Effect of Intensive BP Control on Troponin and Natriuretic Peptide Levels

Quick Takes

  • Intensive blood pressure (BP) lowering from a systolic BP of 120 vs. 140 mm Hg in the SPRINT trial results in a decreased level of NT-proBNP that is explained by the drop in BP.
  • Unexpectedly, analysis of hs-cTnT in the same group shows an increase in hs-cTnT that is mediated by the effect of lowering BP on estimated GFR.
  • Since intensive BP lowering in the SPRINT trial showed benefits in reducing heart failure and all-cause mortality, use of hs-cTnT as a surrogate marker of these benefits is not reliable, as it may be affected by noncardiac factors such as change in GFR. In contrast, use of NT-proBNP as a surrogate marker of these benefits may be of value.

Study Questions:

Does the intensive lowering of systolic blood pressure (SBP) from 140 to 120 mm Hg in the SPRINT trial result in lowering of high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro–B-type natriuretic peptide (NT-proBNP) levels? Also, will increases of levels of these markers be associated with heart failure (HF) and all-cause mortality events?


Stored specimens obtained from subjects at baseline and at 1 year in the SPRINT (Systolic Blood Pressure Intervention Trial) study were analyzed for hs-cTnT and NT-proBNP levels. The effect of intensive SBP lowering to a target of 120 mm Hg compared to 140 mm Hg on continuous and categorial changes in these biomarker levels were analyzed. Their associations with HF and death were assessed using a multivariable-adjusted Cox proportional hazards model.


Randomization to an intensive SBP lowering (<120 mm Hg) resulted in a 3% increase in hs-cTnT and a 10% decrease in NT-proBNP over the course of a year. Similarly, the intensive SBP lowering resulted in a higher proportion of subjects with a ≥50% increase in hs-cTnT and a lower proportion of subjects with a ≥50% increase in NT-proBNP. The changes in hs-cTnT were attenuated by accounting for change in glomerular filtration rate (GFR) (not BP), whereas the changes in NT-proBNP were attenuated by accounting for BP level. Elevations in both hs-cTnT and NT-proBNP were associated with higher risk for HF and death.


One must be careful in using cardiac biomarkers such as hs-cTnT and NT-proBNP as surrogates for hard cardiac endpoints such as HF and death, as these markers can be influenced by noncardiac causes such as renal function. While useful information may be obtained from these measurements, care must be taken to exclude noncardiac factors that may come into play during the performance of a clinical trial.


Well-designed large-scale clinical trials remain the gold standard in pushing forward the frontiers of evidence-based cardiovascular medicine. However, these trials are costly, time-consuming, and require considerable infrastructure and effort on the parts of investigators, subjects, and many others. The use of surrogate biomarkers such as hs-cTnT and NT-proBNP as endpoints have the potential to make such trials easier to complete without having to measure hard endpoints such as HF and death. This analysis shows, however, that such an approach may be fraught with unanticipated noncardiac issues such as changes in GFR that may complicate the final analyses and even suggest a lack of benefit in a study where the clear benefit, using hard (not surrogate) endpoints, is well-established.

Clinical Topics: Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Biomarkers, Blood Pressure, Glomerular Filtration Rate, Heart Failure, Metabolic Syndrome, Myocardial Ischemia, Natriuretic Peptide, Brain, Natriuretic Peptides, Primary Prevention, Renal Insufficiency, Chronic, Troponin, Troponin T

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