European Journal of Cardiovascular Medicine

Acute coronary syndromes (ACS) represent an emerging epidemic in India. With the increasing prevalence of risk factors such as obesity, diabetes, hypertension, dyslipidemia, and others, there has been a corresponding rise in the incidence of ACS¹. As a leading cause of morbidity and mortality, ACS poses a major public health challenge. By 2020, it was estimated that ACS would become a major cause of death in all regions of the world².

Over the past few decades, significant improvements have been achieved in the management of ACS. The introduction of coronary care units in the 1960s, pharmacological reperfusion therapy in the 1980s, and the widespread adoption of catheter-based interventions have all contributed to reductions in hospital mortality rates. Furthermore, the use of aspirin, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and statins has markedly improved long-term survival. Nevertheless, ACS remains a major clinical event with substantial psychological and social implications³⁻⁵.

Red cell distribution width (RDW) is a measure of the variation in red blood cell size, reported routinely as part of the complete blood count (CBC). Although commonly used in the differential diagnosis of anemia, where elevated RDW indicates anisocytosis⁶, emerging evidence suggests that RDW may also have prognostic value in cardiovascular disease. Despite advances in diagnostics and therapeutics, ACS continues to carry a high mortality rate, and treatment strategies are still evolving. Therefore, additional parameters beyond established markers are needed to improve risk stratification in ACS. RDW has been proposed as an independent prognostic marker for cardiovascular events, with elevated RDW identified as a strong predictor of mortality and major adverse cardiac events (MACE) in patients with acute myocardial infarction⁷. Recent studies have confirmed the predictive role of RDW in determining the risk of cardiovascular events, prognosis, and severity of coronary artery disease, with higher RDW values associated with greater cardiovascular risk⁸.

Objectives: To determine RDW in patients with ACS and evaluate its relationship with mortality and major adverse cardiac events.

This prospective study was conducted in the Department of General Medicine, Mandya Institute of Medical Sciences (MIMS), Mandya, from January to December 2019. Patients admitted with acute coronary syndromes (ACS) who met the inclusion criteria were enrolled using purposive sampling. The sample size was set at 100, based on prior hospital data indicating approximately 25 eligible ACS admissions per month after applying exclusion criteria.

Eligible patients were aged >18 years, provided informed consent, and had a confirmed ACS diagnosis defined by electrocardiographic changes suggestive of ACS with elevated cardiac biomarkers (creatine phosphokinase-MB and troponin I) or regional wall motion abnormalities on echocardiography. Exclusion criteria included anaemia (haemoglobin <12 g/dL in males, <11 g/dL in females), prior percutaneous coronary intervention or coronary artery bypass grafting, valvular heart disease, haematological disorders, chronic kidney or liver disease, and recent blood transfusion.

Baseline evaluation included demographic data, cardiovascular risk factors (hypertension, diabetes mellitus, smoking, alcohol intake, family history of premature coronary artery disease, obesity), physical examination, and laboratory investigations. Laboratory workup comprised complete hemogram with peripheral smear and red cell distribution width (RDW) using the Diatron Abacus 5 automated CBC analyser, creatine phosphokinase-MB, troponin I, fasting lipid profile, liver and renal function tests, random blood sugar, and thyroid function tests. Electrocardiography and echocardiography were performed in all patients.

Patients were followed up for three months post-discharge. Contact details were recorded, and reminders were issued 10 days prior to follow-up. Outcomes assessed included repeat hospitalization, mortality, and post-ACS cardiac function, evaluated via repeat electrocardiography and echocardiography in survivors.

Data were entered into Microsoft Excel and analyzed using descriptive statistics (frequencies, percentages, means, standard deviations) and inferential statistics (Chi-square test and other appropriate tests). All investigations were routine clinical procedures, with no experimental interventions performed.

The age distribution of study participants showed that the majority were between 61–70 years (34%), followed by 50–60 years (29%). Patients aged below 50 years accounted for 20%, while 15% were between 71–80 years, and only 2% were older than 80 years. Mean age was 59.97+12.76 years. Males comprised 58% of the study population, with females constituting 42%. Among the risk factors, hypertension (31%) was the most frequent, followed by diabetes mellitus (29%) and dyslipidemia (26%). Smoking was reported in 42% of participants, and alcohol consumption in 19% (Table 1).

Assessment of vital parameters revealed that 84% of patients had a heart rate below 90 bpm, 13% between 90–110 bpm, and only 3% above 110 bpm. Systolic blood pressure (SBP) was less than 140 mmHg in 75% of patients and greater than 140 mmHg in 25%. Diastolic blood pressure (DBP) was below 90 mmHg in 59% and above 90 mmHg in 41% (Table 2).

Regarding cardiac findings, NSTEMI was the most common ACS type, affecting 55% of patients, followed by STEMI (31%) and unstable angina (14%). Among STEMI patients, the anterior wall was the most common site of infarction (45.2%), followed by anterolateral wall (25.8%), inferior wall (22.6%), anteroseptal wall (3.2%), and inferior wall with right ventricular involvement (3.2%). Arrhythmia occurred in 36% of patients, repeat angina in 36%, and heart failure in 38%. Three patients (3%) died during the study period (Table 3).

Analysis of RDW levels showed a statistically significant association with age, with higher RDW (>15) more frequent in patients aged 50–70 years (p = 0.021). Dyslipidemia was significantly associated with higher RDW values (35.3% vs. 6.3%, p = 0.002). No significant association was found with gender, diabetes, hypertension, smoking, or alcohol use (Table 4).

