A Retrospective study of
Correlation of plasma Fibrinogen and Serum Lipids as risk factors for coronary artery disease in Type-2 Diabetes Mellitus
I. INTRODUCTION
• Diabetes affecting nearly 200 million people world wide [Wild et al., 2004].
• Diabetes mellitus is one of the main risk factor of CAD development [NishigakiI
et al., 1981].
• CAD the first killer and the major cause of public health problems in the world
[Hadaegh et al., 2009].
II. REVIEW OF LITERATURE
• Coronary artery disease (CAD) represents - Angina pectoris,
Myocardial Infarction and sudden death [Ronald M and Krauss M
2004].
• Recent and previous studies reported DM is consider one of the main
risk factor of CAD development [Nishigaki et al., 1981].
II. REVIEW OF LITERATURE
• Fibrinogen involved increased rate of CVD in patients with Type 2 DM [Rossen
M et al., 1996].
• High fibrinogen increases high lipid profile which increase the risk of IHD in DM
than controls [J.G. Saluja et al., 2000].
• Fibrinogen in-association with Lipoprotein may play key roles in atherosclerotic
lesion formation, leads to CVD [EB Smith et al., 1992].
PROBLEM STATEMENT IN
CAMBODIA
• CHD Deaths in Cambodia 8.81%, ranks #71 in the world [WHO, 2011].
• Diabetes Mellitus Deaths in Cambodia 3.01%, ranks #72 in the world [WHO,
2011].
• Development of CAD has been increased among Type II Diabetes in Cambodian
Population.
AIM OF THE STUDY
• To address the risk factors associated with coronary artery disease in Type II
Diabetes mellitus.
OBJECTIVES OF THE STUDY
• Evaluate Type II DM with CAD and without CAD patients.
• Analyze male and female Type II diabetes with CAD and without CAD subjects.
• Evaluate ECG abnormalities of Type II DM with CAD patients.
• Compare glucose , fibrinogen and lipid profile (Cholesterol, triglycerides, HDL,
LDL and VLDL) of study Subjects.
III. MATERIALS AND METHODS
• Study Population
• Totally 100 Patients from Sen Sok International University Hospital, Phnom Penh, age
range from 35 to 75.
• Group I- 20 healthy subjects as controls
• Group II- 40 patients of Type 2 diabetes without CAD
• Group III - 40 cases of Type 2 diabetes with CAD
• Study Design
• The Retrospective study
III. MATERIALS AND METHODS
• Inclusion Criteria
• Group I
• Healthy Subjects
• Group II
• Diabetic history, family history, information on smoking and alcoholic habits.
• Group III
• Previous MI, angioplasty, coronary artery by pass grafting and had angiographic
documentation of stents.
• Exclusion Criteria
• Patients without Type-II Diabetic history, patients on drugs like glucocorticoids estrogens
and progesterone and pregnant women.
III. MATERIALS AND METHODS
• Instrumentation
• Electrocardiography
• Electrocardiogram (ECG) was recorded using CARDIPIA 400
III. MATERIALS AND METHODS
• Sample Collection
• Aseptic Blood Collection was performed
• Citrated blood centrifuged (5000 rpm) to obtain Plasma
• Coagulated blood centrifuged (5000 rpm) to obtain Serum
III. MATERIALS AND METHODS
• Fibrinogen measured
by fully automated
coagulation analyzer
Sysmex® CA-500 Series System HumaStar 600 System
Glucose and Lipid profile
analyzed using fully
automated Biochemistry
Analyzer
III. MATERIALS AND METHODS
• Estimation of Study Parameters
➢Plasma Fibrinogen [Clauss A, 1957]
➢Serum Glucose [GOD-PAP Method]
➢Serum Total Cholesterol [CHOD-PAP Method]
➢Serum Triglycerides [GPO-PAP Method]
➢Serum LDL-Cholesterol [Okada M. et al., 1998]
➢Serum HDL-Cholesterol [Gordon T et al., 1997]
➢Serum VLDL-Cholesterol [Calculated]
III. MATERIALS AND METHODS
• Statistical analysis
• Students “t” test for continuous variable and results were obtained in the form of p
(probability) value, using SPSS 16 software.
IV.
