Association of low serum albumin concentration and adverse cardiovascular events in stable coronary heart disease

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Abstract

Objective

Coronary heart disease (CHD) is a leading cause of death in developed countries. Exploration of indicators to identify high risk individuals who develop adverse outcomes despite stable baseline condition is important. This study is to evaluate the association between serum albumin concentration and cardiovascular (CV) outcomes in individuals of stable CHD.

Methods

Seven-hundred–thirty-four participants from Biosignature study, a nationwide prospective cohort study aimed to identity risk factors among patients with stable CHD, were enrolled for analysis. They were divided into low serum albumin group (baseline albumin concentration < 3.5 g/dL, n = 98) and normal albumin group (baseline albumin concentration ≥ 3.5 g/dL, n = 636). The relations between baseline albumin and adverse CV outcomes within 18 months of follow-up were analyzed.

Results

Compared baseline characteristics with normal albumin group, subjects in low albumin group are older, having more diabetic patients, lower hemoglobin level, lower estimated glomerular filtration rate, lower total cholesterol level, lower left ventricular ejection fraction, and higher blood glucose. While there is no significant difference of total CV events between two groups, low serum albumin concentration is associated with an increased risk of all-cause mortality (10.2% vs. 0.5%, p < 0.001) and hard CV events (7.1% vs. 1.4%, p < 0.001). The association remains significant after adjustments for confounders (all-cause mortality, HR: 6.81, 95% CI: 1.01–45.62; hard CV events, HR: 3.68, 95% CI: 1.03–13.19).

Conclusions

Low serum albumin concentration (< 3.5 g/dL) worsens prognosis of patients with stable CHD.

Introduction

Coronary heart disease (CHD) is a leading cause of death in developed countries. Patients with stable CHD are known to have an increased risk of the future cardiovascular (CV) events, thus identifying risk factors among them is warrant for therapeutic prevention [1]. Several biomarkers have been investigated for risk stratifications. Proposed biomarkers usually reflect important pathophysiological states of atherosclerosis: inflammatory process, such as C-reactive protein (CRP), vulnerability of the atheromatous plague, such as myeloperoxidase and soluble CD40 ligand, and hypercoagulable state, such as fibrinogen [2].

Serum albumin, a major protein found in extracellular fluid compartment, contributes to maintain diverse physiological functions [3]. It has been studied to be associated with atherosclerosis with possible mechanisms including response to inflammation [4], [5], [6], fibrinolysis and hemostasis [7], possible inhibition of platelet aggregation [8], the capacity of antioxidant [9], the tendency of blood hyperviscosity [10], and the relation of nutritional status [6]. Epidemiologic studies reported that low serum albumin concentration predicted adverse outcomes in general population [11], [12], [13], [14], [15], acute coronary syndrome [16], [17], [18], stroke [19], heart failure [20], renal failure [21], elderly [22], [23], [24], and malignancy [25]. In current interventional era, serum albumin concentration is also an important predictor of no-reflow phenomenon following primary percutaneous coronary intervention and in-stent restenosis rate after bare-metal stent implantation [26], [27].

This is a prospective study aimed to investigate the association between serum albumin concentration and CV outcomes in patients with stable CHD.

Section snippets

Study population

The Biosignature study was a nationwide prospective cohort study to identify risk factors among CHD patients in stable condition at baseline. Nine medical centers in Taiwan participated in this study. Patients with history of significant CHD, as documented by coronary angiogram, a history of myocardial infarction (MI) as evidenced by 12-lead electrocardiography or hospitalization, or a history of angina with ischemic electrocardiographic changes or positive response to stress test, were

Albumin and baseline patient characteristics

Among the 734 subjects with stable CHD and had baseline albumin measurements, 84% of them were men and the mean age was 62.1 years old. The low albumin group had 98 patients, with a mean albumin concentration of 3.2 ± 0.3 g/dL; the rest 636 patients were in normal albumin group, with a mean albumin concentration of 4.1 ± 0.3 g/dL. Table 1 showed the baseline characteristics of study patients. In low albumin group, the patients were older, lower in average hemoglobin level, eGFR, LVEF, and total

Discussion

In this prospective cohort study, low serum albumin concentration (< 3.5 g/dl) is associated with an increased risk of major adverse CV events and mortality within 18 months. The association remains significant after adjustments for confounders (all-cause mortality, HR: 6.81, 95% CI: 1.01–45.62; hard CV events, HR: 3.68, 95% CI: 1.03–13.19). Several studies have reported that a lower concentration of serum albumin was associated with an increased risk of CV mortality [11], [12], [15] and all-cause

Conflicts of interest

All authors declare no conflicts of interest.

Acknowledgments

Biosignature project is supported by Academia Sinica (project number: BM10501010039). HIY thanks the support from MacKay Memorial Hospital (MMH-E-10403) and Ministry of Science and Technology (MOST 105-2632-B-715-001).

References (31)

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All authors mentioned above take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

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