The type of ACS was significantly related to RDW, with NSTEMI and STEMI more common in patients with higher RDW, while unstable angina was more frequent in those with lower RDW (p = 0.003). Elevated troponin (>1000) was significantly associated with higher RDW (p = 0.003). Left ventricular ejection fraction (LVEF) showed a highly significant correlation, as all patients with LVEF <40% had elevated RDW (p < 0.001). Other parameters, including RBS and HbA1c, showed no statistically significant relationship with RDW (Table 5).

Major adverse cardiac events (MACE) were significantly more frequent in patients with higher RDW values. Arrhythmia occurred in 47.5% of patients with high RDW compared to 12.5% with normal RDW (p < 0.001). Repeat angina and heart failure were exclusively or predominantly seen in the high RDW group (52.9% and 54.4%, respectively; p < 0.001 for both). Mortality was observed only in the high RDW group (4.4%), though this was not statistically significant (p = 0.549) (Table 6).

Table 1: Profile of subjects in the study

Table 2: Distribution of vital parameters among study subjects

Table 3: Distribution of Cardiac findings and mortality among study subjects

Table 4: Association of factors with RDW among study subjects

Chi-Square/Fisher Exact Test+

Table 5: Correlation of type of ACS and Laboratory findings with RDW of study subjects

Chi-Square/Fisher Exact Test+

Table 6: Correlation of major adverse cardiac events with RDW among study subjects.

Chi-Square/Fisher Exact Test

This prospective study examined the relationship between red cell distribution width (RDW) and clinical outcomes in patients with acute coronary syndrome (ACS). Our findings support the growing body of evidence that elevated RDW is associated with worse cardiovascular outcomes, including arrhythmia, recurrent angina, heart failure, and reduced left ventricular ejection fraction (LVEF).

The majority of our patients were aged between 50–70 years (63%), with a mean age profile similar to previous Indian studies by Reddy et al.⁹ and Bhat et al.¹⁰, which reported peak ACS incidence in the sixth decade. In contrast, Western studies, such as that by Tsuboi et al.¹¹, have shown a higher mean age (>65 years), likely reflecting demographic differences and a higher life expectancy in developed countries.

Our study found no significant gender difference in RDW distribution, consistent with the findings of Ani and Ovbiagele¹² and Salvagno et al.¹³, who reported that RDW is not influenced by sex. However, certain studies, including one by Lippi et al.¹⁴, noted slightly higher RDW in females, which may be attributable to differences in baseline haematinics and hormonal status.

Hypertension (31%), diabetes mellitus (29%), and dyslipidemia (26%) were the most common comorbidities. Notably, dyslipidemia showed a significant association with elevated RDW (p = 0.002). This aligns with Tonelli et al.¹⁵, who suggested that RDW may reflect underlying lipid-related oxidative stress and inflammation, both of which contribute to atherosclerosis.

NSTEMI was the most common ACS type (55%), followed by STEMI (31%) and unstable angina (14%). Patients with higher RDW were more likely to have NSTEMI or STEMI, while unstable angina was more common in those with lower RDW. Similar patterns were reported by Uyarel et al.¹⁶ and Zhao et al.¹⁷, who found elevated RDW more prevalent in myocardial infarction compared to unstable angina, likely due to the greater systemic inflammatory and oxidative stress burden in infarction.

We observed a significant correlation between high RDW and elevated troponin levels (>1000 ng/L, p = 0.003), in line with research by Isik et al.¹⁸, which demonstrated that RDW correlates with the extent of myocardial injury. RDW also showed a strong inverse relationship with LVEF, as all patients with LVEF <40% had elevated RDW (p < 0.001). This is consistent with the studies of Al-Najjar et al.¹⁹ and Polat et al.²⁰, which reported that higher RDW values predict left ventricular systolic dysfunction, possibly due to chronic inflammation, impaired erythropoiesis, and neurohormonal activation.

Elevated RDW was significantly associated with arrhythmia (47.5% vs. 12.5%, p < 0.001), recurrent angina (52.9% vs. 0%, p < 0.001), and heart failure (54.4% vs. 3.1%, p < 0.001). Similar associations have been described in meta-analyses by Hu et al.²¹ and Ani and Ovbiagele¹², supporting the role of RDW as a predictor of major adverse cardiac events (MACE). Mortality in our study (3%) was low and not significantly associated with RDW, possibly due to the short follow-up duration and smaller sample size, in contrast to large cohort studies such as that by Cavusoglu et al.²², which demonstrated a significant link between elevated RDW and mortality over longer follow-up.

The relationship between elevated RDW and adverse outcomes in ACS may be explained by several mechanisms, including chronic inflammation, oxidative stress, impaired iron metabolism, and subclinical nutrient deficiencies affecting erythropoiesis²³. Variations in results between studies could be due to differences in population demographics, baseline comorbidities, laboratory cut-offs for RDW, timing of measurement in the ACS course, and follow-up duration.

This study had a relatively small sample size, which may limit the strength of the associations observed. There was no dedicated control group; although unstable angina patients had near-normal RDW values, including patients with non-anginal chest pain could have provided a clearer comparison. Finally, it was not possible to determine whether elevated RDW was pre-existing or developed as a result of the ischemic event. Longer-term prospective studies are needed to clarify this cause–effect relationship.  

RDW values are significantly elevated above normal in patients presenting with acute coronary syndrome. RDW is elevated maximum in patients with STEMI, NSTEMI when compared to unstable angina. There is significant correlation between RDW and incidence of Left ventricular systolic function. RDW values are significantly elevated in patients who suffered from major adverse cardiovascular events. Patients with significantly elevated RDW values, may in future be referred for early invasive revascularization procedures like PCI, CABG. As concerns acute coronary syndrome, RDW values seems to have the features of a good prognostic marker with optimal sensitivity of diagnostic assay and it helps improve our ability to predict adverse events in coronary artery disease. Further its prognostic impact can be utilized in risk stratification and the need for urgent therapeutic intervention.

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