Abstract. Objectives : Peripheral arterial disease (PAD) is one of the macrovascular complications of type 2 diabetes mellitus. unlike other complications, it has ...
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© JAPI • july 2012 • VOL. 60
Original Article
Prevalence of Peripheral Arterial Disease in Type 2 Diabetes Mellitus and its Correlation with Coronary Artery Disease and its Risk Factors AK Agarwal*, Manjeet Singh**, Vivek Arya***, Umesh Garga****, Vivek Pal Singh*****, Vineet Jain****** Abstract Objectives : Peripheral arterial disease (PAD) is one of the macrovascular complications of type 2 diabetes mellitus. Unlike other complications, it has received little attention in the Indian medical literature. There is significant difference in the reported prevalence of PAD and its associated risk factors between Indian and Western studies. In order to assess PAD in diabetics, its associated risk factors and its relationship with coronary artery disease, we conducted a hospital-based, cross-sectional study. Methods: Consecutive patients on regular follow up in our diabetes clinic were included. In addition to a detailed history and physical examination, anthropometric parameters like body mass index, waist circumference and waist hip ratio were measured. Relevant laboratory investigations were performed. Modified Rose questionnaire and Minnesota codes were used to diagnose coronary artery disease (CAD). Colour Doppler examination of the arteries of the lower limbs was performed. Arteries were evaluated both longitudinally and transversely. 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. A cut off of < 0.9 was used to define peripheral arterial disease. Predictors of PAD were assessed using univariate tests of significance. Binary logistic regression was used to identify independent predictors of CAD. Results: We studied 146 patients (79 men and 67 women; mean age 59.4 ± 7.2 years; mean duration of diabetes 8.8 ± 3.8 years). The prevalence of PAD was 14.4% with women having a slightly higher prevalence (14.9%), as compared to men (13.9%) (p=0.864). CAD was present in 28%. Age, duration of diabetes, smoking, systolic and diastolic blood pressures and an HbA1c >7% were significant predictors of PAD. We did not find a correlation between measures of obesity and PAD. Using binary logistic regression, older age (p=0.01), higher HbA 1C levels (p=0.02), microalbuminuria (p=0.03) and deranged lipid profile (total cholesterol, HDL, triglycerides) were found to be significant predictors of CAD. Conclusion: Using ankle brachial index, we found evidence of PAD in 14.3% of type 2 diabetics. Risk factors significantly associated with PAD were - higher age, longer duration of diabetes, higher systolic and diastolic blood pressure, smoking, higher HbA 1C levels and CAD. The prevalence of CAD was higher in patients with PAD (52.38% vs 24% in those without PAD; p=0.007). Thus the presence of PAD should alert the clinician to a high probability of underlying CAD.
P
Introduction
eripheral arterial disease (PAD) is characterized by atherosclerotic occlusive disease of the lower extremities and is a marker for atherothrombotic disease in other vascular beds.1 The prevalence of peripheral arterial disease (PAD) in diabetic patients was found to be 3.2% in a study from South lndia2 and as high as 15.9% in a western population.3 This reportedly low prevalence of PAD in South India is in marked contrast to the high prevalence rate of coronary artery disease (CAD).2,3 A reliable diagnosis of PAD can be made using the ankle-brachial index (ABI). This simple, painless and highly Head, Department of Medicine and Dean, **Academic Junior Resident (3rd year), Department of Medicine, ***Associate Professor, Department of Medicine, ****Professor, Department of Radiodiagnosis, *****Senior Research Associate, ******Senior Resident, Department of Medicine, PGIMER and Dr R M L Hospital, New Delhi – 110001 Received Date: 28.12.2010; Accepted Date : 10.10.2011 *
reproducible test can be performed in a physician’s office and requires only a blood pressure apparatus and a hand-held, continuous-wave doppler probe. The focus of the vascular complications of diabetes has been on coronary artery disease and nephropathy while peripheral vascular disease has largely been ignored, especially in India. Hence, we carried out the present study to assess the prevalence of PAD in type 2 diabetes by measuring ankle brachial index using duplex Doppler ultrasound of the lower limbs and to correlate it with various risk factors. We also sought to evaluate the relationship between PAD and CAD in those with type 2 diabetes.
