Next Article in Journal
Drug-Disease Association Prediction Using Heterogeneous Networks for Computational Drug Repositioning
Next Article in Special Issue
Biomolecules and Cardiovascular Diseases in Women
Previous Article in Journal
Editorial of Special Issue “Hyaluronic Acid in Human Medicine”
Previous Article in Special Issue
Environmental Contaminants Acting as Endocrine Disruptors Modulate Atherogenic Processes: New Risk Factors for Cardiovascular Diseases in Women?
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Biomolecules
Volume 12
Issue 10
10.3390/biom12101496
biomolecules-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Prognostic Value of High-Sensitivity Cardiac Troponin in Women

by
Giandomenico Bisaccia
1,
Fabrizio Ricci
1,2,*,
Mohammed Y. Khanji
3,4,5,
Giulia Gaggi
6,7,
Andrea Di Credico
6,7,
Sabina Gallina
1,
Angela Di Baldassarre
6,7 and
Barbara Ghinassi
6,7
1
MIUR Department of Excellence, Department of Neuroscience, Imaging and Clinical Sciences, University “G. d’Annunzio” of Chieti-Pescara, Via Luigi Polacchi, 66100 Chieti, Italy
2
Department of Clinical Sciences, Lund University, E-205 02 Malmö, Sweden
3
Newham University Hospital, Barts Health NHS Trust, Glen Road, Plaistow, London E13 8SL, UK
4
Barts Heart Centre, Barts Health NHS Trust, West Smithfield, London EC1A 7BE, UK
5
NIHR Barts Biomedical Research Centre, William Harvey Research Institute, Queen Mary University, London EC1A 7BE, UK
6
Reprogramming and Cell Differentiation Lab, Center for Advanced Studies and Technology (CAST), 66100 Chieti, Italy
7
Department of Medicine and Aging Sciences, University “G. d’Annunzio” of Chieti-Pescara, 66100 Chieti, Italy
*
Author to whom correspondence should be addressed.
Biomolecules 2022, 12(10), 1496; https://doi.org/10.3390/biom12101496
Submission received: 22 September 2022 / Revised: 13 October 2022 / Accepted: 14 October 2022 / Published: 17 October 2022
(This article belongs to the Special Issue Biomolecules and Cardiovascular Disease in Women)
Browse Figure
Review Reports Versions Notes

Abstract

:
High-sensitivity cardiac troponin assays have become the gold standard for diagnosing acute and chronic myocardial injury. The detection of troponin levels beyond the 99th percentile is included in the fourth universal definition of myocardial infarction, specifically recommending the use of sex-specific thresholds. Measurable concentrations below the proposed diagnostic thresholds have been shown to inform prognosis in different categories of inpatients and outpatients. However, clinical investigations from the last twenty years have yielded conflicting results regarding the incremental value of using different cut-offs for men and women. While advocates of a sex-specific approach claim it may help reduce gender bias in cardiovascular medicine, particularly in acute coronary syndromes, other groups question the alleged incremental diagnostic and prognostic value of sex-specific thresholds, ultimately asserting that less is more. In the present review, we aimed to synthesize our current understanding of sex-based differences in cardiac troponin levels and to reappraise the available evidence with regard to (i) the prognostic significance of sex-specific diagnostic thresholds of high-sensitivity cardiac troponin assays compared to common cut-offs in both men and women undergoing cardiovascular disease risk assessment, and (ii) the clinical utility of high-sensitivity cardiac troponin assays for cardiovascular disease prevention in women.

Graphical Abstract

1. Introduction

Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide, accounting for an estimated 18.6 million deaths in 2019 [1]. Preventative strategies are recommended by international guidelines to reduce the burden of CVD in the general population, along with its social, clinical, and financial costs [2]. So far, most of the scientific evidence in the cardiovascular literature has been developed with an underrepresentation of women, in both experimental and clinical contexts, despite growing knowledge on significant sex-based biological differences in the cardiovascular system [3,4,5,6]. The use of clinically meaningful biomarkers may help us to reduce the gap between men and women in the field of cardiovascular medicine and research [7]. Cardiac biomarkers are objectively measured features of physiological and disease-related processes with a plethora of possible applications, ranging from disease diagnosis to staging, prognosis, and the prediction of response to interventions [8,9]. Among all proposed cardiac biomarkers, cardiac troponins and natriuretic peptides have emerged as some of the most powerful and cost-effective clinical tools to diagnose and risk-stratify patients with suspected CVD [10,11,12]. In 2018, the European Society of Cardiology, American College of Cardiology, American Heart Association, and World Heart Foundation issued the fourth universal definition of myocardial infarction (MI), defining MI as a rise and/or fall in cardiac troponin with at least one value above the 99th percentile upper reference limit (URL) [13]. Although its main clinical use lies in the detection of patients with acute coronary syndromes, in recent years, the widespread clinical availability of high-sensitivity cardiac troponin testing and the subsequent detection of low-grade troponin elevation in patients without acute coronary syndromes [14] have determined an increasing interest in deploying cardiac troponins as potential prognostic markers in the general population. The more widespread use of high-sensitivity assays in the general population has opened the door to the detection of measurable troponin concentrations below the 99th percentile, which have been shown to predict all-cause mortality [15] and major cardiovascular events [14,16]. The use of high-sensitivity cardiac troponin assays was recently recommended for CV risk prognostication in the general population [17,18]. The possible mechanisms underlying the observed associations have been previously investigated [19,20,21]. The presence of detectable troponin levels has been linked to subclinical myocardial injury, and higher troponin concentrations have been associated with a higher prevalence of underlying coronary artery disease and left ventricular hypertrophy. However, the potential role of cardiac troponin assays for cardiovascular disease prevention in the general population is not fully understood. Further knowledge in this field is needed, particularly for CVD prevention in women, who are likely to face significant gender bias in cardiac testing [22,23].

