Medical Hypotheses 145 (2020) 110323

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Medical Hypotheses
journal homepage: www.elsevier.com/locate/mehy

Statistical and entropy-based features can efficiently detect the short-term T

effect of caffeinated coffee on the cardiac physiology
Bikash K. Pradhan, Kunal Pal
⁎

Department of Biotechnology and Medical Engineering, National Institute of Technology, Rourkela 769008, India

ARTICLE INFO ABSTRACT

Keywords: An electrocardiograph (ECG) is the most effective way to find the changes in cardiac physiology. It is the re-
ECG presentation of the electrical activities of the heart and can be understood using different waves, peaks, and
Coffee intervals. Several factors affect the functionality of the heart that includes lifestyle, stress, daily diet, etc. Coffee,
Statistical features the most widely consumed beverage in the world, is an integral part of everyday life. Caffeine, the prime
Entropy
constituent of coffee, is believed to affect the heart physiology. However, the effect of consumption of caffei-
Random forest
nated coffee on the cardiac electrophysiological changes, estimated from the morphological features (e.g., peaks,
waves, intervals), is controversial. This has led to the exploration of other feature extraction methods to detect
the changes accurately. In recent years, the statistical and entropy-based features have emerged as an efficient
method to extract hidden patterns from the ECG signal. These features have been successfully explored in ar-
rhythmia detection, noise removal, biometric identification, etc. Hence, we hypothesized that the statistical and
entropy-based features could be efficiently used in detecting the changes in the ECG signal after coffee con-
sumption. For the evaluation of our hypothesis, 5-sec ECG segments were extracted from the recorded ECG
signals from 14 volunteers in pre- and post-coffee consumption conditions. From each segment, the statistical
and entropy-based features were computed. Then, the statistically significant features were extracted using
Wilcoxon's signed-rank test. The results showed a significant difference in the statistical parameters post-con-
sumption of coffee. Further, to validate our findings, several machine learning models were used for the auto-
matic detection of these changes, and the results show the highest classification accuracy of 75%. The results
support our hypothesis that the statistical and entropy-based features can efficiently detect the changes in the
ECG signals, which is induced by coffee consumption. The findings of the proposed hypothesis may open up a
new research arena of detecting the presence of different drugs and alcohol in the human body by analyzing the
ECG signals.

Introduction
In recent times, there has been extensive technological advance-
ment across the globe. This has allowed improvement in computational
capabilities, which has led to the introduction of several computational
methods. The computational methods can extract complex information
from the biopotential signals like electroencephalogram [1], electro-
myogram [2], electrocardiogram [3], and electrooculogram [4]. These
complex data are used for a variety of applications that include disease
diagnosis, biometric identification, face recognition, and many more.
Among the various biopotential signals, the electrocardiogram (ECG)
signal is one of the most widely collected biopotential signals. The heart
muscles of the atria and ventricles sequentially undergo depolarization
and repolarization process, which results in the generation of the ECG
signals. In other words, the ECG signals are generated due to the
electrophysiological events that are associated with the heart muscles.
An electrical impulse, generated at the sino-atrial node, travels through
the heart and excites the heart muscles at differential times. This results
in the formation of different waves. Atria, the upper chambers of the
heart, is responsible for the generation of the P-wave. The ventricles,
the lower chambers of the heart, are associated with the generation of
the QRS complex. The T-wave is generated during the recovery process
of the ventricles from the contraction phase. Any change in these waves
can be an indicator of the alteration in cardiac physiology. Several
factors, like lifestyle and daily diet, may lead to changes in cardiac
physiology. The information extracted from the ECG signals can not
only help to investigate the functionality of the heart but also for the
detection of physiological abnormalities of the heart.

