Cardiac Biomarkers Could ID High-Risk Kidney Disease Patients

Veronica Hackethal, MD

October 28, 2019

Scientists have found that two biomarkers — high-sensitivity troponin (hs-TnT and N-terminal prohormone BNP (NT-proBNP) — are linked to increased risk for poor cardiovascular outcomes in patients with chronic kidney disease (CKD).

The study was published in Mayo Clinic Proceedings by Shravya Vinnakota, MBBS, of the Department of Internal Medicine at the Mayo Clinic, Rochester, and colleagues.

NT-proBNP, a precursor to brain natriuretic peptide (BNP), and hs-troponin are both cleared by the kidneys. Clinicians have therefore been hesitant to use them to predict cardiovascular outcomes in people with CKD because of concerns that they may be falsely elevated in these patients.

But, "In this study we demonstrated that NT-proBNP and hs-TnT have prognostic value regardless of kidney function," senior author Horng H. Chen, MB, BCh, told Medscape Medical News by email.

"Hence, these two biomarkers can be used to help clinicians...identify patients with kidney disease who are at highest risk for adverse cardiac events and [who] would be candidates for aggressive risk factor modification to prevent adverse outcomes," added Chen, a cardiologist who specializes in heart failure at the Mayo Clinic.

Does Impaired Kidney Function Alone Up Risk of CVD?

Cardiovascular disease (CVD) claims more lives in people with CKD than complications of kidney disease. This can be explained in part by shared common risk factors including hypertension, diabetes, hyperlipidemia, smoking, and obesity.

However, there is growing evidence that impaired kidney function and raised albuminuria levels are risk factors for CVD independent of traditional factors such as hypertension and diabetes.

In addition, there are pathologic mechanisms that are unique to CKD that promote vascular disease, thus contributing to the increased burden of CVD, Vinnakota and colleagues explain.

However, there is a paucity of studies stratifying cardiovascular risk in patients with CKD, they add.

Heart Attack Risk Almost Doubled in Those With Significant CKD

The researchers therefore set out to classify participants by renal function, characterize trends of cardiac biomarker activation and left ventricular function, and report cardiovascular outcomes over a 10-year follow-up period using data from a retrospective study, including 1981 participants from the Olmsted County Heart Function Study.

Participants were aged 45 years and older between January 1997 and December 2000, and had had a clinical evaluation, medical record review, lab tests, and echocardiogram. Follow-up was a median 10.2 years. Results were adjusted for age and sex.

The prevalence of stage 3 CKD (eGFR < 60 mL/min/1.73m2) was 6.4% (126/1981). In the remainder of the group, 52.3% (1036/1981) had mild renal insufficiency (eGFR 60-89 mL/min/1.73m2) and 41.3% (819/1981) had normal kidney function.

Compared to participants with normal kidney function, those with stage 3 CKD had a 38% increased risk of the primary outcome, a composite of myocardial infarction (MI), congestive heart failure (CHF), stroke, and all-cause mortality (HR, 1.38; P = .02).  

Similarly, those with stage 3 CKD had almost double the MI risk (HR, 1.95; P = .006), and were also at higher risk for stroke, CHF, and death individually, compared with those with normal kidney function, although the latter three results were not statistically significant.

Furthermore, people with NT-proBNP and hs-TnT levels in the highest tertile were at greater risk for adverse cardiovascular outcomes including CHF, MI, stroke, and all-cause mortality, compared to those with lower levels of the biomarkers.

And the degree of kidney impairment, as estimated by eGFR, did not significantly affect the results, suggesting renal impairment was not the only reason for elevation of the biomarkers

The authors note some study limitations, however.

Because most participants were white, the results may not apply to more diverse groups. The study also lacked information about duration and severity of coexisting medical conditions and cardiac medications, which could have affected outcomes. And cardiac biomarkers were only measured at the start of the study, so whether they changed over time is unknown.

Lower Thresholds of Biomarkers for Prediction of Poor Outcomes

Further analysis suggested an optimal cut-point for the overall study group of 97.1 pg/mL for NT-proBNP and 3.8 ng/L for hs-TnT; these values were similar to the third tertile for both biomarkers, say the researchers.

"In comparison with prior studies, these data suggest lower thresholds of both biomarkers for prediction of poor outcomes," they note.

"Our findings validate the importance of monitoring these levels in patients with CKD and propose an additional tool to identify those at highest risk for adverse cardiovascular events," the authors state.

Nevertheless, more work is needed to confirm the results and whether "these cardiac biomarkers could identify high-risk CKD patients for aggressive management of cardiovascular risk factors," they conclude.

The authors have reported no relevant financial relationships.

Mayo Clin Proc. Published online October 23, 2019. Abstract

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