2. Cardiac Troponins: A Translational Overview

The cardiac troponin complex is part of the cardiomyocyte contractile apparatus. It comprises three proteins, cTnI, cTnT, and cTnC, enabling the regulation of cardiac excitation–contraction coupling [24]. The release of cardiac troponins from the cardiomyocyte may occur due to different pathophysiological processes [25]. Established causes of troponin secretion include inflammation, necrosis, apoptosis, exocytosis, and physiological myocyte turnover. Since troponin C in the cardiomyocyte has an identical structure to its skeletal muscle counterpart, the elevation of the serum levels of this protein is not specific to cardiac disease. As such, myocardial injury is ascertained if detectable cardiac troponin concentrations are found above the 99th percentile of the upper reference limit (URL) [13]. An acute cardiac event is to be suspected when cardiac troponin levels exhibit a rise-or-fall pattern. In a clinical scenario suggestive of overt ischemia (e.g., typical ischemic chest pain and ischemic electrocardiographic changes), myocardial injury may be adjudicated as acute myocardial infarction; instead, in the absence of clinical signs and symptoms of ischemia, troponin elevation could be due to either chronic release or acute, nonischemic myocardial injury [26]. Noncommunicable diseases associated with continuous troponin release include chronic heart failure, cardiomyopathies, hypertensive heart disease, and chronic kidney disease. Acute nonischemic injury is instead found in patients with myocarditis, acute heart failure, and systemic diseases, including sepsis and pulmonary embolism.
Although the diagnostic threshold for myocardial injury lies at the 99th percentile URL, detectable concentrations below the proposed cut-off have been shown to confer prognostic information in the general population [15]. A meta-analysis of 28 studies involving 154,052 participants without baseline cardiovascular disease (CVD) found that individuals in the top tercile of the normal cardiac troponin distribution have a significantly increased risk of future CVD events [14]; more recently, a meta-analysis of 24 studies comprising 203,202 community-dwelling individuals demonstrated a significant association between elevated cardiac troponin concentrations and cardiovascular events, heart failure hospitalization, and cardiovascular as well as all-cause death [27]. It has been further suggested that the individual’s temporal trajectory of cardiac troponin levels may be additionally informative of future patient outcomes [28]. Cardiac troponin levels were shown to reflect the left ventricular mass index [19,20], as well as the presence of significant coronary artery disease [20]. Significantly, a cohort study enrolling 880 women tested with a high-sensitivity assay found cardiac troponin I to be higher in patients with pregnancy-induced hypertension or preeclampsia [29]. There is evidence to suggest that such increased levels may normalize over time in women with controlled hypertension [30]. Moreover, cardiac troponin levels were shown to provide accurate prognostic information in community-dwelling individuals with diabetes [31] and chronic heart failure [32,33], as well as in patients with left ventricular hypertrophy [34] and valvular heart disease [35]. Interestingly, a genome-wide association study on Scottish outpatients found that genetic causes of increased serum levels differ between cardiac troponin I and T, with cTn-I being a more specific marker of cardiovascular disease [36].

3. Why Is Troponin an (Almost) Ideal Biomarker?

The measurement of cardiac troponin concentrations offers several unique advantages over other traditional cardiac biomarkers. Cardiac troponins are tissue-specific, are highly stable in vitro, and can be obtained from both plasma and serum; moreover, cardiac troponin assays are inexpensive, fast, and highly reliable and have been shown to outperform historical gold-standard tests in the diagnosis of acute myocardial infarction [37,38,39]. From a technical standpoint, high-sensitivity cardiac troponins have a very low limit of detection and offer the benefit of very little biological variability [18]. Moreover, these assays have a high degree of individuality [40], allowing for serial results to correctly reflect subtle changes in troponin secretion.

4. The Case for Sex-Specific Troponin Cut-Offs

Sex-based differences in the cardiovascular system have long been established [41,42]. Normal reference values of cardiac dimensions are greater in men than in women across all age groups, both at echocardiography and on cardiovascular magnetic resonance imaging and despite adjustment for body surface area [43,44]. Epidemiological studies also show sex-related differences in CVD prevalence and features [4]. Women with acute coronary syndromes still represent a clinical challenge: they are less frequently diagnosed, often present with atypical symptoms, have a greater burden of non-obstructive disease, and suffer higher morbidity and mortality compared with men. Structural flaws in the management of women with ischemic heart disease have been highlighted [4,23]. In this context, the use of sex-specific 99th percentile URLs for high-sensitivity troponin assays has been proposed to reduce treatment disparities [45,46] and was recommended in the fourth universal definition of MI [13], although uncertainty persists regarding the additional value of a sex-specific approach [47].
The notion that sex-based differences may exist in the mechanisms of release, diagnostic yield, and prognostic significance of cardiac troponins is not novel, and there has been an ongoing debate in the medical community regarding the most appropriate approach to the clinical use of these biomarkers. Different cohorts of apparently healthy individuals have demonstrated that men have higher levels than women [7,48,49,50]. This finding has been related to genotypic and phenotypic differences between sexes [51]. Men have higher indexed ventricular mass, cardiomyocyte volume, and protein content and may be exposed to higher shear stress due to significantly higher blood pressure levels. Cardiac inflammatory, pro-fibrotic, and apoptotic pathways show sexual dimorphisms as well, partly explained by hormonal modulation [52,53]. However, initial efforts at characterizing sex-specific cardiac troponin levels in unstable coronary patients did not show significant differences between sexes. A Swedish study published in the year 2000 consisting of 1455 such patients (36% females) demonstrated the equivalent prognostic performance of cardiac troponin concentrations in men and women with the use of contemporary standard-sensitivity assays [54]. However, sexual dimorphism in cardiac troponin levels was subsequently reported, with higher cardiac troponin I in males demonstrated in patients with acute myocardial injury [55]. Higher 99th percentile values for cardiac troponin I were also demonstrated in men in a cohort of apparently healthy adults [56], a finding later confirmed [16,57]. A higher troponin T concentration was also observed in community-dwelling adult males [19], as well as in the elderly [58]. With regard to prognostic significance, a cardiac troponin I cut-off of >7.6 ng/mL was specifically identified for the prediction of major adverse cardiovascular events in postmenopausal women undergoing cardiac surgery [59], and the leveraging of sex-specific cut-offs was advocated [60]. At the same time, the diagnostic accuracy of baseline troponin levels to detect myocardial infarction was found to be independent of sex in patients from the CHECKMATE cohort [61], again calling into question the real-world necessity for the use of a sex-based approach [62]. However, the studies outlined so far have based their investigations on standard sensitivity cardiac troponin assays; the advent of high-sensitivity assays eventually shuffled the cards [7,15,48,63,64]. With the new assays, the prevalence of detectable cardiac troponin levels increased from <5% (standard assays) to >80% (high-sensitivity assays) in healthy individuals.
Male sex was confirmed as a predictor of high-sensitivity cardiac troponin I and T concentrations in the elderly [65,66], and further evidence was provided that the use of sex-specific cut-offs was superior to a sex-neutral cut-off in patients suspected of having acute coronary syndromes [67]. Moreover, high-sensitivity cardiac troponin I levels were reported to better predict all-cause mortality among females presenting to the emergency department [68] and to better prognosticate in women with non-ST-elevation acute coronary syndromes [48], contradicting previous evidence obtained with use of standard-sensitivity assays [54] and with fourth-generation assays [69]. The results of the UTROPIA study confirmed the higher prognostic yield of sex-specific cut-offs to predict adverse cardiovascular events in emergency department patients [70]. Further, a study powered to identify sex- and age-specific cut-offs for cardiac troponin T with the use of a high-sensitivity assay demonstrated the poor diagnostic yield of a uniform 14 ng/mL cut-off in both sexes and across multiple age groups [71]. Despite growing evidence that sex-specific cut-offs add to the prognostication of women in the general population, the incremental benefit of a sex-specific approach, with the use of personalized thresholds for men and women, over the use of a single multivariable model adjusted for sex is uncertain, since no head-to-head comparison studies for these two approaches are available to date.