⁎
Corresponding author.
E-mail address: kpal.nitrkl@gmail.com (K. Pal).

https://doi.org/10.1016/j.mehy.2020.110323
Received 29 August 2020; Received in revised form 19 September 2020; Accepted 26 September 2020
0306-9877/ © 2020 Elsevier Ltd. All rights reserved.
B.K. Pradhan and K. Pal Medical Hypotheses 145 (2020) 110323

Coffee is the most widely consumed psychoactive beverage in the

world that has been an integral part of human life for centuries. It is the
primary dietary source of caffeine and contains hundreds of other
bioactive compounds like lipid, protein, carbohydrate, vitamins, mi-
nerals, nitrogenous, and phenolic compounds. After consuming this
delectable beverage, people often experience a temporary boost in en-
ergy, mood, and alertness. Caffeine, the prime constituent of coffee, has
proven cardioactive effects. There are a good number of researchers
who have tried to understand the impact of coffee consumption on the
morphology of ECG signals. But the changes reported in the electro-
cardiograph are equivocal. Uddin et al. (2014) has demonstrated the
effect of caffeinated beverages (coffee and tea) on the electro-
cardiographical parameters such as different peaks and intervals [5]. A
thorough analysis of the peaks of different waves indicates that the
consumption of caffeinated beverages impacts the amplitude and dif-
ferent intervals to a significant level. It further increases the RR interval
that results in a hike in heart rate. Similarly, in another study, a con-
siderable increase in QT interval after caffeine consumption was ob-
served [6]. Contradicting findings have also been reported by the var-
ious researcher that shows no changes in the QT interval [7], QRS
complex, and P-waves after consuming caffeinated beverages [8]. All
these studies employed only the morphological features (e.g., the am-
plitude of different peaks and duration of the intervals) of the ECG
signals for the evaluation. Unfortunately, the diagnosis of the ab-
normality in the heart using the morphological features of the ECG
signals has been considered as tricky. This is because the changes in the
patterns of the morphological features of the ECG signals are not dis-
tinguishable to the human eye. Further, it has also been reported that
the morphological features are associated with noise, which often leads
to inaccurate result [9]. This has led to the attempt to develop other
computational methods in quantifying the changes in the ECG para-
meters.
In recent years, the statistical and entropy-based feature has
emerged as an efficient method in extracting the hidden pattern from
the ECG signals. The statistical feature includes moments such as mean,
variance, kurtosis, skewness, log energy entropy, shannon entropy, etc.
Several researchers have reported that the statistical features are more
reliable means of predicting the changes in a time series signal, in-
cluding ECG and electroencephalogram (EEG) signals, as compared to
the morphological features [10,11]. Engin et al. (2014) have demon-
strated that the statistical features (higher-order cumulant, wavelet
entropy, and autoregressive coefficients) were useful in discriminating
the ECG beats [12]. Apart from these features, other statistical features
such as mean, mode, median, maximum, minimum, kurtosis, skewness,
average power, standard deviation have also been reported in different
studies for the arrhythmia detection [13–15]. Alotaiby et al. (2019)
have shown that the statistical features were not limited to the appli-
Fig. 1. Block diagram of the workflow of the preliminary study.
cation of arrhythmia detection and can also be used for biometric
identification [16]. Besides, these features, when employed using dif-
ferent computer-aided methods, such as Machine Learning classifiers, coffee. Hereafter, the word “caffeinated coffee” would be regarded as
Neural Networks, etc., can detect the hidden patterns within the ECG coffee. Our hypothesis was based on the principle that if caffeinated
signals. The computer-aided technologies can help in the detection and coffee affects the cardiac electrophysiology, then a significant change
diagnosis of the alteration in cardiac physiology or abnormalities. will be observed in the statistical features of the ECG signals after the
Though research on ECG signal processing has significantly advanced, consumption of the coffee. These changes in the cardiac electro-
the analysis of the changes in the cardiac physiology after the con- physiology can be further validated by classifying the ECG signals,
sumption of caffeinated coffee has not been explored yet. Hence, the which are acquired before and after the consumption of coffee.
current study is an attempt to find whether the statistical features of the
ECG signals are capable of detecting the cardiac electrophysiological Hypothesis evaluation
changes after the consumption of caffeinated coffee. The block diagram
of the workflow of the study is represented in Fig. 1. A preliminary study was conducted for the evaluation of our hy-
pothesis, where fifteen participants were included for the study.
Hypothesis Smoking, alcohol, and sport/high-level physical activity were chosen as
the exclusion criteria for the participants to avoid the effect of lifestyle
We reasonably assume that the statistical and entropy-based ECG on the autonomic nervous system activity. The volunteers were asked to
features would be useful in differentiating the changes in the cardiac sign a consent form before data acquisition as a record of their will-
electrophysiology that is caused due to the consumption of caffeinated ingness to participate in the study. All the participants were requested

