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Table of Content - Volume 21 Issue 3 - March 2022


 

Study of prevalence of peripheral arterial disease in type-2 diabetes mellitus and its correlation with coronary artery disease using ankle-brachial index at a tertiary hospital

 

Akshaykumar Arjunagi1, Pratap P Budhya2*, Naveen Golabhavi3

 

1,2Senior Resident, 3Assistant Professor, Department of General Medicine, Belagavi Institute of Medical Sciences, Belagavi, INDIA.

Email: drnaveenbg.md@gmail.com

 

Abstract              Background: Diabetes and cardiovascular diseases are rapidly gaining pandemic proportions in South East Asia. Present study was undertaken to study the prevalence of PVD in type 2 diabetes measuring ankle brachial index using duplex Doppler ultrasound of the lower limbs and to correlate its occurrence with various risk factors. Material and Methods:Present study was cross-sectional, prospective and observational study, conducted in patients, > 30 years age, either gender, diagnosed as diabetics (WHO criteria) being treated by dietary restrictions and / or oral hypoglycemic agents and / or insulin for at least 6 months. Colour Doppler scan of the arteries of the lower limbs was performed and ankle Brachial Index was measured. Results: Patients were divided into two subgroups as PVD (Peripheral Vascular Disease) - ABI <0.9 or abnormal waveform and Non-PVD (ABI > 0.9). Prevalence of PVD in the study group was 14% with women having a slightly higher prevalence (16.9%), as compared to men (14.3%).Age, duration of diabetes, smoking, SBP, DBP and HbA1C were found to be significantly different between the two groups (p<.05). The mean age, duration of diabetes and hypertension were higher in the PVD group than in the non-PVD group. Dyslipidaemic and glucose intolerant patients had PVD more often. CAD was found more often in the PVD group (81.3%) as compared to the non- PVD group (34.5%). Microalbuminuria was commoner in the PVD group (38%) as compared to the non-PVD group (28%). Higher values of HbA1C were seen in the PVD group whereas microalbuminuria was more in the non-PVD group. Total cholesterol, LDL and triglyceride levels were comparable, but low HDL levels were more often seen in the PVD group. Conclusion: Risk factors associated with PVD were age, duration of diabetes, systolic and diastolic blood pressure, smoking, HbA1C, high total cholesterol low HDL and CAD and correlation was significant.

Keywords: peripheral arterial disease, duration of diabetes, HbA1C, coronary artery disease.

 

INTRODUCTION

Diabetes and cardiovascular diseases are rapidly gaining pandemic proportions in South East Asia. Even though the majority of diabetics are from urban areas, the scenario is changing rapidly due to socio-economic transition occurring in rural areas.1 Decreased physical activity and changes in dietary habits favour the occurrence of diabetes in Indians, who already have a racial and genetic susceptibility for the disease.2 The reasons for the higher incidence of diabetes in Indians include increased insulin resistance, genetic predisposition and environmental factors, particularly those associated with urbanisation. Insulin resistance is thought to promote atherosclerosis, in part through its associated metabolic abnormalities. Patients with diabetes mellitus suffer from an excess of premature and severe atherosclerosis.3 Peripheral arterial disease (PAD) is a manifestation of atherosclerosis characterized by atherosclerotic occlusive disease of the lower extremities and is a marker for atherothrombotic disease in other vascular beds.4 In newly detected diabetics, the prevalence of PVD is 3.5% vs. 7.8% in known diabetic subjects. PVD is uncommon till middle age and then the prevalence rate rises dramatically. Age more than 50 years and hypertension are closely associated with PVD.5,6 Using more sophisticated screening techniques like duplex colour Doppler or high-resolution ultrasound about 30% of those with a normal ankle brachial index have demonstrable plaques/ stenosis in the peripheral arteries. Present study was undertaken to study the prevalence of PVD in type 2 diabetes measuring ankle brachial index using duplex Doppler ultrasound of the lower limbs and to correlate its occurrence with various risk factors.

              

MATERIAL AND METHODS

Present study was cross-sectional, prospective and observational study, conducted in department of general medicine, XXX medical College and hospital, XXXX. Study period was of 2 years (from September 2019 and August 2020). The study protocol has been approved for ethical issues also by the institutional committee.

