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INTERNATIONAL JOURNAL OF MEDICAL AND APPLIED SCIENCES

Research Paper
Microalbumin in Urine as Cardiovascular Disease risk marker in
patients of acute chest pain.
Smita Sharma 1,Ramakant Dixit 2,Veena SinghGhalaut1, Dhuruv Chaudhary1
1. Departments of Biochemistry & RespiratoryMedicine, Post graduate institute of Medical
Sciences, Rohtak, India
2. Department of Respiratory Medicine, JLN Medical College, Ajmer, India

Abstract
In the present study we have tried to highlight the importance of future policies on screening for
Microalbuminuria for the management of chest pain as an independent risk factor for CVD. In the present
study, Microalbuminuria was estimated in patients of acute chest pain.The patients were divided in to two
study groups(gp-1 patients of chest pain with CVD& gp-2 patients of chest pain of causes other than CVD) one
healthy control group Microalbuminuria was estimated by Nephalometery.Continuous variables are presented
as means±Standard deviation and analysed using ANOVA&
Chi-square test with p<0.05 as minimum level
of significance w as applied. The relative risk of positive outcome of Microalbuminuria ( >30 mg/L) was 6.250
with 95% confidence interval ranging from 2.346 to 16.653 and the associated p<0.05. Taking cut off value of
Microalbuminuria 30 mg/L, the Sensitivity in Group-1 was 86%,Specificity 64% and Positive Predictive value
86%.The relative risk in Group-2 can not be calculated,as all the patients in this group were having
normoalbuminuria. Sensitivity, Specificity & Positive predictive value of Microalbuminuria was also higher in
gp-1(CVD) patients as compared to other two groups. Therefore, Microalbuminuria can be used as important
biomarkers in screening CVD.
Key words: C-reactive protein, Microalbuminuria, coronary disease, chest pain.

INTRODUCTION
Chest pain is one of the most common
challenges for the clinicians in the
emergency department. Microalbuminuria
refers to urinary albumin excretion (UAE)
(30-300 mg/24 hours) that is not
detectable by routine methods. Data from
Losartan intervention for end point study
indicates that the relationship between
urinary
albumin
excretion
and
cardiovascular risk holds true well below
the levels currently used to define

Microalbuminuria. Furthermore, there is
evidence that regression of left ventricular
hypertrophy parallels the reduction of
albuminuria and is related to it, to some
degree regardless of blood pressure
changes[1]. It has been reported that
markers of inflammation such as CReactive Protein , Interleukin-6 and
Tumor necrosis factor-α, indicate that low
grade inflammation is associated with the
progression of Microalbuminuria and with
an increased risk
of atherosclerotic
disease [2]. Microalbuminuria even in

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Volume 1 Issue 1 2012
INTERNATIONAL JOURNAL OF MEDICAL AND APPLIED SCIENCES
healthy individuals is a risk factor for
chest pain associated with cardiovascular
events. The pathophysiologic mechanism
underlying the association between
albumin excretion and CVD is not fully
understood.
One
hypothesis
is
that
Microalbuminuria may be marker of CVD risk
because it reflects subclinical vascular damage
in the kidneys and other vascular beds. It may
also signify systemic endothelial dysfunction
that predisposes to future cardiovascular
events. Based on this theory, periodic
screening for Microalbuminuria could allow
early identification of vascular disease and
help to stratify overall cardiovascular risk.

MATERIAL AND METHODS
The study group comprised of 50 patients
of acute chest pain of cardiovascular
disease(CVD)(group-1), 50 patients of
acute chest pain secondary to causes other
than CVD (group-2)
admitted to
emergency department and 50 age & sex
matched healthy control (group-3). ).
Patients excluded from the study were of
respiratory disease like pulmonary
embolism, pulmonary tuberculosis, and
pleurisy, gastro-esophageal disease like
gall bladder disease, peptic ulcer &
diabetes mellitus, hypertension etc. The
presence of unstable angina was
determined by
chest pain within the preceding 72 hours
with or without ST-T-wave changes, or
positive cardiac biochemical markers
(creatine kinase-myocardial band ). The
presence of ST-segment elevation
myocardial infarction was determined by
>30 minutes of continuous chest pain, new
ST-segment elevation ≥2 mm on at least 2
contiguous electrocardiographic leads, and
creatine kinase-MB (CK-MB) >3 times

