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International Multispecialty Journal of Health (IMJH) ISSN: [2395-6291] [Vol-4, Issue-3,March- 2018]
Page | 66
Micro-albuminuria in non-diabetic, non-hypertensive
cardiovascular disease (CVD) patients: A case control study
Dr. Sunil Kumar Mahavar1, Dr. Sarla Mahawar2, Dr. Mayank Gupta3§,
Dr. Raman Sharma4
1Assistant Professor, Department of Internal Medicine, S.M.S Medical College, Jaipur (Rajasthan), India
2Associate Professor, Department of Biochemistry, J.L.N. Medical College, Ajmer (Rajasthan), India
3§Senior Resident, Department of Internal Medicine, S.M.S Medical College, Jaipur(Rajasthan), India
4Senior Professor, Department of Internal Medicine, S.M.S Medical College, Jaipur(Rajasthan), India
Abstract—Cardiovascular disease (CVD) is a prominent health problem and micro-albunemia is one of
the major causes of morbidity and mortality in these CVDs in developing countries. This case control
study was designed to find out burden of micro-albuminuria in non-diabetic non-hypertensive CVD
patients and its associating factors. In this study, 50 Non Diabetic Non Hypertensive CVD Patients were
submitted to a complete clinical and laboratory evaluation. Patients with known micro-albuminuria,
UTI and congestive heart failure were excluded. These cases were compared with matched controls. It
was observed that 36% of non-diabetic, non-hypertensive CVD patients had microalbuminuric by
Clinitek method. There was a positive association between dyslipidaemia and micro-albuminuria was
also observed in this study. The microalbuminuric CVD patients (non-diabetic, non-hypertensive) had
significantly elevated levels of serum cholesterol (p<0.05), triglycerides (p<0.05) and LDL (p<0.05) as
compared to normoalbuminuric patients. It can be concluded from this study that the micro-albuminuria
was present in more than one third of non-diabetic non-hypertensive CVD patients. Older age group,
Body Mass Index (BMI) and lipid profile had significant relationship with the presence of micro-
albuminuria.
Keywords: Cardiovascular disease (CVD), Triglycerides, Micro-albuminuria.
I. INTRODUCTION
Cardiovascular disease (CVD) is fast emerging as a prominent health problem and is one of the major
causes of morbidity and mortality in the developing countries. It accounts for approximately 12 million
deaths annually and is the commonest cause of death globally.1
The risk factors very well associated with development of coronary heart disease includes age above 60
years, male sex, sedentary life style, diabetes, hypertension, hyper-cholesterolaemia, obesity, family
history of cardiovascular disease, increase oxidative stress and certain dietary factors. Micro-
albuminuria is also associated with an increased risk for cardiovascular morbidity and mortality.2
Authors2,3,4 have reported 6% to 10%. increased risk for cardiovascular morbidity and mortality with
microalbuminia.
Micro-albuminuria is also an independent predictor of cardiovascular disease in both diabetic and non-
diabetic patients and may be a stronger indicator for future cardiovascular events than hypertension or
serum cholesterol.5,6
The present study is undertaken to find out the problem of micro-albuminuria in non-diabetic non-
hypertensive CVD patients and its associating factors.
International Multispecialty Journal of Health (IMJH) ISSN: [2395-6291] [Vol-4, Issue-3,March- 2018]
Page | 67
II. METHODOLOGY
This present study is a hospital based case control type of observational study conducted at S.M.S.
Medical College and Hospital in Jaipur.
This study was conducted to find out the burden of micro-albuminuria in non-diabetic non-hypertensive
CVD patients and to study its associating risk factors like age, sex, obesity, dyslipidaemia.
The subjects selected for study were grouped as follows viz :
1. Group I "Study group'' i.e. Non Diabetic Non Hypertensive CVD Patients (N=50) (IHD and
myocardial infarction patients).
2. Group I "Control group" (N=25): This group consisted of age, sex, and BMI matched healthy
subjects. They were taken from medical or paramedical staff, attendants of patients and general
public.
Cases with confirmed micro-albuminuria i.e. urinary excretion rate>300 mg/day or presence of other
renal disease, urinary tract infection or recent intercurrent illness and patients having evidence of
congestive heart failure were excluded. Written informed consent were taken from all subjects after
getting approved this study protocol by the ethics committee of the institute.
