Association of Low Serum Albumin Levels and its In-hospital Adverse Outcomes among Patients Presenting with Acute Coronary Syndrome in a Tertiary Care Hospital of West Bengal, India

1. Specialist Medical Officer, Department of General Medicine, Basirhat District Hospital, Basirhat, West Bengal, India. 2. Assistant Professor, Department of Physiology, IPGME&R, Kolkata, West Bengal, India. 3. Assistant Professor, Department of General Medicine, Tamralipto Government Medical College, Tamluk, West Bengal, India. 4. Associate Professor, Department of General Medicine, IPGME&R, Kolkata, West Bengal, India. 5. Retired Professor and Head, Department of General Medicine, R.G. Kar Medical College, Kolkata, West Bengal, India.

Abstract

Introduction: Acute Coronary Syndrome (ACS) is characterised by hypercoagulability and inflammation. In the acute presentation of Ischaemic Heart Disease (IHD), such as ACS, serum albumin may also play an important role. Many patients with an ischaemic cerebrovascular accident, a condition similar to ACS, had low serum albumin levels.

Aim: To estimate serum albumin levels in patients with ACS and their relation to hospital adverse outcomes.

Materials and Methods: The present prospective observational study was conducted in the Department of General Medicine at R.G. Kar Medical College and Hospital, West Bengal, India. The duration of the study was 18 months, from July 2019 to October 2020. Patients with ACS were included irrespective of age, sex, race, and predisposing factors such as Hypertension (HTN), Diabetes Mellitus (DM), hyperthyroidism, and dyslipidaemia. A total of 125 patients were included, and details such as relevant history, examination findings, laboratory investigation, Electrocardiography (ECG), Echocardiography (ECHO), chest X-ray Posteroanterior (PA) view were included. Chi-square test and logistic regression were applied.

Results: A total of 94 (75.2%) patients were male. 49 (39.2%) study patients had DM. A total of 10 (8%) patients presented with cardiac arrest at admission. In-hospital death occurred in 9 (7.2%) cases. 59 (47.2%) patients had a normal serum albumin level (3.5-4.5). 61 (48.8%) had mild to moderate hypoalbuminaemia (2.5-3.5), and only 5 (4%) had severe hypoalbuminaemia (<2.5). The association of in-hospital complications vs serum albumin level was statistically significant (p<0.0001). A multivariate logistic regression analysis showed that male gender (p-value=0.026), smoking (p-value=0.008), arrhythmia (p-value=0.002), increased creatinine (p-value=0.032), and hypoalbuminaemia (p<0.001) were statistically significant independent predictors of in-hospital adverse outcomes.

Conclusion: The low serum albumin level, measured immediately on hospital admission in ACS patients, was associated with in-hospital complications, and when adjusted for other covariates, hypoalbuminaemia predicts in-hospital adverse outcomes independently.

Coronary event, Hypoalbuminaemia, In-house complication, Single centre study

The ACS is a hypercoagulable and inflammatory state that occurs due to the mismatch between myocardial oxygen supply and demand, resulting in the following processes that lead to the formation of thrombus: plaque rupture and erosion causing disruption of unstable coronary plaque or a protruding calcified module leading to the formation of intracoronary thrombus and an inflammatory response. In patients with Non-ST-elevation Myocardial Infarction (NSTEMI), there are multiple such vulnerable plaques (1). The normal physiological concentration of serum albumin has an antioxidant mechanism that provides significant reduction in myocardial injury from ischaemia and reperfusion (2),(3). Albumin helps in the formation of prostaglandin D2 and inhibits thromboxane synthase. Hence, albumin enhances the inhibition of platelet aggregation. Several conditions are associated with elevated blood viscosity, which is an important risk factor for atherosclerosis, cardiovascular disease, and its adverse consequences (4). In various clinical conditions, serum albumin is traditionally considered a reliable biomarker for risk prediction. Low serum albumin has been shown to be associated with an increased risk of cardiovascular mortality and all-cause mortality (5),(6). There is still insufficient evidence regarding the factors affecting outcomes after ACS.

In recent times, the clinical manifestation and prognosis of Cardiovascular Disease (CVD) have altered due to emerging medical therapies and innovative revascularisation procedures. Therefore, it is important to identify new biomarkers and reevaluate the significance of traditional risk markers.