Methods Consecutive patients with type 2 diabetes mellitus attending the Diabetes clinic in the Department of Medicine at PGIMER and Dr. Ram Manohar Lohia Hospital, New Delhi for at least six months were recruited for the study. Each patient gave
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Table 1 : Demographic and clinical profile of patients in the study group
Age (years) (Mean ± SD) Duration of diabetes (years) (Mean ± SD) History of hypertension Family history of diabetes Smoking
Men (n=79) 60 ± 7 9.2 ± 3.9
Women (n=67) 58 ± 7
Total (n=146) 59 ± 7
8.3 ± 3.6 8.8 ± 3.8
41 (51.90 ) 36 (53.7 ) 77 (52.7 ) 40 (50.6 ) 44 (65.7 ) 84 (57.5 ) 4 (5.06 ) 0 (0 ) 4 (2.7)
Note: Figures in parentheses are percentages. None of the differences between men and women was statistically significant.
written, informed consent to participate in the study and the study protocol was approved by the institutional review board including ethical issues. Inclusion criteria for the study 1.
A diagnosis of type 2 diabetes mellitus as per WHO criteria.
2.
Treatment with dietary restrictions and / or oral hypoglycaemic agents and / or insulin for at least 6 months.
Patients with the following conditions, which would interfere with the measurement of the ankle brachial index, were excluded: 1.
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Trauma, surgery or amputation involving the lower limb
2. Leg ulcers 3.
Deep vein thrombosis
4.
Filariasis or lower limb swelling due to other causes which would impair Doppler image quality.
A detailed history was obtained from each patient. This included age, sex, smoking, alcohol intake, diabetes mellitus – duration, treatment; hypertension – duration, treatment; symptoms of coronary artery disease; family history of diabetes, coronary artery disease, hypertension or cerebrovascular accident. Each patient was examined with particular attention to blood pressure (as per JNC7 criteria),4 body mass index (weight (kg) / height (metre)2) and central obesity (defined as a waist hip ratio of > 0.85 in females and > 0.95 in males). Investigations performed included a resting 12-lead electrocardiogram recorded as per WHO recommendations,6 fasting and post-prandial blood glucose, blood urea, serum creatinine, uric acid, total and HDL cholesterol, triglycerides and glycated hemoglobin (HbA1c). Values for VLDL and LDL cholesterol were calculated using Friedewald’s method7. Microalbuminuria (30-300 mg of albumin excretion per day) was assessed using the immunoturbidimetric assay. Colour Doppler scan: The arteries of the lower limbs were assessed using a general purpose linear probe with image frequency of 5.7-10.0 Mhz. Arteries were evaluated both longitudinally and transversely by ALT 3500 HDL ultrasound machine (M/S Phillips). 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 arms. Similarly, ankle blood pressure was measured 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
Table 2: Prevalence of cardiovascular risk factors in the study group Risk factor Hypertension Smoking Family history of diabetes BMI >23Kg/m2 BMI>25Kg/ m2 Central obesity HbA1C >7% Serum total cholesterol >200 mg / dl Serum LDL >140 mg / dl Serum HDL cholesterol < 40 mg / dl Serum triglycerides > 150 mg / dl Microalbuminria/Albuminuria (mg / 24 hrs.)