Detailed physical examination was carried out with emphasis on blood pressure, height and weight.
Blood samples were collected after at least twelve hours overnight fasting for complete blood counts,
blood glucose (fasting and postprandial), glycated hemoglobin (HbA1c), blood urea, serum creatinine,
lipid profile (including total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density
lipoprotein cholesterol [HDL-C] and triglycerides [TG]) of all participants. Complete urine examination,
urinary albumin excretion rate / creatinine ratio in morning urine sample was also done along with ECG
(standard 12 leads).
Data was analyzed with the help of SPSS trial version 16 statistical software using student ‘t’ test and chi
square test. For significance p value <0.05 was considered as significant.
III. RESULTS
Study and control groups were matched as per age (p=0.145), sex (p=0.986), height (p=0.652) and
weight (p=0.122) only BMI was significantly more in study group than control group i.e. mean BMI
25.0±2.64 and 22.3±2.8 kg/m2 respectively. (Table 1)
Table 1
Comparison of basic characteristics of study and control group
S. No. Characteristics Study Group (N=50)
Control Group
(N=25)
P value LS
1 Sex ratio (Male: Female) 34:16 18:07 0.986 NS
2 Age (Mean ± SD) in Years 50.3±7.1 47.5±9.0 0.145 NS
3 Weight (Mean ± SD) in Kg 60.7±.7.2 57.9±7.5 0.122 NS
4 Height (Mean ± SD) in Meters 1.54±0.17 1.56±0.20 0.652 NS
5 BMI (Mean ± SD) in kg/m2 25.0±2.64 22.3±2.8 <0.05 S
All the individuals in control group were negative on micro albumin test whereas in study group 36%
were positives on micro albumin test i.e. 36% of non-diabetic non-hypertensive C.V.D cases were
having microalbunemia. male 38.24 31.25% (Table 2)
International Multispecialty Journal of Health (IMJH) ISSN: [2395-6291] [Vol-4, Issue-3,March- 2018]
Page | 68
When this positivity of micro-albunemia was seen as per sex, it was found positive in 38.24% of males
and 31.25% of female. This distribution of positivity of micro-albunemia as per sex was without
significance difference (p>0.05). (Table 2)
Table 2
Comparison of basic Micro-albunemia status of study and control group
S. No. Characteristics
Study Group (N=50) Control Group (N=25)
Male Female Total Male Female Total
1 Micro albumin Test Negative 21 11 32 18 07 25
2 Micro Albumin Test Positive 13 05 18 0 0 0
When level of serum cholesterol, serum triglycerides, serum LDL and serum HDL was compared in
both study and control groups, serum cholesterol was found 163 .0+28.4 V/s 196.44+31.4), serum
triglycerides 107.0+44.5 V/s 137.0+30.5, serum LDL 88.0+47.0 V/s 129.7+30., serum HDL 49.0+3.50
V/s 44.1+5.0, in study and control groups respectively. These lipid levels were found significantly more
(P<0.05) in study group i.e. non-diabetic non-hypertensive C.V.D. patients compared to controls. (Table
3)
Table 3
Comparison of serum lipid levels of study and control group
S. No. Serum Lipid level (mg/dl) Study Group (N=50)
Control Group
(N=25)
P value LS
1 Serum cholesterol (Mean ± SD) 196.44+31.4 163.0+28.4 <0.05 S
2 Serum Triglycerides (Mean ± SD) 137.0+30.5 107.0+44.5 <0.05 S
3 Serum LDL (Mean ± SD) 129.7+30.0 88.0+47.0 <0.05 S
4 Serum HDL (Mean ± SD) 44.1+5.0 49.0+3.50 <0.05 S
When association of lipid profile with micro albunemia was discovered it was revealed that serum
cholesterol, serum triglycerides and serum LDL in microalbuminurics were 216.0+33.6, 156.2+32.2 and
142.0+32.0 mg/dl which was significantly more in cases with micro-albunemia as where it was
188.6+27.7, 130.0+27, 117.0+28 and 45.0+5.30 respectively. There was no significant difference in
serum HDL between two groups. (Table 4)
Table 4
Comparison of lipid profile of Normoalbuminuric and Microalbuninuric
S.
No.
