Cardiovascular Therapeutics

Review Article

Sex-Specific Cut-Offs for High-Sensitivity Cardiac Troponin: Is Less More?

Table 1

Studies reporting percentile values for hs-cTnT in different reference populations. †=median [IQR]; =only range provided; CI: confidence interval; cTn: cardiac troponin; eGFR: estimated glomerular filtration rate; UK: United Kingdom; US: United States; ARIC: Atherosclerosis Risk in Communities study; CHS: Cardiovascular Health Study; DHS: Dallas Heart Study.


Study	Study objective	Year	Location	Study population	Age, mean ± SD	Population, according to sex		percentile (ng/L) [95% CI]		Comments
Study	Study objective	Year	Location	Study population	Age, mean ± SD	Males (%)	Females (%)	Males	Females

hs-cTnT (Roche Diagnostics)

Collinson et al. [40]	To determine the effect of patient selection on the reference percentile	2012	UK	545	58	259 (47.5)	286 (52.5)	22.8	12.8	Reference population selection based on: medical history, biomarkers and cardiac imaging

Apple et al. [61]	To systematically assess percentiles of cTn concentrations in a single population for a large number of assays	2012	US	524	18-64	272 (52)	252 (48)	20	13	Reference population selection based only on health questionnaire interviews

Giannitsis et al. [62]	To validate the hs-cTnT assay	2010	US	616	44 ± 13.8	309 (50.2)	307 (49.8)	14.5	10	Reference population selection based only on medical records

Saenger et al. [75]	To evaluate the analytical performance of the hs-cTnT assay in a multicenter, international trial	2011	US, Europe	533	37	268 (50.3)	265 (49.7)	15.5	9	Reference population selection based only on medical records

				1600 (whole cohort)	61 ± 14	872 (54.6)	728 (45.4)	21.8	16.3	Reference population selection based on medical history, biomarkers and cardiac imaging; population stratified by age; Various subpopulations included: high heterogeneity and reference population unable to achieve the recommended statistical power to determine the percentile for each subgroup
Franzini et al. [76]	To determine the upper reference limit for cTnT in Italian apparently healthy subjects	2015	Italy	553	<20	270 (48.8)	283 (51.2)	10.9	6.8
				872	20-64	503 (57.7)	369 (42.3)	23.2	10.2
				175	>65	99 (56.6)	76 (43.4)	36.8	28.6

Mingels et al. [77]	To study the improvements made by new hs-cTn assays in detecting exercise-induced cTn release	2009	US	479	51	264 (55.1)	215 (44.9)	16	8	Reference population selection based only on medical records

				1540 (whole cohort)	57 ± 8	733 (47.6)	807 (52.4)	16	12	Reference population selection based on: medical history and biomarkers; population stratified by age
Kimenai et al. [78]	To assess sex-specific and age-specific percentile upper reference limits of hs-cTnT and hs-cTnI in a single reference cohort	2016	Netherlands	283	40-49	120 (42.4)	163 (57.6)	16	12
				946	50-64	443 (46.8)	503 (53.2)	14	12
				311	65-75	170 (54.7)	141 (45.3)	28	27

Koerbin et al. [79]	To evaluate the analytical characteristics of the hs-cTnT assay	2010	Australia	111	25-74	62 (55.9)	49 (44.1)	12.9	11	Reference population selection based on medical history, biomarkers and cardiac imaging

				DHS: 1978	43.2 ± 9.6	873 (44.1)	1105 (55.9)	17	11	Reference population selection based on: progressive cohorts restriction based on clinical history, imaging and/or laboratory tests
Gore et al. [44]	To determine the percentile values in three large community-based subcohorts, restricted by healtiness criteria	2014	US	ARIC: 7575	61 ± 9	2972 (39.2)	4603 (60.8)	26	15
				CHS: 1374	72 ± 6	489 (35.6)	885 (64.4)	34	24

Mueller et al. [80]	To assess percentile in a blood donors population	2016	Austria	402	35	259 (64.4)	143 (35.6)	13.9	11.3	Reference population selection based on: no overt cardiovascular disease, eGFR>90 ml/min

Ungerer et al. [81]	Determine and compare percentile cut-offs of 3 cTn assays in a cohort of blood donors	2016	Australia	2004	Male: 43.7	1299 (64.8)	705 (35.2)	31.3 [90% CI: 25.0-57.5]	20.2 [90% CI: 9.9-51.7]	Reference population selection based on: health questionnaire
Ungerer et al. [81]		2016	Australia	2004	Female: 33.2	1299 (64.8)	705 (35.2)	31.3 [90% CI: 25.0-57.5]	20.2 [90% CI: 9.9-51.7]

Yang et al. [95]	Establish percentile in a healthy Chinese population	2016	China	1725	Male: 54 ± 20	818 (47.4)	907 (52.6)	Several according to age	Several according to age	Reference population selection based on clinical history, physical examination, lab tests
Yang et al. [95]	Establish percentile in a healthy Chinese population	2016	China	1725	Female: 54 ± 19	818 (47.4)	907 (52.6)	Several according to age	Several according to age

Monneret et al. [107]	Establish age and sex specific percentile in patients without CKD	2018	France	2707	Male: 62	1548 (57.2)	1159 (42.8)	Several according to age	Several according to age	Reference population selection based on age partitioning and outliers removal. Cut-off obtained with an analytical imprecision-based approach
Monneret et al. [107]		2018	France	2707	Female: 63	1548 (57.2)	1159 (42.8)	Several according to age	Several according to age

Welsh et al. [108]	Evaluating the influence of several variables, including sex, on the percentile levels of hs-cTnT and hs-cTnI	2018	Scotland	19501	35-65	8126 (41.7)	11375 (58.3)	Several according to age	Several according to age	Reference population selection based on general population; health questionnaire; lab tests