the normal limit. The presence of non-STsegment elevation myocardial infarction
was diagnosed by chest pain, and positive
cardiac biochemical markers (creatine
kinase-myocardial band ) without new STsegment elevation.
Early morning
midstream urine sample was collected and
was analyzed for Microalbuminuria.
Informed consent was taken from all the
subjects.
CRP was measured by
quantitative turbidimetric method and
Microalbuminuria was estimated by
Nephalometery. The cholesterol and CKMB (Creatine Kinase -Myocardial
Fraction).CRP levels were also measured
in all cases. CRP was assessed by the
immunoturbidimetric CRP-Latex (II) hs
assay
using
an
Olympus
5431
autoanalyzer Continuous variables are
presented as means ± Standard deviation
and analyzed using ANOVA & Chisquare test with p<0.05 as minimum level
of significance was applied. The serum
levels of total cholesterol, triglyceride,
low-density lipoprotein-cholesterol (LDLC),
and
high-density
lipoprotein
cholesterol were measured by standard
enzymatic methods.
RESULTS
CK-MB in Group-1 was 190.16 U/L,
Group-2 was 10.04 U/L and Group-3 was
10.93 U/L (p<0.05).(Figure 1) Total
Cholesterol in Group-1 patients was
204.22 mg%, Group-2 was 155.08 mg%
and Group-3 was 156.08 mg% (p<0.05)
Mean low density lipoprotein (LDL) in
Group-1
was
123.14±36.55
(4789),Group-2 was 73.28±10.65 (47-111)
and in Group-3 was 74.12±11.89 (47207).Significant difference was found
between serum cholesterol and LDL levels
(p <0.05). C - reactive protein (CRP) in
serum in Group-1 was 30.350 mg/L,

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INTERNATIONAL JOURNAL OF MEDICAL AND APPLIED SCIENCES
Group-2 was 33.678 mg/L and Group-3
was 3.444 mg/L (p<0.05).(Table1) Serum
CRP was found to be increased i.e.>10
mg/L in 82% cases of Group-1 as
compared to 6% increase in Group-3 .The
relative
risk
for
positive
outcome(CRP>10mg/L) in Group-1 was
13.667 with a 95% CI ranging from 4.52841.253; the associated p-value is <0.05.
Taking cut off value of CRP 10 mg/L, the
Sensitivity in group-1 was 93%,Specificity
83% and Positive Predictive value
93%.This means that there is 13-fold
increased risk in Group-1,and this increase
is statistically significant(p<0.05).(Table
2) Microalbuminuria in Group-1 was
35.795 mg/L, Group-2 was 17.340 mg/L
and in Group-3 was 12.661 mg/L
(p<0.05). (Table 1) The relative risk of
positive outcome of Microalbuminuria
(>30 mg/L) was 6.250 with 95%
confidence interval ranging from 2.346 to
16.653 and the associated p<0.05. Taking
cut off value of Microalbuminuria 30
mg/L, the Sensitivity in Group-1 was 86%,
Specificity 64% and Positive Predictive
value 86% (see Table-1). The relative risk
in Group-2 could not be calculated, as all
the patients in this group were having
normoalbuminuria.
The relationship between c reactive
protein and urine for microalbumin
was found to be equal to 0.314* which is
significant at five percent level of
significance. This correlation is found out
by the method of Karl Pearson’s
coefficient method.
Mean value for Urine for Micro
albumin in Females is 35.8157 and p-value
is 0.007. Mean value for urine for micro
albumin in Males is 36.0737 and p-value
is 0.00.Since p-value is < 0.05, hence it is
statistically significant.

DISCUSSION
In the present study we have tried to
highlight the importance of future policies
on screening for Microalbuminuria for the
management of chest pain as an
independent risk factor for CVD.
In
the present study, the relative risk of
positive outcome of Microalbuminuria
(>30 mg/L) in Group-1 was 6.250 with
95% confidence interval ranging from
2.346 to 16.653 and the associated p<0.05.
In Heart Outcomes Prevention (HOPE)
trials, Microalbuminuria was associated
with an adjusted relative risk of 1.83 for
major CV events, 2.09 for all-cause
mortality and 3.23 for hospitalization for
congestive heart failure, with a similar
relative risks in subjects with or without
diabetes [3]. In our study there was 6-fold
increased risk of Microalbuminuria in
CVD patients, and this increase is
statistically
significant
(p
<0.05).
Damsgaard et al [4] reported a greater
incidence of cardiovascular e vents in
elderly nondiabetic individuals with
increased urinary albumin excretion
(UAE) than in those with normal UAE
after a follow-up of 62-83 months.that
UACR measured during the first week
after AMI is independently associated with
increased long-term risk for in-hospital
and
six-month
mortality
[5].
Microalbuminuria was associated with a
higher number of vulnerable plaque
components in ACS and diabetic patients.
More intensive medical therapy is needed
to stabilize the vulnerable plaque if
microalbuminuria is observed in diabetic
ACS patients [6].
Taking cut off value of
Microalbuminuria 30 mg/L, the Sensitivity
in Group-1 was 86%, Specificity 64% and
Positive Predictive value 86%.
As
Sensitivity, Specificity and Positive