N (%) 77 (52.74) 4 (2.74) 84 (57.53) 113 (77.40) 82 (56.16) 88 (60.27) 70 (47.95) 57 (39.04) 34 (23.29) 93 (63.70) 41 (28.08) 44 (30.14 )
legs was taken as the true ABI.8 An ABI of < 0.9 was defined as a low ABI indicative of peripheral arterial disease. CAD was diagnosed by a history of angina (Modified Rose questionnaire), ECG changes (Minnesota codes), or any past history of CAD or any treatment given for CAD.6 Smoking status was defined as :Smoker: smoking ≥ 1 cigarette/ bidi per day at the time of the study or quit smoking < 10 years back and non-smoker: never smoked/left smoking for ≥10 years. Statistics Continuous data are presented as means and standard deviations and categorical data as proportions. The differences between patients with and without PAD in terms of risk factors were assessed using Student’s t test for continuous variables and chi square test for dichotomous variables. Binary logistic regression was used to evaluate independent predictors of CAD.
Results A total of 146 patients (79 men and 67 women) with type 2 diabetes were included in the study. Demographic and clinical features of these patients are shown in Table 1. The age of the patients ranged from 39 to 80 years with a mean age of 59 years. The duration of diabetes ranged from 1 to 25 years with a mean of 8.8 years. More than half the patients (52.7%) were hypertensive and very few (2.7%) smoked. The mean systolic blood pressure was 136 ± 11 mm Hg and mean diastolic blood pressure was 86 ± 5 mm Hg. BMI ranged from 16.2 – 37.3 kg/m2 with mean BMI being 26.24 ± 3.8 kg/m2. Men had a higher mean Waist hip ratio (0.96 ± 0.08) than women (0.89 ± 0.07) (p < .001). Most patients had fairly good blood glucose control (mean HbA1c 7.1 ± 0.9 %). However, diabetic control as measured by FBG, PPBG and HbA1C was better in men than in women. This difference was significant only for PPBG which was higher in women (mean 222.8 ± 79.2) than in men (189.4 ± 57) (p=0.005). CAD, as assessed by the Rose questionnaire and Minnesota codes, was present in 28% of patients (26.5% of men and 29% of women; p=0.66). The prevalence of risk factors for CAD in the study group is shown in Table 2. Based on ABI, the prevalence of PAD was found in 21 patients out of 146 (14.4%) with women having a slightly higher prevalence (10 out of 67; 14.9%), as compared to men (11 out of 79; 13.9%) (p=0.864). Of those with PAD, 6 patients (28.6%) were symptomatic. The
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Fig. 1c : Decreased flow in the anterior tibial artery. Fig. 1a : Longitudinal scan of a lower limb artery showing a plaque (arrow). The red area shows blood flow signal.
Fig. 1d : Absent flow in the dorsalis pedis artery. Fig. 1b : Lower limb artery showing intimal thickening with calcified plaques.
those with and those without PAD, no statistically significant differences were found.
most common symptom was intermittent claudication which was present in all symptomatic patients. None of our patients gave a history of nocturnal pain or a cold sensation in the feet. On clinical examination, 3 patients (14.3%) had decreased peripheral pulses. However, none of the patients had ulcers, gangrene, skin changes or dependent pallor.
Binary logistic regression (Table 4) was used to assess significant independent predictors of CAD. Older age (p=0.01), higher HbA1C levels (p=0.02), microalbuminuria (p=0.03) and deranged lipid profile (total cholesterol, HDL, triglycerides) were found to be significant predictors of CAD.
