Review Article

Page 1 of 8

The role of albumin level in cardiovascular disease: a review of

recent research advances
Goro Yoshioka1, Atsushi Tanaka1, Yuhei Goriki2, Koichi Node1
1
Department of Cardiovascular Medicine, Saga University, Saga, Japan; 2Department of Cardiology, Ureshino Medical Hospital, Ureshino, Japan
Contributions: (I) Conception and design: G Yoshioka, A Tanaka; (II) Administrative support: G Yoshioka, A Tanaka; (III) Provision of study materials
or patients: G Yoshioka, A Tanaka; (IV) Collection and assembly of data: G Yoshioka, A Tanaka; (V) Data analysis and interpretation: G Yoshioka, A
Tanaka; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.
Correspondence to: Goro Yoshioka; Atsushi Tanaka. Department of Cardiovascular Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan.
Email: [email protected]; [email protected].

Abstract: Serum albumin is a major component of serum protein that is widely used in clinical practice
as an indicator of nutritional or inflammatory status. In clinical practice, serum albumin level is generally
used to monitor the courses of several diseases, including hypovolemic state, burns, shock, surgical bleeding.
Several studies have indicated that serum albumin level is associated with the prognoses of patients with
cardiovascular disease (CVD). Low albumin level has been shown to be useful in predicting adverse events,
especially in coronary artery disease. In addition, albumin level has been already reported to be useful for
predicting cardiac events, such as cardiovascular death and hospitalization for heart failure (HF), in the acute
and remote phases of acute coronary syndrome (ACS). Furthermore, the predictive value of albumin level
for bleeding events has been reported, indicating the possibility of a comprehensive prediction of adverse
events after ACS. However, since serum albumin levels fluctuate depending on a patient’s general condition,
the need for reassessment during the chronic phase of CVD has been discussed. In this review, we discuss
the existing evidence on serum albumin level as a residual risk factor for coronary artery disease and outline
future prospects for risk stratification using albumin level.

Keywords: Acute myocardial infarction (AMI); cardiovascular disease (CVD); heart failure (HF); bleeding; serum
albumin

Received: 16 August 2022; Accepted: 07 December 2022; Published online: 28 December 2022.
doi: 10.21037/jlpm-22-57
View this article at: https://dx.doi.org/10.21037/jlpm-22-57

Serum albumin leakage of albumin from the gastrointestinal tract (1).

Albumin level may also decrease as a result of redistribution
Serum albumin is an essential nutritional indicator, the
from the intravascular space to the interstitial space due to
major factor of oncotic pressure, and the modulator of
increased capillary permeability, or as a reflection of poor
body fluids (1). In clinical setting, serum albumin level is nutritional status and liver function (4).
recognized as a simple and essential nutritional indicator Regarding the action and pathophysiology of albumin,
and is generally used to evaluate the clinical courses of it is believed to have a significant relationship with cardiac
various diseases, including shock status, burns, bleeding dynamics and inflammation and has several characteristics
event, trauma, hemorrhage, acute respiratory distress in common with the aggravating factor of cardiovascular
syndrome, terminal renal dysfunction, nutritional therapy, disease (CVD) (5). Thus, several studies have been
and post-resuscitation (2,3). Decrease in serum albumin conducted to clarify the relationship between serum
level is common in critically ill patients and is mainly due albumin level and CVD.
to increased wasting, bleeding due to inflammation, and In daily clinical setting, the serum albumin level under

© Journal of Laboratory and Precision Medicine. All rights reserved. J Lab Precis Med 2023;8:7 | https://dx.doi.org/10.21037/jlpm-22-57
Page 2 of 8 Journal of Laboratory and Precision Medicine, 2023