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Volume 1 Issue 1 2012
INTERNATIONAL JOURNAL OF MEDICAL AND APPLIED SCIENCES
Predictive value in non-coronary cases
(Group-2) was less than coronary cases.
Microalbuminuria can be viewed as risk
factors of CVD in the presence of
increased
known
biomarker
CKMB,CRP,Total Cholesterol,LDL-C and
Microalbuminuria has predictive role. We
recommend
measurement
of
Microalbuminuria to be included as a
baseline risk factor in patients with acute
myocardial infarction and in future trials
in patients with coronary heart disease.

[3] Gerstein HC, Mann JF, Yi Q.
Albuminuria and risk of cardiovascular
events, death, and heart failure in diabetic
and nondiabetic individuals. JAMA 2001;
286: 421-26.
[4] Damsgaard E, Froland A, Jorgensen O,
Mogensen C. Prognostic value of urinary
excretion rate and other risk factors in
elderly diabetic patients and nondiabetic
control subjects surviving the first five
years after assessment. Dibetologia 1993;
36: 1030-36.

REFERENCES
[1] Ibsen H, Oslen MH. Reduction in
albuminuria translates to reduction in
cardiovascular events in hypertensive
patients: Losartan intervention for end
point reduction in hypertension study.
Hypertension 2005; 45: 198-2.
[2] Ridker PM, Rifai N, Pfeffer MA, Sacks
FM, Moye LA, Goldman S, et al.
Inflammation, pravastatin, and the risk of
coronary
events
after
myocardial
infarction in patients with average
cholesterol levels. Cholesterol and
Recurrent Events (CARE) Investigators.
Circulation 1998; 98: 839-44.

[5] Apostolovic S, Stanojevic D, Djordjevic
V, Tomasevic RJ, Martinovic S S
.Prognostic
significance
of
microalbuminuria in patients with acute
myocardial
infarction.Clin
Lab.2011;57(3-4):229-35.
[6] Hong YJ,Jeong M H,Choi YH,Song
JA,Ahmed K, Kim DH, Lee KH.
Relationship between microalbuminuria
and vulnerable plaque components in
patients with acute coronary syndrome
and with diabetes mellitus.Virtual
histology-intravascular ultrasound. Circ
J.2011;75(12):2893-901.

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Microalbuminuria CVD risk marker chest pain