5. Cardiac Troponins and Prognosis of Community-Dwelling Women

To date, the prognostic yield of high-sensitivity cardiac troponins for the cardiovascular risk stratification of women in the general population has been investigated in several studies (Table 1).
In the Women’s Health Study, serum levels of cardiac troponin T were measured with the use of a high-sensitivity assay in two separate cohorts, diabetic and non-diabetic female health professionals, with a total sample size of 1064 females who were followed up for 12 years [72]. The authors found that the prevalence of detectable troponin T was significantly higher in women with diabetes (45% versus 30%), and detectable levels were associated with cardiovascular outcomes in diabetic women only, suggesting subclinical myocardial injury in these patients. In 2014, the results of the FINRISK study on 7899 participants without baseline CVD were published [64]. In this cohort, the use of high- and super-sensitivity cardiac troponin I assays was associated with significantly increased predictive ability for cardiovascular events, including incident heart failure and myocardial infarction, even after adjustment for traditional risk factors, C-reactive protein, and N-terminal pro-brain natriuretic peptide. However, no sex differences were demonstrated.
A large study of 15,340 Europeans (51% females) tested with a high-sensitivity cardiac troponin I assay for the prediction of future cardiovascular events found a lower threshold for high risk in women, namely, 4.7 pg/mL, as compared with 7.0 pg/mL for men [16]. In this study, with a very long follow-up period of 20 years, the authors found that the application of a sex-specific approach resulted in substantial risk reclassification, with the additional identification of individuals at high risk of future events. More recently, a Scottish study reported on the prognostic significance of the serum levels of cardiac troponins I and T as assessed by high-sensitivity troponin assays in 19,501 adult individuals (58% women) followed up for a median of 7.8 years. The cohort had a low prevalence of CVD at baseline (3.2% in women and 6.3% in men). They found that cardiac troponin levels were stronger predictors of future cardiovascular events in women [73].
A stronger association between cardiac troponin T levels and the risk of incident heart failure was reported in women from the Atherosclerosis Risk in Communities (ARIC) study [32]. Subsequently, it was independently demonstrated, in patients from the same cohort, that the addition of time trajectories of cardiac troponin T to an adjusted model comprising traditional risk factors, N-terminal pro–brain natriuretic peptide, and baseline cardiac troponin T provided additional information on the future risk of incident heart failure, as well as on incident coronary disease and death [28]. In this study, the use of sex-specific cut-offs did not further improve the model performance. In 2019, more results from the ARIC were published for individuals without baseline CVD who had high-sensitivity cardiac troponin I measured [74]. This study confirmed the stronger association of cardiac troponin levels with cardiovascular outcomes in women, including for cardiac troponin I, and showed that cardiac troponins were complementary to one another in the prediction of future events.
Table
Table 1. Main studies on the sex-specific prognostic significance of high-sensitivity cardiac troponin assays in outpatient populations.
Table 1. Main studies on the sex-specific prognostic significance of high-sensitivity cardiac troponin assays in outpatient populations.
YearStudyTarget PopulationCountrySample Size (n)Female SexCardiac Troponin Assay (s)Main OutcomeFollow-UpMain Findings
2021Generation Scotland [73]General populationScotland19,50158%Roche Elecsys hs-TnT
Abbott Architect STAT hs-TnI		CV events7.8 yearsHR of 9.7 in women (compared to 5.6 in men) when a threshold of 10 ng/L was applied for hs-TnI
2019ARIC [74]Participants free of CVD at baselineUnited States812158%Abbott Architect STAT hs-TnICV events15 yearsStronger association of TnI and CHD in women (HR of 1.54 in women versus 1.29 in men)
2017Busselton Health Study [75]General populationAustralia393957%Abbott Architect STAT hs-TnIAF hospitalization20 yearsSimilar prognostic value between sexes (aHR of 1.22 in women and 1.17 in men)
2016ARIC [28]General populationUnited States883859%Roche Elecsys hs-TnTCHD, HF, all-cause mortality14 yearsClinical equipoise between common and sex-specific approaches
2016AGES-Reykjavik
[76]		Community-dwelling elderlyIceland576458%Abbott Architect STAT hs-TnICV events, all-cause mortality8.9 yearsSimilar prognostic value between sexes (aHR of 1.27 in women and 1.23 in men for all-cause death)
2015ActiFE Ulm [77]Community-dwelling elderlyGermany142243%Roche Elecsys hs-TnT
Abbott Architect STAT hs-TnI		All-cause mortality4 yearsHigher prognostic value in women (aHR of 3.33 in women and 1.92 in men for hs-TnI)
2015HUNT [78]General populationFinland971054%Abbott Architect STAT hs-TnICV mortality6.4 yearsHigher prognostic value in women (aHR of 1.44 in women versus 1.10 in men)
2015HUNT [79]General populationFinland911455%Abbott Architect STAT hs-TnIIncident HF, incident MI (composite)13.9 yearsHigher prognostic value in women (aHR of 1.50 in women versus 1.27 in men)
2014MORGAM [16]General populationScotland15,34051%Abbott Architect STAT hs-TnICV events20 yearsLower threshold for high risk in women (aHR of 1.35 in women versus 1.26 in men; threshold of 4.7 ng/mL and 7.0 ng/mL in women and men, respectively)
2014FINRISK [64]Participants free of CVD at baselineFinland789950%Abbott Architect STAT hs-TnI
Abbott Architect STAT cs-TnI
Singulex Erenna Cardiac ss-TnI		CV events, incident HF, incident MI, all-cause death14 yearsSimilar prognostic value between sexes, except for MI (aHR of 1.19 in women versus 1.17 in men), HF (aHR of 1.12 in women as compared with 1.24 in men), and all-cause death (aHR of 1.11 in women versus 1.03 in men)
2013ARIC [32]General populationUnited States986866%Roche Elecsys hs-TnTIncident HF10.4 yearsHigher prognostic value in women (HR of 5.3 in women and 4.3 in men with hs-TnT values > 25 ng/L)
2011Women’s Health Study [72]Women free of CVD at baselineUnited States1076100%Roche Elecsys hs-TnTCV events, CV mortality12.3 yearsPrognostic significance in diabetic, but not non-diabetic, women
AF, atrial fibrillation; aHR, adjusted hazard ratio; CHD, coronary heart disease; CV, cardiovascular; CVD, cardiovascular disease; HF, heart failure; HR, hazard ratio; hs-TnI, high-sensitivity cardiac troponin I; hs-TnT, high-sensitivity cardiac troponin T.
In the HUNT study, a cohort of 9712 Norwegian outpatients was followed up for a median of 6 years, and their high-sensitivity cardiac troponin I levels were obtained at baseline [78]. In the cohort, men had a higher crude rate of cardiovascular death, but this effect was no longer present when adjusting for cardiac troponin I concentrations. An overall stronger association between cardiac troponin I levels and cardiovascular death was reported for women. A subsequent analysis targeted at the prediction of myocardial infarction and incident heart failure was published for this cohort study, where the authors showed that cardiac troponin I was more strongly associated with these outcomes in women [79]. Cardiac troponin levels were also found to better predict all-cause mortality in asymptomatic elderly women as compared with age-matched men [77], although this finding was not confirmed in the AGES-Reykjavik cohort [76]. Finally, cardiac troponin I was also found to predict atrial-fibrillation-related hospitalizations, but no effect of sex was found in a cohort of Australian community-dwellers [75].

