Introduction:

Cardiovascular disease (CVD) remains the leading cause of death and illness
worldwide,
accounting for one-third of deaths worldwide. Among the cardiovascular diseases, Acute
Coronary Syndrome (ACS) ranks the most prevalent as Myocardial infarction [1,2,3,4]. ACS
affects around 126 million individuals worldwide, accounting for 38% of deaths in females
and 44% in males[5].In the United States, coronary heart disease accounts for 53% of
cardiovascular-related deaths, with approximately 782,000 myocardial infarction cases
occurring . Whereas in developing countries like India, 68% of morbidity is due to non-
communicable disease, in which ACS was the major cause . The annual prevalence of acute
coronary syndrome (ACS) ranges from 2.5% to 12.6% in urban areas, compared to
1.4% to 4.6% in rural areas. Patients presenting with acute coronary syndrome (ACS)
without ST-segment elevation are diagnosed with either unstable angina (UA) or non-
ST-elevation myocardial infarction (NSTEMI). [8,9].Unstable angina (UA) and non-ST-
elevation myocardial infarction (NSTEMI) are closely related conditions with similar
pathophysiologic origins and clinical presentations, differing primarily in severity[5].
Clinically, NSTEMI differs from the UA with cardiac-specific biomarkers (Troponin T or I
or Creatinine kinase)[9].Patients presenting with NSTEMI or unstable angina (UA) are
typically older and at greater risk for cardiovascular complications. Despite advances in
therapeutic interventions over the past decade, NSTEMI continues to contribute
significantly to morbidity and mortality.[10].
Acute coronary syndrome (ACS) is more likely to occur in individuals over 65 years of age
and those with conditions such as hypertension, diabetes mellitus, and chronic kidney
disease, high LDL cholesterol, low physical activity, excessive alcohol consumption,
COVID-19 infection, and atherosclerosis [2,4].The Thrombolysis in Myocardial Infarction
(TIMI) risk score is a simple, validated tool used to stratify patients with unstable
angina (UA) and NSTEMI into risk categories for major adverse cardiac events
(MACE)[11,12,13].The TIMI risk score was originally developed for use in patients
presenting with unstable angina (UA) and non-ST-elevation myocardial infarction
(NSTEMI)[11,13]. It has been extensively validated in emergency departments treating
cardiac chest pain, thereby representing the highest level of evidence available[15,16,17].It
serves as an effective risk stratification tool for predicting 14-day in-hospital mortality
in patients with NSTEMI [17]. This tool includes seven prognostic parameters: age > 65
years, three or more risk factors for CAD (hypertension, diabetes, smoking), known CAD
stenosis, severe angina, aspirin use in the past seven days, elevated cardiac biomarkers, and
ST deviation segment[12,13]. The necessity for stratification is twofold: it aids in making
clinical decisions regarding patient management and predicting major adverse cardiac
events[11,13,18]. Nonetheless, the validation of the TIMI score has predominantly been
developed in developed nations, and the literature from developing countries remains limited
despite the higher burden of disease[19]. Therefore, our study evaluated the prognostic
relevance of the TIMI risk score in acute coronary syndrome.

Materials and Methods: This prospective observational study was carried out over one
year at a tertiary care hospital located in the urban area of Anantapur City, Andhra
Pradesh, India. A total of 250 patients, aged over 18 years, diagnosed with coronary
artery disease and presenting with symptoms of non-ST-elevation myocardial infarction
(NSTEMI) or unstable angina (UA), were included in the study and admitted to the
cardiology department. Patients who had previously undergone cardiac surgeries or
interventions were excluded from the study.

