Prognostic significance of elevated troponin in non-cardiac hospitalized patients: A systematic review and meta-analysis

Figures & data

Figure 1. Study selection process.

Table I. Characteristics of studies included in systematic review.

Author	Study period	Type of study	Study population	No. of patients	Primary study outcome	Troponin type	Troponin threshold	Timing of troponin measurement	Length of follow-up
Afonso (2011)	Jan 2000–Jul 2006	Retrospective	Hypertensive emergency	567	Mortality	Troponin I	3 different assays (cut-offs changed over time)	Within 12 h of admission with peak TnI used	Mean 3.1 years
Al-Mallah (2008)	Jan 1998–Dec 2000	Retrospective	DKA	96	In-hospital and 2-year mortality and MACE	Troponin I	> 1 ng/dL	During DKA treatment	2 years
Baillard (2003)	Jan 2000–2001	Prospective	COPD exacerbation	71	In-hospital mortality	Troponin I	> 0.5 ng/mL	At admission and at 24 h	Until discharge
Balasubramaniyam (2012)	2012	Retrospective	Pneumonia	220	In-hospital mortality	Troponin I	> 0.4 ng/mL	At admission and at 24 h	Until discharge
Bova (2005)	2005	Prospective	Pulmonary embolism	60	In-hospital and 3-month mortality	Troponin T	> 0.01 ng/mL	Not specified	3 months
Choon-ngram (2008)	Dec 2004–Aug 2005	Prospective	*SIRS, sepsis or septic shock	40	In-hospital mortality	Troponin T	≥ 0.1 ng/mL	At admission and 6 h later	Until discharge
Fadaii (2009)	2005	Prospective	Respiratory ICU	87	In-hospital mortality	Troponin I	> 3.1 (units not specified)	At admission	Until discharge
Giannitsis (2000)	Apr 1996–Nov 1998	Prospective	Pulmonary embolism	56	In-hospital mortality	Troponin T	≥ 0.1 ng/mL	Within 24 h of admission	Until discharge
Hajsadeghi (2012)	Jan–Jul 2008	Prospective	Medical ICU patients	135	In-hospital mortality	Troponin T	> 0.1 μg/L	Within 24 h of admission	Until discharge
Hoiseth (2011)	Jan 2005–Nov 2006	Prospective	Acute COPD exacerbation	70	Mortality	High-sensitivity troponin T	≥ 14 ng/L	At time of admission	Median 1.9 years
Janata (2009)	Jan 1998–Dec 2006	Prospective	Pulmonary embolism	737	In-hospital and 1-year mortality	Troponin T	> 0.03 ng/mL	In ER at time of presentation	1 year
Jimenez (2008)	Jan 2003–Dec 2005	Prospective	Pulmonary embolism	318	30-day mortality	Troponin I	≥ 0.1 ng/mL	At time of admission	30 days
John (2010)	2010	Retrospective	Sepsis	1690	28-day mortality	Troponin I	≥ 0.06 ng/mL	Admission frozen samples used	28 days
Kalla (2008)	May 2005–2006	Prospective	Bacteraemia	159	In-hospital mortality	Troponin I	≥ 0.11 μg/L	Within 4 days of positive blood culture	Until discharge
Kelly (2013)	2013	Retrospective	COPD exacerbation	252	In-hospital mortality	Troponin I	> 0.04 ng/mL	At time of ER assessment	Until discharge
Kim (2005)	2005	Prospective	Medical ICU	215	10-day and 30-day mortality	Troponin I	≥ 0.1 μg/L	Within 24 h of admission	30 days
King (2005)	Sep 2002–Jun 2013	Prospective	Medical ICU	128	28-day mortality	Troponin I	> 0.7 ng/mL	Within 6 h of admission	28 days
Lankeit (2011)	2011	Prospective	Normotensive acute pulmonary embolism	526	Adverse 30-day outcome including all-cause mortality	High-sensitivity troponin T	≥ 14 pg/mL	At time of admission	6 months
Minkin (2005)	2005	Retrospective	Medical ICU	221	In-hospital mortality	Troponin I	≥ 1.2 μg/L	Within 24 h of admission	Until discharge
Ng (2010)	2000–2007	Retrospective	Acute pulmonary embolism	1023	In-hospital and long-term mortality	Troponin T	≥ 0.1 μg/L	At time of admission	Mean 3.8 years
Palmieri (2008)	Jun 2000–2003	Prospective	Pulmonary embolism	89	Development of haemodynamic instability and mortality	Troponin I	> 0.1 μg/L	At admission, 24 h and 48 h	Until discharge
Stein (2008)	2008	Retrospective	Medical ICU	240	In-hospital mortality and length of ICU stay	Troponin I	> 0.09 ng/mL	Peak troponin (timing not specified)	6 Months post-discharge
Tiruvoipati (2012)	Jul 2004–Jun 2010	Retrospective	Septic patients in ICU	293	In-hospital mortality	Troponin I	> 0.1 μg/L	Within 12 h of admission	Until discharge
Vasile (2009)	Aug 2000–Jul 2005	Retrospective	ICU patients with acute GI bleeding	1076	In-hospital, 30-day and long-term (> 1 y) mortality	Troponin T	≥ 0.01 μg/L	At admission and within 6 h	Mean 2 years
Vasile (2010)	Jan 2001–Dec 2005	Retrospective	ICU patients with acute respiratory disease	4433	In-hospital, 30-day and long-term (> 1 y) mortality	Troponin T	≥ 0.01 μg/L	At admission and within 6 h	Mean 4 years
Ver Elst (2000)	2000	Prospective	ICU patients with septic shock	46	Left ventricular dysfunction and in-hospital mortality	Troponin I	≥ 0.4 μg/L	At admission and after 24 h	Until discharge
Wu (2004)	Jan–Dec 1999	Retrospective	Non-cardiac general medical ICU	108	ICU mortality and 180-day mortality	Troponin I	> 0.5 ng/mL	At time of admission	180 days

*systemic inflammatory response syndrome.

