Clinical Inquiries

Elevated troponin but no CVD: What’s the prognosis?

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References

EVIDENCE-BASED ANSWER:

Patients with elevated troponin levels and chronic renal disease, pulmonary hypertension, pulmonary embolism, chronic obstructive pulmonary disease, sepsis, or acute ischemic stroke have a 2- to 5-fold increased risk of death, even in the absence of known cardiovascular disease (TABLE)1-6 (strength of recommendation: B, meta-analysis, multiple prospective and retrospective observational studies.)

EVIDENCE SUMMARY

To investigate the prognostic value of troponin on overall mortality, a multicenter prospective study followed 847 patients 18 years and older (mean age 59 years) with end-stage renal disease whose troponin T levels were measured 3 months from the start of peritoneal dialysis or hemodialysis until transplantation or death.1 At enrollment, 566 patients had a troponin level of ≤0.04 ng/dL, 188 had a value between 0.05 and 0.10 ng/dL, and 93 had a level of more than 0.10 ng/dL.

Using Cox regression, patients whose troponin levels were more than 0.10 ng/dL had an increased hazard ratio (HR) for all-cause mortality of 2.2 (95% confidence interval [CI], 1.7-2.8) compared with patients who had levels ≤0.04 ng/dL. Cardiovascular mortality also was higher (HR=1.9; 95% CI, 0.9-3.7) with troponin elevations, but didn’t reach statistical significance. Investigators found no significant differences in mortality risk between patients on peritoneal or hemodialysis, patients with or without a history of acute myocardial infarction, or patients who suffered cerebrovascular accidents.

Elevated troponin raises risk of death 5-fold in pulmonary embolism patients
A meta-analysis of 20 trials with a total of 1985 patients assessed the prognostic value of troponin for short-term mortality in patients admitted with acute pulmonary embolism.2 Sixteen studies (1527 patients) were prospective trials and the remainder (458 patients) were retrospective trials. Investigators obtained troponin levels for all patients at admission. They used several different troponin assays (both I and T), but most of the studies used the assay manufacturers’ cutoff points (exceeding the 99th percentile).

High troponin levels were associated with a 5-fold increased risk of short-term death, defined as in-hospital death up to 30 days after discharge (19.7% with elevated troponin vs 3.7% with normal troponin; odds ratio [OR]=5.24; 95% CI, 3.3-8.4).

Increased risk of death among those with pulmonary hypertension, COPD A prospective single-center study of 56 patients with chronic pulmonary hypertension found that the 14% of those whose troponin T was elevated (≥0.01 ng/mL) had a lower survival rate than the other patients. Patients who either had a positive troponin on initial assessment or developed troponin elevation within the 2-year follow-up period had a cumulative 24-month survival rate of 29%, compared with 81% for their troponin T-negative counterparts (P=.001).3

In a retrospective single-center observational study of 396 patients hospitalized from 2000 to 2003 for an exacerbation of chronic obstructive pulmonary disease and followed until 2005, troponin T levels ≥0.04 ng/mL within 24 hours of admission were associated with increased all-cause mortality (HR=1.64; 95% CI, 1.15-2.34; P=.006).4

Patients with elevated troponin levels and certain conditions have a 2- to 5-fold increased risk of death, even without known cardiovascular disease.

Elevated troponin I is an independent predictor of mortality in severe sepsis

A double-blind, placebo-controlled, phase 3 trial evaluated the effect of drotrecogin alfa (activated)—withdrawn from the market in 2011—on survival of patients with severe sepsis.5 Investigators used positive troponin I levels (≥0.06 ng/mL) as a prognostic indicator of mortality. Patients who were troponin-positive had a 28-day mortality rate of 32%, compared with 14% in the troponin-negative group (P<.0001).

A bias of this study is that the patients with positive troponin levels tended to be older and more critically ill. However, in a multivariate model, troponin I still remained an independent predictor of mortality.

Elevated troponin predicts increased death risk in up to 20% of stroke patients

A systematic review of 15 trials with a total of 2901 patients evaluated the relationship between troponin levels and stroke.6 Investigators assessed the prevalence of elevated troponin in acute stroke patients, the association of elevated troponin levels with electrocardiographic changes, and the overall morbidity and mortality associated with troponin levels. Thirteen of the 15 studies used a troponin T or I level obtained within 72 hours of admission and a cut-off level of 0.1 ng/mL. The remaining 2 studies used troponin I cut-off levels >0.2 and 0.4 ng/mL.

Evidence-based answers from the Family Physicians Inquiries Network

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