Serum cardiac troponin T (cTnT) levels at baseline and over time are independently associated with all-cause mortality in older patients with stage 4 and 5 chronic kidney disease (CKD), according to results from the Swedish EQUAL trial. Researchers concluded that longitudinal cTnT measurement—to identify changes and/or increases in cTnT levels—may help identify and follow those patients at highest risk.
Their results are published in the Journal of the American College of Cardiology.
“The elevation of cTn levels among patients with CKD is not spurious but foreshadows a worse prognosis. Previous studies established an association between baseline cTnT and mortality in dialysis-dependent and nondependent CKD populations. Longitudinal measurements of cTnT may provide additional information on the trajectory of the biomarker, which may better reflect the underlying physiology of (sub)clinical cardiovascular disease compared with a single measurement,” according to Nicholas C. Chesnaye, PhD, of the ERA-EDTA Registry, Department of Medical Informatics, Academic Medical Center, University of Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands, and colleagues.
Several previous meta-analyses have shown that an elevated cTnT at baseline was independently associated with a roughly 3-fold increase in mortality risk in CKD patients, whether they required dialysis or not.
“However, beyond the cTnT level at the time of measurement, it remains unknown whether the speed of change in cTnT or the cumulative exposure to cTnT (reflecting patient history) provides clinically relevant information. Such information could help improve the identification and surveillance of subjects with a high mortality risk,” they explained.
In the EQUAL study, Chesnaye and colleagues included 176 Swedish patients ages 65 years or older (mean age: 75.4 years; 67.6% male) with stage 4-5 CKD who were not on dialysis. Using joint models for longitudinal and time-to-event data, they studied the longitudinal association between cTnT and survival.
Looking at comorbidities, most patients (92.0%) were hypertensive and 37.5% had diabetes. Mean albumin-to-creatinine ratio (ACR) was 51.9, and mean estimated glomerular filtration rate (eGFR) was 17.5 mL/min/1.73 m2. Over a median follow-up of 2.4 years, Chesnaye and colleagues collected a median of six cTnT measurements per patient (927 total). They noted that patients with preexisting diabetes, atrial fibrillation (16.5%), and chronic heart failure (17.0%) more frequently presented with higher baseline cTnT levels.
Sixty deaths occurred during the 483 years of follow-up data gathered. Overall 5-year survival was 57% (95% CI: 46%-69%) and inversely correlated with baseline cTnT tertile (P<0.0001). Compared with patients in the lowest cTnT tertile, those in the highest cTnT tertile had a 9.1-times higher risk of death.
Longitudinal cTnT was found to be associated with mortality risk. At any timepoint, every SD increase in cTnT was associated with a 3.2-fold increase in mortality risk (HR: 3.3; 95% CI: 2.5-4.6). Researchers also found an association between increased mortality risk and the slope of the cTnT trajectory (HR: 3.2; 95% CI: 2.0-6.0). And, when all previous and current measures of cTnT levels were combined, Chesnaye and colleagues found that each 1 SD increase in the area under the cTnT trajectory was associated with a 4.2-fold increase in mortality risk (HR: 4.2; 95% CI: 2.6-7.2).
“Effect estimates remained largely unchanged after adjustment for confounders. In a sensitivity analysis, we adjusted for time-updated confounders, including dialysis treatment, using a time-dependent Cox model, which had no meaningful impact on the HRs,” they added.
“The findings by Chesnaye et al are primarily associative and limited at deriving causality. Thus, any management decisions based on longitudinal cTn measurements must await validation in prospective trials. However, in the previously described context, the clinical implications are exciting to ponder. The enhanced predictive capability provided by longitudinal ’delta’ cTnT levels and the speed of change and/or area under the curve among asymptomatic patients with advanced CKD could help identify a subset at the highest risk of mortality, particularly when transitioning to dialysis. Information obtained from longitudinal increases in cTnT levels could be potentially clinically actionable, as a reminder to the clinician to ensure implementation of the most aggressive measures for CV risk prevention available in their therapeutic armamentarium,” wrote Gautam R. Shroff, MB, BS, of Hennepin Healthcare and University of Minnesota Medical School, Minneapolis, and colleagues in an accompanying editorial.
And although these results are valuable, Shroff et al outlined the absolute need for further study of these associations, citing cost efficacy, psychological impact, changing kidney function, testing asymptomatic patients, differences in cTn assays, and the ease or difficulties inherent in implementing such longitudinal testing and interpretation into clinical practice as areas in need of clarification.
“In summary, the study by Chesnaye et al offers a flash of optimism to the nephrocardiology community with regard bridging the chasm of a perilous transition. This study moves us a step closer to the direction of understanding more individualized risks in a high-risk population that may potentially benefit from a more customized approach of risk recognition, and hopefully, mitigation,” concluded Shroff and colleagues.
Main funding for this study was received from the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA). Contributions came from the Swedish Medical Association (SLS), the Stockholm County Council ALF Medicine and Center for Innovative research (CIMED), the Italian Society of Nephrology (SIN-Reni), the Dutch Kidney Foundation (SB 142), the Young Investigators grant in Germany, and the National Institute for Health Research (NIHR) in the United Kingdom.
Chesnaye and Shroff reported no disclosures.
Liz Meszaros, Deputy Managing Editor, BreakingMED™
Kaiser Health News
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