The predictive value of pro brain natriuretic peptide (ProBNP) levels to determine the presence and severity of coronary artery disease in patients with a positive or inconclusive exercise stress test

Abstract

Cardiovascular disease (CVD) is one of the major causes of premature deaths worldwide. In South Africa, approximately 195 people die from cardiovascular diseases each day. The earlier coronary artery disease (CAD) is detected, the better the prognosis. NT- pro- brain natriuretic peptide (NT-proBNP) is a cardiac neurohormone that is secreted in the cardiac ventricles in response to excessive stretching of heart muscle cells. Brain natriuretic peptide (BNP) is currently being used as a marker of left ventricular dysfunction but limitations are evident in patients with sepsis, volume overload, stroke and acute mitral regurgitation. OBJECTIVES: The main objective of this study was to identify a possible value of NT- proBNP level which indicates CAD. It also aimed to compare NT- proBNP levels with the number of diseased vessels; to assess the association between proBNP levels and patients’ age and gender; to determine the percentage of false positive proBNP levels; to determine the probability of false positive exercise stress testing and to correlate NT- proBNP levels with LVEDP. METHODS: Sixty patients were recruited from the Cardiology Department at St Anne’s hospital to participate in this trial. They were divided into two groups; Group A, the control group, consisted of thirty patients with a positive EST and Group B, the experimental group, consisted of thirty patients with an inconclusive EST. After the EST, all patients from both groups were required to have a NT- proBNP blood test, a left and right coronary angiogram and a left ventriculogram. iii RESULTS: Results of the study showed that post EST NT- proBNP levels, in both groups, increased in the presence of CAD (p<0.001). For the positive EST group, the area under the ROC curve was 0.975 which was highly statistically significantly different from the null hypothesis value of 0.5 (p<0.001) and a cut- off value of 120 pg/ml was identified with the highest sensitivity (95.7%) and specificity (100%). For patients in the inconclusive EST group, the area under the ROC curve was 0.912 which was highly statistically significantly different from the null hypothesis value of 0.5 (p<0.001) and a cut-off value of 85 pg/ml was identified with the highest sensitivity (87.5%) and specificity (86.4%). There was a statistically significant difference between the median NT- proBNP values of males and females in the group of patients with positive EST (p=0.048). The values were higher in males. However, there was no significant difference between the genders in the group with an inconclusive EST. A strong and significant correlation (p<0.001) between left ventricular end diastolic pressures (LVEDP) and number of disease vessels was demonstrated. The probability of a false positive result for EST was 24.1%. and the probability of a false negative result was 25.8%. CONCLUSION: Results of the study showed that post EST NT- proBNP levels, in both groups, increased in the presence of CAD and could accurately predict the presence of CAD. Cut- off values of 120 pg/ml for the positive EST group and 85 pg/ml for the inconclusive EST group were identified with the highest sensitivity and specificity. In the positive EST group, a trend of increasing NT-proBNP with age was and NT-proBNP values were higher in males. The positive EST was relatively accurate at predicting CAD; however, 75.9% of patients with an inconclusive EST did not have CAD.Exercise stress testing in this regard, is therefore relatively inaccurate at predicting CAD in patients with inconclusive ESTs, and the need for an additional tool, such as NT-proBNP measurements post inconclusive EST is warranted in the determination of the presence of CAD.