Do Cardiac Biomarkers NT-proBNP and hsTnT Predict Microvascular Events in Patients With Type 2 Diabetes? Results From the ADVANCE Trial

Welsh, Paul; Woodward, Mark; Hillis, Graham S.; Li, Qiang; Marre, Michel; Williams, Bryan; Poulter, Neil; Ryan, Louise; Harrap, Stephen B; Patel, Anushka; Chalmers, John; Sattar, Naveed

doi:10.2337/dc13-2625

Cited by 34 publications

(45 citation statements)

References 35 publications

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“…Support for our findings comes from studies demonstrating an association between troponin levels and diabetic nephropathy [7] and progression to end-stage renal disease [6]. …”

Section: Discussionsupporting

confidence: 81%

“…If correct, then it would be reasonable to hypothesise that cardiovascular disease (CVD) biomarkers may improve on risk stratification using conventional risk factors for diabetic CKD. Support for this hypothesis comes from previous studies demonstrating an association between the development of end-stage renal disease and biochemical markers of CVD, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT), in people with type 2 diabetes, even after adjustment for eGFR and albuminuria [6, 7]. Markers of subclinical atherosclerosis have also been linked with renal disease progression including ankle brachial pressure index (ABI) and carotid intima media thickness (cIMT), along with markers of arterial stiffness, such as pulse wave velocity (PWV).…”

Section: Introductionmentioning

confidence: 99%

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Cardiovascular disease biomarkers are associated with declining renal function in type 2 diabetes

et al. 2017

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Aims/hypothesisWe investigated whether biochemical cardiovascular risk factors and/or markers of subclinical cardiovascular disease were associated with the development of reduced renal function in people with type 2 diabetes.MethodsA cohort of 1066 Scottish men and women aged 60–74 years with type 2 diabetes from the Edinburgh Type 2 Diabetes Study were followed up for a median of 6.7 years. New-onset reduced renal function was defined as two eGFRs <60 ml−1 min−1 (1.73 m)−2 at least 3 months apart with a > 25% decline from baseline eGFR. Ankle brachial pressure index (ABI), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT) were measured at baseline. Pulse wave velocity (PWV) and carotid intima media thickness were measured 1 year into follow-up. Data were analysed using Cox proportional hazards models.ResultsA total of 119 participants developed reduced renal function during follow-up. ABI, PWV, NT-proBNP and hsTnT were all associated with onset of decline in renal function following adjustment for age and sex. These associations were attenuated after adjustment for additional diabetes renal disease risk factors (systolic BP, baseline eGFR, albumin:creatinine ratio and smoking pack-years), with the exception of hsTnT which remained independently associated (HR 1.51 [95% CI 1.22, 1.87]). Inclusion of hsTnT in a predictive model improved the continuous net reclassification index by 0.165 (0.008, 0.286).Conclusions/interpretationOur findings demonstrate an association between hsTnT, a marker of subclinical cardiac ischaemia, and subsequent renal function decline. Further research is required to establish the predictive value of hsTnT and response to intervention.

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“…Support for our findings comes from studies demonstrating an association between troponin levels and diabetic nephropathy [7] and progression to end-stage renal disease [6]. …”

Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Cardiovascular disease biomarkers are associated with declining renal function in type 2 diabetes

et al. 2017

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“…The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation (19). Levels of baseline high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-B type natriuretic peptide (NTproBNP), and hs-CRP were also measured in stored samples (20)(21)(22). sRAGE was measured by ELISA (Quantikine; R&D Inc., Minneapolis, MN).…”

Section: Study Samplementioning

confidence: 99%

Relationship Between Levels of Advanced Glycation End Products and Their Soluble Receptor and Adverse Outcomes in Adults With Type 2 Diabetes

