USA: Intensive Lowering of Systolic Blood Pressure (SBP) and Cardiac Biomarkers

Intensive lowering of systolic blood pressure (SBP) increases hs-cTnT, mediated by the effect of SBP lowering on reduced kidney filtration. In contrast, intensive SBP lowering reduced NT-proBNP, which was explained by the drop in SBP.

These findings from the SPRINT trial published in the journal Circulation highlight the importance of noncardiac factors impacting variation in cardiac biomarkers and raise questions about hs-cTnT's potential role as a surrogate marker for death or heart failure in SBP-lowering studies.

Given the crucial role of cardiac injury and neurohormonal activation in the pathways leading from hypertension to heart failure and strong observations seen between its sequelae on NT-proBNP (N-terminal pro-B-type natriuretic peptide) and hs-cTnT (high-sensitivity cardiac troponin T) levels, Jarett D. Berry, University of Texas Southwestern Medical School, Dallas (JDB, R.D.T., J.A.d.), and colleagues hypothesized that intensive SBP lowering would decrease hs-cTnT and NT-proBNP levels.

For this purpose, they measured hs-cTnT and NT-proBNP at baseline and one year from stored specimens in the Systolic Blood Pressure Intervention Trial (SPRINT). Biomarkers changes were assessed continuously on the log scale and per categories (≥50% decrease, ≥50% increase, or <50% change). The effect of intensive SBP lowering was assessed on continuous and categorical changes in biomarker levels using multinomial and linear logistic regression models, respectively. They also evaluated the association between changes in biomarkers on death and heart failure.

Study Findings

• Randomization to intensive SBP lowering (versus standard SBP management) led to a 3% increase in hs-cTnT levels over a 1-year follow-up (geometric mean ratio, 1.03) and a higher proportion of participants with ≥50% increase (odds ratio, 1.47).
• Randomization to intensive SBP lowering, however, led to a 10% decrease in NT-proBNP (geometric mean ratio, 0.90) and a lower probability of ≥50% increase in NT-proBNP (odds ratio, 0.57).
• The association of randomized treatment assignment on change in hs-cTnT was attenuated entirely after accounting for changes in estimated glomerular filtration rate over follow-up, whereas the association of treatment with NT-proBNP was attenuated entirely after adjusting for SBP changes.
• Increases in hs-cTnT and NT-proBNP from baseline to 1 year were linked with a higher risk for heart failure and death, with no significant interactions by treatment assignment.

"These findings highlight the importance of noncardiac factors impacting variation in cardiac biomarkers and bring into question the potential role of hs-cTnT as a surrogate marker for death or heart failure in SBP-lowering studies," the authors concluded.

Reference

Berry JD, Chen H, Nambi V, Ambrosius WT, Ascher SB, Shlipak MG, Ix JH, Gupta R, Killeen A, Toto RD, Kitzman DW, Ballantyne CM, de Lemos JA. Effect of Intensive Blood Pressure Control on Troponin and Natriuretic Peptide Levels: Findings From SPRINT. Circulation. 2022 Dec 19. doi: 10.1161/CIRCULATIONAHA.122.059960. Epub ahead of print. PMID: 36533535.