Inclusion criteria: Patients, > 30 years age, either gender, diagnosed as diabetics (WHO criteria) being treated by dietary restrictions and / or oral hypoglycaemic agents and / or insulin for at least 6 months, Diabetes mellitus: Fasting venous plasma glucose concentration more than or equal to 126 mg% or postprandial plasma glucose more than or equal to 200 mg% on 2 or more occasions in accordance with WHO criteria or known case of diabetes mellitus on diet control/insulin/oral hypoglycaemic agents.7

Exclusion criteria: Patients with history of Leg trauma, fracture, Leg surgery, amputation, Leg ulcers. Patients with history Deep vein thrombosis, Filariasis. Patients with lower limb swelling (impairs quality image)

Each patient gave written, informed consent to participate in the study A detailed history included Age, Sex, Smoking Alcohol intake, Diabetes mellitus/ Hypertension (duration, treatment), Symptoms of coronary artery disease, a history of CABG or PTCA. Family history of diabetes, coronary artery disease, hypertension, CVA was recorded in CRF. Standing height (meter), Weight (in kg), Waist circumference (in cms), Hip circumference (in cms), Pulse, Blood pressure were measured. A resting 12-lead electrocardiogram (ECG) was taken. After eight hours of fasting, venous samples were collected for estimation of Blood glucose, Blood urea, Serum creatinine, Uric acid, Serum cholesterol, HDL cholesterol, Serum triglycerides, VLDL and LDL, Glycated haemoglobin (HbA1C). Urinary albumin estimation was done. Colour Doppler scan - of the arteries of the lower limbs was performed using a general purpose linear probe with Image frequency of 5.7-10.0 Mhz. Arteries were have been evaluated both longitudinally and transversely by EVB 700 HV ultrasound machine of Hitachi. Ankle Brachial Index - With patients in the supine position, brachial artery systolic pressure was first measured by palpatory method and then by Doppler blood flow method in both the arms. The resumption of blood flow by Colour Doppler technique was seen as the sphygmomanometer cuff pressure was gradually released. The first wave seen during deflation of cuff was taken as systolic blood pressure. The higher reading was taken as brachial arterial systolic pressure. Similarly, ankle blood pressure was taken first by palpatory method with the cuff placed just above the ankle and then by measuring Doppler blood flow in the dorsalis pedis artery or the posterior tibial artery of both feet. Individual ABI was obtained for each leg by dividing corresponding ankle pressure by the brachial pressure. The lower of the values obtained for the two legs was taken as the true ABI for that patient. 8 A cut-off point of 0.9 was defined as a low ABI. The data was collected, entered in Microsoft excel and analysed with SPSS version 23. Statistical significance of the difference was determined using the MANN-WHITNEY U TEST. Statistical significance was defined as a P value of less than 0.5.

 


RESULTS

Doppler examination of all four limbs was performed in all patients and their ABI was calculated. Patients were divided into two subgroups as PVD (Peripheral Vascular Disease) - ABI <0.9 or abnormal waveform and Non-PVD (ABI > 0.9). Prevalence of PVD in the study group was 14% with women having a slightly higher prevalence (16.9%), as compared to men (14.3%). Age, duration of diabetes, smoking, SBP, DBP and HbA1C were found to be significantly different between the two groups (p<.05). The mean age, duration of diabetes and hypertension were higher in the PVD group than in the non-PVD group. Dyslipidaemic and glucose intolerant patients had PVD more often. CAD was found more often in the PVD group (81.3%) as compared to the non- PVD group (34.5%). In comparison to the non-PVD group, patients with PVD had a higher prevalence of hypertension, smoking, obesity (measured by BMI) and a higher HbA1C. On taking a BMI cut point as >25 kg/m2 to define obesity, 58.33% of patients without PVD had BMI >25 kg/m2 whereas a 50% of patients with PVD were obese. Of the 21 patients in the PVD group 11 patients (52.38%) had CAD and of the 125 patients in the non-PVD group 30(24%) had CAD.