Serum Lipid level (mg/dl)
Normoalbuminuric
(N=32)
Microalbuninuric
(N=18)
P value LS
1 Serum cholesterol (Mean ± SD) 188.6+27.7 216.0+33.6 <0.05 S
2 Serum Triglycerides (Mean ± SD) 130.0+27.0 156.2+32.2 <0.05 S
3 Serum LDL (Mean ± SD) 117.0+28.0 142.0+32.0 <0.05 S
4 Serum HDL (Mean ± SD) 45.0+5.30 43.2+4.7 >0.05 NS
IV. DISCUSSION
The present study was conducted on 25 age, sex, height and weight matched healthy controls and 50
non-diabetic non-hypertensive CVD patients. In this study microalbunia was found in 36% of non-
diabetic non-hypertensive CVD cases.
In the present study the level of serum cholesterol (216.0+33.6 V/s 188.6+27.7), serum triglyceride
(156.2+32.2 V/s 130.0+27.7 and serum LDL (142.0+32.0 V/s 117.0+28.0) were found higher in
microlbuminuric than normoalbuminuric and this difference was statistically significant (P<0.05)
International Multispecialty Journal of Health (IMJH) ISSN: [2395-6291] [Vol-4, Issue-3,March- 2018]
Page | 69
whereas the serum HDL (43.2+4.7 V/s 45.0+5.3) was lower in microalbuminuric than
normoalbuminuric but the difference was not statistically significant (P>0.05).
Haffner SM et al (1990) demonstrated an association of micro-albuminuria with a number of
cardiovascular risk factors, namely hypertension, hyperinsulinemia, hyper-triglyceridaemia and self
reported myocardial infarction in non-diabetic subjects.7
The presence of micro-albuminuria predicts vascular disease in non diabetic population makes it more
universal marker of early death from cardiovascular disease in human beings (Yudkin et al 1988), thus
the onset of micro-albuminuria in diabetic and non diabetic patients signals atherogenic milieu.8
V. CONCLUSION
This study aimed to find out burden of micro-albuminuria in non-diabetics, non -hypertensive CVD
acses and its associating factors. Microalbunemia was found in 36% of non-diabetic, non-hypertensive
CVD patients detected to be microalbuminuric by Clinitek method.
There was a positive association was found between dyslipidaemia and micro-albuminuria. The
microalbuminuric CVD patients (non-diabetic, non-hypertensive) had significantly elevated levels of
serum cholesterol (p<0.05), triglycerides (p<0.05) and LDL (p<0.05) as compared to normoalbuminuric
patients.
CONFLICT OF INTEREST
None declared till now.
REFERENCES
[1] Agewall S, wikstrand J, Ljungman S, Fagerberg B, for the Risk Factor intervention study Group. Usefulness of micro-
albuminuria in predicting cardiovascular mortality in treated hypertensive men with and without diabetes mellitus. Am J
Cardiol. 1997;80:164-169.
[2] Bhandari Sudhir, Prognostic significance of micro-albuminuria in diabetes and its correlation with various complication
and lipid profile. JAPI 2000;48(1).
[3] Karalliedde J, Viberti G. Micro-albuminuria and cardiovascular risk. Am J Hypertens.2004 Oct; 17(10):986-93.
[4] Reboldi G, Gentile G, Angeli F, Verdecchia P. Micro-albuminuria and hypertension. Minerva Med. 2005 Aug;
96(4):261-75
[5] Kuusisto J, Mykkanen L, Pyorala K, Laakso M. Hyperinsulinemic micro-albuminuria: a new risk indicator for coronary
heart disease.Circulation 1995;91:831-37.
[6] Jones CA, Francis ME, Eberhardt MS, Chavers B, Coresh J, Engelgau M, Kusek JW, Byrd-Holt D, Narayan KM,
Herman WH, Jones CP, Salive M, Agodoa LY: Micro-albuminuria in the US population: Third National Health and
Nutrition Examination Survey. Am J Kidney Dis 39: 445– 459, 2002
[7] Haffner SM, Stern MP, and Gruber KK micro-albuminuria: Potential marker for increased cardiovascular risk factors in
non-diabetes subjects? Arteriosclerosis 1990;10:727-731.
[8] Yudkin JS, Stehouwer CDA, Emeis JJ, Coppact SW. C-reactive protein in healthy subjects: associations with obesity,
insulin resistance,and endothelial dysfunction.ArteriosclerosisThrombVascBiol 1999; 19:972-8.