Development of CVD

Several studies have indicated that LSA is an independent

predictor of the development of HF (9,10). A registry study
of 2,907 patients (9) and a large observational study of 5,795
CVD
Inflammation
LSA
health checkup patients who were followed up for 9.6 years
Loss of albumin
demonstrated that LSA is an independent risk factor for the
development of chronic HF. This result was consistent after
Atrial fibrillation adjusting for various inflammatory markers and body mass
Coronary artery disease
Cardiogenic shock index (BMI) (10).
Heart failure Several reports have been published regarding the
association between albumin level and arrhythmia (11,12).
Figure 1 Relationship between cardiovascular disease and low
Albumin level has been shown to be an independent
serum albumin level. CVD, cardiovascular disease; LSA, low serum
prognostic factor for the development of atrial fibrillation,
albumin.
the most common arrhythmia in real-world clinical
settings. In an observational study of 8,870 patients (8-year
observation period) without CVD, LSA was a predictor
3.5 g/dL is generally considered as hypoalbuminemia.
of the development of atrial fibrillation in women. This
However, there was no universal and clear definition of the
result was independent of other cardiac diseases, BMI, and
low serum albumin (LSA) level to predict adverse events
inflammatory markers (12). An observational study of 830
in cardiovascular medicine. Recent studies demonstrated
patients with CVD who underwent coronary artery bypass
an increased risk of cardiovascular events even at levels of
surgery showed the usefulness of serum albumin level in the
3.5–4.0 g/dL (6,7). In our previous study for patients
development of postoperative atrial fibrillation (13).
admitted due to acute myocardial infarction (AMI), the serum
albumin level under <3.8 g/dL was an independent predictor
of adverse cardiac events at chronic phase of AMI (8). Prognostic factors for CVD
Therefore, we tentatively consider the serum albumin
LSA is considered a predictive factor for the development
level under 3.8 g/dL as LSA of the risk factor in the area of and prognosis of CVD. In addition, LSA has been reported
cardiovascular medicine. to be a useful predictor of HF. In a study of 352 patients
Previous reviews in 2010s have already summarized with chronic HF, LSA at initial presentation was associated
clinical evidence between serum albumin level and CVD (4). with elevated N-terminal pro-B-type natriuretic peptide
However, evidence including albumin level and bleeding (NT-proBNP) levels and increased long-term mortality (14).
event after CVD was not well taken in account. LSA has also been shown to be an independent predictor
Furthermore, although serum albumin levels fluctuate of short- and long-term events in patients with acute
depending on a patient’s general condition, the need and HF. A study of 546 patients with non-ischemic acute HF
significance for reassessment during the chronic phase of showed that LSA at admission is an independent predictor
CVD has not been sufficiently discussed. of adverse cardiac events (15). In these reports, the adverse
In this review, we discuss the existing studies and recent effects of LSA were attributed to malnutrition, decrease
evidence on the association between serum albumin level, in hepatic synthesis, elevated vascular permeability, and/or
especially LSA, and CVD and present future prospects for renal dysfunction. Other reports have linked albumin level
risk assessment of CVD, including coronary artery disease. to adverse outcomes in a wide range of CVDs, including
venous thromboembolism (16,17).
In a study of 204 patients with chronic coronary
Serum albumin and CVD
syndrome conducted over a 708-day observation period,
Reports on serum albumin and CVD are extensive. LSA the results showed that LSA predicted adverse cardiac
level has been reported to be associated with CVD, such as events, including all-cause mortality, stroke, and myocardial
heart failure (HF), atrial fibrillation, and coronary artery infarction (MI) (18). Furthermore, a study of 1,316 patients
disease (Figure 1). with chronic coronary syndrome and chronic kidney