Some of the typical findings on Doppler ultrasound are shown in Figures 1A, 1B, 1C and 1D. The differences between the PAD and the non-PAD groups in terms of risk factors were assessed using Student’s t test for continuous variables and chi square test for discrete variables. These results are summarized in Table 3. Of the 21 patients with PAD, 11 (52.38%) had CAD. Of the remaining 125 patients without evidence of PAD, 30 (24%) had CAD. This difference was statistically significant by the chi square test (p=0.007). Age, duration of diabetes, systolic BP, diastolic BP and HbA1C >7% were found to be significantly different between the two groups. On comparing the use of ACE inhibitors, statins, insulin, sulphonylureas, metformin and pioglitazone between
Discussion In this cross-sectional study on 146 type 2 diabetes patients, the mean age was 59.4 ± 7.2 years and the mean duration of diabetes was 8.8 ± 3.8 years. The group had 2.74% smokers, 57.5% of patients gave a positive family history of diabetes and 52.7% were hypertensive. The prevalence of PAD as detected by Doppler ultrasound (ABI) was 14.4 %. Previous studies by Marinelli et al,10 Janka et al,3 Walters et al,11 Migdalis et al12 and the Fremantle diabetes study by Paul et al13 found the prevalence of PAD to be 33%, 15.9%, 23.5%, 44% and 13.6%, respectively. Few Indian studies have assessed PAD in diabetics. Two large studies from South India, namely, by Mohan et al14 (n=4941) and CUPS2 (n=1262) found a prevalence of PAD in diabetics to be 3.9% and 6.3%, respectively. CUPS, a community based study,
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Table 3: Cardiovascular disease risk factors in PAD and non-PAD subgroups. Risk factor Age (years) Mean + SD Duration of diabetes (years) Mean + SD Hypertension Smoking CAD SBP (mmHg) DBP (mmHg) BMI (Kg/m2) Waist Hip Ratio Fasting blood glucose (mg%) Post–prandial blood glucose (mg%) Total cholesterol (mg%) Serum LDL (mg%) Serum HDL (mg%) Serum triglycerides (mg%) HbA1C (%) Urinary microalbuminuria/albuminuria mg / 24 hrs.
Non-PAD 58 ± 6 8±3 63 (50.4) 2 (1.6) 30 (24) 135 ±10 86 ± 0.5 26.23 ±3.79 0.93 ±0.08 144 ± 47 205 ± 68 182 ± 43 108 ± 41 47 ± 16 129 ± 62 6.9 ± 0.9 68 ± 254
PAD 67 ± 7 12 ± 5 14 (66.7) 2 (9.5) 11 (52.38) 144 ± 10 89 ± 5 26.26 ±3.60 0.92 ±0.11 147 ± 60 200 ± 77 180 ± 43 116 ± 54 43 ± 11 125 ± 44 7.7 ± 0.9 24 ± 19
P value 0.001 0.001 0.169 0.1 0.007 0.001 0.005 0.977 0.754 0.833 0.748 0.893 0.448 0.187 0.770 0.001 0.468
Note: Figures in parentheses are percentages. BMI = body mass index; SBP = systolic blood pressure DBP= diastolic blood pressure CAD = coronary artery disease
Table 4: Binary logistic regression to assess independent predictors of CAD. Variable Sex Age BMI Waist hip Ratio Family h/o diabetes Duration of diabetes Smoking Hypertension HbA1C Total cholesterol LDL cholesterol HDL cholesterol Triglycerides Microalbuminuria Waist circumference PAD
Regression coefficient 0.75 0.22 0.17
p value 0.46 0.01 0.29
-13.44
0.05
-0.02 0.33 -3.18 0.31 4.31 0.12 -0.01 -0.13 -0.02 -0.09 0.11 -2.55
0.98 0.20 0.20 0.69 0.02 0.01 0.32 0.02 0.04 0.03 0.20 0.10
found a lower prevalence of PAD than our study which was hospital based. Two recent studies from North India, one by Agrawal et al15 (n=4400) and the other by Madhu et al16 (n=364) found the prevalence of PAD in diabetics to be 18.1% and 13.73%, respectively. The former study was performed on outpatients with a study design similar to ours. In the Fremantle diabetes study, age, duration of diabetes, higher systolic blood pressure and higher BMI were found to be significant predictors of PAD.13 In the study by Agrawal et al a significant correlation was found between age,duration of diabetes and prevalence of PAD.15 In both CUPS2 and in the study by Mohan et al14 age and higher systolic blood pressure predicted PAD.2 Systolic blood pressure was also shown to be a predictor of PAD in the study by Janka et al.3 In our study, both age and duration of diabetes were
significant predictors of PAD. The prevalence of hypertension was 50% in patients without PAD as compared to 66% in those with PAD. Mean systolic blood pressure was 134 ± 10 in the non – PAD group as compared to 144 ± 10 in the PAD group (p