et al. 2015

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OBJECTIVEThis study explored whether activation of the receptor for advanced glycation end products (RAGE) is implicated in the development of diabetes complications. RESEARCH DESIGN AND METHODSA case-cohort study was performed in 3,763 participants with prevalent diabetes in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. The hazard ratios (HRs) for death, major cardiovascular events, and new or worsening nephropathy were derived using Cox regression models, and the ability of sRAGE and AGE levels to reclassify the risk of nephropathy was assessed. RESULTSAfter adjustment for a range of possible confounders and other risk factors, sRAGE levels were associated with all-cause mortality (HR 1.11 for a 1-SD increase of log sRAGE [95% CI 1.00-1.22]; P = 0.045) and new or worsening nephropathy (HR 1.20 for a 1-SD increase of log sRAGE [95% CI 1.02-1.41]; P = 0.032). Circulating AGE levels were also independently associated with new or worsening nephropathy (HR 1.21 for a 1-SD increase [95% CI 1.08-1.36]; P = 0.001). Both markers also significantly improved the accuracy with which the 5-year risk of new or worsening nephropathy could be predicted (net reclassification index in continuous model, 0.25 for sRAGE and 0.24 for AGE levels). CONCLUSIONSIn adults with type 2 diabetes, increased levels of sRAGE are independently associated with new or worsening kidney disease and mortality over the next 5 years. Higher levels of AGE are also associated with an increased risk of adverse renal outcomes. The AGE/RAGE axis may be of importance in the prevention and management of diabetes complications.Diabetes is associated with an increased risk of adverse renal and cardiovascular outcomes, which are only partially reduced by intensive glycemic control. This may be because of the long-lasting (legacy) effects of poor glycemic control over many years (1). Potential mediators of this "metabolic karma" include the long-lasting posttranslational molecular modifications induced by hyperglycemia, known as advanced

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“…The eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equation 15. Levels of baseline high‐sensitivity cardiac troponin T, NT‐proBNP (N‐terminal pro–brain natriuretic peptide), and high sensitivity C‐reactive protein were also measured on stored samples 16, 17, 18. Plasma 8‐oxo‐2′‐dG was measured by ELISA (StressMarq Biosciences Inc).…”

Section: Methodsmentioning

confidence: 99%

Relationship Between Plasma 8‐OH‐Deoxyguanosine and Cardiovascular Disease and Survival in Type 2 Diabetes Mellitus: Results From the ADVANCE Trial

Thomas

Woodward

et al. 2018

JAHA

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Background8‐Oxo‐2′‐deoxyguanosine (8‐oxo‐2′‐dG) is a biomarker of oxidative DNA damage that is associated with cardiovascular disease and premature mortality in the general population. Although oxidative stress has a proven role in cardiovascular complications in diabetes mellitus, evidence for a relationship between plasma 8‐oxo‐2′‐dG and major cardiovascular outcomes in diabetes mellitus is weak.Methods and ResultsA case‐cohort study was performed in 3766 participants with prevalent diabetes mellitus in the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation) trial (http://ClinicalTrials.gov number NCT00145925). The hazard ratios for mortality and major acute cardiovascular events were derived using Cox regression models. During a median of 5 years of follow‐up, 695 (18.4%) participants in this enriched cohort died (including 354 deaths from cardiovascular disease). Individuals with higher levels of 8‐oxo‐2′‐dG were more likely to die. After adjusting for cardiovascular disease risk factors, the hazard ratio for a 1‐SD increase in plasma 8‐oxo‐2′‐dG was 1.10 (95% confidence interval, 1.01–1.20; P=0.03). This was driven by an independent association between plasma 8‐oxo‐2′‐dG and cardiovascular death (hazard ratio, 1.23; 95% confidence interval, 1.10–1.37 [P<0.001]). By contrast, no association was seen between 8‐oxo‐2′‐dG and noncardiovascular disease death (of which cancer was the major single cause). 8‐Oxo‐2′‐dG was also not significantly associated with either nonfatal myocardial infarction or nonfatal stroke.ConclusionsIn adults with type 2 diabetes mellitus, increased levels of 8‐oxo‐2′‐dG are independently associated with all‐cause mortality and cardiovascular mortality in adults with longstanding type 2 diabetes mellitus who participated in the ADVANCE trial, consistent with the role of oxidative damage in the development and progression of cardiovascular decompensation in diabetes mellitus.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00145925.

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Do Cardiac Biomarkers NT-proBNP and hsTnT Predict Microvascular Events in Patients With Type 2 Diabetes? Results From the ADVANCE Trial

Cited by 34 publications

References 35 publications

Cardiovascular disease biomarkers are associated with declining renal function in type 2 diabetes

Cardiovascular disease biomarkers are associated with declining renal function in type 2 diabetes

Relationship Between Levels of Advanced Glycation End Products and Their Soluble Receptor and Adverse Outcomes in Adults With Type 2 Diabetes

Relationship Between Plasma 8‐OH‐Deoxyguanosine and Cardiovascular Disease and Survival in Type 2 Diabetes Mellitus: Results From the ADVANCE Trial

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