© Journal of Laboratory and Precision Medicine. All rights reserved. J Lab Precis Med 2023;8:7 | https://dx.doi.org/10.21037/jlpm-22-57
Journal of Laboratory and Precision Medicine, 2023 Page 3 of 8

disease demonstrated that LSA at admission is a predictive conducted a single-center, retrospective observational
factor for major adverse cardiac events (including all-cause study of 2,253 consecutive patients with AMI (8). In that
mortality, stroke, and MI) in remote phase (19). These study, the group with LSA (cutoff: 3.8 g/dL) in the acute
reports suggest that the primary cause of the negative phase of AMI showed a significantly increased frequency of
effect of LSA is inflammation associated with severe adverse cardiac events (combined outcome of cardiovascular
atherogenesis. death and re-hospitalization for HF) in the chronic phase,
indicating that LSA could be a prognostic factor for adverse
cardiac events in patients with AMI. The results were
Serum albumin and acute coronary syndrome
consistent for each component of cardiovascular death and
(ACS)
re-hospitalization for HF in the chronic phase of AMI,
Technological advances in primary reperfusion therapy, again demonstrating the clinical impact of risk stratification
pharmacy, and physical therapy for ACS have reduced the after AMI.
incidence of short-term mortality in patients with ACS (20). Regarding other adverse events, a single-center
The rate of in-hospital mortality among patients with ACS registry study demonstrated that LSA is useful for the risk
has improved as well, especially in the primary percutaneous stratification of bleeding events after PCI in patients with
coronary intervention (PCI) era (21). However, despite ACS, which is consistent with the results for the group
advances in multidisciplinary acute care for MI, the clinical without traditional bleeding risk factors (31). This finding
need to manage the risks of HF and mortality, which are was also reported in a multicenter registry study on AMI (32).
elevated in the remote phase of MI, remains unmet (22). In addition, a study of 1,724 consecutive patients with
Hence, risk stratification for the prevention of HF and AMI undergoing PCI showed that LSA at admission is an
mortality should be performed in the early phase of independent predictor of chronic bleeding events. However,
MI. Previous studies have shown that the following are serum albumin levels are extremely variable during the
important risk factors for HF and mortality in patients with acute phase of AMI owing to acute inflammation and
MI: patient characteristic, electrocardiographic features, circulatory dynamics (1). Some studies in which C-reactive
and factors of reperfusion therapy, ventricular function, protein/albumin ratio was used to account for the effects of
and frailty status (23,24). Risk scores, such as the Global inflammation showed its usefulness in predicting adverse
Registry of Acute Coronary Events (GRACE) score, have cardiac events during hospitalization after coronary artery
been established and are widely used (25,26). Albumin bypass surgery (33,34). Nevertheless, albumin levels may
level is taken into account in some scores. Prognostic change with post-discharge medication use and change in
nutritional index is calculated using serum albumin and nutritional intake status. Therefore, serum albumin levels
total lymphocyte count; geriatric nutritional risk index measured in the acute phase of AMI alone may have limited
is calculated using serum albumin level and BMI; and predictive ability in the remote phase. The measurement of
controlling nutritional status score is calculated using the serum albumin levels during the chronic phase of AMI is
serum albumin level, total cholesterol, and total lymphocyte expected to improve risk stratification. However, systematic
counts. These scores were also used as nutritional indicators reassessment in the chronic phase of AMI has not yet been
and serve as significant prognostic factors in clinical fully established or implemented in real-world clinical
outcomes in CVD (27-29). However, the clinical significance settings. Hence, clinical evidence of the impact of such
of albumin itself was not well identified in those existing chronic transitions on post-MI prognosis is lacking. There
models using multiple factors. Therefore, we examined the are only a few studies on the association between chronic-
prognostic role of serum albumin level in CVD. phase serum albumin levels and long-term cardiovascular
The prognostic impact of serum albumin level, a simple event. We conducted a single-center, retrospective,
indicator, on cardiac events in the remote phase after observational study of 1,424 consecutive patients with
ACS has been reported in several studies. A retrospective AMI to determine the changes in albumin levels from the
observational study of 7,192 patients with ACS showed that acute phase of AMI to the chronic phase (one year later) in
LSA (cutoff: 3.5 g/dL) at admission is an independent risk actual clinical practice (35). The results of the study suggest
factor for in-hospital death and development of HF (6). that LSA (cutoff: 3.8 g/dL) in the chronic phase of AMI,
There have also been several reports on hypoalbuminemia irrespective of the serum albumin level in the acute phase
and the long-term prognosis of ACS (6,30). Our group of AMI, is a predictive indicator for long-term outcomes

