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  <front>
    <journal-meta />
    <article-meta>
      <title-group>
        <article-title>Building Models for Predicting Mortality after Myocardial Infarction in Conditions of Unbalanced Classes, Including the Influence of Weather Conditions</article-title>
      </title-group>
      <contrib-group>
        <aff id="aff0">
          <label>0</label>
          <institution>Voronezh State University</institution>
          ,
          <addr-line>1 Universitetskaya pl., Voronezh, 394006</addr-line>
          ,
          <country country="RU">Russia</country>
        </aff>
      </contrib-group>
      <fpage>0000</fpage>
      <lpage>0002</lpage>
      <abstract>
        <p>The key direction in modern medicine is the development of software systems that allow us to analyze a large amount of data in an adaptive way and interpret the results obtained, ensuring high accuracy of results. Predicting mortality from myocardial infarction (MI) and identifying significant factors influencing this mortality is an urgent task, since the share of cardiovascular diseases annually accounts for more deaths than any other cause. The purpose of this study is to develop a machine learning model based on the gradient boosting technique for predicting mortality from MI, identifying the most significant signs, assessing the influence of meteorological factors, and improving the accuracy of predicting using data balancing methods. The paper used a depersonalized sample of all residents of the Voronezh region who had a STROKE in 2015-2017. The archive of weather data for 2015-2017 was taken from the site rp5.ru. Data analysis and model development were performed in the Python programming language version 3.6. Five undersampling strategies were reviewed and the method that achieves the highest prediction accuracy was chosen - the cluster centroid method.</p>
      </abstract>
      <kwd-group>
        <kwd>Undersampling</kwd>
        <kwd>Gradient boosting</kwd>
        <kwd>Predicting mortality</kwd>
        <kwd>Myocardial infarction</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>-</title>
      <p>
        Myocardial infarction (MI) is the most common and most fatal problem [
        <xref ref-type="bibr" rid="ref1">1</xref>
        ]. In
medicine, information technologies are being actively introduced, which allow both to
facilitate the work of staff and to reduce the mortality rate of the population. Enough
software systems have been developed to predict diseases, reduce the risk of deaths, and
select an effective method of treating patients depending on the nature of the disease.
During solving such problems, the greatest attention is paid to improving the accuracy
of the model and optimizing the software product. Improving the accuracy of the
developed model can be achieved by more thorough pre-processing of data, or by
considering additional factors that affect the result of predicting [
        <xref ref-type="bibr" rid="ref2">2</xref>
        ].
      </p>
      <p>
        Machine learning algorithms are often referred to as black box models because there
is no clear explanation of how exactly the model comes to predictions. Medicine is an
industry where the interpretation of results is an important step. When determining
signs that affect the risk of disease, you can eliminate these factors in a timely manner
with the help of targeted medical intervention. Many works are devoted to identifying
the dependence of the morbidity and mortality of the population on climatic conditions
[
        <xref ref-type="bibr" rid="ref3 ref4">3,4</xref>
        ]. However, the results presented in these studies are inconsistent. The dependence
of the functioning of the cardiovascular system on seasonality, fluctuations in the
average daily temperature, humidity or pressure differ in different territorial zones, which
is facilitated by the geographical location of the region, air pollution, the degree of
adaptation of the population to the natural conditions of the place of residence, and so
on. In order to check the presence of such dependences according to the data of the
Voronezh region, climatic indicators were added to the clinical and medical indicators
[
        <xref ref-type="bibr" rid="ref5">5</xref>
        ].
      </p>
      <p>Thus, the purpose of this study was to construct models for predicting one-year
mortality among residents of the Voronezh region who underwent MI, based on
meteorological, socio-demographic, and clinical factors. The initial data were provided by the
Voronezh Regional Cardiology Dispensary.</p>
      <p>
        To build the model, one of the popular methods was chosen – gradient boosting,
which is highly accurate [
        <xref ref-type="bibr" rid="ref6">6</xref>
        ].
      </p>
      <p>
        In recent years, many works have been published devoted to predicting mortality
from cardiovascular diseases, including those using gradient boosting methods [
        <xref ref-type="bibr" rid="ref7 ref8 ref9">7, 8,
9</xref>
        ]. The difference in this study lies in the addition of climatic indicators, as well as in
a practical study of the effectiveness of class balancing methods in relation to the
available source data.