Table 1: General characteristic

Variables

Non-PVD (N=84)

PVD (N=16)

P value

Age in years

 

 

 

31-40

6(7.1%)

0(0%)

0.03 8

41-50

19(22.6%)

2(12.5%)

51-60

28(33.3%)

4(25%)

61-70

24(28.6%)

9(56.3%)

>70

7(8.3%)

1(6.3%)

Gender

 

 

 

Male

54(64.3%)

11(68.8%)

0.731

Female

30(35.7%)

5(31.3%)

BMI (kg/m2)

 

 

 

<18.5

1(1.2%)

0(0%)

0.875

18.5-23

13(15.5%)

2(12.5%)

23-25

21(25%)

6(37.5%)

25-30

37(44%)

6(37.5%)

>30

12(14.3%)

2(12.5%)

Duration of DM (in years)

 

 

 

1-5

16(19%)

1(6.3%)

0.010*

6-10

44(52.4%)

4(25%)

11-15

21(25%)

8(50%)

>15

3(3.6%)

3(18.8%)

Family history of DM

 

 

 

No

69(82.1%)

14(87.5%)

0.601

Yes

15(17.9%)

2(12.5%)

Treatment

 

 

 

OHA

84(100%)

16(100%)

0.091+

Insulin

34(40.5%)

13(81.3%)

Statins

63(75%)

9(56.3%)

Habits

 

 

 

Smoking

15(17.9%)

7(43.8%)

0.039

Tobacco

30(35.7%)

6(37.5%)

Alcohol

17(20.2%)

4(25%)

Comorbidities

 

 

 

HTN

30(35.7%)

11(68.8%)

0.006

CAD

29(34.5%)

13(81.3%)

Signs and Symptoms

 

 

 

Symptoms of PVD

3(3.6%)

0(0%)

1.000

Signs of PVD

4(4.8%)

1(6.3%)

1.000

Microalbuminuria was commoner in the PVD group (38%) as compared to the non-PVD group (28%). In the biochemical evaluation, fasting blood glucose levels, post prandial blood glucose levels and kidney function test values were comparable between the non-PVD and PVD groups. Higher values of HbA1C were seen in the PVD group whereas microalbuminuria was more in the non-PVD group. Total cholesterol, LDL and triglyceride levels were comparable, but low HDL levels were more often seen in the PVD group.

Table 2: Biochemical variables

Variables

Non-PVD (N=84)

PVD (N=16)

Total (n=100)

P value

FBS

141.31±45.14

126.75±21.39

138.98±42.50

0.211

PPBS

198.12±60.49

186.50±59.58

196.26±60.20

0.482

HbA1c

6.76±0.68

8.25±0.95

7.00±0.91

<0.001

Urea

32.46±10.84

33.44±16.46

32.62±11.82

0.764

Creatinine

1.01±0.28

1.01±0.36

1.01±0.29

0.970

Uric acid

5.60±1.44

5.32±1.54

5.55±1.45

0.483

Urinary microalbuminuria/ albuminuria (mg/24 hrs)

67.73±253.80

23.53±19.21

 

<0.001

The mean total cholesterol, serum LDL, serum HDL and serum triglyceride levels were, 181.00±42.45 mg%, 108.53±45.15 mg%, 46.75±16.9 mg% and 134.64±64.49 mg%, respectively. High total cholesterol (>200 mg%), high serum LDL (>140 mg%), low serum HDL (<40 mg%) and high serum triglycerides (>150 mg%) were present in 35%, 52%, 58% and 32% of patients, respectively. The study found significant differences, as high total cholesterol levels (68.8% vs 36.8%), low HDL levels (75% vs 54.8%) in the PVD group.

Table 3: Lipid profile abnormalities (dyslipidaemias)

 

Non-PVD (n=84)

PVD) (n=16)

P-value

Total cholesterol (mg/dl)

 

 

 

  • <200

60(71.4%)

5(31.3%)

 

0.002**

  • >200

24(28.6%)

11(68.8%)

HDL (mg/dl)

 

 

 

  • <40

46(54.8%)

12(75%)

 

<0.001**

  • >40

38(45.2%)

4(25%)

LDL (mg/dl)

 

 

 

  • <100

39(46.4%)

9(56.3%)

 

0.471

  • >100

45(53.6%)

7(43.8%)

TGL mg/dl)

 

 

 

  • <150

58(69%)

10(62.5%)

 

0.607

  • >150

26(31%)

6(37.5%)

 


