1.16-2.16), 1.85 (95% CI 1.37-2.52) and 2.75 (95% CI 2.03-3.71) in the second, third and fourth quartile, respectively. Adjusting for NT-proBNPeGFR or inflammation (interleukin-6 and high-sensitive CRP) confirmed results. suPAR predicts all-cause and cardiovascular death over a period of ten years in persons undergoing coronary angiography, independent of the natriuretic peptide NT-proBNP, kidney function and of markers of systemic inflammation. Future investigation into a potential causal role of suPAR in cardiovascular disease is warranted.

SUBMITTER: Sommerer C

PROVIDER: S-EPMC6346054 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Soluble urokinase plasminogen activation receptor and long-term outcomes in persons undergoing coronary angiography.

Sommerer Claudia C Zeier Martin M Morath Christian C Reiser Jochen J Scharnagl Hubert H Stojakovic Tatjana T Delgado Graciela E GE März Winfried W Kleber Marcus E ME

Scientific reports 20190124 1

Soluble urokinase plasminogen activation receptor (suPAR) is risk factor for kidney disease and biomarker for cardiovascular outcomes but long term longitudinal analyses in a large European cohort have not been perfomed. To hus, we studied suPAR in participants of the Ludwigshafen Risk and Cardiovascular Health study over a very long follow-up time of nearly 10 years. We estimated overall risk of all-cause and cardiovascular death by Cox proportional hazards regression according to quartiles of ...[more]

PMID: 30679668

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Project description:Background and objectivesSoluble urokinase plasminogen activator receptor is a novel biomarker strongly predictive of cardiovascular outcomes implicated in the pathogenesis of kidney disease. Soluble urokinase plasminogen activator receptor levels, however, correlate with declining kidney function. It is unclear whether soluble urokinase plasminogen activator receptor levels remain associated with outcomes in patients with ESRD.Design, setting, participants, & measurementsWe measured plasma soluble urokinase plasminogen activator receptor levels in 1175 patients (mean age =66±8 years old, 54% men) with type 2 diabetes mellitus on hemodialysis participating in the German Diabetes and Dialysis Study followed for a median of 4 years for outcomes including all-cause death, cardiovascular events, and infection-related mortality. Survival analysis was performed using stepwise Cox proportional hazards models adjusted for potential confounders. Also, adjustments were made for inflammatory markers (C-reactive protein and leukocyte count) and the oxidative stress marker asymmetric dimethyl arginine to investigate potential mediators of the relationship between soluble urokinase plasminogen activator receptor and outcomes.ResultsMedian soluble urokinase plasminogen activator receptor levels were 10,521 pg/ml (interquartile range, 9105-12,543 pg/ml). When stratified by tertiles, patients with soluble urokinase plasminogen activator receptor >11,633 pg/ml (third tertile) had adjusted 1.6-fold higher mortality (hazard ratio, 1.60; 95% confidence interval, 1.27 to 2.03) compared with those with low soluble urokinase plasminogen activator receptor <9599 pg/ml (first tertile). Risks of sudden death and stroke were higher (adjusted hazard ratio, 1.98; 95% confidence interval, 1.27 to 3.09 and adjusted hazard ratio, 1.74; 95% confidence interval, 1.05 to 2.90, respectively), together accounting for higher incidence of cardiovascular events (adjusted hazard ratio, 1.48; 95% confidence interval, 1.15 to 1.89). Associations with outcomes persisted after adjusting for C-reactive protein, leukocyte count, and asymmetric dimethyl arginine. Addition of soluble urokinase plasminogen activator receptor to a risk factor model modestly improved risk discrimination for all-cause death (?C statistic, 0.02; 95% confidence interval, 0.00 to 0.03) and cardiovascular events (?C statistic, 0.02; 95% confidence interval, 0.00 to 0.05).ConclusionsThe association of soluble urokinase plasminogen activator receptor levels with outcomes persists in patients on hemodialysis. Additional study is warranted to characterize the underlying pathways of that association, which may yield opportunities to develop new therapeutic strategies.

Project description:BackgroundPatients 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.MethodsA 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.ResultsIn 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).ConclusionPAD 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.

Project description:BACKGROUND AND OBJECTIVES:Black Americans with and without APOL1 kidney disease risk variants face high risk of ESKD. Soluble urokinase-type plasminogen activator receptor (suPAR), a circulating signaling protein and marker of immune activation, constitutes a promising biomarker of CKD-associated risks. We aimed to quantify the associations between serum suPAR concentration and adverse outcomes in Black Americans with and without APOL1 kidney disease risk variants, over and above iodine-125 iothalamate measured GFR and proteinuria. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:Using data from the African-American Study of Kidney Disease and Hypertension, a multicenter clinical trial followed by a cohort phase with a median total follow-up of 9.7 years (interquartile range, 6.5-10.9 years), we examined the associations of suPAR with CKD progression (defined as doubling of serum creatinine or ESKD), ESKD, worsening proteinuria (defined as pre-ESKD doubling of 24-hour urine protein-to-creatinine ratio to ?220 mg/g), and all-cause death. RESULTS:At baseline, the median suPAR was 4462 pg/ml, mean measured GFR was 46 ml/min per 1.73 m2, and median 24-hour urine protein-to-creatinine ratio was 80 mg/g. After controlling for baseline demographics, randomization arm, GFR, proteinuria, APOL1 risk status, and clinical risk factors, there was a 1.26-times higher risk for CKD progression per SD higher baseline log-transformed suPAR (hazard ratio [HR], 1.26; 95% confidence interval [95% CI], 1.11 to 1.43; P<0.001). Higher suPAR was also independently associated with risk of ESKD (HR, 1.36; 95% CI, 1.17 to 1.58; P<0.001) and death (HR, 1.25; 95% CI, 1.08 to 1.45; P=0.003). suPAR was only associated with worsening proteinuria in patients with two APOLI risk alleles (HR, 1.46; 95% CI, 1.08 to 1.99; P=0.02). CONCLUSIONS:Higher suPAR was associated with various adverse outcomes in Black Americans with CKD, with and without APOL1 kidney disease risk variants, independently of proteinuria and GFR.

Dataset Information

Soluble urokinase plasminogen activation receptor and long-term outcomes in persons undergoing coronary angiography.

Publications

Soluble urokinase plasminogen activation receptor and long-term outcomes in persons undergoing coronary angiography.

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