Factors Influencing the 99th Percentile of Cardiac Troponin I Evaluated in Community-Dwelling Individuals at 70 and 75 Years of Age

Abstract

BACKGROUND We aimed to investigate the effects of sex, prevalent cardiovascular disease (CVD), and aging on the 99th percentile of cardiac troponin I (cTnI). METHODS cTnI was measured using a high-sensitivity assay (Abbott Diagnostics) in 814 community-dwelling individuals at both 70 and 75 years of age. We determined the cTnI 99th percentiles separately using nonparametric methods in the total sample, in men and women, and in individuals with and without CVD. RESULTS The cTnI 99th percentile at baseline was 55.2 ng/L for the total cohort. Higher 99th percentiles were noted in men (69.3 ng/L) and individuals with CVD (74.5 ng/L). The cTnI 99th percentile in individuals free from CVD at baseline (n = 498) increased by 51% from 38.4 to 58.0 ng/L during the 5-year observation period. Relative increases ranging from 44% to 83% were noted across all subgroups. Male sex [odds ratio, 5.3 (95% CI, 1.5–18.3)], log-transformed N-terminal pro-B-type natriuretic peptide [odds ratio, 1.9 (95% CI, 1.2–3.0)], and left-ventricular mass index [odds ratio, 1.3 (95% CI, 1.1–1.5)] predicted increases in cTnI concentrations from below the 99th percentile (i.e., 38.4 ng/L) at baseline to concentrations above the 99th percentile at the age of 75 years. CONCLUSIONS cTnI concentration and its 99th percentile threshold depend strongly on the characteristics of the population being assessed. Among elderly community dwellers, higher concentrations were seen in men and individuals with prevalent CVD. Aging contributes to increasing concentrations, given the pronounced changes seen with increasing age across all subgroups. These findings should be taken into consideration when applying cTnI decision thresholds in clinical settings.

The 99th percentile of reference population for cTnI and cTnT assay: methodology, pathophysiology and clinical implications

“…increase in apparently healthy adult subjects aged over 65 years [10,13]. This finding was confirmed in studies using the highly sensitive cTnI method [14,27]. The progressive increase of circulating cTnT levels in apparently healthy adult subjects over 65 years was confirmed in the same period, when the highly sensitive ECLIA method became commercially available [11,12,26,[35][36][37].…”

“…Of particular importance is the evaluation of negative and positive predictive values, as reported in the 2015 ESC guidelines [32] to support the use of algorithms for rapid ruling-out and ruling-in of AMI, which strongly depends on the demographic and clinical characteristics of ED patients [42]. However, the inclusion/exclusion criteria and the demographic and clinical characteristics of ED patient populations vary greatly from study to study [27][28][29][104][105][106][107][108][109]. It is therefore not surprising that contradictory results were reported in a recent multicenter study [115] conducted to validate the performance of rapid algorithms for rulingin or ruling-out AMI, as suggested in the 2105 ESC guidelines.…”

“…Even in the 382 participants who were without cardiovascular disease at the age of 75 years, the 99th percentile increased from 31.6 ng/L to 51.3 ng/L (relative increase, 62%). cTnI values were higher in males (n = 403; median: 4.1 ng/L, range 25th-75th percentiles: 3.0-6.4 ng/L) than females (n = 411; median: 3.0 ng/L, range 25th-75th percentiles: 2.2-4.1 ng/L) [27]. Furthermore, at unadjusted logistic regression, male gender, NT-proBNP and left ventricular mass index were significantly associated with an increase in cTnI concentrations [27].…”

“…the criteria for considering the reference population "healthy") [17,[25][26][27][28][29], but also on the analytical performances of cTn methods, as well as on the mathematical algorithms used for calculating the 99th URL [10,14,15,17,18,25,26].…”

“…Regarding the elderly, Eggers et al [27] measured cTnI values with the highly sensitive ARCHITECT method in a cohort of 814 participants both at baseline (men age 70.2 [SD 0.2] years, 49.5% males) and after a 5-year follow-up. Even in the 382 participants who were without cardiovascular disease at the age of 75 years, the 99th percentile increased from 31.6 ng/L to 51.3 ng/L (relative increase, 62%).…”