© Journal of Laboratory and Precision Medicine. All rights reserved. J Lab Precis Med 2023;8:7 | https://dx.doi.org/10.21037/jlpm-22-57
Page 4 of 8 Journal of Laboratory and Precision Medicine, 2023

Peak CPK Use of ACE-I/ARBs

Primary PCI Male

Use of MRAs
Younger age
Preserved renal function
Younger age

At admission 1-year follow-up

No LSA
No LSA 74.8%
No remote LSA
(Albumin level ≥3.8 g/dL)
88.4%
79.7%
Improved
13.6%

New-onset
4.9%
LSA
Remote LSA
(Albumin <3.8 g/dL)
11.6%
20.3% Persistent
6.7%

Older age

Reduced renal function

No use of
MRAs
Use of statins

Figure 2 Risk factors for changes in albumin status. Adjusted for age, sex, body mass index, coronary risk factors (hypertension,
dyslipidemia, diabetes mellitus, smoking, family history of cardiovascular disease), history of malignant tumor, onset-to-admission time, pre-
thrombolysis in myocardial infarction grade, percutaneous coronary intervention, max creatine phosphokinase level, estimated glomerular
filtration rate, length of hospital stay, use of statins at discharge, use of beta-blockers at discharge, use of angiotensin-converting enzyme
inhibitors or angiotensin II receptor blockers at discharge, use of mineralocorticoid receptor antagonists at discharge, left ventricular
ejection fraction in the acute phase, cardiogenic shock, acute myocardial infarction due to lesions in left anterior descending artery, and acute
myocardial infarction due to lesions in the left main trunk. CPK, creatine phosphokinase; PCI, percutaneous coronary intervention; ACE-I/
ARB, angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker; MRA, mineralocorticoid receptor antagonist; LSA, low
serum albumin.

in AMI patients. In particular, our report demonstrated vascular permeability, and frailty have been suggested as
that use of statins and renin-angiotensin-aldosterone adverse effects of LSA on cardiovascular events. LSA may
system inhibitors at discharge might positively associated induce increased peripheral edematous and pulmonary
with serum albumin levels (Figure 2). Thus, albumin congestion, even at lower left ventricular end systolic
level measured in the chronic phase can be a prognostic pressures, acting as an aggravating factor for HF (4).
indicator, even in patients who survive the acute phase of Such changes are likely to contribute to new onset of HF,
AMI. However, careful monitoring is needed, especially for particularly in patients with reduced cardiac function after
AMI patients with remote LSA. ACS. Serum albumin level is widely known as a marker of
inflammation. However, previous reports have shown an
association between LSA status and left ventricular remodeling
Pathophysiological speculation of serum through the activation of cardiac inflammation (36).
albumin for adverse events Furthermore, pathophysiological evaluation has shown
that excessive inflammation contributes to left ventricular
Effect of serum albumin on HF after ACS
remodeling associated with new development of HF (37).
Malnutrition status, decrease in hepatic synthesis, elevated The acute phase of ACS causes inflammation and temporarily

© Journal of Laboratory and Precision Medicine. All rights reserved. J Lab Precis Med 2023;8:7 | https://dx.doi.org/10.21037/jlpm-22-57
Journal of Laboratory and Precision Medicine, 2023 Page 5 of 8

decreases albumin levels (35). Inflammation and low albumin comparison with non-improved subgroup (35). However,
levels may have an additive negative impact on cardiovascular it is still uncertain whether the higher the albumin levels,
outcomes. Thus, further research on the association between the better the prognosis in CVD. Third, evidence about the
inflammation and cardiac dysfunction is warranted. impact of interventions for increasing serum albumin levels
on CVD is also uncovered. Albumin infusion therapy was
significantly associated with a reduced risk of rebleeding
Effect of serum albumin on bleeding events after ACS
and short-term mortality in patients with cirrhosis admitted
Previous studies have indicated that the vulnerability for acute gastrointestinal bleeding (41). In contrast,
of capillaries in systemic organs may be due to LSA (1). recent retrospective observational study on the effect of
Protein metabolism plays an important role in tissue albumin replacement in patients with HF did not show
neogenesis and maintenance. Decreased albumin level is the significant clinical benefits of the therapy (42). Thus,
associated with tissue fragility, which consequently leads the significance of interventions for LSA seems to remain
to fragility in vascular tissues and has a negative impact on controversial, which may partly result from differences in
bleeding events. Furthermore, LSA reflects malnutrition the methods of intervention and/or patient backgrounds,
associated with vitamin C and K deficiencies. Vitamins C including disease status, among studies.
and K are essential for the coagulation system and play Serum albumin levels have been frequently used as
important roles in hemostasis during bleeding (38). Patients a nutritional indicator. However, they could not reflect
with LSA may simultaneously have vitamin deficiencies, immediate changes in the nutritional and/or inflammatory
which in turn may influence bleeding events after ACS. statuses. Because prealbumin have shorter biologic half-
These multisystem factors may be responsible for increase life (2 days), compared with that of albumin (20 days),
in bleeding events after ACS in patients with LSA. it would be sensitive to immediate changes in nutrition
However, the precise mechanism underlying high bleeding or inflammation (43). In a recent observational study,
risk in patients with LSA is not well uncovered. prealbumin was an independent factor to predict the
development of HF after AMI (38). However, the clinical
impact of prealbumin on cardiovascular events remains to
Limitation and future perspectives on the association
be poorly understood. Association between prealbumin and
between serum albumin and CVD
serum albumin level, especially LSA, was also still unclear.
First, the detailed pathophysiological mechanisms
underlying the serum albumin levels and adverse outcome
Conclusions
are still uncertain. Future studies should be focused on
albumin fluctuations from the acute to the chronic phase Serum albumin level has evolved as an indicator of
of CVD, because albumin fluctuations may help clarify nutrition and inflammation status, and its use in predicting
the pathophysiology underlying the association between the prognosis of CVD has recently been reported. Its
albumin level and CVD. Second, regarding the elevated usefulness in predicting bleeding events in coronary artery
albumin levels, there was little study examining the impact disease has also been reported, indicating its potential for
of non-LSA and elevated level of serum albumin levels in comprehensive prediction of adverse events after ACS.
CVD. In an observational study for Korean, a higher serum Furthermore, evaluation of serum albumin levels in the
albumin level was associated with an increased prevalence chronic phase of ACS has shown the importance of risk
of metabolic syndrome (39). At the same time, an obesity stratification and post-ACS reassessment of LSA for the
paradox, in which overweight have a better prognosis improvement of long-term prognosis. Further research on
compared with non-overweight/non-obese patients (40), is the pathophysiology of albumin level is needed to provide
also well-known. Accordingly, there might be a possibility insight into the causal relationship between albumin levels
that an elevated level of serum albumin could play a and adverse events in CVD patients, which is currently
protective role in cardiovascular medicine. In our recent unclear.
study, among 289 AMI patients with LSA (<3.8 g/dL) at
acute phase of AMI, 194 AMI patients (67.1%) showed
Acknowledgments
improvement of albumin level (≥3.8 g/dL) at chronic phase.
This improved subgroup demonstrated better outcomes in The authors thank Kensaku Nishihira, MD, and Yoshisato

© Journal of Laboratory and Precision Medicine. All rights reserved. J Lab Precis Med 2023;8:7 | https://dx.doi.org/10.21037/jlpm-22-57
Page 6 of 8 Journal of Laboratory and Precision Medicine, 2023

Shibata, MD (Miyazaki Medical Association Hospital, nutritional markers in hemodialysis patients. Nutr Hosp
Miyazaki City, Japan) for their study support. 2014;31:1317-22.
Funding: This work was supported by the Japan Society 4. Arques S. Human serum albumin in cardiovascular
for the Promotion of Science (KAKENHI, Grant number: diseases. Eur J Intern Med 2018;52:8-12.
JP21K08130) and Takeda Science Foundation. 5. Arques S. Serum albumin and cardiovascular diseases:
A comprehensive review of the literature. Ann Cardiol
Angeiol (Paris) 2018;67:82-90.
Footnote
6. González-Pacheco H, Amezcua-Guerra LM, Sandoval J,
Provenance and Peer Review: This article was commissioned et al. Prognostic Implications of Serum Albumin Levels in
by the Guest Editor (Tatsuo Shimosawa) for the series “New Patients With Acute Coronary Syndromes. Am J Cardiol
Biomarkers in Non-communicable Diseases” published in 2017;119:951-8.
Journal of Laboratory and Precision Medicine. The article has 7. Xia M, Zhang C, Gu J, et al. Impact of serum albumin
undergone external peer review. levels on long-term all-cause, cardiovascular, and cardiac
mortality in patients with first-onset acute myocardial
Conflicts of Interest: All authors have completed the infarction. Clin Chim Acta 2018;477:89-93.
ICMJE uniform disclosure form (available at https:// 8. Yoshioka G, Tanaka A, Nishihira K, et al. Prognostic
jlpm.amegroups.com/article/view/10.21037/jlpm-22-57/ Impact of Serum Albumin for Developing Heart Failure
coif). The series “New Biomarkers in Non-communicable Remotely after Acute Myocardial Infarction. Nutrients
Diseases” was commissioned by the editorial office without 2020;12:2637.
any funding or sponsorship. The authors have no other 9. Gopal DM, Kalogeropoulos AP, Georgiopoulou VV, et al.
conflicts of interest to declare. Serum albumin concentration and heart failure risk The
Health, Aging, and Body Composition Study. Am Heart J
Ethical Statement: The authors are accountable for all 2010;160:279-85.
aspects of the work in ensuring that questions related 10. Filippatos GS, Desai RV, Ahmed MI, et al.
to the accuracy or integrity of any part of the work are Hypoalbuminaemia and incident heart failure in older
appropriately investigated and resolved. adults. Eur J Heart Fail 2011;13:1078-86.
11. Wang Y, Du P, Xiao Q, et al. Relationship Between Serum
Open Access Statement: This is an Open Access article Albumin and Risk of Atrial Fibrillation: A Dose-Response
distributed in accordance with the Creative Commons Meta-Analysis. Front Nutr 2021;8:728353.
Attribution-NonCommercial-NoDerivs 4.0 International 12. Mukamal KJ, Tolstrup JS, Friberg J, et al. Fibrinogen and
License (CC BY-NC-ND 4.0), which permits the non- albumin levels and risk of atrial fibrillation in men and
commercial replication and distribution of the article with women (the Copenhagen City Heart Study). Am J Cardiol
the strict proviso that no changes or edits are made and the 2006;98:75-81.
original work is properly cited (including links to both the 13. Karabacak K, Kubat E, Akyol FB, et al. The C-reactive
formal publication through the relevant DOI and the license). protein/albumin ratio as a new predictor for postoperative
See: https://creativecommons.org/licenses/by-nc-nd/4.0/. atrial fibrillation after coronary artery bypass graft surgery.
J Card Surg 2020;35:2747-53.
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doi: 10.21037/jlpm-22-57
Cite this article as: Yoshioka G, Tanaka A, Goriki Y, Node K.
The role of albumin level in cardiovascular disease: a review of
recent research advances. J Lab Precis Med 2023;8:7.

© Journal of Laboratory and Precision Medicine. All rights reserved. J Lab Precis Med 2023;8:7 | https://dx.doi.org/10.21037/jlpm-22-57