Associations of High-Sensitivity Troponin and Natriuretic Peptide Levels With Outcomes After Intensive Blood Pressure Lowering

Abstract

IMPORTANCE Elevated high-sensitivity cardiac troponin T (hscTnT) and N-terminal pro-B-type natriuretic peptide (NTproBNP) levels are associated with risk of heart failure (HF) and mortality among individuals in the general population. However, it is unknown if this risk is modifiable.OBJECTIVE To test the hypothesis that elevated hscTnT and NTproBNP levels would identify individuals with the greatest risk for mortality and HF and the largest benefit associated with intensive systolic blood pressure (SBP) lowering.DESIGN, SETTING, AND PARTICIPANTS This is a nonprespecified post hoc analysis of the multicenter, prospective, randomized clinical Systolic Blood Pressure Intervention Trial (SPRINT), conducted from October 20, 2010, to August 20, 2015. A total of 9361 patients without diabetes with increased risk for cardiovascular disease were randomized to receive intensive vs standard SBP lowering. Statistical analysis was performed on an intention-to-treat basis from September 30, 2019, to July 29, 2021.INTERVENTIONS Participants were randomized to undergo intensive (<120 mm Hg) or standard (<140 mm Hg) SBP lowering. High-sensitivity cardiac troponin T and NTproBNP levels were measured from stored specimens collected at enrollment, with elevated levels defined as 14 ng/L or more for hscTnT (to convert to micrograms per liter, multiply by 0.001) and 125 pg/mL or more for NTproBNP (to convert to nanograms per liter, multiply by 1.0). MAIN OUTCOMES AND MEASURESThe primary outcome of this ancillary study was HF and mortality. RESULTSOf the 9361 participants enrolled in SPRINT, 8828 (5578 men [63.2%]; mean [SD] age, 68.0 [9.5] years) had measured hscTnT levels and 8836 (5585 men [63.2%]; mean [SD] age, 68.0 [9.5] years) had measured NTproBNP levels; 2262 of 8828 patients (25.6%) had elevated hscTnT levels, 3371 of 8836 patients (38.2%) had elevated NTproBNP, and 1411 of 8828 patients (16.0%) had both levels elevated. Randomization to the intensive SBP group led to a 4.9% (95% CI, 1.7%-7.5%) absolute risk reduction (ARR) over 4 years in death and HF (421 events) for those with elevated hscTnT and a 1.7% (95% CI, 0.7%-2.5%) ARR for those without elevated levels. Similarly, for those with elevated NTproBNP, the ARR for death and HF over 4 years was 4.6% (95% CI, 2.3%-6.5%) vs 1.8% (95% CI, 0.9%-2.5%) in those without elevated levels. For those with elevated levels of both biomarkers, the ARR for death and HF over 4 years was 7.8% (95% CI, 3.3%-11.3%) vs 1.7% (95% CI, 0.8%-2.3%) in those with neither biomarker elevated. No significant treatment group by biomarker category interactions were detected. CONCLUSIONS AND RELEVANCEIntensive SBP control led to large absolute differences in death and HF among patients with abnormal hscTnT and NTproBNP levels. These findings demonstrate that risk associated with elevation of these biomarkers is modifiable with intensive BP control. A prospective, randomized clinical trial is needed to evaluate whether these biomarkers may help guide selection of patients for intensive SBP lowering.

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

“…For example, the 4‐year absolute risk reduction of randomization to the intensive‐treatment group versus standard‐treatment group for all‐cause mortality among individuals without elevated hs‐cTnT and NT‐proBNP was 0.97%, whereas the 4‐year absolute risk reduction was 7.00% among individuals with both biomarkers elevated. 23 We speculate that participants with high cardiac biomarker levels have substantial multimorbidity at baseline that predisposes them to SAEs regardless of their lower achieved BP and use of additional antihypertensive medications following randomization to the intensive‐treatment group. These findings suggest that combined elevations in hs‐cTnT and NT‐proBNP indicate a high SAE risk, but also identify a subset with substantial absolute benefit from intensive BP lowering and no excess risk of harms compared with standard BP lowering.…”

“…Both hs‐cTnT and NT‐proBNP were measured from freshly thawed serum samples using an electrochemiluminescence immunoassay on the Roche Cobas 6000 platform (Roche Diagnostics, Indianapolis, IN) as previously described. 23 The hs‐cTnT assay (5th Generation) has an imprecision of 3.4% at 28.3 ng/L and 2.3% at 2076 ng/L, with a lower limit of quantitation of 6 ng/L. The NT‐proBNP assay has an imprecision of 2.9% at 140.3 pg/mL and 2.7% at 4563 pg/mL, with a lower limit of detection of 5 pg/mL.…”

“… 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 Recently, elevations in hs‐cTnT and NT‐proBNP have been shown to identify SPRINT participants who derive the greatest absolute benefit from intensive BP lowering. 23 Elevations in hs‐cTnT and NT‐proBNP in older adults are also associated with risk of falls, orthostatic hypotension, and hospitalizations with AKI. 24 , 25 , 26 However, it remains unknown whether cardiac biomarkers provide prognostic information about SAEs during hypertension treatment.…”

High sensitivity troponins: A potential biomarkers of cardiovascular risk for primary prevention

“…The SPRINT study, designed to assess the correlation of a reduction in CV risk with a drastic drop in blood pressure, identified that patients with the highest hs-cTnT values are associated with a higher mortality, and that blood pressure lowering treatment reduces most of the risk in these patients ( 74 ).…”

Kidney Function Specific Reference Limits for N-terminal Pro Brain Natriuretic Peptide and High Sensitivity Troponin T: The Systolic Blood Pressure Intervention Trial

“…NT-proBNP and hsTnT were measured from stored specimens collected at enrollment (using the Roche COBAS 6000 platform). 7 We determined the proportion of SPRINT participants who were above the 95th and 99th percentile thresholds developed in CRIC, overall and across strata by eGFR category. 5 In secondary analyses, we described these proportions across strata of sex, race, and age.…”