  • 1. INTERNATIONAL JOURNAL OF MEDICAL AND APPLIED SCIENCES Research Paper Microalbumin in Urine as Cardiovascular Disease risk marker in patients of acute chest pain. Smita Sharma 1,Ramakant Dixit 2,Veena SinghGhalaut1, Dhuruv Chaudhary1 1. Departments of Biochemistry & RespiratoryMedicine, Post graduate institute of Medical Sciences, Rohtak, India 2. Department of Respiratory Medicine, JLN Medical College, Ajmer, India Abstract In the present study we have tried to highlight the importance of future policies on screening for Microalbuminuria for the management of chest pain as an independent risk factor for CVD. In the present study, Microalbuminuria was estimated in patients of acute chest pain.The patients were divided in to two study groups(gp-1 patients of chest pain with CVD& gp-2 patients of chest pain of causes other than CVD) one healthy control group Microalbuminuria was estimated by Nephalometery.Continuous variables are presented as means±Standard deviation and analysed using ANOVA& Chi-square test with p<0.05 as minimum level of significance w as applied. The relative risk of positive outcome of Microalbuminuria ( >30 mg/L) was 6.250 with 95% confidence interval ranging from 2.346 to 16.653 and the associated p<0.05. Taking cut off value of Microalbuminuria 30 mg/L, the Sensitivity in Group-1 was 86%,Specificity 64% and Positive Predictive value 86%.The relative risk in Group-2 can not be calculated,as all the patients in this group were having normoalbuminuria. Sensitivity, Specificity & Positive predictive value of Microalbuminuria was also higher in gp-1(CVD) patients as compared to other two groups. Therefore, Microalbuminuria can be used as important biomarkers in screening CVD. Key words: C-reactive protein, Microalbuminuria, coronary disease, chest pain. INTRODUCTION Chest pain is one of the most common challenges for the clinicians in the emergency department. Microalbuminuria refers to urinary albumin excretion (UAE) (30-300 mg/24 hours) that is not detectable by routine methods. Data from Losartan intervention for end point study indicates that the relationship between urinary albumin excretion and cardiovascular risk holds true well below the levels currently used to define Microalbuminuria. Furthermore, there is evidence that regression of left ventricular hypertrophy parallels the reduction of albuminuria and is related to it, to some degree regardless of blood pressure changes[1]. It has been reported that markers of inflammation such as CReactive Protein , Interleukin-6 and Tumor necrosis factor-α, indicate that low grade inflammation is associated with the progression of Microalbuminuria and with an increased risk of atherosclerotic disease [2]. Microalbuminuria even in 1 www.earthjournals.org Volume 1 Issue 1 2012
  • 2. INTERNATIONAL JOURNAL OF MEDICAL AND APPLIED SCIENCES healthy individuals is a risk factor for chest pain associated with cardiovascular events. The pathophysiologic mechanism underlying the association between albumin excretion and CVD is not fully understood. One hypothesis is that Microalbuminuria may be marker of CVD risk because it reflects subclinical vascular damage in the kidneys and other vascular beds. It may also signify systemic endothelial dysfunction that predisposes to future cardiovascular events. Based on this theory, periodic screening for Microalbuminuria could allow early identification of vascular disease and help to stratify overall cardiovascular risk. MATERIAL AND METHODS The study group comprised of 50 patients of acute chest pain of cardiovascular disease(CVD)(group-1), 50 patients of acute chest pain secondary to causes other than CVD (group-2) admitted to emergency department and 50 age & sex matched healthy control (group-3). ). Patients excluded from the study were of respiratory disease like pulmonary embolism, pulmonary tuberculosis, and pleurisy, gastro-esophageal disease like gall bladder disease, peptic ulcer & diabetes mellitus, hypertension etc. The presence of unstable angina was determined by chest pain within the preceding 72 hours with or without ST-T-wave changes, or positive cardiac biochemical markers (creatine kinase-myocardial band ). The presence of ST-segment elevation myocardial infarction was determined by >30 minutes of continuous chest pain, new ST-segment elevation ≥2 mm on at least 2 contiguous electrocardiographic leads, and creatine kinase-MB (CK-MB) >3 times the normal limit. The presence of non-STsegment elevation myocardial infarction was diagnosed by chest pain, and positive cardiac biochemical markers (creatine kinase-myocardial band ) without new STsegment elevation. Early morning midstream urine sample was collected and was analyzed for Microalbuminuria. Informed consent was taken from all the subjects. CRP was measured by quantitative turbidimetric method and Microalbuminuria was estimated by Nephalometery. The cholesterol and CKMB (Creatine Kinase -Myocardial Fraction).CRP levels were also measured in all cases. CRP was assessed by the immunoturbidimetric CRP-Latex (II) hs assay using an Olympus 5431 autoanalyzer Continuous variables are presented as means ± Standard deviation and analyzed using ANOVA & Chisquare test with p<0.05 as minimum level of significance was applied. The serum levels of total cholesterol, triglyceride, low-density lipoprotein-cholesterol (LDLC), and high-density lipoprotein cholesterol were measured by standard enzymatic methods. RESULTS CK-MB in Group-1 was 190.16 U/L, Group-2 was 10.04 U/L and Group-3 was 10.93 U/L (p<0.05).(Figure 1) Total Cholesterol in Group-1 patients was 204.22 mg%, Group-2 was 155.08 mg% and Group-3 was 156.08 mg% (p<0.05) Mean low density lipoprotein (LDL) in Group-1 was 123.14±36.55 (4789),Group-2 was 73.28±10.65 (47-111) and in Group-3 was 74.12±11.89 (47207).Significant difference was found between serum cholesterol and LDL levels (p <0.05). C - reactive protein (CRP) in serum in Group-1 was 30.350 mg/L, 2 www.earthjournals.org Volume 1 Issue 1 2012