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B.K. Pradhan and K. Pal Medical Hypotheses 145 (2020) 110323

Table 1 decision tree [23]. The algorithm divides the entire sample (parent
The list of statistically significant features obtained from Wilcoxon's signed- node) into many homogeneous subgroups, called a child node. At each
rank test. partition, the variable that can split the data into the homogeneous
Sl. no. Attribute Mean ± SD p-value groups in an efficient manner is identified. This process continues until
no further divisions are reached, or a pre-defined number of partitions
Before After is reached. Subsequently, the final decision tree is constructed [24].
ADB is one of the most widely used ensemble classifiers that is used in
1 MED −0.013 ± 0.009 −0.014 ± 0.010 0.003
2 VAR 0.041 ± 0.020 0.043 ± 0.021 0.000 machine learning [21]. During each iteration, the error rate of the week
3 STD 0.197 ± 0.050 0.202 ± 0.050 0.000 classifier is computed. Consequently, the weights of the base learner are
4 RMS 0.197 ± 0.050 0.197 ± 0.050 0.000 updated during each of the iterations. In other words, the signal seg-
5 SKW 2.284 ± 0.871 2.227 ± 0.876 0.020
ments that are incorrectly classified in the previous classifier are now
6 RE0.2 5.170 ± 0.048 5.175 ± 0.045 0.004
7 RE0.5 1.878 ± 0.044 1.881 ± 0.041 0.013 weighted more heavily than those that are correctly classified. The base
8 RE0.8 0.281 ± 0.010 0.282 ± 0.009 0.038 learner consists of a group of week classifiers, and the classification
9 RE2.0 6.021 ± 0.294 6.040 ± 0.298 0.047 from these sequences is then computed by following a weighted ma-
10 RE2.3 9.992 ± 0.486 10.024 ± 0.496 0.041 jority voting method to decide the final prediction [25]. GBT uses a
11 RE2.6 14.922 ± 0.721 14.972 ± 0.738 0.039
boosting method to generate base models sequentially. The prediction
12 RE2.9 20.804 ± 0.997 20.877 ± 1.021 0.038
13 RE3.2 27.634 ± 1.313 27.732 ± 1.708 0.040 accuracy can be enhanced by creating multiple models and then em-
14 RE3.5 35.406 ± 1.670 35.532 ± 1.708 0.042 phasizing on the training data that are difficult to estimate. GBT adds
15 RE3.8 44.116 ± 2.067 44.273 ± 2.111 0.044 each base model strategically to minimize the loss function, which is
16 RE4.1 53.761 ± 2.504 53.952 ± 2.552 0.048
averaged over the training data. The loss function is the deviation of the
17 TE0.2 15644.080 ± 522.860 15697.860 ± 491.740 0.004
18 TE0.5 41.958 ± 3.658 42.263 ± 3.460 0.016
predicted value from the true value and can be computed either using
19 TE0.8 0.772 ± 0.050 0.775 ± 0.048 0.041 mean squared error or absolute error [26]. RF develops many decision
20 TE2.6 0.6153 ± 2.46E−05 0.615 ± 0.098 0.049 trees using a randomly chosen feature vector following a bagging
strategy [18]. The random vector chosen is independent of the previous
random vectors. The decision trees are grown using the training set and
to abstain from food before 2 h of the ECG signal recording. They were the random vector, which results in a collection of tree-structured
asked to sit in a relaxed position in a wooden chair. Vernier EKG sensor classifiers. Later, these classification trees are used to vote for a given
(Vernier Software & Technology Pvt. Ltd., USA) was used for the ac- input vector to get a class level. ETC is a recursive supervised learning
quisition of the ECG signals in the lead-I configuration. method that uses many randomly constructed trees for prediction. Its
The ECG signals were extracted from all the participants before and operation is similar to that of RF. The best split in the node is found by
after 10 min of consumption of caffeinated coffee (100 ml with analyzing the subset of all available features. However, instead of
24.89 mg of caffeine). A single recording of 5 min ECG signal was di- choosing the best threshold for each feature, as in the case of RF, a
vided into 45 trials of a duration of 5 sec each [17]. The sampling single threshold is chosen for every feature. From these splits, the one
frequency of the record was maintained at 1 kHz. These ECG segments that leads to the most remarkable change in the used score is then se-