DISCUSSION

Diabetes affects nearly every vascular bed. Patients with diabetes mellitus suffer from high incidence of premature and severe atherosclerosis. The Framingham study pointed out the cause of the much higher incidence of cardiovascular complications in diabetic patients. These individuals have a much higher serum concentration of lipids and a higher occurrence of obesity leading to advanced atherosclerosis.9 In a study identifying coronary risk factors in 167 type 2 diabetic patients Walia et al.10 found 53.12 and 8.86 years as the mean age of their patients and the mean duration of diabetes, respectively. 28.6% of diabetic men had a history of smoking and (or) consuming alcohol and 20.4% had a family history of CAD. Central obesity was observed in 46.7% of the patients (more in women) and 31.74% of patients were hypertensive. Percentage of women who had hypertension was higher than that for men i.e., 33.8% and 30%, respectively. Poor glycemic control (HbA1c >9.5%) was found in 16.8%, hypertriglyceridaemia in 52.5% and, microalbuminuria in 35.93% of all patients. CAD was diagnosed in 15.57% of patients and when liberal ECG criteria were applied, a prevalence of 37.7% was found in this study. In the present study, the mean age of the subjects was 57.84 ±11.28 years (men– 58.69±11.55 years and women – 56.84 ±10.75 years). The mean duration of diabetes was 8.99±3.78 years (men – 9.62±4.27 years and women – 8.37±3.33 years). The group under study had 22% subjects who were smokers, 17% who gave a positive family history of diabetes and 41% of patients were hypertensive. A mean BMI was 26.39±3.72 Kg /m² (26.50±3.78 of men and 25.83±3.41 of women). Poor glycaemic control (HbA1c >7%) was present in 43% of patients. 32% had hyertriglyceridaemia (>150 mg/dl) and 58 % had low HDL levels (<40mg/dl). Microalbuminuria was found in 25 % of patients. The discrepancy between the two studies can be attributed to differences in the populations studied, objectives, defining criteria and the methodology used. For example, Walia et al.10 had defined poor glycaemic control as HbA1c >9.5% whereas we defined HbA1c >7% as poor glycaemic control; our definition of hypertension is based on JNC 7 criteria.11 After a baseline evaluation for cardiovascular risk factors, all patients were subjected to Doppler ultrasound of all four limbs to calculate ABI. A cut off value of 0.9 was used to diagnosis peripheral vascular disease. ABI has a sensitivity of about 90% and a specificity of about 98% for detecting PVD. The limitations of ABI are, It may be normal in patients with aorto-iliac disease and in well collateralised patients at rest. It may be artifactually normal or "supernormal” in patients with arterial calcification. The prevalence of PVD as detected by Doppler ultrasound (ABI) was 16% (men- 16.9% and women- 14.3%) which is comparable with the prevalence found in previous studies. Two large studies namely by Mohan et al.12 (n=4941) and CUPS5 (n=1262) found a prevalence of PVD in diabetics of 3.9% and 6.3% respectively. CUPS was a community based study unlike ours which was hospital based. This could account for the higher prevalence of PVD in our patients compared to those in CUPS. Agrawal et al.13 (n=4400) and Madhu et al.14 (n=364) found prevalence of PVD in diabetics to be 18.1% and 13.73% respectively. The Fremantle diabetes study15, Subjects with PVD had a mean age of 70.7±13.2 years with a mean duration of diabetes of 5 years. Both variables, age and duration of diabetes, attained statistical significance (p< .05) as predictors of PVD. In the study by Agrawal et al.13 a significant correlation was found between age, duration of diabetes and prevalence of PVD. In CUPS5, a significant correlation was shown between age and PVD. In our study, the mean age was 57.84±11.28 years (men– 58.69±11.55 years and women - 56.84±10.75 years) and mean duration of diabetes was 8.99±3.78 years (men– 9.62±4.27 years and women– 8.37±3.33 years). Both age and duration of diabetes were significant predictions of PVD, a finding similar to that of previous studies.