RESULTS
Gender
|
Control
(Group I) |
Diabetic without CAD
(Group II) |
Diabetic with CAD
(Group III) |
Male
|
13 (65%)
|
23 (58%)
|
20 (50%)
|
Female
|
7 (35%)
|
17 (43%)
|
20 (50%)
|
Total
|
20
|
40
|
40
|
TOTAL & GENDER WISE PERCENTAGE OF
STUDY SUBJECTS
AGE GROUP WISE DIFFERENCE AMONG TYPE-2
DIABETES WITHOUT CAD PATIENTS
STUDY SUBJECTS
AGE GROUP WISE DIFFERENCE AMONG TYPE-2
DIABETES WITHOUT CAD PATIENTS
Age groups in years
|
No. of Male cases & (%)
|
No. of Female cases &
(%) |
35-45
|
3 (7.5%)
|
5 (12.5%)
|
46-55
|
9 (22.5)
|
2 (5%)
|
56-65
|
4 (10%)
|
6 (15%)
|
66-75
|
7 (17.5%)
|
4 (10%)
|
Total
|
23
|
17
|
AGE GROUP WISE DIFFERENCE AMONG TYPE-2
DIABETES WITH CAD PATIENTS
Age groups in years
|
No. of Male cases & (%)
|
No. of Female cases & (%)
|
35-45
|
5 (12.5%)
|
7 (17.5%)
|
46-55
|
4 (10%)
|
3 (7.5%)
|
56-65
|
3 (7.5%)
|
4 (10%)
|
66-75
|
8 (20%)
|
6 (15%)
|
Total
|
20
|
20
|
CARDIAC PAIN CHARACTERISTICS
AMONG TYPE II DIABETES WITH CAD
PATIENTS
84%
86%
88%
90%
92%
94%
96%
98%
100%
100% 100% 100% 100%
95% 95% 95%
90% 90% 90%
Clinical symptoms
ECG CHANGES AMONG TYPE II DIABETES
WITH CAD
S. No
|
Gender
|
ST Depression (%)
|
1
|
Male (20)
|
100%
|
2
|
Female (20)
|
100%
|
COMPARISON OF GLUCOSE LEVELS OF
STUDY SUBJECTS
Glucose
|
N
|
Mean
|
StDev
|
P Value
|
Group I (Control)
|
20
|
101.55
|
5.0936
|
P<0.0001
|
Group II ( Diabetic without
CAD) |
40
|
202.325
|
46.6934
|
P<0.0001
|
Group III Diabetic with CAD
|
40
|
369.275
|
71.7671
|
P<0.0001
|
COMPARISON OF GLUCOSE LEVELS AMONG
MALES AND FEMALES
Control (Group I)
|
Diabetic without CAD
(Group II) |
Diabetic with CAD
(Group III) |
||||
Gender
|
Male
|
Female
|
Male
|
Female
|
Male
|
Female
|
Glucose
Mean ±SD |
100.6±4.90
|
103.1±5.4
|
195.7± 53.4
|
211.2±35.2
|
359.9±60.9
|
378.6±81.6
|
P<0.0001 – Group I Vs
Group II Males & Females
P<0.0001 – Group I Vs
Group III Males & Females
P<0.0001 – Group II Vs
Group III Males & Females
COMPARISON OF FIBRINOGEN LEVEL
AMONG THREE GROUPS
Group II Males & Females
P<0.0001 – Group I Vs
Group III Males & Females
P<0.0001 – Group II Vs
Group III Males & Females
COMPARISON OF FIBRINOGEN LEVEL
AMONG THREE GROUPS
Fibrinogen
|
N
|
Mean
|
StDev
|
P Value
|
Group I (Control)
|
20
|
284.1
|
37.6394
|
P<0.0001
|
Group II ( Diabetic without
CAD) |
40
|
397.625
|
21.1959
|
P<0.0001
|
Group III (Diabetic with
CAD) |
40
|
440.6
|
13.2
|
P<0.0001
|
COMPARISON OF FIBRINOGEN LEVEL AMONG
MALES AND FEMALES
Control(Group I)
|
Diabetic without CAD
(Group II) |
Diabetic with CAD
(Group III) |
||||
Gender
|
Male
|
Female
|
Male
|
Female
|
Male
|
Female
|
Fibrinogen
Mean ± SD |
273.0±34.7
|
304.5±36.2
|
387.4 ± 5.1
|
411.4±26.6
|
434.6±16.0
|
446.65±5.1
|
P<0.0001 – Group I Vs
Group II Males & Females
P<0.0001 – Group I Vs
Group III Males & Females