      </p>
      <p>During processing real data, there are often situations when the share of examples of
one class in the training dataset is too small (minority class), and another is strongly
represented (a majority class). Depending on the task, the problem of class imbalance
can lead to a serious bias towards the majority class, a decrease in predicting efficiency
and an increase in the number of false predictions. In tasks of a medical nature, this is
especially important. When analyzing diagnostic results, there is often a problem of
uneven distribution of classes in the training sample, since the number of patients
suffering from a particular disease in the initial data is significantly lower (or, conversely,
higher) than the number of healthy patients. Misclassification of the patient may lead
to a lack of timely action. One approach to solve this problem is to use various sampling
strategies. There are two ways to restore class balance. In the first case, delete a certain
number of examples of the majority class (undersampling), in the second – increase the
number of examples of the minority class (oversampling). This article discusses various
undersampling methods and compares their accuracy.
2
2.1</p>
    </sec>
    <sec id="sec-2">
      <title>Materials and Methods</title>
      <sec id="sec-2-1">
        <title>Description of Source Data</title>
        <p>For the analysis, we used depersonalized data on all patients who were admitted to
Voronezh region’s hospitals in 2015-2017 with a diagnosis of MI, and dependencies in
the sample with fatal cases of myocardial infarction (MI) for the same years. Total
recorded cases of MI in 2015 – 3810, 2016 – 3837, 2017 – 3679. In 2015, 2016 and 2017,
there were 684, 657 and 606 fatal cases of MI, respectively.</p>
        <p>The source file contained information on 15 attributes presented in Table 1. The
analyzed dataset was supplemented with six meteorological indicators. Weather data
were downloaded from the rp5.ru website archive. Data preprocessing was performed
using the Oracle SQL developer integrated development environment in the SQL
language.</p>
        <p>Attribute’s type
Categorical variable
Continuous variable</p>
        <p>Attribute
Gender, whether the myocardial infarction is repeated (MI),
localization, KILLIP class, whether the patient underwent thrombolytic
therapy (TLT), percutaneous coronary intervention (PCI), whether
the patient has a history of diabetes mellitus (DM), atrial fibrillation
(AF), acute cerebral circulation disorder (CCD), chronic obstructive
pulmonary disease (COPD), chronic cardiovascular failure (CHF),
arterial hypertension (AH)
Age, Maximum of the temperature (Max_T), humidity, atmospheric
pressure, wind speed, cloudiness
When working with a real sample of data, there is often a situation often when the
volume of one class are much larger than the volume of another. This data is called
unbalanced. Building a model in such a situation may turn out to be ineffective and the
error of the predicted data will be large. For medical issues, the data balancing stage is
important. The predominance of the number of cases of one class leads to a shift in the
model towards the majority class. Mortality prediction is a type of "early warning" tasks
of an event. It is more important to predict the onset of death than to assume that the
patient will survive and get the opposite result. Since the number of patients who died
in the initial sample is much less than the number of survivors, it is necessary to balance
the training data to correctly build a predictive model and reduce false negative results.</p>
        <p>
          The class with the largest number of cases is called majority, with the smallest
minority. The class of the deceased in the problem under consideration is the minority
class. Various sampling strategies are used to correct the class imbalance [
          <xref ref-type="bibr" rid="ref11">11</xref>
          ].
Rebalancing can be done in two ways: undersampling and oversampling. Oversampling
is a duplication of minority class examples. Depending on what ratio of classes is
needed, the number of random records for duplication is selected. Duplication occurs
according to certain algorithms, for example SMOTE or ASMO. Undersampling is the
removal of majority class examples.
        </p>
        <p>Killip class (%)</p>
        <p>I
II
III</p>
        <p>VI
Age
PCI (%)</p>
        <p>Yes</p>
        <p>No
CHF (%)</p>
        <p>H I
H IIА
H IIБ
H III</p>
        <p>No
CCD (%)</p>
        <p>Ischemic stroke
TIA
Hemorrhagic stroke</p>
        <p>No
COPD (%)</p>
        <p>Yes</p>
        <p>No
Cloudiness
Max_T
Undersampling is considered the simplest and at the same time the most correct in the
tasks of medical research. Therefore, it was this method that was chosen to solve the
problem. The undersampling technique can be implemented in several ways. To
achieve the highest prediction accuracy, five algorithms were considered, and the
accuracy of their work was compared.</p>
      </sec>
      <sec id="sec-2-2">
        <title>Algorithm for randomly deleting examples. To achieve the required class ratio,</title>
        <p>instances of the majority class are randomly deleted. The number of deleted records is
determined empirically. The advantages of this method include simplicity of
implementation and high performance. The main drawback is the high probability of losing
significant data.</p>
        <p>The method of cluster centroids. This strategy removes examples of the majority
class using cluster analysis methods. The majority class is divided into the number of
classes according to the number of instances of the minority class by the k-average
method. Then the centroids of each class are selected, which eventually form a new
class. The main advantage of this approach is that it preserves important topological
properties of the sample.</p>
        <p>Strategy for searching for Tomek links. All entries of the majority class that are
included in the Tomek link are considered "noisy" and deleted. A pair (Ei, Ej) is called
a Tomek link if there is no example of El such that the set of inequalities is valid:
(, ) &lt; (, )
{(, ) &lt; (, )
(1)
d – is the distance between the samples Ei, Ej.</p>
      </sec>
      <sec id="sec-2-3">
        <title>The concentrated nearest neighbor rule. All examples are classified by the rule of</title>
        <p>
          the nearest neighbor. It then removes any instance whose class label differs from the
class in at least two of its three nearest neighbors. The idea of this method is to remove
instances from a majority class that is near or around the boundary of another class in
order to improve the accuracy of classifying minority instances rather than majority
instances [
          <xref ref-type="bibr" rid="ref12">12</xref>
          ].
