TIMI Risk Index

Clinical background

In acute coronary syndrome, early risk stratification is decisive for prioritising resources and triaging patients to the right level of care. The challenge in the early phase is that the information available is often limited: laboratory values and ECG interpretation may be delayed, and clinical risk scores requiring complete data are not always applicable at first contact. The TIMI Risk Index fills precisely this gap by requiring only three variables that are always available at the bedside — heart rate, age and systolic blood pressure — and yet giving a meaningful estimate of mortality risk in ST-elevation myocardial infarction (STEMI).

Calculating the TIMI Risk Index

The formula is:

$$\text{TIMI Risk Index} = \frac{\text{Heart rate} \times \left(\frac{\text{Age}}{10}\right)^2}{\text{Systolic blood pressure}}$$

The index is thus the heart rate in beats/min multiplied by the square of age divided by 10, all divided by the systolic blood pressure in mmHg. A 75-year-old patient with a heart rate of 100 and a systolic blood pressure of 120 has, for example, an index of $100 \times (7{.}5)^2 / 120 \approx 46{.}9$. All three variables are continuous, and the index rises with increasing age and heart rate and with falling systolic blood pressure, reflecting the physiological logic that advanced age, tachycardia and hypotension each signal severe cardiogenic shock or decompensation.

The index was originally derived from patients with STEMI in clinical trials of fibrinolysis, in which the median index was around 20 [1]. In the large validation study in the National Registry of Myocardial Infarction (NRMI)-3 and -4, comprising 153,486 STEMI patients in American practice, the median index was higher, 26.9, reflecting a broader and more heterogeneous population than in the original trials [1]. The outcome modelled was in-hospital mortality, and the index was tested both as a continuous variable and grouped into risk categories.

Interpretation in practice

The TIMI Risk Index is primarily a continuous measure; the higher the value, the higher the mortality risk. In the NRMI cohort, mortality ranged from 0.9% in the lowest risk group to 53.2% in the highest, with a statistically significant trend across groups [1]. Among patients given reperfusion therapy, mortality was 0.6% in the lowest and 60% in the highest group, and among those not given reperfusion the corresponding figures were 1.9% and 52.2% [1].

The index can be used for early triage: a high value on arrival should lead to immediate prioritisation of aggressive treatment and monitoring, while a low value supports standard management. It is important to stress, however, that the index does not replace clinical assessment or full risk stratification with established instruments that require laboratory values and the ECG, but rather serves as a first filter before those data are available.

Since the calculator does not define fixed bands for interpretation, the index should be read as a continuous risk measure in which higher values correspond to higher risk. In the original fibrinolytic cohort the median was around 20, and in NRMI around 27 [1]; values well above these should raise suspicion of an increased mortality risk and prompt prompt investigation and treatment.

Validation and performance

In the large NRMI validation, a c-statistic of 0.79 was achieved for the whole STEMI cohort, 0.81 among patients given reperfusion therapy and 0.71 among those not given it [1]. Discrimination was lower among older patients, in whom the score distribution shifted towards higher risk but performance was nonetheless maintained with a c-statistic of 0.71 [1].

An external validation in the Canadian EFFECT cohort (11,510 patients with acute myocardial infarction in Ontario) confirmed the performance of the index outside the original American registries. Here the c-statistic was 0.82 for STEMI and 0.80 for NSTEMI, with overlapping confidence intervals, and calibration was good [2]. Here too, discrimination was lower among patients aged 65 and over, with a c-statistic of 0.74 [2].

The index has also been tested in NSTEMI populations separately. In an analysis of 337,192 NSTEMI patients from NRMI, the index showed a graded relationship with mortality, with a more than 30-fold difference between the lowest and highest deciles and a c-statistic of 0.73 [3]. Overall mortality in the NSTEMI group was 10.9%, higher than in STEMI patients given reperfusion (6.6%) but lower than in STEMI patients without reperfusion (18.7%) [3].

In an Asian validation from Malaysia (4,701 STEMI patients), the c-statistic was 0.785 for the whole population, 0.764 among patients with diabetes and 0.761 among patients with renal impairment [4]. Calibration was good for the whole population and for patients with diabetes, but poorer for patients with renal impairment, where a chi-squared goodness-of-fit test gave p = 0.006 [4].

In a Chinese cohort (3,389 STEMI patients), related indices based on age and shock index (the age shock index and the age-modified shock index) were compared with the TIMI Risk Index and the GRACE score for post-discharge mortality. The age-based shock indices performed comparably to the classical scores for short-term mortality, with an AUC around 0.75, with no significant differences in AUC or NRI [5].

Limitations

The TIMI Risk Index uses only three variables and therefore lacks several factors of known prognostic importance in acute coronary syndrome, among them troponin levels, electrocardiographic findings, signs of heart failure and comorbidity such as diabetes and renal disease. The instrument is therefore best suited as an initial bedside tool, not as a complete basis for decision.

Performance is poorer in older patients, in whom the c-statistic falls to around 0.71 to 0.74 in different cohorts [1, 2]. This is particularly problematic because age enters the formula as a squared term, so that the index rises steeply with increasing age and may exaggerate the risk in some older patients who also have a low blood pressure. At the same time, a normal or low index in an older patient with a subtle presentation may give false reassurance.

Calibration deteriorates in patients with renal impairment [4], which limits the reliability of the index in this group. In patients given fibrinolysis, the related age-based shock indices have not shown a significant association with post-discharge prognosis [5], and it is conceivable that the performance of the index is also affected by the type of reperfusion treatment.

Finally, most of the validation evidence rests on American and North American registries from the first decade of the 2000s. The Asian validation supports its use but with a lower c-statistic and calibration problems in subgroups [4]. Data from Swedish or European cohorts are lacking specifically for this instrument.

References

1. Wiviott SD et al. Performance of the thrombolysis in myocardial infarction risk index in the National Registry of Myocardial Infarction-3 and -4: a simple index that predicts mortality in ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2004;44(4):783–9. PMID: 15312859
2. Bradshaw PJ et al. Validation of the Thrombolysis In Myocardial Infarction (TIMI) risk index for predicting early mortality in a population-based cohort of STEMI and non-STEMI patients. Can J Cardiol. 2007;23(11):871–6. PMID: 17245483
3. Wiviott SD et al. Application of the Thrombolysis in Myocardial Infarction risk index in non-ST-segment elevation myocardial infarction: evaluation of patients in the National Registry of Myocardial Infarction. J Am Coll Cardiol. 2006;47(8):1553–8. PMID: 16630990
4. Selvarajah S et al. An Asian validation of the TIMI risk score for ST-segment elevation myocardial infarction. PLoS One. 2012;7(7):e40249. PMID: 22815733
5. Wang S et al. Age shock index and age-modified shock index are valuable bedside prognostic tools for postdischarge mortality in ST-elevation myocardial infarction patients. Ann Med. 2024;56(1):2311854. PMID: 38325361