of 5-sec duration were then used for further processing. In the next lected [27]. The final model that can efficiently differentiate the two
stage, several informative and non-redundant statistical values, called groups of ECG segments (pre- and post-consumption of coffee) has been
features, were extracted from each 5-sec segment. The features ex- proposed after comparing the performance of these CMs.
tracted in the current study are comprised of three groups: the lower-
order statistical features include arithmetic mean (MEAN), median Hypothesis consequence and discussion
(MED), standard deviation (STD), summation (SUM), variance (VAR),
and root mean square (RMS), while the higher-order statistical features The results obtained in the preliminary study shows that several
include kurtosis (KUR) and skewness (SKW). The entropy-based fea- statistical features, extracted from each 5-sec ECG segment, exhibit
tures that include Shannon entropy (SE), log energy entropy (LEE), significant changes after 10 min of coffee consumption. The segment-
Tsallis entropy (TE), and Renyi Entropy (RE) were calculated. Both RE based method is well-explored and was implemented for the analysis of
and TE are the extension of SE, and was computed based on the order of various biopotential signals [28–30]. Further, the use of smaller seg-
“q” (where q ≠ 1) [18]. A series of RE and TE values of different orders ments in the predictive analysis will reduce the computational burden
were calculated by tailoring the value of q. In this study, the q value with an increase in its application [31]. Hence, smaller segments of 5-
was varied from 0.1 to 5 at an interval of 0.3. RE and TE of order q are sec were considered during the process of evaluation. The prior study
represented as 'REq' and 'TEq,' respectively. A total of 44 features was suggests that the effect of coffee reaches a peak after 30 min of con-
computed from each of the 5-sec ECG segments (Table S1). sumption. However, the effects start manifesting in the human body
Wilcoxon's signed-rank test was employed to identify the statisti- within 10 min of consumption [32]. Considering the information that is
cally significant features among the two groups (pre- and post-coffee available in the literature, the current study was designed where ECG
consumption). The significance of a feature was evaluated using the p- signals were recorded post-10 min of coffee consumption. The sig-
value. The features that had a p-value < 0.05 were considered as nificance of these features was evaluated using Wilcoxon's signed-rank
statistically significant features and were used as the input for the test. This test was employed as most of the calculated features did not
computation of the optimal feature set. The optimal feature set was show a normal distribution. Hence, a nonparametric statistical testing
identified using the RFE algorithm. The feature values were normalized method (Wilcoxon's signed-rank test) was adopted. The Wilcoxon's
before performing the feature selection to avoid the overweighting of signed-rank test is usually employed for two-paired samples (before and
the features that have a higher range of values. In the current study, after) when the data are interval scaled [33]. Herein, the hypothesis
various classification models (CMs) such as Extra Trees Classifier (ETC) tests whether the median difference between the two groups of data is
[19], Classification and regression tree (CART) [20], Adaboost (ADB) zero or not. The features that had a p-value less than 0.05 was con-
[21], Gradient boosting tree (GBT) [21], and Random forest (RF) [22] sidered to be statistically significant. Four lower-order features (MED,
were used in conjunction with the RFE algorithm. STD, VAR, RMS), one higher-order feature (SKW), and several entropy-
CART is a recursive partitioning algorithm that is mostly used in based features (RE0.2, RE0.5, RE0.8, RE2.0, RE2.3, RE2.6, RE2.9,
data mining-based analyses. The algorithm is employed on both cate- RE3.2, RE3.5, RE3.8, RE4.1, TE0.2, TE0.5, TE0.8, TE2.6) were statis-
gorical and numerical data. It uses historical data to construct a tically different among the pre- and post-stimulus condition (Table 1).

