Prognostic Implications of Biomarker Assessments in Patients With Type 2 Diabetes at High Cardiovascular Risk

Scirica, Benjamin M.; Bhatt, Deepak L.; Braunwald, Eugene; Raz, Itamar; Cavender, Matthew A.; Im, KyungAh; Mosenzon, Ofri; Udell, Jacob A.; Hirshberg, Boaz; Pollack, Pia S.; Steg, Philippe Gabriel; Jarolím, Petr; Morrow, David A.

doi:10.1001/jamacardio.2016.3030

Cited by 86 publications

(82 citation statements)

References 40 publications

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“…In older adults, cardiovascular and in-flammatory biomarkers are related to CVD outcomes over a relatively short follow-up interval. 8 Although adolescents with T2D have a significant lifetime risk for CVD, they may have a lower short-term risk for adverse outcomes than adults. These biomarkers also have been associated with other adverse outcomes.…”

Section: Discussionmentioning

confidence: 99%

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Cardiac Biomarkers in Youth with Type 2 Diabetes Mellitus: Results from the TODAY Study

Gidding¹,

Bjornstad²,

Katz³

et al. 2018

The Journal of Pediatrics

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Objectives To examine cardiac biomarkers over time in youth-onset type 2 diabetes, and relate serum concentrations to cardiovascular disease risk factors, and left ventricular structure and function. Study design TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) was a multicenter randomized trial of 3 treatments including 521 participants with type 2 diabetes, aged 10–17 years, and with 2–6 years of follow-up. Participants were 36% male, obese, and ethnically diverse. Annual serum concentrations of brain natriuretic peptide, troponin, tumor necrosis factor (TNF)-α, receptors 1 and 2 were related to blood pressure, body mass index, hemoglobin A1c, and left ventricular ejection fraction, diastolic function, relative wall thickness, and mass. Results Elevated concentrations of brain natriuretic peptide (≥100 pg/mL), TNF-α (≥5.6 pg/mL) and troponin (≥0.01 ng/mL), were present in 17.8%, 18.3%, and 34.2% of the cohort, respectively, at baseline, and in 15.4%, 17.1%, and 31.1% at the end of the study, with wide variability over time, without persistence in individuals or clear relationship to glycemia or cardiovascular structure/function. TNF receptors concentrations were increased at baseline and not significantly different from end-of-study concentrations. Adverse echocardiographic measures were more likely in the highest TNF receptor tertile (all P < .05): higher left ventricular mass (39.3 ± 9.0 g/m2.7), left atrial internal dimension (3.7 ± 0.4 cm) and E/Em ratio, a measure of diastolic dysfunction (6.2 ± 1.9). After adjustment for body mass index, these relationships were no longer significant. Conclusions Elevated serum concentrations of cardiac biomarkers were common in youth with type 2 diabetes, but their clinical significance is unclear and will require further long-term study.

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Section: Discussionmentioning

confidence: 99%

“…5–7 In adults with T2D, measurement of cardiovascular and inflammatory biomarkers adds to CVD risk stratification. 8,9 …”

mentioning

confidence: 99%

Cardiac Biomarkers in Youth with Type 2 Diabetes Mellitus: Results from the TODAY Study

Gidding¹,

Bjornstad²,

Katz³

et al. 2018

The Journal of Pediatrics

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“…However, as the incidences of outcomes differ between patients with HF8 and patients with a recent ACS9 in a stable phase, it is less established how natriuretic peptides are associated with cardiovascular outcomes, especially subsequent MI and stroke, in the latter population 3, 10, 11, 12, 13, 14. Concentrations of natriuretic peptides may be affected by both asymptomatic myocardial ischemia15, 16 and atrial fibrillation,17, 18 which could make BNP and NT‐proBNP relevant as predictors of MI and stroke.…”

Section: Introductionmentioning

confidence: 99%

Role of B‐Type Natriuretic Peptide and N‐Terminal Prohormone BNP as Predictors of Cardiovascular Morbidity and Mortality in Patients With a Recent Coronary Event and Type 2 Diabetes Mellitus

Wolsk

Claggett

Pfeffer

et al. 2017

JAHA

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BackgroundNatriuretic peptides are recognized as important predictors of cardiovascular events in patients with heart failure, but less is known about their prognostic importance in patients with acute coronary syndrome. We sought to determine whether B‐type natriuretic peptide (BNP) and N‐terminal prohormone B‐type natriuretic peptide (NT‐proBNP) could enhance risk prediction of a broad range of cardiovascular outcomes in patients with acute coronary syndrome and type 2 diabetes mellitus.Methods and ResultsPatients with a recent acute coronary syndrome and type 2 diabetes mellitus were prospectively enrolled in the ELIXA trial (n=5525, follow‐up time 26 months). Best risk models were constructed from relevant baseline variables with and without BNP/NT‐proBNP. C statistics, Net Reclassification Index, and Integrated Discrimination Index were analyzed to estimate the value of adding BNP or NT‐proBNP to best risk models. Overall, BNP and NT‐proBNP were the most important predictors of all outcomes examined, irrespective of history of heart failure or any prior cardiovascular disease. BNP significantly improved C statistics when added to risk models for each outcome examined, the strongest increments being in death (0.77–0.82, P<0.001), cardiovascular death (0.77–0.83, P<0.001), and heart failure (0.84–0.87, P<0.001). BNP or NT‐proBNP alone predicted death as well as all other variables combined (0.77 versus 0.77).ConclusionsIn patients with a recent acute coronary syndrome and type 2 diabetes mellitus, BNP and NT‐proBNP were powerful predictors of cardiovascular outcomes beyond heart failure and death, ie, were also predictive of MI and stroke. Natriuretic peptides added as much predictive information about death as all other conventional variables combined.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01147250.

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“…Finally in 2015, the TECOS trial, conducted in 14,671 patients with T2D, showed that the DPP-4i sitagliptin, compared to placebo, had no effect on a composite endpoint made of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina during a follow-up of 3 years (22). These disappointing results were further complicated by the finding, in the SAVOR trial, of a 27% relative excess risk of hospitalization for heart failure associated with the use of saxagliptin (23).…”

Section: Lack Of Clinical Evidencementioning

confidence: 99%

Direct effects of DPP-4 inhibition on the vasculature. Reconciling basic evidence with lack of clinical evidence

Fadini

Albiero

Avogaro

2015

Vascular Pharmacology

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Prognostic Implications of Biomarker Assessments in Patients With Type 2 Diabetes at High Cardiovascular Risk

Abstract: clinicaltrials.gov Identifier: NCT01107886.

Cited by 86 publications

References 40 publications

Cardiac Biomarkers in Youth with Type 2 Diabetes Mellitus: Results from the TODAY Study

Cardiac Biomarkers in Youth with Type 2 Diabetes Mellitus: Results from the TODAY Study

Role of B‐Type Natriuretic Peptide and N‐Terminal Prohormone BNP as Predictors of Cardiovascular Morbidity and Mortality in Patients With a Recent Coronary Event and Type 2 Diabetes Mellitus

Direct effects of DPP-4 inhibition on the vasculature. Reconciling basic evidence with lack of clinical evidence

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