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Micro-albuminuria in non-diabetic, non-hypertensive cardiovascular disease (CVD) patients: A case control study

  • 1. International Multispecialty Journal of Health (IMJH) ISSN: [2395-6291] [Vol-4, Issue-3,March- 2018] Page | 66 Micro-albuminuria in non-diabetic, non-hypertensive cardiovascular disease (CVD) patients: A case control study Dr. Sunil Kumar Mahavar1, Dr. Sarla Mahawar2, Dr. Mayank Gupta3§, Dr. Raman Sharma4 1Assistant Professor, Department of Internal Medicine, S.M.S Medical College, Jaipur (Rajasthan), India 2Associate Professor, Department of Biochemistry, J.L.N. Medical College, Ajmer (Rajasthan), India 3§Senior Resident, Department of Internal Medicine, S.M.S Medical College, Jaipur(Rajasthan), India 4Senior Professor, Department of Internal Medicine, S.M.S Medical College, Jaipur(Rajasthan), India Abstract—Cardiovascular disease (CVD) is a prominent health problem and micro-albunemia is one of the major causes of morbidity and mortality in these CVDs in developing countries. This case control study was designed to find out burden of micro-albuminuria in non-diabetic non-hypertensive CVD patients and its associating factors. In this study, 50 Non Diabetic Non Hypertensive CVD Patients were submitted to a complete clinical and laboratory evaluation. Patients with known micro-albuminuria, UTI and congestive heart failure were excluded. These cases were compared with matched controls. It was observed that 36% of non-diabetic, non-hypertensive CVD patients had microalbuminuric by Clinitek method. There was a positive association between dyslipidaemia and micro-albuminuria was also observed in this study. The microalbuminuric CVD patients (non-diabetic, non-hypertensive) had significantly elevated levels of serum cholesterol (p<0.05), triglycerides (p<0.05) and LDL (p<0.05) as compared to normoalbuminuric patients. It can be concluded from this study that the micro-albuminuria was present in more than one third of non-diabetic non-hypertensive CVD patients. Older age group, Body Mass Index (BMI) and lipid profile had significant relationship with the presence of micro- albuminuria. Keywords: Cardiovascular disease (CVD), Triglycerides, Micro-albuminuria. I. INTRODUCTION Cardiovascular disease (CVD) is fast emerging as a prominent health problem and is one of the major causes of morbidity and mortality in the developing countries. It accounts for approximately 12 million deaths annually and is the commonest cause of death globally.1 The risk factors very well associated with development of coronary heart disease includes age above 60 years, male sex, sedentary life style, diabetes, hypertension, hyper-cholesterolaemia, obesity, family history of cardiovascular disease, increase oxidative stress and certain dietary factors. Micro- albuminuria is also associated with an increased risk for cardiovascular morbidity and mortality.2 Authors2,3,4 have reported 6% to 10%. increased risk for cardiovascular morbidity and mortality with microalbuminia. Micro-albuminuria is also an independent predictor of cardiovascular disease in both diabetic and non- diabetic patients and may be a stronger indicator for future cardiovascular events than hypertension or serum cholesterol.5,6 The present study is undertaken to find out the problem of micro-albuminuria in non-diabetic non- hypertensive CVD patients and its associating factors.