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B.K. Pradhan and K. Pal Medical Hypotheses 145 (2020) 110323

Fig. 2. Optimal feature detection using recursive feature elimination method in (a) Extra-tree classifier, (b) Classification and regression tree, (c) Adaboost, (d)
Gradient boosted tree, and (e) Random forest.

Table 2
Performance matrices of each tree-based ensemble classifier.
Sl no. Classifier Accuracy Sensitivity Precision F-measure AUC

1 Extra tree classifier 0.736 ± 0.037 0.743 ± 0.069 0.735 ± 0.043 0.741 ± 0.037 0.832 ± 0.028
2 Classification and regression tree 0.723 ± 0.048 0.709 ± 0.068 0.724 ± 0.065 0.719 ± 0.063 0.729 ± 0.049
3 Adaboost 0.642 ± 0.056 0.648 ± 0.085 0.635 ± 0.075 0.638 ± 0.071 0.703 ± 0.053
4 Gradient boosted tree 0.729 ± 0.044 0.724 ± 0.082 0.727 ± 0.059 0.723 ± 0.054 0.802 ± 0.047
5 Random forest 0.751 ± 0.039 0.742 ± 0.057 0.750 ± 0.059 0.752 ± 0.060 0.844 ± 0.038

This supports our hypothesis that the statistical and entropy-based further the effectiveness of these statistical features in distinguishing
features can efficiently differentiate the alteration in the ECG signal the changes in the ECG signal. For this purpose, five trees based en-
after the consumption of caffeinated coffee. We also intended to classify semble classification models (CMs) were considered. The reason behind
the two groups of data using the significant features. This is to validate using an ensemble classifier is its advantage to reduce the

4
B.K. Pradhan and K. Pal
Fig. 3. Performance of the Random Forest-based classification algorithm. (a) Performance measures before and after applying the feature reduction method, and (b)
Percentage change in the classification performance after applying the feature reduction method.
misclassification rate of a weak classifier by introducing as well as
aggregating several classifiers [34]. Herein, the main idea was to make
a prediction of several classifiers on the original data and then make a
strong prediction by combining all the predictions. However, without
using all significant features, an optimal number of features was con-
sidered in each model. This was due to the reason that the combination
of feature set also plays an important role in defining the classification
accuracy. The RFE method recursively eliminates a feature (based on a
feature ranking method), builds the CM, and then recalculates the ac-
curacy using the remaining attributes. This process continues until a
single feature remains. During the process of recursion, the feature set
that leads to the minimum root mean square error (RMSE) and the
standard deviation or maximum accuracy is chosen as optimal for a CM
(Fig. 2). A comparison of the accuracy of these models shows that the
RF classifier outperforms the rest of the models (Table 2). For the
generalization of our results, 10-fold cross-validation was used [35].
The average accuracy, sensitivity, precision, F-measure, and area under
the curve (AUC) obtained from the RF algorithm were 75.1%, 74.2%,
75.0%, 75.2%, and 84.4%, respectively. It has been reported in the
literature that RF classifiers showed good accuracy, controlled output
variance, and low probability to overfit [22]. Along with these ad-
vantages, the learning strategy used in RF, also called bagging [18],
maybe the reason behind its improved performance as compared to
other classification models. Further, in RF, the weak learners are fed
with different training sets, thus decreasing the variance of the model
without increasing the bias. This provides diversity to the ensemble
classifier. The higher accuracy obtained in the RF model supports our
hypothesis that the consumption of caffeinated coffee induces short-
term changes in the ECG signals. Further, a comparison of the RF
classifiers that employ either all the features of selected features (Fig. 3)
has been reported. The results suggested that the feature selection
method allowed an increase in classification performance accuracy and
an overall decrease in the feature dimension.
The current study hypothesized that the changes in the ECG signal
after the consumption of caffeinated coffee could be best distinguish-
able using statistical features of the ECG signal. The hypothesis was
evaluated using different Machine Learning models. The preliminary
study conducted herein supports our hypothesis. This also concludes
that the application of ECG segments is not limited to only cardiac
abnormalities such as arrhythmia, and can also be used to detect the
short-term effect of coffee consumption. In the future, the statistical and
entropy-based features of the ECG signals may be used to evaluate
whether they can distinguish between the different dosage of coffee. A
potential extension of this study can be the detection of different
5
Medical Hypotheses 145 (2020) 110323
caffeinated beverages, including tea and soft drinks. Further, the results
obtained in the current study also give new directions to the researcher
working in the field of automatic drugs and alcohol detection using
smaller segments of ECG.
Conflict of interest
The authors declare no conflict of interest.
Ethical statement
The author, Dr. Kunal Pal, has obtained the ethical clearance from
the Institutional Ethical Committee vide letter no. Ref.# NITRKL/IEC/
FORM-2/002; dated16/8/2017 for the acquisition of the ECG signals.
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://
doi.org/10.1016/j.mehy.2020.110323.
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