The association of low serum albumin with Coronary Artery Disease (CAD) and mortality has been shown in different populations in several studies (7),(8),(9). In ACS, which is an acute phase of IHD, where serum albumin might have an important role, low serum albumin has been shown to be an important predictor of mortality in acute ischaemic stroke, a condition resembling ACS (10). However, the impact of hypoalbuminaemia on the outcome of ACS has not been well studied. Therefore, the objectives of the present study were to estimate serum albumin levels in patients presenting with ACS and predict in-hospital outcomes according to serum albumin levels.

Material and Methods

The present study was a prospective observational study, conducted in the Department of General Medicine at R.G. Kar Medical College, Kolkata, West Bengal, India. The duration of the study was 18 months, from July 2019 to October 2020. Approval of Institutional Ethics Committee was taken prior to the study (Approval no. RKC/309). A written informed consent was taken from each patient prior to their inclusion in the study.

Inclusion criteria: Patients with ACS who were admitted in General Medicine Ward of the Hospital irrespective of age, sex, race and predisposing factors such as DM, HTN, thyroid disease and dyslipidaemia were included.

Exclusion criteria: Chronic Kidney Disease (CKD) (beyond stage III), chronic liver disease, presence of stroke, recent history of trauma and skeletal muscle injury, malignancy, known patients with chronic inflammatory disease and ongoing infectious disease, venous thromboembolism, patients with heart failure, cardiogenic shock, arrhythmia or valvular heart diseases were excluded.

Sample size calculation: Statistical formula for sample size: N={(Z1-α/2)2xPxQ}/L2. In the present study, putting the below mentioned values (Z1-α/2)=1.96 considering 95% confidence level P=prevalence of adverse outcomes among ACS patients with hypoalbuminaemia i.e., 20% Q=100-P i.e., 80L=precision or margin of error which is less than 10 and less than P, here, the value taken is 7. So, calculating the above equation the sample size (N) of this study was 125. Samples were chosen by systematic random sampling and every 4th patient was selected as their study sample after choosing the first patient randomly. Hence, the authors included 138 patients for the study. 13 patients denied participating in the study, so, the final study sample was 125.

Study Procedure

According to a study conducted by Hartopo AB et al., there was 20% prevalence of adverse outcomes among ACS patients with hypoalbuminaemia (11). All ACS patient admitted in General Medicine ward at R.G. Kar Medical College and Hospital for management and who had given consent for participation in the present study were evaluated with relevant history taking, examination, laboratory investigations ECG, ECHO, digital chest X-ray PA view. The following outcomes were assessed during hospital admission: Heart failure, arrhythmia, arrhythmia with Left Ventricular Failure (LVF), arrhythmia with pleural effusion, cardiogenic shock and death.

The following is the criteria by which ACS patients were diagnosed and selected for data collection:

Definitions and criteria of Acute Coronary Syndrome (ACS)

a. C Clinical criteria (1):

Typical presentation was with severe chest discomfort with one of these three features:

• Occurrence at rest or with minimal exertion lasting for >10
minutes.
• Relatively recent onset i.e., within prior two weeks.
• A crescendo pattern i.e., distinctly more severe, prolonged or frequent than previous episode.
Common site of discomfort: Substernal with radiation to left arm, left shoulder and or upwards to
neck or jaw.

b. ECG criteria of AC S (12),(13),(14):

a. ST-elevation Myocardial Infarction (STEMI): Elevation of origin of ST segment at its junction (J point) with QRS complex in two or more contiguous leads of

• 0.1 mv (1 mm) in any lead except V2 and V3.
• In V2 and V3 ST J point elevation of
• 0.25 mv (2.5 mm) in men <40 years of age.
• 0.20 mv (2 mm) in men ≥40 years of age.
• 0.15 mv (1.5 mm) in women.

c. Non ST-elevation Acute Coronary Syndrome (NSTE-ACS):

• New down sloping or horizontal ST segment depression ≥0.05 mv in two contiguous leads.
• T wave inversion ≥0.1 mv in two contiguous leads with prominent R wave or R:S ratio >1

d. A Acute Myocardial Infarction (MI) in presence of Left Bundle Brunch Block (LBBB):


• ST elevation ≥1 mm and concordant with a predominantly negative QRS.
• ST depression ≥1 in leads V1, V2 or V3
• ST elevation ≥5 mm and discordant with a predominantly negative QRS.

e. A Angina equivalent (1):

• Dyspnoea
• Epigastric discomfort
• Nausea
• Weakness

Serum Albumin was estimated by dye binding (bromocresol green) method. Patients were classified according to albumin levels into normal albumin group (3.5-4.5 gm/dL), mild to moderate hypoalbuminaemia (2.5-3.5 gm/dL) and severe hypoalbuminaemia (<2.5 gm/dL) group (15),(16). N-Terminal Pro-B type Natriuretic Peptide (NT-ProBNP) was estimated using serum sample by Enzyme-linked Immunosorbent Assay (ELISA) method. A value more than 125 pg/mL was taken as elevated level (17).