In our study there was no correlation found between obesity and PVD. Our results along with those of other Indian studies like CUPS17 and the study by Agrawal et al.13, suggest that unlike in Western populations, obesity does not appear to be a significant risk factor for PVD in Indian diabetics The majority of patients had well controlled diabetes. The mean HbA1c was 7.00±0.91%. On comparing the two groups, mean HbA1c was 6.76±0.68 mg% in the non-PVD group as compared to 8.25±0.95 in the PVD group. Using a cut off level of >7 mg% for poor control, 44.2% had poor glycaemic control in the non-PVD group compared to 68.52% in the PVD group. The mean fasting and post-prandial blood glucose levels in our study were 138.98±42.50 mg% and 196.26±60.20 mg% Blood glucose levels were comparable in the PVD and the non-PVD groups. HbA1C was significantly associated with PVD (p<0.05). Walters et al.15 and Janka et al.6 also found such an association as blood sugar values were found to be significant predictors of PVD. These studies suggest a relationship between poor glycaemic control and PVD. Our findings underscore the importance of achieving glycaemic control targets in order to prevent PVD. In our study shows, a low HDL level (defined as HDL level <40 mg%) was seen in 54.58% of patients in the non- PVD group as compared to 75% of patients with PVD (p=0.001). High total cholesterol levels (defined as cholesterol level > 200 mg %) were found more often in the PVD than the non-PVD group (68.8% vs 28.6%). High LDL levels (defined as LDL level >100 mg%) were seen more often in the non PVD than in the PVD group (53.6% vs 43.8%). Walters et al.15 and Mohan et al.12 found serum total cholesterol levels to be one of the predictive factors for PVD. Although the comparison in our study was not found to be statistically significant, high odds ratio of 2.35 for serum LDL and an odds ratio of 1.88 for total cholesterol suggests a relationship between poor lipid control and PVD. The prevalence of CAD was 81.3% in PVD patients and 34.5% in non- PVD patients. This difference was statistically significant (p= 0.007) Similarly, the Cardiovascular Health Study17, a prospective study to evaluate the association of PVD and CAD, enrolled 5,888 participants above 65 years of age. ABI was measured at the baseline. The crude mortality rate at 6 years was highest (32.3%) in those with prevalent CVD and a low ABI, and lowest in those with neither of these findings (8.7%). The risk for incident congestive heart failure (relative risk [RR]=1.61) and for total mortality (RR=1.62) in those without CVD at baseline but with a low ABI remained significantly elevated even after adjustment for cardiovascular risk factors. For each 0.1 decrement in the ABI below 1.0, event rates increased. Even within this group a low ABI was associated with increased age- and gender- adjusted risk of total and CVD mortality and remained independently associated with CVD mortality. Krishaswamy et al.18 showed that PVD was common in elderly people with coronary artery disease. PVD was found to be present in 19 patients (23.7 %). In study by Leng et al.19 1,592 subjects aged 55-74 years were selected randomly and the presence of peripheral arterial disease was determined and classified into claudicants, major and minor asymptomatic patients. Claudicants had a significantly increased risk of developing angina compared with normals (RR: 2.31, 95% Cl : 1.04-5.10), and asymptomatic subjects had a slightly increased risk of myocardial infarction and stroke. Deaths from cardiovascular disease were more likely in both claudicants (RR : 2.67, 95% Cl :1.34-5.29) and subjects with major (RR : 2.08, 95% Cl : 1.13-3.83) or minor asymptomatic disease (RR : 1.74, 95% Cl : 1.09-2.76). At baseline 288 subjects (18.2%) had an ABI index ≤0.9. After five years, subjects with an index ≤0.9 at baseline had an increased risk of non-fatal myocardial infarction (RR 1.38, 95% CI 0.88 to 2.16), stroke (RR 1.98,95% CI 1.05 to 3.77), cardiovascular death (RR 1.85,95% CI 1.15 to 2.97), and all-cause mortality (RR 1.58,95% CI 1.14 to 2.18) after adjustment for age, sex, coronary disease, and diabetes at baseline. In study by Sodhi et al.20., ultrasonic evaluation of ABI was dine in 195 individuals aged 40 years and above. After logistic regression analysis it was found that abnormal ABI (i.e. ≤ 0.9) was significantly associated with established cardiovascular risk factors, such as smoking and hypertension.  A low ABI was associated with increased age and gender adjusted risk of total and CVD mortality and remained independently associated with CVD mortality. The risk for incident congestive heart failure in those without CVD at baseline but with a low ABI remained significantly elevated after adjustment for cardiovascular risk factors.21 Because ABI is one of the first obvious indicators of atherosclerosis, some authors have proposed using it to screen for atherosclerotic disease to direct more aggressive treatment in patients at the highest risk for cardiovascular events.22 ABI could easily be measured at the annual control visits recommended for diabetic patients.

 

CONCLUSION

Risk factors associated with PVD were age, duration of diabetes, systolic and diastolic blood pressure, smoking, HbA1C, high total cholesterol low HDL and CAD and correlation was significant. This study also showed a higher prevalence of CAD in patients with PVD. However, further studies, with a larger sample size, are needed to investigate the possible mechanisms linking PVD and CAD and to determine whether PVD predicts the development and progression of CAD.

 

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