  • 2. International Multispecialty Journal of Health (IMJH) ISSN: [2395-6291] [Vol-4, Issue-3,March- 2018] Page | 67 II. METHODOLOGY This present study is a hospital based case control type of observational study conducted at S.M.S. Medical College and Hospital in Jaipur. This study was conducted to find out the burden of micro-albuminuria in non-diabetic non-hypertensive CVD patients and to study its associating risk factors like age, sex, obesity, dyslipidaemia. The subjects selected for study were grouped as follows viz : 1. Group I "Study group'' i.e. Non Diabetic Non Hypertensive CVD Patients (N=50) (IHD and myocardial infarction patients). 2. Group I "Control group" (N=25): This group consisted of age, sex, and BMI matched healthy subjects. They were taken from medical or paramedical staff, attendants of patients and general public. Cases with confirmed micro-albuminuria i.e. urinary excretion rate>300 mg/day or presence of other renal disease, urinary tract infection or recent intercurrent illness and patients having evidence of congestive heart failure were excluded. Written informed consent were taken from all subjects after getting approved this study protocol by the ethics committee of the institute. Detailed physical examination was carried out with emphasis on blood pressure, height and weight. Blood samples were collected after at least twelve hours overnight fasting for complete blood counts, blood glucose (fasting and postprandial), glycated hemoglobin (HbA1c), blood urea, serum creatinine, lipid profile (including total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C] and triglycerides [TG]) of all participants. Complete urine examination, urinary albumin excretion rate / creatinine ratio in morning urine sample was also done along with ECG (standard 12 leads). Data was analyzed with the help of SPSS trial version 16 statistical software using student ‘t’ test and chi square test. For significance p value <0.05 was considered as significant. III. RESULTS Study and control groups were matched as per age (p=0.145), sex (p=0.986), height (p=0.652) and weight (p=0.122) only BMI was significantly more in study group than control group i.e. mean BMI 25.0±2.64 and 22.3±2.8 kg/m2 respectively. (Table 1) Table 1 Comparison of basic characteristics of study and control group S. No. Characteristics Study Group (N=50) Control Group (N=25) P value LS 1 Sex ratio (Male: Female) 34:16 18:07 0.986 NS 2 Age (Mean ± SD) in Years 50.3±7.1 47.5±9.0 0.145 NS 3 Weight (Mean ± SD) in Kg 60.7±.7.2 57.9±7.5 0.122 NS 4 Height (Mean ± SD) in Meters 1.54±0.17 1.56±0.20 0.652 NS 5 BMI (Mean ± SD) in kg/m2 25.0±2.64 22.3±2.8 <0.05 S All the individuals in control group were negative on micro albumin test whereas in study group 36% were positives on micro albumin test i.e. 36% of non-diabetic non-hypertensive C.V.D cases were having microalbunemia. male 38.24 31.25% (Table 2)
  • 3. International Multispecialty Journal of Health (IMJH) ISSN: [2395-6291] [Vol-4, Issue-3,March- 2018] Page | 68 When this positivity of micro-albunemia was seen as per sex, it was found positive in 38.24% of males and 31.25% of female. This distribution of positivity of micro-albunemia as per sex was without significance difference (p>0.05). (Table 2) Table 2 Comparison of basic Micro-albunemia status of study and control group S. No. Characteristics Study Group (N=50) Control Group (N=25) Male Female Total Male Female Total 1 Micro albumin Test Negative 21 11 32 18 07 25 2 Micro Albumin Test Positive 13 05 18 0 0 0 When level of serum cholesterol, serum triglycerides, serum LDL and serum HDL was compared in both study and control groups, serum cholesterol was found 163 .0+28.4 V/s 196.44+31.4), serum triglycerides 107.0+44.5 V/s 137.0+30.5, serum LDL 88.0+47.0 V/s 129.7+30., serum HDL 49.0+3.50 V/s 44.1+5.0, in study and control groups respectively. These lipid levels were found significantly more (P<0.05) in study group i.e. non-diabetic non-hypertensive C.V.D. patients compared to controls. (Table 3) Table 3 Comparison of serum lipid levels of study and control group S. No. Serum Lipid level (mg/dl) Study Group (N=50) Control Group (N=25) P value LS 1 Serum cholesterol (Mean ± SD) 196.44+31.4 163.0+28.4 <0.05 S 2 Serum Triglycerides (Mean ± SD) 137.0+30.5 107.0+44.5 <0.05 S 3 Serum LDL (Mean ± SD) 129.7+30.0 88.0+47.0 <0.05 S 4 Serum HDL (Mean ± SD) 44.1+5.0 49.0+3.50 <0.05 S When association of lipid profile with micro albunemia was discovered it was revealed that serum cholesterol, serum triglycerides and serum LDL in microalbuminurics were 216.0+33.6, 156.2+32.2 and 142.0+32.0 mg/dl which was significantly more in cases with micro-albunemia as where it was 188.6+27.7, 130.0+27, 117.0+28 and 45.0+5.30 respectively. There was no significant difference in serum HDL between two groups. (Table 4) Table 4 Comparison of lipid profile of Normoalbuminuric and Microalbuninuric S. No. Serum Lipid level (mg/dl) Normoalbuminuric (N=32) Microalbuninuric (N=18) P value LS 1 Serum cholesterol (Mean ± SD) 188.6+27.7 216.0+33.6 <0.05 S 2 Serum Triglycerides (Mean ± SD) 130.0+27.0 156.2+32.2 <0.05 S 3 Serum LDL (Mean ± SD) 117.0+28.0 142.0+32.0 <0.05 S 4 Serum HDL (Mean ± SD) 45.0+5.30 43.2+4.7 >0.05 NS IV. DISCUSSION The present study was conducted on 25 age, sex, height and weight matched healthy controls and 50 non-diabetic non-hypertensive CVD patients. In this study microalbunia was found in 36% of non- diabetic non-hypertensive CVD cases. In the present study the level of serum cholesterol (216.0+33.6 V/s 188.6+27.7), serum triglyceride (156.2+32.2 V/s 130.0+27.7 and serum LDL (142.0+32.0 V/s 117.0+28.0) were found higher in microlbuminuric than normoalbuminuric and this difference was statistically significant (P<0.05)
  • 4. International Multispecialty Journal of Health (IMJH) ISSN: [2395-6291] [Vol-4, Issue-3,March- 2018] Page | 69 whereas the serum HDL (43.2+4.7 V/s 45.0+5.3) was lower in microalbuminuric than normoalbuminuric but the difference was not statistically significant (P>0.05). Haffner SM et al (1990) demonstrated an association of micro-albuminuria with a number of cardiovascular risk factors, namely hypertension, hyperinsulinemia, hyper-triglyceridaemia and self reported myocardial infarction in non-diabetic subjects.7 The presence of micro-albuminuria predicts vascular disease in non diabetic population makes it more universal marker of early death from cardiovascular disease in human beings (Yudkin et al 1988), thus the onset of micro-albuminuria in diabetic and non diabetic patients signals atherogenic milieu.8 V. CONCLUSION This study aimed to find out burden of micro-albuminuria in non-diabetics, non -hypertensive CVD acses and its associating factors. Microalbunemia was found in 36% of non-diabetic, non-hypertensive CVD patients detected to be microalbuminuric by Clinitek method. There was a positive association was found between dyslipidaemia and micro-albuminuria. The microalbuminuric CVD patients (non-diabetic, non-hypertensive) had significantly elevated levels of serum cholesterol (p<0.05), triglycerides (p<0.05) and LDL (p<0.05) as compared to normoalbuminuric patients. CONFLICT OF INTEREST None declared till now. REFERENCES [1] Agewall S, wikstrand J, Ljungman S, Fagerberg B, for the Risk Factor intervention study Group. Usefulness of micro- albuminuria in predicting cardiovascular mortality in treated hypertensive men with and without diabetes mellitus. Am J Cardiol. 1997;80:164-169. [2] Bhandari Sudhir, Prognostic significance of micro-albuminuria in diabetes and its correlation with various complication and lipid profile. JAPI 2000;48(1). [3] Karalliedde J, Viberti G. Micro-albuminuria and cardiovascular risk. Am J Hypertens.2004 Oct; 17(10):986-93. [4] Reboldi G, Gentile G, Angeli F, Verdecchia P. Micro-albuminuria and hypertension. Minerva Med. 2005 Aug; 96(4):261-75 [5] Kuusisto J, Mykkanen L, Pyorala K, Laakso M. Hyperinsulinemic micro-albuminuria: a new risk indicator for coronary heart disease.Circulation 1995;91:831-37. [6] Jones CA, Francis ME, Eberhardt MS, Chavers B, Coresh J, Engelgau M, Kusek JW, Byrd-Holt D, Narayan KM, Herman WH, Jones CP, Salive M, Agodoa LY: Micro-albuminuria in the US population: Third National Health and Nutrition Examination Survey. Am J Kidney Dis 39: 445– 459, 2002 [7] Haffner SM, Stern MP, and Gruber KK micro-albuminuria: Potential marker for increased cardiovascular risk factors in non-diabetes subjects? Arteriosclerosis 1990;10:727-731. [8] Yudkin JS, Stehouwer CDA, Emeis JJ, Coppact SW. C-reactive protein in healthy subjects: associations with obesity, insulin resistance,and endothelial dysfunction.ArteriosclerosisThrombVascBiol 1999; 19:972-8.