6. Future Perspectives

Several studies published in the last decade have shown significant sex differences in serum levels of cardiac troponins as assessed with high-sensitivity assays, and the detection of serum levels well below the 99th percentile URL has demonstrated excellent prognostic yield in the general population. However, most cardiovascular risk prediction models specifically developed for women do not include cardiac troponins or other surrogates of myocardial damage [80], and cardiac troponin testing is not implemented in daily practice. Another fascinating aspect is the use of cardiac troponins as therapeutic targets. Despite evidence that troponin level lowering is associated with an overall reduction in CV risk in men [81], and that it accurately predicts the therapeutic response in high-risk populations [82], there is currently a lack of such evidence in women. Future research should fill the current knowledge gaps by investigating the molecular pathways involved in the release of cardiac troponins in healthy and diseased cardiomyocytes in basic and translational studies and fully incorporate biological sex fingerprints in clinical studies.

7. Conclusions

In this review, we have synthesized data on the role of cardiac troponins for cardiovascular risk stratification in women, with a focus on community-dwelling populations. Women are still underrepresented in cardiovascular research and underdiagnosed in clinical practice, although progress has been made in the last decade to reduce implicit bias in cardiovascular testing. Evidence is accumulating that high-sensitivity cardiac troponin assays can help leverage gender differences in cardiovascular disease due to the high prognostic yield in ambulatory populations, particularly in women. Cardiovascular practitioners should be encouraged to leverage a sex-based approach to the diagnosis, prognostication, and treatment of cardiovascular disease. Whether this approach should encompass the use of cardiac troponins in the general population is still debated.