P<0.0001 – Group II Vs
Group III Males & Females
COMPARISON OF TOTAL CHOLESTEROL
LEVEL AMONG THREE GROUPS
Group II Males & Females
P<0.0001 – Group I Vs
Group III Males & Females
P<0.0001 – Group II Vs
Group III Males & Females
COMPARISON OF TOTAL CHOLESTEROL
LEVEL AMONG THREE GROUPS
Total Cholesterol
|
N
|
Mean
|
StDev
|
P Value
|
Group I (Control)
|
20
|
173.8
|
11.919
|
P<0.0001
|
Group II ( Diabetic without
CAD) |
40
|
195.6
|
9.0718
|
P<0.0001
|
Group III Diabetic with CAD
|
40
|
228.9
|
36.2285
|
P<0.0001
|
COMPARISON OF TOTAL CHOLESTEROL
LEVEL AMONG MALES AND FEMALES
Control
|
Diabetic without CAD
|
Diabetic with CAD
|
||||
Gender
|
Male
|
Female
|
Male
|
Female
|
Male
|
Female
|
Cholestero
l Mean ±SD |
173.1±9.
1 |
175±16.7
|
195.5±8.9
|
195.7±9.5
|
232.9±35.9
|
224.9±36.
9 |
P<0.0001 – Group I Vs
Group II Males & Females
P<0.0001 – Group I Vs
Group III Males & Females
P<0.0001 – Group II Vs
Group III Males & Females
COMPARISON OF TRIGLYCERIDE LEVEL
AMONG THREE GROUPS
Group II Males & Females
P<0.0001 – Group I Vs
Group III Males & Females
P<0.0001 – Group II Vs
Group III Males & Females
COMPARISON OF TRIGLYCERIDE LEVEL
AMONG THREE GROUPS
Triglyceride
|
N
|
Mean
|
StDev
|
P Value
|
Group I (Control)
|
20
|
158.2
|
7.5366
|
P<0.0001
|
Group II ( Diabetic without CAD)
|
40
|
189.075
|
7.1302
|
P<0.0001
|
Group III Diabetic with CAD
|
40
|
210.2
|
27.4032
|
P<0.0001
|
COMPARISON OF TRIGLYCERIDE LEVEL
AMONG MALES AND FEMALES
Control
|
Diabetic without CAD
|
Diabetic with CAD
|
||||
Gender
|
Male
|
Female
|
Male
|
Female
|
Male
|
Female
|
Triglyceride
Mean ± SD |
158.3±6.6
|
158±9.5
|
187.8±7.8
|
190.7±5.7
|
215.9±33.
6 |
204.5±18.4
|
P<0.0001 – Group I Vs
Group II Males and
Females
P<0.0001 – Group I Vs
Group III Males and
Females
P value equals 0.0004
Group II Vs Group III Males
P value equals 0.0054
Group II Vs Group III
Females
COMPARISON OF HDL LEVEL AMONG
THREE GROUPS
Group II Males and
Females
P<0.0001 – Group I Vs
Group III Males and
Females
P value equals 0.0004
Group II Vs Group III Males
P value equals 0.0054
Group II Vs Group III
Females
COMPARISON OF HDL LEVEL AMONG
THREE GROUPS
HDL Cholesterol
|
N
|
Mean
|
StDev
|
P Value
|
Group I (Control)
|
20
|
59.65
|
2.8335
|
P<0.0001
|
Group II ( Diabetic without
CAD) |
40
|
38.825
|
3.7203
|
P<0.0001
|
Group III (Diabetic with CAD)
|
40
|
27
|
1.1323
|
P<0.0001
|
COMPARISON OF HDL LEVEL AMONG
MALES AND FEMALES
Control (Group I)
|
Diabetic without CAD
(Group II) |
Diabetic with CAD
(Group III) |
||||
Gender
|
Male
|
Femal
e |
Male
|
Female
|
Male
|
Female
|
HDL
Mean ± SD |
59.2±2.7
|
60.4±2.9
|
37.8±4.4
|
40.1±1.7
|
27.1±1.07
|
26.9±1.2
|
P<0.0001 – Group I Vs
Group II Males & Females
P<0.0001 – Group I Vs
Group III Males & Females
P<0.0001 – Group II Vs
Group III Males & Females