        </p>
        <p>The general parameter of XGBoost. This is a built-in data balancing method in the
XGBoost – scale_pos_weight gradient boosting method, which allows you to increase
the weight of the minority class examples.
2.3</p>
      </sec>
      <sec id="sec-2-4">
        <title>Gradient Boosting and Quality Metrics</title>
        <p>The gradient boosting machine learning model was used to predict the mortality of
patients from MI. Five-fold cross-validation was used to train the model to correct
hyperparameters, the final testing was carried out on a deferred validation set, the volume
of which is 20% of the initial data.</p>
        <p>
          Gradient boosting is a machine learning technique, the main idea of which is the
iterative process of sequentially building partial models. Each new model is trained
using information about the errors made at the previous stages, and the resulting
function is a linear combination of the entire ensemble of models, considering the
minimization of some penalty function [
          <xref ref-type="bibr" rid="ref13">13</xref>
          ]. This approach improves the generalizing ability
and stability of the classification. This algorithm is distinguished by its high accuracy,
which in most cases exceeds the accuracy of other methods.
        </p>
        <p>One of the advantages of this method is its high performance, which is important
when working with large data sets. The gradient boosting method is resistant to outliers,
which are normal when working with real data.</p>
        <p>In machine learning tasks, various metrics are used to assess the quality of models.
When calculating these metrics, a classification error matrix is used. Based on the
matrix elements for each class, the following indicators are calculated: (TP) – True
Positive (the number of correctly predicted samples of class 1), (FN) – False Negative (the
number of false negative samples, incorrectly predicted class 0), (TN) – True Negative
(correctly predicted class 0), (FP) – False Positive (number of false positives,
incorrectly predicted class 1). The main metric of classification problems is the proportion
of correct answers, which is calculated using the formula:
accuracy = (TP+TN)/(TP+TN+FP+FN)
(2)</p>
        <p>However, this indicator is ineffective for unbalanced samples. More often, the
indicators are considered precision (precision) – the proportion of true positive examples
from the total number of positively predicted examples, and recall – the proportion of
true positive examples from the total number of positive examples.</p>
        <p>precision = TP/(TP+FP)
recall = TP/(TP+FN)
(3)
(4)</p>
        <p>
          Recall is preferable when evaluating models in medical problems. This metric helps
to reduce the number of false negative predictions. Medical diagnostics has its own
metrics that determine the accuracy of the method [
          <xref ref-type="bibr" rid="ref14">14</xref>
          ]. Sensitivity (true positive
proportion) reflects the proportion of positive results that are correctly identified as such
and the ratio of the number of deaths classified as deaths to the total number of deaths
is calculated. If the deceased is considered a positive class, this metric coincides with
recall. Specificity (true negative proportion) reflects the proportion of negative results
that are correctly identified as such and the ratio of the number of survivors classified
as survivors to the total number of survivors is calculated:
        </p>
        <p>Specificity= TN/(TN+FP)
(5)</p>
        <p>
          To create an optimal diagnostic system, it is necessary to find a compromise between
the obtained indicators of sensitivity and specificity of the models. A common way to
visualize the relationship between these metrics is to use the ROC-curve – a graphical
characteristic of the quality of a binary classifier, the dependence of the sensitivity on
the indicator (1-specificity) when varying the threshold of the decision rule of the
model. The optimal position for the ROC curve is as close as possible to the upper left
corner where specificity and sensitivity are at their maximum. The value of AUC ROC
– the area under the ROC-curve is a compromise metric widely used in medical
research [
          <xref ref-type="bibr" rid="ref11">11</xref>
          ].