Author Contributions

Conceptualization, F.R., S.G., A.D.B. and B.G.; writing—original draft preparation, G.B., F.R., M.Y.K., G.G. and A.D.C.; writing—review and editing, S.G., A.D.B. and B.G. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by PRIN Italian Ministry of University and Research (MUR), grant number PRIN 2017ATZ2YK_003.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Global Burden of Disease Collaborative Network. Global Burden of Disease Study 2019 (GBD 2019) Reference Life Table; Institute for Health Metrics and Evaluation (IHME): Seattle, WA, USA, 2021. [Google Scholar]
  2. Bucciarelli, V.; Bianco, F.; Mucedola, F.; Di Blasio, A.; Izzicupo, P.; Tuosto, D.; Ghinassi, B.; Bucci, I.; Napolitano, G.; Di Baldassarre, A.; et al. Effect of Adherence to Physical Exercise on Cardiometabolic Profile in Postmenopausal Women. Int. J. Environ. Res. Public Health 2021, 18, 656. [Google Scholar] [CrossRef]
  3. Maffei, S.; Guiducci, L.; Cugusi, L.; Cadeddu, C.; Deidda, M.; Gallina, S.; Sciomer, S.; Gastaldelli, A.; Kaski, J.-C. Women-Specific Predictors of Cardiovascular Disease Risk—New Paradigms. Int. J. Cardiol. 2019, 286, 190–197. [Google Scholar] [CrossRef] [PubMed]
  4. Aggarwal, N.R.; Patel, H.N.; Mehta, L.S.; Sanghani, R.M.; Lundberg, G.P.; Lewis, S.J.; Mendelson, M.A.; Wood, M.J.; Volgman, A.S.; Mieres, J.H. Sex Differences in Ischemic Heart Disease: Advances, Obstacles, and Next Steps. Circ. Cardiovasc. Qual. Outcomes 2018, 11, e004437. [Google Scholar] [CrossRef] [PubMed]
  5. Izzicupo, P.; Ghinassi, B.; D’Amico, M.A.; Di Blasio, A.; Gesi, M.; Napolitano, G.; Gallina, S.; Di Baldassarre, A. Effects of ACE I/D Polymorphism and Aerobic Training on the Immune–Endocrine Network and Cardiovascular Parameters of Postmenopausal Women. J. Clin. Endocrinol. Metab. 2013, 98, 4187–4194. [Google Scholar] [CrossRef] [Green Version]
  6. Izzicupo, P.; D’Amico, M.A.; Di Blasio, A.; Napolitano, G.; Nakamura, F.Y.; Di Baldassarre, A.; Ghinassi, B. Aerobic Training Improves Angiogenic Potential Independently of Vascular Endothelial Growth Factor Modifications in Postmenopausal Women. Front. Endocrinol. 2017, 8, 363. [Google Scholar] [CrossRef] [Green Version]
  7. Apple, F.S.; Jaffe, A.S. Men Are Different than Women: It’s True for Cardiac Troponin Too. Clin. Biochem. 2014, 47, 867–868. [Google Scholar] [CrossRef] [PubMed]
  8. Biomarkers Definitions Working Group. Biomarkers and Surrogate Endpoints: Preferred Definitions and Conceptual Framework. Clin. Pharmacol. Ther. 2001, 69, 89–95. [Google Scholar] [CrossRef]
  9. Ricci, F.; De Caterina, R. Isolated Creatine Kinase-MB Rise with Normal Cardiac Troponins: A Strange Occurrence with Difficult Interpretation. J. Cardiovasc. Med. 2011, 12, 736–740. [Google Scholar] [CrossRef] [PubMed]
  10. Omran, F.; Kyrou, I.; Osman, F.; Lim, V.G.; Randeva, H.S.; Chatha, K. Cardiovascular Biomarkers: Lessons of the Past and Prospects for the Future. Int. J. Mol. Sci. 2022, 23, 5680. [Google Scholar] [CrossRef]
  11. Ricci, F.; Neumann, J.T.; Rübsamen, N.; Sörensen, N.A.; Ojeda, F.; Cataldo, I.; Zeller, T.; Schäfer, S.; Hartikainen, T.S.; Golato, M.; et al. High-Sensitivity Troponin I with or without Ultra-Sensitive Copeptin for the Instant Rule-out of Acute Myocardial Infarction. Front. Cardiovasc. Med. 2022, 9, 895421. [Google Scholar] [CrossRef]
  12. Ricci, F.; Di Scala, R.; Massacesi, C.; Di Nicola, M.; Cremonese, G.; De Pace, D.; Rossi, S.; Griffo, I.; Cataldo, I.; Martinotti, S.; et al. Ultra-Sensitive Copeptin and Cardiac Troponin in Diagnosing Non-ST-Segment Elevation Acute Coronary Syndromes—The COPACS Study. Am. J. Med. 2016, 129, 105–114. [Google Scholar] [CrossRef] [Green Version]
  13. Thygesen, K.; Alpert, J.S.; Jaffe, A.S.; Chaitman, B.R.; Bax, J.J.; Morrow, D.A.; White, H.D.; Executive Group on behalf of the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). Eur. Heart J. 2019, 40, 237–269. [Google Scholar] [CrossRef] [Green Version]
  14. Willeit, P.; Welsh, P.; Evans, J.D.W.; Tschiderer, L.; Boachie, C.; Jukema, J.W.; Ford, I.; Trompet, S.; Stott, D.J.; Kearney, P.M.; et al. High-Sensitivity Cardiac Troponin Concentration and Risk of First-Ever Cardiovascular Outcomes in 154,052 Participants. J. Am. Coll. Cardiol. 2017, 70, 558–568. [Google Scholar] [CrossRef]
  15. de Lemos, J.A.; Drazner, M.H.; Omland, T.; Ayers, C.R.; Khera, A.; Rohatgi, A.; Hashim, I.; Berry, J.D.; Das, S.R.; Morrow, D.A.; et al. Association of Troponin T Detected With a Highly Sensitive Assay and Cardiac Structure and Mortality Risk in the General Population. JAMA 2010, 304, 2503–2512. [Google Scholar] [CrossRef] [PubMed]
  16. Zeller, T.; Tunstall-Pedoe, H.; Saarela, O.; Ojeda, F.; Schnabel, R.B.; Tuovinen, T.; Woodward, M.; Struthers, A.; Hughes, M.; Kee, F.; et al. High Population Prevalence of Cardiac Troponin I Measured by a High-Sensitivity Assay and Cardiovascular Risk Estimation: The MORGAM Biomarker Project Scottish Cohort. Eur. Heart J. 2014, 35, 271–281. [Google Scholar] [CrossRef] [Green Version]
  17. Farmakis, D.; Mueller, C.; Apple, F.S. High-Sensitivity Cardiac Troponin Assays for Cardiovascular Risk Stratification in the General Population. Eur. Heart J. 2020, 41, 4050–4056. [Google Scholar] [CrossRef] [PubMed]
  18. Clerico, A.; Zaninotto, M.; Passino, C.; Aspromonte, N.; Piepoli, M.F.; Migliardi, M.; Perrone, M.; Fortunato, A.; Padoan, A.; Testa, A.; et al. Evidence on Clinical Relevance of Cardiovascular Risk Evaluation in the General Population Using Cardio-Specific Biomarkers. Clin. Chem. Lab. Med. CCLM 2021, 59, 79–90. [Google Scholar] [CrossRef]
  19. Wallace, T.W.; Abdullah, S.M.; Drazner, M.H.; Das, S.R.; Khera, A.; McGuire, D.K.; Wians, F.; Sabatine, M.S.; Morrow, D.A.; de Lemos, J.A. Prevalence and Determinants of Troponin T Elevation in the General Population. Circulation 2006, 113, 1958–1965. [Google Scholar] [CrossRef] [Green Version]
  20. Rahman, F.; Zhang, Z.; Zhao, D.; Budoff, M.J.; Palella, F.J.; Witt, M.D.; Evans, R.W.; Jacobson, L.P.; Korley, F.K.; Guallar, E.; et al. Association of High-Sensitivity Troponin with Cardiac CT Angiography Evidence of Myocardial and Coronary Disease in a Primary Prevention Cohort of Men: Results from MACS. J. Appl. Lab. Med. 2019, 4, 355–369. [Google Scholar] [CrossRef] [PubMed]
