Banerjee, Aditi

Abstract Background/Introduction Macrotroponin refers to high-molecular-weight troponin complexes bound to immunoglobulins, shown to cause persistently elevated troponin values often unrelated to myocardial injury. We hypothesized that its frequency might increase with age and differ between men and women, reflecting potential age-related cardiac changes and sex-specific risk profiles. Purpose To assess whether macrotroponin frequency varies across age groups and by sex within the upper sex-specific 90th percentile of troponin values in a healthy Danish reference population. Methods Among 1,307 participant samples with normal-range NT-proBNP, HbA1c, and eGFR ≥90 mL/min/1.73m2, 147 samples with troponin I within the upper levels of the sex-specific 90th percentile for the Siemens Atellica assay were further tested for macrotroponin I using Protein A/G immunoglobulin depletion and sucrose gradient ultracentrifugation. Samples were only deemed macrotroponin-positive by concordantly positive results. After excluding 29 samples with low troponin values due to analytical dilution constraints, 118 participants remained. Macrotroponin I frequency was compared across three age groups (<40, 40–60, and >60 years) and between sexes. Logistic regression was used to adjust for creatinine levels. Results Of 118 samples tested (48% females), macrotroponin I was present in 88 (75%), with similar frequencies in women (80%) and men (77%). Macrotroponin I frequency did not differ significantly across age groups (p=0.26) or between sexes (p>0.5) (Table 1, Figure 1). Logistic regression revealed no significant associations between macrotroponin I and age group, sex, or creatinine levels (all p > 0.5). Conclusion Macrotroponin I was highly frequent in the highest troponin ranges in a healthy reference population and showed no relationship with age or sex. The presence of macrotroponin I may impact clinical management in a considerable number of patients, but further investigation is required in clinical studies.

Abstract Background Cardiac troponin (cTn) levels exceeding the 99th percentile upper reference limit and a rise/fall pattern are key for diagnosing myocardial injury and infarction. Macrotroponins, formed by patient anti-cTn antibodies targeting cTn, can cause persistently elevated cTn levels without ongoing myocardial injury. The frequency and impact of macrotroponin interference on cTn 99th percentiles are unclear. This study compares sex-specific 99th percentiles for 2 cTn assays, before and after excluding macrotroponin-positive samples, focusing on the top 10% of cTn levels. Methods We examined 1058 plasma samples from healthy individuals previously used for Danish cTn 99th percentiles. Following International Federation of Clinical Chemistry and Laboratory Medicine educational recommendations, macrotroponin presence was assessed in the top 10% cTn samples using immunoglobulin G (IgG) depletion screening and a reference sucrose gradient, confirming macrotroponin when both methods concurred. Due to analytical dilution constraints, [the highest] 88 of 135 Siemens Atellica high-sensitivity cTnI (hs-cTnI) samples were analyzed with both methods. All 106 Roche hs-cTnT samples were negative using IgG depletion, and sucrose analysis was limited to the highest 70 samples. Results Macrotroponin was found in 76% (67/88) of Siemens samples but in none of the Roche samples (0/70). Excluding macrotroponin-affected samples lowered the Siemens 99th percentiles from 117 ng/L to 22 ng/L in men and from 37 ng/L to 9 ng/L in women. The 99th/50th percentile ratio for Siemens decreased from 12- to 29-fold to 3- to 7-fold, approaching the Roche ratios. Conclusions Macrotroponin significantly influenced the Siemens Atellica hs-cTnI 99th percentiles, suggesting important clinical implications that warrant further prospective studies. The 99th/50th percentile ratio may help evaluate macrotroponin interference in troponin assays.