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. 2022 Mar 15;11(6):e023314.
doi: 10.1161/JAHA.121.023314. Epub 2022 Mar 4.

Associations of High-Sensitivity Troponin and Natriuretic Peptide Levels With Serious Adverse Events in SPRINT

Simon B Ascher  1   2 , Rebecca Scherzer  1 , Jame A de Lemos  3 , Michelle M Estrella  1 , Vasantha K Jotwani  1 , Pranav S Garimella  4 , Alexander L Bullen  4   5 , Walter T Ambrosius  6 , Christie M Ballantyne  7 , Vijay Nambi  7   8 , Anthony A Killeen  9 , Joachim H Ix  4   5 , Michael G Shlipak  1 , Jarett D Berry  3
Affiliations

Associations of High-Sensitivity Troponin and Natriuretic Peptide Levels With Serious Adverse Events in SPRINT

Simon B Ascher et al. J Am Heart Assoc. .

Abstract

Background Assessing the risk of serious adverse events (SAEs) during hypertension treatment is important for understanding the benefit-harm trade-offs of lower blood pressure goals. It is unknown whether high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) provide information about SAEs. Methods and Results In SPRINT (Systolic Blood Pressure Intervention Trial), hs-cTnT and NT-proBNP were measured at baseline in 8828 (94.3%) and 8836 (94.4%) participants, respectively. Multivariable Cox proportional hazards models were used to evaluate hs-cTnT and NT-proBNP associations with a composite of SPRINT's SAEs of interest: hypotension, syncope, bradycardia, acute kidney injury, electrolyte abnormalities, and injurious falls. Elevations in hs-cTnT and NT-proBNP were associated with increased composite SAE risk (hazard ratio [HR] per 2-fold higher hs-cTnT: 1.15; 95% CI, 1.06‒1.25; HR per 2-fold higher NT-proBNP: 1.09; 95% CI, 1.05‒1.14). Compared with both hs-cTnT and NT-proBNP in the lower tertiles, both biomarkers in the highest tertile was associated with increased composite SAE risk (HR, 1.56; 95% CI, 1.32‒1.84). Composite SAE risk was higher in the intensive-treatment group than in the standard-treatment group for participants with both biomarkers in the lower tertiles, but similar between treatment groups for participants with both biomarkers in the highest tertile (P for interaction=0.008). Conclusions Elevations in hs-cTnT and NT-proBNP individually and in combination are associated with higher composite SAE risk in SPRINT. The differential impact of blood pressure treatment on SAE risk across combined biomarker categories may have implications for identifying individuals with more favorable benefit-harm profiles for intensive blood pressure lowering.

Keywords: SPRINT; adverse events; brain natriuretic peptide; hypertension; troponin.

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Figures

Figure 1
Figure 1. Cumulative incidence of the composite SAE outcome stratified by combined hs‐cTnT and NT‐proBNP categories.
Composite SAE outcome indicates hypotension, syncope, bradycardia, acute kidney injury, electrolyte abnormalities, or injurious falls. Combined biomarker categories include: (1) both hs‐cTnT and NT‐proBNP in the lower two sex‐specific tertiles, (2) one of hs‐cTnT or NT‐proBNP in the highest sex‐specific tertile, (3) both hs‐cTnT and NT‐proBNP in the highest sex‐specific tertile. hs‐cTnT indicates high‐sensitivity cardiac troponin T; NT‐proBNP, N‐terminal pro‐B‐type natriuretic peptide; and SAE, serious adverse event.
Figure 2
Figure 2. Restricted cubic splines of hazard ratios and 95% CIs for the associations of hs‐cTnT and NT‐proBNP with risk of the composite SAE outcome.
The composite SAE outcome indicates hypotension, syncope, bradycardia, acute kidney injury, electrolyte abnormalities, or injurious falls. Hazard ratios (solid blue lines) with 95% confidence intervals (shaded areas) for the composite SAE outcome by baseline hs‐cTnT (panel A) and NT‐proBNP (panel B) levels are displayed. Estimates were obtained from multivariable Cox proportional hazards models that included demographics (age, sex, race), intervention arm, cardiovascular risk factors (body mass index, alcohol use, smoking status, prevalent cardiovascular disease, estimated glomerular filtration rate, and urine albumin‐to‐creatinine ratio), vitals (heart rate, systolic BP, diastolic BP, and orthostatic hypotension), dizziness, frailty, medications (statin use, total medication burden, number of antihypertensive medications, and antihypertensive medication class), and the other cardiac biomarker. BP indicates blood pressure; hs‐cTnT, high‐sensitivity cardiac troponin T; NT‐proBNP, N‐terminal pro‐B‐type natriuretic peptide; and SAE, serious adverse event.
Figure 3
Figure 3. Proportion of SPRINT participants who experienced the composite SAE outcome stratified by combined hs‐cTnT and NT‐proBNP categories
Composite SAE outcome indicates hypotension, syncope, bradycardia, acute kidney injury, electrolyte abnormalities, or injurious falls. Combined biomarker categories include: (1) both hs‐cTnT and NT‐proBNP in the lower 2 sex‐specific tertiles, (2) one of high‐sensitivity cardiac troponin T or NT‐proBNP in the highest sex‐specific tertile, (3) both hs‐cTnT and NT‐proBNP in the highest sex‐specific tertile. BP, blood pressure; and SAE, serious adverse event.
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