  21. Martelli, F.; Ghinassi, B.; Lorenzini, R.; Vannucchi, A.M.; Rana, R.A.; Nishikawa, M.; Partamian, S.; Migliaccio, G.; Migliaccio, A.R. Thrombopoietin Inhibits Murine Mast Cell Differentiation. Stem Cells 2008, 26, 912–919. [Google Scholar] [CrossRef] [PubMed]
  22. Chang, A.M.; Mumma, B.; Sease, K.L.; Robey, J.L.; Shofer, F.S.; Hollander, J.E. Gender Bias in Cardiovascular Testing Persists after Adjustment for Presenting Characteristics and Cardiac Risk. Acad. Emerg. Med. 2007, 14, 599–605. [Google Scholar] [CrossRef] [PubMed]
  23. Daugherty, S.L.; Blair, I.V.; Havranek, E.P.; Furniss, A.; Dickinson, L.M.; Karimkhani, E.; Main, D.S.; Masoudi, F.A. Implicit Gender Bias and the Use of Cardiovascular Tests Among Cardiologists. J. Am. Heart Assoc. 2017, 6, e006872. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  24. Bers, D.M. Cardiac Excitation–Contraction Coupling. Nature 2002, 415, 198–205. [Google Scholar] [CrossRef] [PubMed]
  25. Raber, I.; McCarthy, C.P.; Januzzi, J.L. A Test in Context: Interpretation of High-Sensitivity Cardiac Troponin Assays in Different Clinical Settings. J. Am. Coll. Cardiol. 2021, 77, 1357–1367. [Google Scholar] [CrossRef]
  26. Sandoval, Y.; Januzzi, J.L.; Jaffe, A.S. Cardiac Troponin for Assessment of Myocardial Injury in COVID-19. J. Am. Coll. Cardiol. 2020, 76, 1244–1258. [Google Scholar] [CrossRef]
  27. Aimo, A.; Georgiopoulos, G.; Panichella, G.; Vergaro, G.; Passino, C.; Emdin, M.; Clerico, A. High-Sensitivity Troponins for Outcome Prediction in the General Population: A Systematic Review and Meta-Analysis. Eur. J. Intern. Med. 2022, 98, 61–68. [Google Scholar] [CrossRef] [PubMed]
  28. McEvoy, J.W.; Chen, Y.; Ndumele, C.E.; Solomon, S.D.; Nambi, V.; Ballantyne, C.M.; Blumenthal, R.S.; Coresh, J.; Selvin, E. Six-Year Change in High-Sensitivity Cardiac Troponin T and Risk of Subsequent Coronary Heart Disease, Heart Failure, and Death. JAMA Cardiol. 2016, 1, 519–528. [Google Scholar] [CrossRef] [Green Version]
  29. Ravichandran, J.; Woon, S.Y.; Quek, Y.S.; Lim, Y.C.; Noor, E.M.; Suresh, K.; Vigneswaran, R.; Vasile, V.; Shah, A.; Mills, N.L.; et al. High-Sensitivity Cardiac Troponin I Levels in Normal and Hypertensive Pregnancy. Am. J. Med. 2019, 132, 362–366. [Google Scholar] [CrossRef] [PubMed]
  30. Muijsers, H.E.C.; Westermann, D.; Birukov, A.; van der Heijden, O.W.H.; Drost, J.T.; Kräker, K.; Haase, N.; Müller, D.N.; Herse, F.; Maas, A.H.E.M.; et al. High-Sensitivity Cardiac Troponin I in Women with a History of Early-Onset Preeclampsia. J. Hypertens. 2020, 38, 1948–1954. [Google Scholar] [CrossRef] [PubMed]
  31. Whelton, S.P.; McEvoy, J.W.; Lazo, M.; Coresh, J.; Ballantyne, C.M.; Selvin, E. High-Sensitivity Cardiac Troponin T (Hs-CTnT) as a Predictor of Incident Diabetes in the Atherosclerosis Risk in Communities Study. Diabetes Care 2017, 40, 261–269. [Google Scholar] [CrossRef] [PubMed]
  32. Nambi, V.; Liu, X.; Chambless, L.E.; de Lemos, J.A.; Virani, S.S.; Agarwal, S.; Boerwinkle, E.; Hoogeveen, R.C.; Aguilar, D.; Astor, B.C.; et al. Troponin T and N-Terminal Pro–B-Type Natriuretic Peptide: A Biomarker Approach to Predict Heart Failure Risk—The Atherosclerosis Risk in Communities Study. Clin. Chem. 2013, 59, 1802–1810. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  33. Aimo, A.; Januzzi, J.L.; Vergaro, G.; Ripoli, A.; Latini, R.; Masson, S.; Magnoli, M.; Anand, I.S.; Cohn, J.N.; Tavazzi, L.; et al. Prognostic Value of High-Sensitivity Troponin T in Chronic Heart Failure: An Individual Patient Data Meta-Analysis. Circulation 2018, 137, 286–297. [Google Scholar] [CrossRef] [PubMed]
  34. Lewis, A.A.; Ayers, C.R.; Selvin, E.; Neeland, I.; Ballantyne, C.M.; Nambi, V.; Pandey, A.; Powell-Wiley, T.M.; Drazner, M.H.; Carnethon, M.R.; et al. Racial Differences in Malignant Left Ventricular Hypertrophy and Incidence of Heart Failure: A Multicohort Study. Circulation 2020, 141, 957–967. [Google Scholar] [CrossRef] [PubMed]
  35. Chin, C.W.L.; Shah, A.S.V.; McAllister, D.A.; Joanna Cowell, S.; Alam, S.; Langrish, J.P.; Strachan, F.E.; Hunter, A.L.; Maria Choy, A.; Lang, C.C.; et al. High-Sensitivity Troponin I Concentrations Are a Marker of an Advanced Hypertrophic Response and Adverse Outcomes in Patients with Aortic Stenosis. Eur. Heart J. 2014, 35, 2312–2321. [Google Scholar] [CrossRef] [PubMed]
  36. Welsh, P.; Preiss, D.; Hayward, C.; Shah, A.S.V.; McAllister, D.; Briggs, A.; Boachie, C.; McConnachie, A.; Padmanabhan, S.; Welsh, C.; et al. Cardiac Troponin T and Troponin I in the General Population: Comparing and Contrasting Their Genetic Determinants and Associations with Outcomes. Circulation 2019, 139, 2754–2764. [Google Scholar] [CrossRef]
  37. Keller, T.; Zeller, T.; Peetz, D.; Tzikas, S.; Roth, A.; Czyz, E.; Bickel, C.; Baldus, S.; Warnholtz, A.; Fröhlich, M.; et al. Sensitive Troponin I Assay in Early Diagnosis of Acute Myocardial Infarction. N. Engl. J. Med. 2009, 361, 868–877. [Google Scholar] [CrossRef] [Green Version]
  38. Saenger, A.K.; Jaffe, A.S. Requiem for a Heavyweight: The Demise of Creatine Kinase-MB. Circulation 2008, 118, 2200–2206. [Google Scholar] [CrossRef]
  39. Kitamura, M.; Hata, N.; Takayama, T.; Hirayama, A.; Ogawa, M.; Yamashina, A.; Mera, H.; Yoshino, H.; Nakamura, F.; Seino, Y. High-Sensitivity Cardiac Troponin T for Earlier Diagnosis of Acute Myocardial Infarction in Patients with Initially Negative Troponin T Test—Comparison between Cardiac Markers. J. Cardiol. 2013, 62, 336–342. [Google Scholar] [CrossRef] [Green Version]
  40. Diaz-Garzon, J.; Fernandez-Calle, P.; Sandberg, S.; Özcürümez, M.; Bartlett, W.A.; Coskun, A.; Carobene, A.; Perich, C.; Simon, M.; Marques, F.; et al. Biological Variation of Cardiac Troponins in Health and Disease: A Systematic Review and Meta-Analysis. Clin. Chem. 2021, 67, 256–264. [Google Scholar] [CrossRef]
  41. Salerni, S.; Di Francescomarino, S.; Cadeddu, C.; Acquistapace, F.; Maffei, S.; Gallina, S. The Different Role of Sex Hormones on Female Cardiovascular Physiology and Function: Not Only Oestrogens. Eur. J. Clin. Invest. 2015, 45, 634–645. [Google Scholar] [CrossRef]
  42. Bakir, S.; Oparil, S. Sexual Dimorphism in Cardiovascular Disease. In Molecular Cardiology in Clinical Practice; Sanders, M., Kostis, J.B., Eds.; Basic Science for the Cardiologist; Springer US: Boston, MA, USA, 1999; Volume 2, pp. 187–217. ISBN 978-0-7923-8602-5. [Google Scholar]