COMPARISON OF LDL LEVEL AMONG
THREE GROUPS
Group II Males & Females
P<0.0001 – Group I Vs
Group III Males & Females
P<0.0001 – Group II Vs
Group III Males & Females
COMPARISON OF LDL LEVEL AMONG
THREE GROUPS
LDL Cholesterol
|
N
|
Mean
|
StDev
|
Group I (Control)
|
20
|
139.75
|
8.6077
|
Group II ( Diabetic without
CAD) |
40
|
175.775
|
16.4978
|
Group III Diabetic with CAD
|
40
|
186.3
|
14.0753
|
P<0.0001 – Group I Vs Group II
P value equals 0.0029 – Group II
Vs Group III
P<0.0001 – Group I Vs Group III
COMPARISON OF LDL LEVEL AMONG
MALES AND FEMALES
P value equals 0.0029 – Group II
Vs Group III
P<0.0001 – Group I Vs Group III
COMPARISON OF LDL LEVEL AMONG
MALES AND FEMALES
Control (Group I)
|
Diabetic without CAD
(Group II) |
Diabetic with CAD
(Group III) |
||||
Gender
|
Male
|
Female
|
Male
|
Female
|
Male
|
Female
|
LDL
Mean ± SD |
138.4±8.9
|
142.1±7.9
|
180.7±4.6
|
169.0±23.4
|
189.8±14.8
|
182.7±12.6
|
P<0.0001 – Group I Vs
Group II Males and Females
P<0.0001 – Group I Vs
Group III Males and
Females
P value equals 0.0004 -
Group II Vs Group III Males
P value equals 0.0017
Group II Vs Group III
COMPARISON OF VLDL LEVEL AMONG
THREE GROUPS
Group II Males and Females
P<0.0001 – Group I Vs
Group III Males and
Females
P value equals 0.0004 -
Group II Vs Group III Males
P value equals 0.0017
Group II Vs Group III
COMPARISON OF VLDL LEVEL AMONG
THREE GROUPS
VLDL Cholesterol
|
N
|
Mean
|
StDev
|
P Value
|
Group I (Control)
|
20
|
21.15
|
1.0894
|
P<0.0001
|
Group II ( Diabetic without
CAD) |
40
|
36
|
1.3205
|
P<0.0001
|
Group III (Diabetic with CAD)
|
40
|
42.325
|
2.7586
|
P<0.0001
|
COMPARISON OF VLDL LEVEL AMONG
MALES AND FEMALES
Control (Group I)
|
Diabetic without CAD
(Group II) |
Diabetic with CAD
(Group III) |
||||
Gender
|
Male
|
Female
|
Male
|
Female
|
Male
|
Female
|
VLDL
Mean ± SD |
21.0 ± 1.0
|
21.2 ± 1.2
|
36±1.1
|
36 ± 1.5
|
42.3 ± 1.8
|
42.3 ± 3.4
|
P<0.0001 – Group I Vs
Group II Males & Females
P<0.0001 – Group I Vs
Group III Males & Females
P<0.0001 – Group II Vs
Group III Males & Females
V. DISCUSSION
• Male diabetic subjects were slightly higher than females in the present study.
• Recent study found 72% males and 28% were females [Khursheed et al., 2011].
• The present study observed ST segment depression among all CAD patients.
• Earlier studies also reported ST segment depression CAD cases [Menotti et al.,
1997; De Bacquer et al., 1998; Menotti et al., 2001; Larsen et al., 2002;
Knutsen et al., 1988].
V. DISCUSSION
• The present study found raised plasma fibrinogen with cardio diabetic patients.
• Several reports stated raised plasma fibrinogen positively associated with the CHD
[Lowe GDO, et al., 1997, Rosengren A, et al., 1996, Sweetnam PM, et al., 1996,
Woodward M et al., 1998, Folsom AR, et al., 1997].