  • 3. INTERNATIONAL JOURNAL OF MEDICAL AND APPLIED SCIENCES Group-2 was 33.678 mg/L and Group-3 was 3.444 mg/L (p<0.05).(Table1) Serum CRP was found to be increased i.e.>10 mg/L in 82% cases of Group-1 as compared to 6% increase in Group-3 .The relative risk for positive outcome(CRP>10mg/L) in Group-1 was 13.667 with a 95% CI ranging from 4.52841.253; the associated p-value is <0.05. Taking cut off value of CRP 10 mg/L, the Sensitivity in group-1 was 93%,Specificity 83% and Positive Predictive value 93%.This means that there is 13-fold increased risk in Group-1,and this increase is statistically significant(p<0.05).(Table 2) Microalbuminuria in Group-1 was 35.795 mg/L, Group-2 was 17.340 mg/L and in Group-3 was 12.661 mg/L (p<0.05). (Table 1) The relative risk of positive outcome of Microalbuminuria (>30 mg/L) was 6.250 with 95% confidence interval ranging from 2.346 to 16.653 and the associated p<0.05. Taking cut off value of Microalbuminuria 30 mg/L, the Sensitivity in Group-1 was 86%, Specificity 64% and Positive Predictive value 86% (see Table-1). The relative risk in Group-2 could not be calculated, as all the patients in this group were having normoalbuminuria. The relationship between c reactive protein and urine for microalbumin was found to be equal to 0.314* which is significant at five percent level of significance. This correlation is found out by the method of Karl Pearson’s coefficient method. Mean value for Urine for Micro albumin in Females is 35.8157 and p-value is 0.007. Mean value for urine for micro albumin in Males is 36.0737 and p-value is 0.00.Since p-value is < 0.05, hence it is statistically significant. DISCUSSION In the present study we have tried to highlight the importance of future policies on screening for Microalbuminuria for the management of chest pain as an independent risk factor for CVD. In the present study, the relative risk of positive outcome of Microalbuminuria (>30 mg/L) in Group-1 was 6.250 with 95% confidence interval ranging from 2.346 to 16.653 and the associated p<0.05. In Heart Outcomes Prevention (HOPE) trials, Microalbuminuria was associated with an adjusted relative risk of 1.83 for major CV events, 2.09 for all-cause mortality and 3.23 for hospitalization for congestive heart failure, with a similar relative risks in subjects with or without diabetes [3]. In our study there was 6-fold increased risk of Microalbuminuria in CVD patients, and this increase is statistically significant (p <0.05). Damsgaard et al [4] reported a greater incidence of cardiovascular e vents in elderly nondiabetic individuals with increased urinary albumin excretion (UAE) than in those with normal UAE after a follow-up of 62-83 months.that UACR measured during the first week after AMI is independently associated with increased long-term risk for in-hospital and six-month mortality [5]. Microalbuminuria was associated with a higher number of vulnerable plaque components in ACS and diabetic patients. More intensive medical therapy is needed to stabilize the vulnerable plaque if microalbuminuria is observed in diabetic ACS patients [6]. Taking cut off value of Microalbuminuria 30 mg/L, the Sensitivity in Group-1 was 86%, Specificity 64% and Positive Predictive value 86%. As Sensitivity, Specificity and Positive 3 www.earthjournals.org Volume 1 Issue 1 2012
  • 4. INTERNATIONAL JOURNAL OF MEDICAL AND APPLIED SCIENCES Predictive value in non-coronary cases (Group-2) was less than coronary cases. Microalbuminuria can be viewed as risk factors of CVD in the presence of increased known biomarker CKMB,CRP,Total Cholesterol,LDL-C and Microalbuminuria has predictive role. We recommend measurement of Microalbuminuria to be included as a baseline risk factor in patients with acute myocardial infarction and in future trials in patients with coronary heart disease. [3] Gerstein HC, Mann JF, Yi Q. Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA 2001; 286: 421-26. [4] Damsgaard E, Froland A, Jorgensen O, Mogensen C. Prognostic value of urinary excretion rate and other risk factors in elderly diabetic patients and nondiabetic control subjects surviving the first five years after assessment. Dibetologia 1993; 36: 1030-36. REFERENCES [1] Ibsen H, Oslen MH. Reduction in albuminuria translates to reduction in cardiovascular events in hypertensive patients: Losartan intervention for end point reduction in hypertension study. Hypertension 2005; 45: 198-2. [2] Ridker PM, Rifai N, Pfeffer MA, Sacks FM, Moye LA, Goldman S, et al. Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events (CARE) Investigators. Circulation 1998; 98: 839-44. [5] Apostolovic S, Stanojevic D, Djordjevic V, Tomasevic RJ, Martinovic S S .Prognostic significance of microalbuminuria in patients with acute myocardial infarction.Clin Lab.2011;57(3-4):229-35. [6] Hong YJ,Jeong M H,Choi YH,Song JA,Ahmed K, Kim DH, Lee KH. Relationship between microalbuminuria and vulnerable plaque components in patients with acute coronary syndrome and with diabetes mellitus.Virtual histology-intravascular ultrasound. Circ J.2011;75(12):2893-901. 4 www.earthjournals.org Volume 1 Issue 1 2012