  43. Kou, S.; Caballero, L.; Dulgheru, R.; Voilliot, D.; De Sousa, C.; Kacharava, G.; Athanassopoulos, G.D.; Barone, D.; Baroni, M.; Cardim, N.; et al. Echocardiographic Reference Ranges for Normal Cardiac Chamber Size: Results from the NORRE Study. Eur. Heart J. Cardiovasc. Imaging 2014, 15, 680–690. [Google Scholar] [CrossRef] [Green Version]
  44. Kawel-Boehm, N.; Hetzel, S.J.; Ambale-Venkatesh, B.; Captur, G.; Francois, C.J.; Jerosch-Herold, M.; Salerno, M.; Teague, S.D.; Valsangiacomo-Buechel, E.; van der Geest, R.J.; et al. Correction to: Reference Ranges (“Normal Values”) for Cardiovascular Magnetic Resonance (CMR) in Adults and Children: 2020 Update. J. Cardiovasc. Magn. Reson. 2021, 23, 114. [Google Scholar] [CrossRef] [PubMed]
  45. Vigen, R.; de Lemos, J.A. Can High-Sensitivity Troponins Help to Level the Playing Field in Cardiovascular Disease Prevention between Women and Men? Clin. Chem. 2021, 67, 1301–1303. [Google Scholar] [CrossRef] [PubMed]
  46. Lobo, R.; De Michieli, L.; Jaffe, A.S. Sex-Specific 99th Percentile URLs for Cardiac Troponin Assays—Their Time Has Come. Clin. Chem. 2021, 67, 197–200. [Google Scholar] [CrossRef] [PubMed]
  47. Chang, A.M. Concerns about Using Sex-Specific Cutoffs for Cardiac Troponin Testing. Clin. Chem. 2021, 67, 201–203. [Google Scholar] [CrossRef]
  48. Eggers, K.M.; Venge, P.; Lindahl, B.; Lind, L. Cardiac Troponin I Levels Measured With a High-Sensitive Assay Increase Over Time and Are Strong Predictors of Mortality in an Elderly Population. J. Am. Coll. Cardiol. 2013, 61, 1906–1913. [Google Scholar] [CrossRef] [Green Version]
  49. Everett, B.M.; Zeller, T.; Glynn, R.J.; Ridker, P.M.; Blankenberg, S. High-Sensitivity Cardiac Troponin I and B-Type Natriuretic Peptide as Predictors of Vascular Events in Primary Prevention: Impact of Statin Therapy. Circulation 2015, 131, 1851–1860. [Google Scholar] [CrossRef]
  50. McKie, P.M.; AbouEzzeddine, O.F.; Scott, C.G.; Mehta, R.; Rodeheffer, R.J.; Redfield, M.M.; Burnett, J.C.; Jaffe, A.S. High-Sensitivity Troponin I and Amino-Terminal Pro–B-Type Natriuretic Peptide Predict Heart Failure and Mortality in the General Population. Clin. Chem. 2014, 60, 1225–1233. [Google Scholar] [CrossRef] [Green Version]
  51. Lau, E.S.; Binek, A.; Parker, S.J.; Shah, S.H.; Zanni, M.V.; Van Eyk, J.E.; Ho, J.E. Sexual Dimorphism in Cardiovascular Biomarkers: Clinical and Research Implications. Circ. Res. 2022, 130, 578–592. [Google Scholar] [CrossRef]
  52. Di Blasio, A.; Izzicupo, P.; Di Baldassarre, A.; Gallina, S.; Bucci, I.; Giuliani, C.; Di Santo, S.; Di Iorio, A.; Ripari, P.; Napolitano, G. Walking Training and Cortisol to DHEA-S Ratio in Postmenopause: An Intervention Study. Women Health 2018, 58, 387–402. [Google Scholar] [CrossRef]
  53. Izzicupo, P.; Di Blasio, A.; Di Credico, A.; Gaggi, G.; Vamvakis, A.; Napolitano, G.; Ricci, F.; Gallina, S.; Ghinassi, B.; Di Baldassarre, A. The Length and Number of Sedentary Bouts Predict Fibrinogen Levels in Postmenopausal Women. Int. J. Environ. Res. Public. Health 2020, 17, 3051. [Google Scholar] [CrossRef]
  54. Säfström, K.; Swahn, E.; Lindahl, B. Risk Stratification in Unstable Coronary Artery Disease. J. Am. Coll. Cardiol. 2000, 35, 1791–1800. [Google Scholar] [CrossRef] [Green Version]
  55. Schwarzenberger, J.C.; Sun, L.S.; Pesce, M.A.; Heyer, E.J.; Delphin, E.; Almeida, G.M.; Wood, M. Sex-Based Differences in Serum Cardiac Troponin I, a Specific Marker for Myocardial Injury, after Cardiac Surgery. Crit. Care Med. 2003, 31, 689–693. [Google Scholar] [CrossRef] [PubMed]
  56. Apple, F.S.; Quist, H.E.; Doyle, P.J.; Otto, A.P.; Murakami, M.M. Plasma 99th Percentile Reference Limits for Cardiac Troponin and Creatine Kinase MB Mass for Use with European Society of Cardiology/American College of Cardiology Consensus Recommendations. Clin. Chem. 2003, 49, 1331–1336. [Google Scholar] [CrossRef] [Green Version]
  57. Clerico, A.; Fortunato, A.; Ripoli, A.; Prontera, C.; Zucchelli, G.C.; Emdin, M. Distribution of Plasma Cardiac Troponin I Values in Healthy Subjects: Pathophysiological Considerations. Clin. Chem. Lab. Med. 2008, 46, 804–808. [Google Scholar] [CrossRef]
  58. Daniels, L.B.; Laughlin, G.A.; Clopton, P.; Maisel, A.S.; Barrett-Connor, E. Minimally Elevated Cardiac Troponin T and Elevated N-Terminal Pro-B-Type Natriuretic Peptide Predict Mortality in Older Adults. J. Am. Coll. Cardiol. 2008, 52, 450–459. [Google Scholar] [CrossRef] [Green Version]
  59. Stearns, J.D.; Dávila-Román, V.G.; Barzilai, B.; Thompson, R.E.; Grogan, K.L.; Thomas, B.; Hogue, C.W. Prognostic Value of Troponin I Levels for Predicting Adverse Cardiovascular Outcomes in Postmenopausal Women Undergoing Cardiac Surgery. Anesth. Analg. 2009, 108, 719–726. [Google Scholar] [CrossRef] [Green Version]
  60. Wu, A.H.B. Gender-Specific Decision Limits for Cardiac Troponin for Risk Stratification? Anesth. Analg. 2009, 108, 686–688. [Google Scholar] [CrossRef] [PubMed]
  61. Shoaibi, A.; Tavris, D.R.; McNulty, S. Gender Differences in Correlates of Troponin Assay in Diagnosis of Myocardial Infarction. Transl. Res. 2009, 154, 250–256. [Google Scholar] [CrossRef]
  62. Motiwala, S.R.; Sarma, A.; Januzzi, J.L.; O’Donoghue, M.L. Biomarkers in ACS and Heart Failure: Should Men and Women Be Interpreted Differently? Clin. Chem. 2014, 60, 35–43. [Google Scholar] [CrossRef]
  63. Reichlin, T.; Hochholzer, W.; Bassetti, S.; Steuer, S.; Stelzig, C.; Hartwiger, S.; Biedert, S.; Schaub, N.; Buerge, C.; Potocki, M.; et al. Early Diagnosis of Myocardial Infarction with Sensitive Cardiac Troponin Assays. N. Engl. J. Med. 2009, 361, 858–867. [Google Scholar] [CrossRef] [Green Version]
  64. Neumann, J.T.; Havulinna, A.S.; Zeller, T.; Appelbaum, S.; Kunnas, T.; Nikkari, S.; Jousilahti, P.; Blankenberg, S.; Sydow, K.; Salomaa, V. Comparison of Three Troponins as Predictors of Future Cardiovascular Events—Prospective Results from the FINRISK and BiomaCaRE Studies. PLoS ONE 2014, 9, e90063. [Google Scholar] [CrossRef] [PubMed]
  65. Eggers, K.M.; Lind, L.; Venge, P.; Lindahl, B. Factors Influencing the 99th Percentile of Cardiac Troponin I Evaluated in Community-Dwelling Individuals at 70 and 75 Years of Age. Clin. Chem. 2013, 59, 1068–1073. [Google Scholar] [CrossRef] [Green Version]