3
        </p>
      </sec>
    </sec>
    <sec id="sec-3">
      <title>Results and Discussion</title>
      <p>Building a machine learning model and data analysis was performed using the libraries
of the Python programming language. The gradient boosting model was built using the
tools of XGBClassifier library. XGBoost is an optimized distributed library that is
highly efficient, flexible and portable: you can train many models with different loss
functions. The developed code is applicable in the main common environments
(Kubernetes, Hadoop, SGE, MPI, Task).</p>
      <p>Table 3 presents the metrics of the quality of the model's assessment, which were
obtained based on true and false answers on the test sample: sensitivity, specificity,
percentage of correct answers, and shows the percentage of correct answers in the final
cross-validation. Table 4 shows the most significant features. The significance of each
factor is calculated as the average normalized result of the decrease in the branching
criterion caused by this factor. The branching criterion calculates the measure of
uncertainty at the nodes of the trees. The Gini index was used as such a criterion.
The most significant feature is index of heart failure severity on the Killip scale. This
is the expected result, since this indicator is determined by specialists when the patient
is admitted to the hospital and characterizes the severity of the patient's condition during
the initial visual examination. Age is expected to be a significant factor; survival is
worse in patients belonging to the older age group. Also, predictors influencing the
results include indicators: whether percutaneous coronary interventions (PCI) were
performed, whether the patient has chronic heart failure (CHF), has a history of stroke
(CCD) and chronic obstructive pulmonary disease (COPD). It can be noted that in
comparison with clinical indicators, meteorological factors are less significant, however,
there is an influence of cloudiness indicators (Cloudiness) and maximum daily
temperature (Max_T).</p>
      <p>As noted earlier, the initial sample has an imbalance in the data for the predicted
variable – there are much more patients who survived after MI than who died.
Therefore, despite the rather high indicators of Accuracy and AUC ROC, in Table 3 it can be
seen that the constructed model has an extremely low sensitivity index (Sensitivity),
which is unacceptable for the task of predicting mortality, since the model is poorly
able to identify patients with a high risk of mortality.</p>
      <p>An undersampling method is used to balance the classes, which can lead to an
increase in the sensitivity of the machine learning model. The following undersampling
strategies were considered: the random deletion of examples, the cluster centroid
method, the Tomek link search strategy, and the concentrated nearest neighbor rule.
Also considered is the built-in method of balancing data in the XGBoost gradient
boosting method – scale_pos_weight.</p>
      <p>Table 5 shows the main metrics for assessing the quality of the model: Accuracy
(train) – the accuracy of the resulting model on the training set, sensitivity, specificity,
Accuracy (test) – the proportion of correct answers on the test set, the area of the
ROCcurve. Based on the results of the model quality metrics, we can conclude that the best
indicators of accuracy when using strategies of random deletion, cluster centroids and
Tomek links. In this case, the method of cluster centroids provides the highest
sensitivity.</p>
      <p>Method
Random undersampling
Cluster centriods undersampling
TomekLinks undersampling
NearMiss undersampling
Scale pos weight</p>
      <p>To assess the impact of weather conditions, the same models were built for a dataset
without weather attributes. Table 6 presents the results. Comparing the indicators in
Table 5 and Table 6, we can conclude that considering weather conditions helps to
improve the accuracy of the model and has an impact on predicting mortality from MI.
All (Training)
TomekLinks undersampling
Random undersampling
Cluster centroids undersampling</p>
      <p>NearMiss undersampling
4</p>
    </sec>
    <sec id="sec-4">
      <title>Conclusion</title>
      <p>This study was conducted to build a gradient boosting model for predicting mortality
after myocardial infarction and to determine the most significant factors for mortality
in MI. The accuracy of the model was improved by balancing the original sample using
undersampling. The accuracy of five sampling strategies has been demonstrated. The
most effective methods are the method of random removal of samples, the method of
cluster centroids and the method of Tomek links. The best accuracy (Accuracy) was
obtained using the Tomek links method (on test data, it is equal to 0.85). The best
sensitivity is provided by the cluster centroid method.</p>
      <p>With the help of the constructed model, significant factors were found for predicting
mortality after the onset of myocardial infarction. The most significant are: Killip class,
age, percutaneous coronary interventions, whether the patient has chronic heart failure,
whether there is a history of stroke and chronic obstructive pulmonary disease, as well
as weather factors – cloudiness and maximum daily temperature.</p>
      <p>Acknowledgments. The research was supported by the Russian Foundation for Basic
Research (RFBR), project № 20-37-90029.</p>
    </sec>
  </body>
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