PPV, NPV and Troponin

If you ask most interns how to rule out NSTEMI biochemically, they will tell you to check a troponin level (plus or minus a myoglobin level) "q6 hours X3".  That 18 hours can mean the difference between admission and outpatient follow-up, and which can be a burden on patients and incur unnecessary healthcare costs.

Actual numbers obtained in the study. UA=unstable angina

An interesting paper by Scharnhorst et al. in the American Journal of Clinical Pathology suggests that myocardial necrosis can be ruled out much faster with modern troponin assays.  In a prospective, single center observational study, they evaluated the ability of a troponin of <0.06 micrograms/L or a rise in baseline troponin levels of 30% or more over two hours to diagnose myocardial infarction.  The gold standard was the synthetic diagnosis reached by the attending cardiologist.

They reported their results in terms of sensitivity, specificity, and positive and negative predictive value (PPV and NPV).  These can all be calculated from the table at right.  Sensitivity and specificity were covered in this blog recently; the positive and negative predictive values of a test are even easier to remember.  The PPV is the proportion of positive results which are accurate (in this case 30/43 = 70%) and the negative predictive value is the proportion of negative results which are accurate (in this case 94/94 = 100%).  In English, this means that in the population studied a negative test result predicted with 100% accuracy that no actual mycoardial necrosis had taken place, thus excluding the diagnosis of NSTEMI, but that a positive result was only an indicator of myocardial infarction in 70% of cases.

The important thing to note about PPV/NPV is that they depend on the prevalence of the disease.  We encountered this once previously, but, to review, this is easiest to understand if you think in extremes: 

• If the prevalence of a condition is 100%, then the characteristics of the test are irrelevant - any positive result will be accurate.  
• If the prevalence is 0%, then similarly, it doesn't matter how sensitive the test is - it's always wrong.

What this means clinically is that if you're going to make a decision based on a PPV or NPV quoted in the literature, you have to be comfortable that the prevalence in the study population was similar to the prevalence in your treatment population.

Finally, it's worth noting that these investigators also measured CK-MB and myoglobin and neither added anything to the diagnosis.  The original paper is short, free, and very much worth checking out.

Sensitivity and Specificity

On Wednesday at noon conference we briefly reviewed the concepts of sensitivity and specificity.

Every diagnostic test has a variety of characteristics which can be studied, (including sensitivity, specificity, and predictive values,) and which physicians need to understand the definitions of in order to read the medical literature fluently.  Most important test characteristics can be easily described and calculated using this two-by-two chart:

The sensitivity of a test is the percentage of patients with the disease being studied who also have a positive test result; so it's calculated as A / (A+C).  The specificity is the percentage of patients without the disease who have a negative test result; so it's calculated as D /( D+B).

The study we used to illustrate this was published in Chest this June, and was designed to determine the sensitivity and specificity of procalcitonin and CRP for differentiating between pneumonia and simple exacerbations of asthma and COPD.

I fudged the numbers a little for the demonstration, since they actually reported their results in terms of receiver operating characteristic curves (which are not as complicated as they sound), so I won't review the calculation.  However, it is intriguing that, for a CRP level of >48mg/L, they reported a sensitivity of 91% and a specificity of 93%.  This is one, small study and CRP as a test for pneumonia is certainly not ready for prime time.  However, it's worth considering that, if this does turn out to be true, a cheap blood test might be able to improve antibiotic stewardship in an era of increasing resistance.

Grand Rounds 10.14.11

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