Statistical Analysis

Microsoft excel spreadsheet was used for data entry. Statistical analysis was done by Statistical Package for Social Sciences (SPSS) version 27.0; Inc., Chicago, USA) and GraphPad Prism version 5. Data was summarised as count and percentage for categorical variables and mean and standard deviation for numerical variables. For categorical variables a Chi-square test was used and t-test was used for numerical variables. One-way Analysis of Variance (one-way ANOVA) was used to compare the means of three or more samples for numerical data. Logistic regression analysis was done. The p-value ≤0.05 was taken as statistically significant.

Results

Most of the patients 94 (75.2%) were males and 31 (24.8%) patients were females. A 48.0% of study patients were smoker (Table/Fig 1). Most of the patients (95) had normal pulse rate (60-100 bpm). 20 patients had bradycardia (<60) and 10 patients had tachycardia (>100). Most of the patients had normal Systolic Blood Pressure (SBP) 90/119 56 (44.8%). Patients with SBP <90 were only five and SBP ≥140 were only 22 (17.6%) cases. Total 102 (81.6%) patients had normal Jugular Venus Pressure (JVP). 15 (12%) study patients had raised Jugular Venous Pulse (JVP) and 8 (6.4%) cases had flat JVP.

A total of 55 (44%) patients had raised NT-ProBNP value. Most of the patients had normal chest X-ray findings 82 (65.6%), whereas, 11 (8.8%) cases had apical distribution of vessels. Digital X-ray of chest PA view showed Kerley lines in 9 (7.2%) cases. Normal serum albumin level (3.5-4.5) was found in 59 (47.2%) patients, 61 (48.8%) had mild to moderate hypoalbuminaemia (2.5-3.5) and only 5 (4%) patients had severe hypoalbuminaemia (<2.5) (Table/Fig 2). Most common in-hospital complication was arrhythmia in 26 (20.8%) cases and least common was arrhythmia with pleural effusion in 2 (1.6%) patients. In-hospital death was reported in 9 (7.2%) cases. No in-hospital complications found in 57 (45.6%) cases. A 47 (37.6%) cases were discharged with complication (Table/Fig 3). The association between in-hospital complication vs serum albumin level was statistically significant (p<0.0001) (Table/Fig 4). There was significant association between NT-ProBNP and serum albumin level (<0.001). Among patients in normal albumin group NT-ProBNP was elevated in 10 (16.9%) cases, whereas, it was elevated in 41 (67.2%) cases in mild to moderate hypoalbuminaemia group and 4 (80%) cases in severe hypoalbuminaemia group (Table/Fig 5). A multivariate logistic regression analysis was done which showed smoking (p-value=0.008), male gender (p-value=0.026), arrythmia (p-value=0.002), increased creatinine (p-value=0.032) and hypoalbuminaemia (p<0.001) were statistically significant independent predictors of in-hospital adverse outcomes (Table/Fig 6).

Discussion

The ACS is a hypercoagulable and inflammatory state. IHD and its most serious acute presentation i.e., ACS are most common causes of mortality and morbidity worldwide (1). Arques S et al., found the usefulness of serum albumin as an additional prognostic marker to the usual prognostic variables in older patients with severe acute heart failure (18). In the present study, heart failure was more common in mild to moderate hypoalbuminaemia group (81.3%) than normal albumin group (18.8%) (p<0.001). In ACS patients, Wang W et al., found significantly higher adverse cardiac events in low prealbumin group as compared with normal prealbumin. According to their study with ACS patients, lower serum prealbumin level was shown to be associated with more in-hospital complications (19). In present study, higher adverse event in hypoalbuminaemia groups were found. A significant association was found between serum albumin and NT-ProBNP level (p<0.0001), which was more frequently elevated among patients in mild to moderate hypalbuminaemia (67.2%) and severe hypoalbuminaemia (80%) groups than normal albumin group (16.9%). Jäntti T et al., found that, hypoalbuminaemia was commonly seen in early cardiogenic shock. They also noticed plasma albumin decreased frequently during hospital stay. They found the significant association between plasma albumin early at admission and adverse outcome. The baseline low plasma albumin was associated with mortality which was independent of other known risk factors (20). In present study, mortality was more frequent in mild to moderate hypoalbuminaemia 5 (55.6%) and severe hypoalbuminaemia group 3 (33.3%) than in normal albumin group 1 (11.1%). There was significant association between serum albumin and death (p<0.001). Suzuki S et al., found that Serum albumin was associated with Major Adverse Cardiac Events (MACE) in newly diagnosed stable CAD patients and that association was independent of other risk predictors (21).

