Original Investigation
Pathogenesis and Treatment of Kidney Disease
Association of High-Sensitivity Cardiac Troponin T and Natriuretic Peptide With Incident ESRD: The Atherosclerosis Risk in Communities (ARIC) Study

https://doi.org/10.1053/j.ajkd.2014.08.021Get rights and content

Background

Epidemiologic data for cardiac abnormality predating decreased kidney function are sparse. We investigated the associations of high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro–brain natriuretic peptide (NT-proBNP) with end-stage renal disease (ESRD) risk in a community-based cohort.

Setting & Participants

10,749 white and black participants at the fourth visit (1996-1998) of the Atherosclerosis Risk in Communities (ARIC) Study with follow-up through 2010.

Predictor

hs-cTnT (3, 6, 9, and 14 ng/L) and NT-proBNP (41.6, 81.0, 142.5, and 272.5 pg/mL) levels were divided into 5 categories at the same percentiles (32th, 57th, 77th, and 91th; corresponding to ordinary thresholds of hs-cTnT), with the lowest category as a reference.

Outcomes

Incident ESRD defined as initiation of dialysis therapy, transplantation, or death due to kidney disease.

Measurements

Relative risk and risk prediction of ESRD according to hs-cTnT and NT-proBNP levels based on Cox proportional hazards models.

Results

During a median follow-up of 13.1 years, 235 participants developed ESRD (1.8 cases/1,000 person-years). hs-cTnT and NT-proBNP levels were associated with ESRD risk independently of each other and of potential confounders, including kidney function and albuminuria (adjusted HRs for highest category, 4.43 [95% CI, 2.43-8.09] and 2.28 [95% CI, 1.44-3.60], respectively). For hs-cTnT level, the association was significant even at the third category (HR for 6-8 ng/L of hs-cTnT, 2.74 [95% CI, 1.54-4.88]). Their associations were largely consistent even among persons without decreased kidney function or history of cardiovascular disease. hs-cTnT and NT-proBNP levels both significantly improved ESRD prediction (C statistic differences of 0.0084 [95% CI, 0.0005-0.0164] and 0.0045 [95% CI, 0.0004-0.0087], respectively, from 0.884 with conventional risk factors).

Limitations

Relatively small number of ESRD cases and single measurement of hs-cTnT and NT-proBNP.

Conclusions

hs-cTnT and NT-proBNP levels independently predicted ESRD risk in the general population, with more evident results for hs-cTnT. These results suggest the involvement of cardiac abnormality, particularly cardiac injury, in the progression of reduced kidney function and/or may reflect the useful property of hs-cTnT as an end-organ damage marker.

Section snippets

Study Population

The Atherosclerosis Risk in Communities (ARIC) Study is a prospective cohort of 15,792 individuals aged 45 to 64 years at visit 1 (1987-1989) from 4 US communities (Forsyth County, NC; Jackson, MS; suburban Minneapolis, MN; and Washington County, MD). There were 3 short-term follow-up examinations in 1990 to 1992 (visit 2), 1993 to 1995 (visit 3), and 1996 to 1998 (visit 4). Of 15,792 participants, 11,656 (74%) attended visit 4, at which hs-cTnT and NT-proBNP were measured. For this study, we

Participant Characteristics

Compared with those with lower hs-cTnT levels, individuals with higher hs-cTnT levels were more likely to be older, men, and black and have a generally higher cardiovascular risk profile (eg, higher BMI and blood pressure, higher ACR and NT-proBNP levels, more prevalent diabetes and history of CVD, and lower high-density lipoprotein cholesterol levels and eGFRs; Table 1). Similar patterns were observed among individuals with higher NT-proBNP levels (Table S1, available as online supplementary

Discussion

This study demonstrated that higher hs-cTnT and NT-proBNP levels were associated independently with incident ESRD in the general population. Our results generally are consistent with the previous report from TREAT in which all patients had diabetic nephropathy and anemia.17 We extended the results from TREAT in various aspects. First, we confirmed the associations of hs-cTnT and NT-proBNP levels with ESRD in a population with preserved kidney function, minimizing the concern for reverse

Acknowledgements

The authors thank the staff and participants of the ARIC Study for important contributions.

Some of the data reported here have been supplied by the USRDS. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as an official policy or interpretation of the US government.

Support: The ARIC Study is carried out as a collaborative study supported by National Heart, Lung and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C,

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