The study was conducted with approval from the Institutional Ethics
Committee of the Raghavendra Institute of Pharmaceutical Education and
Research under reference number RIPER/IRB/PP/2023/008. Data was
collected from patient medical records and the electronic health record
database, which included demographics, baseline investigations, and
defined TIMI risk score parameters. After gathering all required data, the
TIMI score was calculated by assigning 1 point when a parameter was
present and 0 when absent.The TIMI Risk Score Tool is based on the
following seven clinical criteria, with each factor contributing one point: (i)
age over 65 years; (ii) presence of three or more traditional risk factors for
coronary artery disease; (iii) known coronary artery disease with ≥50%
stenosis; (iv) aspirin use within the past seven days; (v) severe angina
(two or more episodes within 24 hours); (vi) ST-segment changes ≥0.5
mm on ECG; and (vii) elevated cardiac biomarkers such as troponin or CK-
MB.The total TIMI risk score is calculated by summing the points assigned to each of
the seven factors, with a higher score indicating an increased risk of adverse
events.Patients were monitored for 14 days following their hospital stay, and outcomes
during this period were recorded. The TIMI score was then compared with patient outcomes.
The relative differences were assessed by comparing event rates with increasing TIMI scores,
evaluating the effectiveness of the TIMI risk score in predicting major adverse cardiac events
in patients with acute coronary syndrome.Major adverse cardiac events (MACE)
encompass death, recurrent myocardial infarction, and the need for urgent
revascularization.
RESULTS:
Study comprised 250 people who fulfilled the established inclusion criteria. Among these
participants, 66.4% were identified as females (166n), whereas 33.6% were identified as
males (84n). Additionally, 61.2% of the subjects were classified as being under 65 years of
age (153n), with the remaining 38.2% being aged 65 years or older (97n). The Body Mass
Index (BMI) analysis of the study population indicated that 53.2% were categorized within
the range of 18.5-24.9 (133n), followed by 3.6% within the range of 25-29.9 (59n) and 23.2%
(58n) classified as obese (>30). Furthermore, the following symptoms were documented in
the study population upon hospital admission: chest pain (90.8%), hypertension (58%),
diabetes mellitus (38.4%), smoking (24%), shortness of breath (19.6%), and obesity (3.2%).
Observations from our study indicated that men experienced a greater incidence of adverse
events compared to women. The reported mortality rate was 8.8%. Notably, patients with
diabetes exhibited a significantly higher mortality rate (p = 0.03). Moreover, an elevated
TIMI risk score was strongly associated with an increased mortality risk.

Table 1: Relationship between TIMI score & Adverse events

TIMI Score T Total in Score Group n (%) No. of patients with events
n (%)
0 - -
1 5 (2%) 0
 2 70 (28%) 24 (34%)
3 106 (42.4%) 71 (66%)
4 65 (25.2%) 49(75%)
5 4 (1.6%) 3(75%)

Table 2: Classification of patients by using TIMI risk score

Category TIMI Risk Score Percentage (%)

Low Risk 0-2 75 (30%)
Intermittent Risk 3-4 171(68.4%)
High Risk 5-7 4(1.6%)

Table 3: Baseline characteristics and 14 days outcomes in the study population

Characteristic Survived (n=228) Expired (n=22) P value

Gender
Male 149(59.6%) 16(6.4%) 0.486
Female 79(31.6%) 6(2.4%) 0.213

Age 227(90.8%) 23(9.2%) 0.226

>65 Years (30.8%) (43.4%)

50 - 65 Years (48.4%) (43.4%)

<50Years (20.7%) (13%)

Risk Factors
Hypertension 131(52.4%) 16(6.4%) 0.699
Diabetes 84(33.6%) 12(4.8%) 0.032
Obesity 54(21.6%) 4(1.6%) 0.159
Smoking 51(20.4%) 9(3.6%) 0.266

The study subjects were categorized into three distinct categories based on the TIMI risk
score: low risk (30%), intermediate risk (68.4%), and high risk (1.6%). In our investigation,
42% of patients underwent urgent revascularization, whereas 8% were readmitted due to
recurrent myocardial infarction (MI). The survival rate was significantly lower among
patients over 65 years of age. The incidence of adverse events increased with higher risk
scores for individuals. Among the 250 patients, 42.4% had a TIMI risk score of 3, and within
this cohort, 71 patients experienced adverse events.

Regression analysis was performed to estimate the unadjusted regression coefficients

(independent parameters) effect on the TIMI score of the study, such as age, hypertension,
diabetes, presence of coronary artery disease, smoking, and BMI. These unadjusted
coefficients estimate the individual effect of the study factors on TIMI score in the absence of
other study factors.

Table 4: Individual assessment

Coefficients Unadjusted 95.0% Confidence Interval for Beta p-value

Beta Lower Bound Upper Bound

Age Group (<65) 0.701 0.507 0.894 0.000

Hypertension 0.521 0.321 0.720 0.000

(no)

Diabetes (no) 0.529 0.328 0.731 0.000

Coronary (no) 0.633 0.242 1.024 0.002

Smoking (no) 0.295 0.056 0.533 0.016

BMI 0.007 -0.012 0.026 0.465

Dependent Variable: TIMI score,

*category within the bracket is considered reference.

Table 5: Simultaneous assessment

 Coefficients Adjusted 95.0% Confidence Interval for p-value
Beta

Beta Lower Bound Upper Bound

Age Group 0.706 0.536 0.876 0.000

Hypertension 0.359 0.176 0.541 0.000

Diabetes 0.380 0.200 0.560 0.000

Coronary 0.769 0.442 1.095 0.000

Smoking 0.283 0.082 0.483 0.006

BMI -0.006 -0.021 0.009 0.438

Dependent Variable: TIMI score,

*category within the bracket is considered reference

The results suggest that changing from a lower to a higher age group will alter the TIMI score
by 0.701 units, and this change is observed to be statistically significant. Similarly, moving
from the absence of hypertension to its presence will increase the TIMI score by 0.521 units,
which is also statistically significant. For patients in the diabetes category, the TIMI score
will rise by 0.529 units and is found to be statistically significant. In CAD cases, the TIMI
score increased by 0.633 units and is deemed significant. Smoking habits also influence the
TIMI score, increasing it by 0.295 units, and this is observed to be statistically significant.
However, BMI has no significant effect on the TIMI score. (Table 4)