In a meta-analysis, Wang Y et al., showed the association between low serum albumin and increased risk of atrial fibrillation (22). In present study, arrythmia was developed in 26 (20.8%) cases, of them 16 cases were from mild to moderate hypoalbuminaemia group. Arrythmia and LVF were present in 12 (9.6%) cases. Among them 11 cases were from mild to moderate hypoalbuminaemia group. Hartopo AB et al., found that hypoalbuminaemia was associated with 2.8 fold increased risk of developing adverse outcomes in ACS. Though, after adjustment of other known covariates, hypoalbuminaemia did not predict in-hospital complications significantly (11). In present study, multivariate logistic regression analysis was done where hypoalbuminaemia was a significant independent risk predictor along with other known risk factors like male gender, smoking, increased serum creatinine and arrythmia. Smoking is a known risk factor for atherosclerotic CVD. But, some studies have found lesser in-hospital complications of current smokers after ACS which is known as smoker’s paradox. This phenomenon can be largely explained by lesser other risk factors and co-morbidities of smoker patients [23,24]. In the present study, smoking is significantly associated with in-hospital complication with odds ratio 0.721 indicative of less adverse events for smokers. Though, male gender is a risk factor for IHD, higher in-hospital complications have been shown in female in serval studies [25,26]. Cenko E et al., found higher 30 day mortality in young age female with STEMI even after adjustment of medication, Percutaneous Coronary Intervention (PCI) and other co-morbidities (27). The present study population is male dominant (male 75.2% and female 24.8%). The odds ratio for male gender was 0.869, which indicates less adverse outcome for males than females. Raised creatinine, as seen in renal insufficiency is a known risk factor for CVD. Shlipak MG et al., found higher mortality in patients with renal insufficiency after ACS in elderly patients. One year mortality was 66% for those with moderate renal insufficiency, whereas, it was 46% for mild renal insufficiency and 24% with no renal insufficiency (28). In the present study, 28 (22.4%) cases had raised creatinine (>1.3 mg/dL) and raised creatinine was significantly associated with in-hospital adverse outcome with the odds ratio of 0.809. In a meta-analysis Zhu L et al., found that low serum albumin was a powerful independent predictor of all-cause mortality in hospitalised ACS patients (29). In the present study, authors found that hypoalbuminaemia predicted in-hospital outcome significantly even after adjustment with other covariates.

Limitation(s)

In spite of every sincere effort, present study was not devoid of shortcomings. It was a single centric study with relatively small sample size, which may not be sufficient. Pathogenesis of low serum albumin level remains a matter of speculation as, the authors did not measure the biomarkers associated with low serum albumin.

Conclusion

The present findings indicate that arrhythmia (20.8%) is the most common in-hospital complication, followed by heart failure (12.8%) in ACS patients. Low serum albumin measured at the time of hospital admission was associated with in-hospital adverse outcomes with an odds ratio of 1.667. It was also found that adverse outcomes were significantly associated with the severity of hypoalbuminaemia. Whether the impact of low serum albumin in the early phase of ACS was a result of inflammation or an independent effect needs to be clarified, so further studies are needed. Even after adjustment with other covariates, hypoalbuminaemia independently predicts in-hospital adverse outcomes.

Acknowledgement

The authors are thankful to all faculty residents and staff of Department of Cardiology, R.G. Kar Medical College for their support and cooperation.

DOI and Others

DOI: 10.7860/JCDR/2023/60490.17825

Date of Submission: Sep 29, 2022
Date of Peer Review: Nov 19, 2022
Date of Acceptance: Feb 03, 2023
Date of Publishing: May 01, 2023

AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was Ethics Committee Approval obtained for this study? Yes
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. NA

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