V. DISCUSSION
• Present study found Increased triglycerides, total cholesterol, LDL and
VLDL and decreased HDL levels observed in type 2 diabetes.
• Previous studies reported raised serum cholesterol triglycerides, LDL,
VLDL and Low HDL levels in type 2 diabetes [Ahmad et al., 2003;
Vijay R. M and Gunaseelan. N, 2006; Shiva kumar D. G and A. R.
Patil 2005] .
VI. CONCLUSION
• The overall female Type II DM mellitus subjects are higher than male.
• There were equal number of male and female of CAD cases found among Type II
DM.
• There were more number of CAD cases observed age between 66-75 in males and
35-45 in females.
VI. CONCLUSION
• ST segment depression found among all CAD subjects.
• Significant elevation of fibrinogen and serum lipid profile among Type II diabetes
mellitus with CAD patients than without CAD and control subjects.
• Therefore, plasma fibrinogen and serum lipid profile are better markers for
inducing CAD in type 2 diabetes mellitus.
VII. RECOMMENDATION
• Regular monitoring glucose of Type II diabetes prevent Cardiac complications.
• Checking plasma fibrinogen and serum lipid profile while treating Type II
diabetes patients.
• Early Initiation of anti-diabetic, anti-thrombotic and anti-dyslipidemic agents if
the patient has hyperglycemia, hyperfibrinogenemia and dyslipidemia.
VII. RECOMMENDATION
• Proper diet and regular exercise would be beneficial for Diabetes
patients.
• Diabetes dyslipidemic patients must be cautious of eating rich
carbohydrate and fat containing foods.
• Maintaining normal serum lipid profile during Type II diabetes
mellitus can prevent CAD.
Group II Males & Females
P<0.0001 – Group I Vs
Group III Males & Females
P<0.0001 – Group II Vs
Group III Males & Females
V. DISCUSSION
• Male diabetic subjects were slightly higher than females in the present study.
• Recent study found 72% males and 28% were females [Khursheed et al., 2011].
• The present study observed ST segment depression among all CAD patients.
• Earlier studies also reported ST segment depression CAD cases [Menotti et al.,
1997; De Bacquer et al., 1998; Menotti et al., 2001; Larsen et al., 2002;
Knutsen et al., 1988].
V. DISCUSSION
• The present study found raised plasma fibrinogen with cardio diabetic patients.
• Several reports stated raised plasma fibrinogen positively associated with the CHD
[Lowe GDO, et al., 1997, Rosengren A, et al., 1996, Sweetnam PM, et al., 1996,
Woodward M et al., 1998, Folsom AR, et al., 1997].
V. DISCUSSION
• Present study found Increased triglycerides, total cholesterol, LDL and
VLDL and decreased HDL levels observed in type 2 diabetes.
• Previous studies reported raised serum cholesterol triglycerides, LDL,
VLDL and Low HDL levels in type 2 diabetes [Ahmad et al., 2003;
Vijay R. M and Gunaseelan. N, 2006; Shiva kumar D. G and A. R.
Patil 2005] .
VI. CONCLUSION
• The overall female Type II DM mellitus subjects are higher than male.
• There were equal number of male and female of CAD cases found among Type II
DM.
• There were more number of CAD cases observed age between 66-75 in males and
35-45 in females.
VI. CONCLUSION
• ST segment depression found among all CAD subjects.
• Significant elevation of fibrinogen and serum lipid profile among Type II diabetes
mellitus with CAD patients than without CAD and control subjects.
• Therefore, plasma fibrinogen and serum lipid profile are better markers for
inducing CAD in type 2 diabetes mellitus.
VII. RECOMMENDATION
• Regular monitoring glucose of Type II diabetes prevent Cardiac complications.
• Checking plasma fibrinogen and serum lipid profile while treating Type II
diabetes patients.
• Early Initiation of anti-diabetic, anti-thrombotic and anti-dyslipidemic agents if
the patient has hyperglycemia, hyperfibrinogenemia and dyslipidemia.
VII. RECOMMENDATION
• Proper diet and regular exercise would be beneficial for Diabetes
patients.
• Diabetes dyslipidemic patients must be cautious of eating rich
carbohydrate and fat containing foods.
• Maintaining normal serum lipid profile during Type II diabetes
mellitus can prevent CAD.
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