  66. Webb, I.G.; Yam, S.T.; Cooke, R.; Aitken, A.; Larsen, P.D.; Harding, S.A. Elevated Baseline Cardiac Troponin Levels in the Elderly—Another Variable to Consider? Heart Lung Circ. 2015, 24, 142–148. [Google Scholar] [CrossRef] [PubMed]
  67. Korley, F.K.; Schulman, S.P.; Sokoll, L.J.; DeFilippis, A.P.; Stolbach, A.I.; Bayram, J.D.; Saheed, M.O.; Omron, R.; Fernandez, C.; Lwin, A.; et al. Troponin Elevations Only Detected With a High-Sensitivity Assay: Clinical Correlations and Prognostic Significance. Acad. Emerg. Med. 2014, 21, 727–735. [Google Scholar] [CrossRef]
  68. Kavsak, P.A.; Shortt, C.; Pond, G.; Worster, A. High-Sensitivity Cardiac Troponin I for Predicting Death in a Female Emergency Department Population. Clin. Chem. 2014, 60, 271–273. [Google Scholar] [CrossRef] [Green Version]
  69. Bohula May, E.A.; Bonaca, M.P.; Jarolim, P.; Antman, E.M.; Braunwald, E.; Giugliano, R.P.; Newby, L.K.; Sabatine, M.S.; Morrow, D.A. Prognostic Performance of a High-Sensitivity Cardiac Troponin I Assay in Patients with Non–ST-Elevation Acute Coronary Syndrome. Clin. Chem. 2014, 60, 158–164. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  70. Sandoval, Y.; Smith, S.W.; Sexter, A.; Gunsolus, I.L.; Schulz, K.; Apple, F.S. Clinical Features and Outcomes of Emergency Department Patients With High-Sensitivity Cardiac Troponin I Concentrations Within Sex-Specific Reference Intervals. Circulation 2019, 139, 1753–1755. [Google Scholar] [CrossRef] [PubMed]
  71. Gore, M.O.; Seliger, S.L.; deFilippi, C.R.; Nambi, V.; Christenson, R.H.; Hashim, I.A.; Hoogeveen, R.C.; Ayers, C.R.; Sun, W.; McGuire, D.K.; et al. Age- and Sex-Dependent Upper Reference Limits for the High-Sensitivity Cardiac Troponin T Assay. J. Am. Coll. Cardiol. 2014, 63, 1441–1448. [Google Scholar] [CrossRef] [Green Version]
  72. Everett, B.M.; Cook, N.R.; Magnone, M.C.; Bobadilla, M.; Kim, E.; Rifai, N.; Ridker, P.M.; Pradhan, A.D. Sensitive Cardiac Troponin T Assay and the Risk of Incident Cardiovascular Disease in Women With and Without Diabetes Mellitus: The Women’s Health Study. Circulation 2011, 123, 2811–2818. [Google Scholar] [CrossRef] [PubMed]
  73. Kimenai, D.M.; Shah, A.S.V.; McAllister, D.A.; Lee, K.K.; Tsanas, A.; Meex, S.J.R.; Porteous, D.J.; Hayward, C.; Campbell, A.; Sattar, N.; et al. Sex Differences in Cardiac Troponin I and T and the Prediction of Cardiovascular Events in the General Population. Clin. Chem. 2021, 67, 1351–1360. [Google Scholar] [CrossRef]
  74. Jia, X.; Sun, W.; Hoogeveen, R.C.; Nambi, V.; Matsushita, K.; Folsom, A.R.; Heiss, G.; Couper, D.J.; Solomon, S.D.; Boerwinkle, E.; et al. High-Sensitivity Troponin I and Incident Coronary Events, Stroke, Heart Failure Hospitalization, and Mortality in the ARIC Study. Circulation 2019, 139, 2642–2653. [Google Scholar] [CrossRef]
  75. Zhu, K.; Hung, J.; Divitini, M.; Murray, K.; Lim, E.M.; St John, A.; Walsh, J.P.; Knuiman, M. High-Sensitivity Cardiac Troponin I and Risk of Incident Atrial Fibrillation Hospitalisation in an Australian Community-Based Cohort: The Busselton Health Study. Clin. Biochem. 2018, 58, 20–25. [Google Scholar] [CrossRef]
  76. Thorsteinsdottir, I.; Aspelund, T.; Gudmundsson, E.; Eiriksdottir, G.; Harris, T.B.; Launer, L.J.; Gudnason, V.; Venge, P. High-Sensitivity Cardiac Troponin I Is a Strong Predictor of Cardiovascular Events and Mortality in the AGES-Reykjavik Community-Based Cohort of Older Individuals. Clin. Chem. 2016, 62, 623–630. [Google Scholar] [CrossRef] [Green Version]
  77. Dallmeier, D.; Denkinger, M.; Peter, R.; Rapp, K.; Jaffe, A.S.; Koenig, W.; for the ActiFE Study Group; Rothenbacher, D. Sex-Specific Associations of Established and Emerging Cardiac Biomarkers with All-Cause Mortality in Older Adults: The ActiFE Study. Clin. Chem. 2015, 61, 389–399. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  78. Omland, T.; de Lemos, J.A.; Holmen, O.L.; Dalen, H.; Benth, J.Š.; Nygård, S.; Hveem, K.; Røsjø, H. Impact of Sex on the Prognostic Value of High-Sensitivity Cardiac Troponin I in the General Population: The HUNT Study. Clin. Chem. 2015, 61, 646–656. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  79. Lyngbakken, M.N.; Røsjø, H.; Holmen, O.L.; Nygård, S.; Dalen, H.; Hveem, K.; Omland, T. Gender, High-Sensitivity Troponin I, and the Risk of Cardiovascular Events (from the Nord-Trøndelag Health Study). Am. J. Cardiol. 2016, 118, 816–821. [Google Scholar] [CrossRef]
  80. Baart, S.J.; Dam, V.; Scheres, L.J.J.; Damen, J.A.A.G.; Spijker, R.; Schuit, E.; Debray, T.P.A.; Fauser, B.C.J.M.; Boersma, E.; Moons, K.G.M.; et al. Cardiovascular Risk Prediction Models for Women in the General Population: A Systematic Review. PLoS ONE 2019, 14, e0210329. [Google Scholar] [CrossRef] [Green Version]
  81. Ford, I.; Shah, A.S.V.; Zhang, R.; McAllister, D.A.; Strachan, F.E.; Caslake, M.; Newby, D.E.; Packard, C.J.; Mills, N.L. High-Sensitivity Cardiac Troponin, Statin Therapy, and Risk of Coronary Heart Disease. J. Am. Coll. Cardiol. 2016, 68, 2719–2728. [Google Scholar] [CrossRef]
  82. Januzzi, J.L.; Butler, J.; Jarolim, P.; Sattar, N.; Vijapurkar, U.; Desai, M.; Davies, M.J. Effects of Canagliflozin on Cardiovascular Biomarkers in Older Adults With Type 2 Diabetes. J. Am. Coll. Cardiol. 2017, 70, 704–712. [Google Scholar] [CrossRef]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Bisaccia, G.; Ricci, F.; Khanji, M.Y.; Gaggi, G.; Di Credico, A.; Gallina, S.; Di Baldassarre, A.; Ghinassi, B. Prognostic Value of High-Sensitivity Cardiac Troponin in Women. Biomolecules 2022, 12, 1496. https://doi.org/10.3390/biom12101496

AMA Style

Bisaccia G, Ricci F, Khanji MY, Gaggi G, Di Credico A, Gallina S, Di Baldassarre A, Ghinassi B. Prognostic Value of High-Sensitivity Cardiac Troponin in Women. Biomolecules. 2022; 12(10):1496. https://doi.org/10.3390/biom12101496

Chicago/Turabian Style

Bisaccia, Giandomenico, Fabrizio Ricci, Mohammed Y. Khanji, Giulia Gaggi, Andrea Di Credico, Sabina Gallina, Angela Di Baldassarre, and Barbara Ghinassi. 2022. "Prognostic Value of High-Sensitivity Cardiac Troponin in Women" Biomolecules 12, no. 10: 1496. https://doi.org/10.3390/biom12101496

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop