Abstract
Objectives: to analyse in-hospital outcomes
and prognostic implications of reduced sodium
serum level (S-Na) in patients with acute coronary
syndrome including ST elevation myocardial infarction
(STEMI) and non ST elevation myocardial infarction
(non-STEMI).
Design: A cross sectional study was conducted
on elderly patients.
Participants: One hundred patients aged
> 60 years, both males and females.
Setting: Participants were recruited from cardiology
intensive care unit in Ain Shams University hospitals.
Measurements: All patients had a sodium
level determined at time of admission and after
48 hours, serial ECG and cardiac enzymes (creatine
phosphokinase (CPK) and CPK-MB fraction) levels.
Results: Of 100 patients, 52 patients were
admitted with STEMI and 48 with NSTEMI; 73 were
hyponatremic (S-Na <135 mEq/L) and 27 were
normonatremic (S>or=135 mEq/L). Patients who
had hyponatremia were more likely to die or have
recurrent myocardial infarction in the next 30
days (p <0.05). Hyponatremia, hypotension on
admission, left ventricular ejection fraction
(EF), mean level of cardiac enzymes were significantly
associated with adverse outcome. On multivariate
analysis, hyponatremia was a strong predictor
of adverse outcome (odds ratio 2.4, 95% confidence
interval).
In conclusion, hyponatremia is associated with
30-days adverse outcome in patients presenting
with acute coronary syndrome.
Key words: hyponatremia; acute coronary
syndrome; elderly;
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Introduction
Hyponatremia, defined as a serum sodium concentration
of <135 mmol/L, is the most common electrolyte abnormality
in hospitalized patients (1,2). Hyponatremia often signifies
poor prognosis(3). It is a predictor of mortality in
patients with heart failure (4,5) and in patients with
ST-elevation myocardial infarction (STEMI) (6,7). There
is complex neuro-hormonal activation in acute myocardial
infarction related to activation of the renin-angiotensin
system, release of atrial natriuretic peptide and catecholamines
(8,9). These mechanisms are similar to those in heart
failure and lead to peripheral vasoconstriction and
myocardial hypertrophy, with potential to worsen survival
in acute myocardial infarction. The fall in sodium concentrations
in patients with acute myocardial infarction is related
to the previous mechanisms (6,10). While the prognostic
value of hyponatremia in chronic heart failure is well
established, data on the prognostic importance of hyponatremia
in the setting of acute myocardial infarction are lacking,
also few studies have focused on outcome in the elderly
age group. This study is being undertaken to determine
the prognostic significance of hyponatremia in the setting
of acute coronary syndrome and to determine its usefulness
in predicting short term (30-days) adverse outcomes.
Subjects and Methods
A cross sectional study was conducted on one
hundred elderly males and females. Participants were
recruited from cardiology intensive care unit in Ain
Shams University hospitals. Elderly with the diagnosis
of acute STEMI and non-STEMI were included. During the
hospital stay, all participants underwent comprehensive
geriatric assessment, medication review, cognitive assessment
by which delirious patients were excluded, also subjects
with history of heart failure, renal failure and hepatic
patients were excluded; patients with history of diuretic
use were also excluded.
Patients had clinical examination done and investigations
in the form of serial ECG and cardiac enzymes, Echocardiography,
laboratorial investigations for assessment of other
Co- morbidities as complete blood picture, lipid profile,
renal functions and blood glucose levels, also all participants
had serum sodium levels obtained on admission and at
48 hours.
Laboratorial investigations were collected from medical
reports. Diagnosis of myocardial infarction was done
according to the criteria of the Joint European Society
of Cardiology and American College of Cardiology in
which diagnosis requires a finding of the typical rise
and fall of biochemical markers of myocardial necrosis
in addition to at least 1 of the following (11):
o Ischemic symptoms
o Development of pathologic Q waves
o Ischemic ST-segment changes on electrocardiogram
(ECG) or in the setting of a coronary intervention
Renal insufficiency and anemia were defined as admission
values for creatinine >1.4 mg/dl and <12 mg/dl
for hemoglobin, respectively. The follow-up for myocardial
infarction recurrence and mortality was done through
post discharge phone calls and the follow up duration
was 30 days.
Statistical methods:
The collected data were coded, tabulated, revised and
statistically analyzed using SPSS program (version 20).
Descriptive statistics were done using mean and standard
deviation for numerical parametric data and by number
and percentage for categorical data. Statistical analysis
was done for quantitative variables by using independent
t-test in case of two independent groups, and paired
t-test in related samples with parametric data. Chi-square
test was used for non parametric data and Logistic regression
analysis for predictors of mortality. The level of significance
was taken at P value < 0.05.
Results
Baseline sociodemographic
and clinical Characteristics of Patients are shown in
Table 1.
There is no statistically significant difference between
Na level on admission and after 48 hours as shown in
Table 2.
Comparison between hyponatremic and normonatremic groups
shows no statistically significant difference between
the two groups as regards sociodemographic variables,
Co morbidities (diabetes, hypertension, anemia, renal
impairment or hypercholesterolemia or old stroke), presence
of hypotension on admission, pulmonary edema on admission
or type of myocardial infarction, while ejection fraction
was significantly lower in the hyponatremic group (Table
3).
Relation between baseline patients' characteristics
and outcome is demonstrated in Table 4, which shows
that both hypotension on admission and hyponatremia
are significantly associated with poor outcome (mortality,
MI recurrence).
Significant relation between poor outcome, EF, cardiac
enzymes and sodium level on admission is shown in Table
5.
Significant clinical variables were entered into a multivariate
regression model which showed that hypotension on admission
and hyponatremia are each significantly associated with
30-days adverse outcomes (Table 6).
Table 1 : Baseline Characteristics of Patients
Table 2: Sodium levels at different time points
Table 3: Comparison between hyponatremic and normonatremic
groups as regard sociodemograhic and clinical variables
Table 4: Relation between patient characteristics and
outcome
Table 5 : Relation between hyponatremia at different
time points, cardiac enzymes and cardiac function and
outcome
Table 6: Logistic regression analysis for significant
clinical variables
Discussion
The results of this
cross sectional study demonstrated that hyponatremia
is common in elderly patients presenting with acute
coronary syndrome and that hypotension on admission
and hyponatremia were each significantly associated
with recurrent myocardial infarction or death within
30 days of hospitalization.
Reviewing literature, data from several studies support
the present study results. Flear et al (12) reported
that hyponatremia, hypochloremia, and uremia were common
in patients with confirmed myocardial infarction, with
higher in-hospital mortality in hyponatremic patients,
also Hochman et al (13) reported that hyponatremia in
these patients was correlated with higher mortality
and reflected severity of underlying disease; another
study by Goldberg et al (7) showed an association between
hyponatremia and increased 30-days mortality in patients
with STEMI.
Bogdan et al (14) reported a high prevalence of hyponatremia
within the first 72 hours of transmural myocardial infarction
and Klopotowski et al (15) reported that patients with
acute myocardial infarction developed hyponatremia on
admission or within the first 48 after admission.
In this study age, sex, smoking, diabetes, hypertension,
anemia, renal impairment, hypercholesterolemia, and
pulmonary edema on admission were not associated with
death/myocardial infarction. On the other hand hypotension
on admission, hyponatremia on admission, ejection fraction
and CPK & CPK -MB levels were significantly associated
with recurrent myocardial infarction and death within
30 days and that is agreed with by Qing Tang & Qi
Hua (16) who reported that gender, diabetes, hypertension,
renal insufficiency, and hyperglycemia were not significantly
associated with inhospital mortality and also with Singla
et al (10) who reported that hypotension on admission
and hyponatremia on admission were each significantly
associated with the primary end point (combined incidence
of death or new myocardial infarction within 30 days
of index hospitalization), while diabetes mellitus and
hypertension were not associated with death/myocardial
infarction.
Qing Tang & Qi Hua (16) observed that patients with
hyponatremia had lower ejection fractions than those
without and stated that large infarct size resulted
in ventricular dysfunction and might be responsible
for these adverse outcomes therefore hyponatremia may
be a simple parameter which reflects the presence of
heart failure and that was in agreement with our study
results as well.
Finally, it can be concluded that hyponatremia is considered
a strong predictor for poor short term outcome in elderly
with acute coronary syndrome.
Study limitations
:
Our study has some limitations. Importantly, this was
a small single site observational study also patients
with hyperglycemia were not excluded which may be a
contributing factor for hyponatremia.
Conclusion
Hyponatremia is associated with 30days adverse outcome
in patients presenting with acute coronary syndrome.
Acknowledgements
We are grateful to all the cardiology residents, staff
and all the participating patients. Informed consent
was taken from every elder participating in this study;
also approval was taken from the Head of Cardiology
Department. The study methodology was reviewed and approved
by the Research Review Board of the Geriatrics and Gerontology
Department, Faculty of Medicine, Ain Shams University,
Cairo, Egypt.
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