Table II. Study quality characteristics.

Author	Type of study	Total n	Eligibility criteria clear?	Was troponin the primary variable of interest?	Blinding of outcome assessors?	Patients with complete follow-up	Method of follow-up adjustment
Afonso (2011)	Retrospective cohort	567	Yes	Yes	Not specified	100%	Social security death index
Al-Mallah (2008)	Retrospective cohort	96	Yes	Yes	Not specified	100%	Electronic medical record and death registry query
Baillard (2003)	Prospective cohort	71	Yes	Yes	Not specified	100%	In-hospital
Balasubramaniyam (2012)	Retrospective review	220	Yes	Yes	Not specified	100%	In-hospital
Bova (2005)	Prospective cohort	60	Yes	Yes	Not specified	Not specified	Not specified
Choon-ngram (2008)	Prospective cohort	40	Yes	Yes	Not specified	100%	In-hospital
Fadaii (2009)	Prospective cohort	87	Yes	Troponin and APACHE II score	Not specified	100%	In-hospital
Giannitsis (2000)	Prospective	56	Yes	Yes	Not specified	100%	In-hospital up to 30 days
Hajsadeghi (2012)	Prospective cohort	135	Yes	Yes	Not specified	100%	In-hospital
Hoiseth (2011)	Prospective cohort	70	Yes	Yes	Not specified	Not specified	Not specified
Janata (2009)	Prospective cohort	737	Yes	Yes	Not specified	100%	Hospital records and national death register
Jimenez (2008)	Prospective cohort	318	Yes	Yes	Yes	100%	Patient/proxy interviews and/or hospital chart review
John (2010)	Retrospective	1690	Yes	Yes	Yes	100%	Retrospective follow-up of patients in an RCT
Kalla (2008)	Prospective cohort	159	Yes	Yes	Not specified	100%	In-hospital
Kelly (2013)	Retrospective	252	Yes	Yes	Not specified	100%	In-hospital
Kim (2005)	Prospective cohort	215	Yes	Yes	Not specified	100%	In-hospital
King (2005)	Prospective cohort	128	Yes	Yes	Yes	100%	In-hospital
Lankeit (2011)	Prospective cohort	526	Yes	sPESI score and troponin	Not specified	Not specified	Not specified
Minkin (2005)	Retrospective cohort	221	Yes	Yes	Not specified	100%	In-hospital
Ng (2010)	Retrospective	1023	Yes	Yes	No	100%	Local state death registry
Palmieri (2008)	Prospective cohort	89	Yes	Troponin and right ventricular dysfunction	No	100%	In-hospital
Stein (2008)	Retrospective cohort	240	Yes	Yes	Not specified	100%	In-hospital and 6 months (method of F/U not specified)
Tiruvoipati (2012)	Retrospective cohort	293	Yes	Yes	Not specified	100%	In-hospital
Vasile (2009)	Retrospective cohort	1076	Yes	Yes	No	82%	Rochester Epidemiologic database and Mayo Clinic information for mortality
Vasile (2010)	Retrospective cohort	4433	Yes	Yes	No	91%	Rochester Epidemiologic database and Mayo Clinic information for mortality
Ver Elst (2000)	Prospective cohort	46	Yes	Yes	No	100%	In-hospital
Wu (2004)	Retrospective cohort	108	Yes	Yes	No	Not specified	Not specified

Table III. Summary of findings of meta-analysis.

	Illustrative comparative risks^a (95% CI)
Outcomes	Assumed risk Control	Corresponding risk Elevated troponin	Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Heterogeneity (I^2)
Short-term mortality (follow-up: up to 30 days)	8 per 100	26 per 100 (21–32)	OR 3.88 (2.9–5.19)	7255 (25 studies)	⊕⊕⊕⊖; moderate^b	62%
Long-term mortality (follow-up: more than 6 months)	16 per 100	45 per 100 (26–65)	OR 4.21 (1.84–9.64)	5368 (9 studies)	⊕⊕⊕⊖; moderate^b	96%

CI = confidence interval; OR = odds ratio.

^aAll studies demonstrate an increase in the risk of mortality. The overall effect is large and highly statistically significant (OR 3.88, 95% CI 2.90–5.19, P < 0.0001).

^bGRADE Working Group grades of evidence. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

Figure 2. Forest plot of short-term (in-hospital and ≤ 30 days) mortality in elevated troponin versus normal troponin groups.

Figure 3. Forest plot of long-term (≥ 6 months) mortality in elevated troponin versus normal troponin groups.

Figure 4. Forest plot of short-term mortality with pooled adjusted ORs.

Figure 5. Forest plot of reason for admission; critical illness/ICU.

Figure 6. Forest plot of reason for admission; sepsis.

Figure 7. Forest plot of reason for admission; COPD.

Figure 8. Forest plot of reason for admission; PE.

Figure 9. Forest plot of short-term mortality in troponin I studies.

Figure 10. Forest plot of short-term mortality in troponin T studies.

Figure 11. Forest plot of short-term mortality in retrospective studies.

Figure 12. Forest plot of short-term mortality in prospective studies.