(Table 5) Simultaneous assessment of parameters shows adjusted coefficients that test the
individual parameter effects in the presence of other parameters. As other variables remain
constant, moving from an age of less than 65 years to more than 65 years increases the TIMI
score by 0.706 units, which is statistically significant. Similarly, with other parameters
considered, the TIMI score increases by 0.359 units in the group with hypertension, also
found to be statistically significant. In the group with diabetes, the TIMI score increases by
0.380 units, demonstrating a significant effect on the TIMI risk score. Likewise, in the CAD
group, the TIMI score increases by 0.769 units and is observed to be statistically significant.
Additionally, in the smoking category, the TIMI score increases by 0.283 units, exhibiting a
significant effect. However, as observed in the unadjusted regression estimate, smoking does
not show any significant effect on the TIMI score in the presence of other factors.
DISCUSSION:

The research investigates the predictive value of TIMI risk score for adverse cardiac
outcomes in acute coronary syndrome patients. Our findings indicate that an elevated
TIMI score is significantly correlated with an increased risk of major adverse cardiac
outcomes include recurrent myocardial infarction, morbidity, revascularization, and, in the
most severe cases, mortality. Furthermore, the study emphasizes the widespread use of
TIMI risk score in emergency departments to rapidly identify and stratify patients with
potential ACS according to their risk of adverse outcomes and enabling timely
intervention.

The calculation of the TIMI score takes into account individuals aged over 65 years. In our
study, this demographic constitutes 61.2% of the total population, signifying that elderly
individuals face a heightened risk and encounter more adverse events, accompanied by a
lower survival rate of 30.8%. Similarly, the research conducted by ALIQ et al[19,20]
indicates lower survival rate in older groups. Patients with Non ST elevated myocardial
infarction tend to be older and at higher risk for cardPatients complications[10].
Numerous risk factors can augment the likelihood of Major Adverse Cardiac outcomes
(MACE) in ACS patients, including hypertension, diabetes mellitus, obesity, smoking, and
alcohol consumption. A study conducted by Jacqueline Locks and colleagues found that
61.8% of participants had elevated blood pressure, which notably increased the TIMI risk
score[3]. Similarly, our evaluation revealed that 58.8% of patients reported a history of
hypertension, further raising the TIMI risk score. Additionally, diabetes was linked to a
statistically significant rise in the MACE score of 0.529 (Beta = 0.529, p < 0.05).

Additionally, the smoking habit is strongly associated with a heightened risk of

cardiovascular events. However, BMI does not significantly affect the TIMI risk score.
Moreover, factors such as aspirin usage in the past week, ST segment changes on the ECG,
known CAD, elevated cardiac biomarkers, and more than one angina episode within 24 hours
can influence the TIMI score[21,22].

The TIMI risk score represents a validated instrument utilized for patients diagnosed with
coronary artery disease. It serves to classify these patients according to their risk levels and
aids physicians in making informed clinical decisions[11,13]. Patients who attain low scores,
thereby classified as low risk, are recommended to undergo treatment with aspirin,
clopidogrel, and nitrates. Conversely, patients identified as high risk for major adverse
cardiac events necessitate hospitalization and may require invasive interventions. Our study
found a strong correlation between high risk patient categories and significantly
increased incidence of major adverse cardiac events compared to low risk
categories[3,20].

Our analysis demonstrates that patients with history of diabetes have significantly
increased risk of death within 14 days, which aligns with the findings from the study
proposed by Ryu et al. Diabetes mellitus is primarily correlated with cardiovascular events.
Therefore, effectively managing diabetes is a crucial concern for reducing the risk of major
adverse cardiac events[19,23,24].

The validation and subsequent incorporation of this risk score into clinical practice hold
significant potential for developing nations such as India, where the incidence of ischemic
heart disease is remarkably elevated among middle-aged populations, coupled with a scarcity
of relevant literature.
Conclusion:

Our study substantiates the correlation between elevated TIMI scores and greater
susceptibility to cardiovascular outcomes such as morbidity, myocardial infarction,
revascularization, and mortality. This underscores the critical significance of the TIMI risk
score in the identification of high-risk patients requiring immediate medical intervention.
India, being a developing nation, faced a significant burden of ischemic heart disease,
with notably high prevalence, the implementation of the TIMI risk score has the potential to
enhance patient outcomes and alleviate the financial burden associated with treatment.
Furthermore, additional research is warranted to determine the potential cost-saving
benefits of incorporating the TIMI risk score in to early risk assessments for
cardiovascular patients.

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