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Three Part Question

In [patients with suspected cardiac chest pain] does [measurement of whole blood choline] allow [accurate exclusion of acute coronary syndromes]?

Clinical Scenario

You refer a fifty year-old man, with vague central chest pain but normal ECG, to the Medics for troponin testing at 12 hours. The medical registrar comments that one day this will be a thing of the past, as Emergency Departments will be able to test all patients with suspected cardiac chest pain for whole blood choline, thus referring only those with genuine acute coronary syndromes (ACS). You wonder if she is right.

Search Strategy

OVID Medline 1966 - 2005 July Week 4
Embase 1980 - 2005 Week 32
[exp Myocardial Infarction/ OR exp Coronary Thrombosis/ OR exp Angina, Unstable/ OR (heart attack OR AMI OR MI OR acute adj coronary adj syndrome OR ACS).mp. OR (myocard$ adj (infarct$ or ischaem$ or ischem$)).mp. limit to human and English language

Search Outcome

Altogether 29 papers were identified using Medline and 20 using Embase. Only one paper, identified using both databases, was relevant to the three-part question.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Danne O et al 2003 Germany	327 consecutive patients presenting to the Emergency Department with acute chest pain, discomfort or other signs suggesting cardiac ischaemia, including cardiopulmonary arrest. Blood taken on admission, at 4-6 hours and at 12-24 hours. Mean symptom onset 4.6+/-4.1 hours in 285 patients (could not be determined in 42 patients). Follow up at 30 days in 317 of 327 patients (97%).	Prospective observational cohort	Whole blood choline according to diagnosis	Significantly higher in low-medium risk UA v. non-cardiac chest pain (p<0.01); high-risk UA v. non-cardiac chest pain (p<0.001); NSTEMI v. non-cardiac chest pain (p<0.001); STEMI v. non-cardiac chest pain (p<0.001); LBBB AMI v. non-cardiac chest pain (p<0.001); Other cardiac conditions v. non-cardiac chest pain (p<0.01)	Statistical analysis did not include value of whole blood choline for excluding all ACS on admission.
			Cardiac death or non-fatal cardiac arrest at 30 days	Significantly increased in patients with +ve choline test (>28.2umol/l) on admission (18.2% v. 4.4%, hazard ratio 4.31, p<0.001).
			Secondary end-points at 30 days	Choline was predictive for each: life-threatening arrhythmias (p<0.001), coronary angioplasty (p=0.0004), heart failure (p<0.001).
			Cardiac death or nonfatal cardiac arrest in patients with negative troponin	Significantly increased incidence with +ve choline test (13.4% v. 2.3%, p=0.003)
			Choline for diagnosis of AMI at admission	Sensitivity 40.5%, specificity 78.7%, PPV 51.1%, NPV 70.6%. Thus, following a negative test the patient still has a 29.4% probability of AMI.
			Choline for diagnosis of high-risk UA at admission	Sensitivity 86.4%, specificity 86.2%, PPV 42.2%, NPV 98.2%. (Notably, myoglobin had a sensitivity of 4.5%, CK-MBmass sensitivity 9.5%). Thus patients had a probability of 1.8% for high-risk UA following a -ve test.

Comment(s)

Choline is the major enzymatic product of phospholipase D, which may play a role in the pathophysiological evolution of atherosclerotic plaque destabilisation. The authors of the only study relevant to this three-part question reported that they identified it as a promising marker having discovered elevated levels in the circulating blood of patients with ACS by spectroscopy during a pilot study (Wevers et al, 1994). The relevant study suggests that whole blood choline is a strong independent predictor of 30-day mortality in patients with chest pain presenting to the Emergency Department. As such, it may be useful for risk stratification in these patients. However, the data suggests that this marker alone is unlikely to be sufficiently sensitive to rule out ACS on admission. Further research, possibly incorporating choline into a multimarker strategy, is warranted.

Editor Comment

Abbreviations: AMI: Acute myocardial infarction STEMI: ST elevation myocardial infarction NSTEMI: Non-ST elevation myocardial infarction UA: Unstable angina ACS: Acute coronary syndrome PPV: Positive predictive value NPV: Negative predictive value LBBB: Left bundle branch block

Clinical Bottom Line

Choline is a strong independent predictor of mortality in patients presenting with chest pain. However, it is insufficiently sensitive to rule out ACS on admission. Further research is necessary.

References

1. Danne O; Mockel M; Lueders C; Mugge C; Zshunke GA; Lufft H; Muller C; Frei U Prognostic implications of elevated whole blood choline levels in acute coronary syndromes American Journal of Cardiology 2003; 91: 1060-1067
2. Wevers RA; Engelke U; Heerschap A High-resolution 1H-NMR spectroscopy of blood plasma for metabolic studies Clinical Chemistry 1994; 40: 1245-1250