|Year : 2013 | Volume
| Issue : 1 | Page : 26-30
Hypertension and lower extremity peripheral artery disease: An overlooked association
Umuerri E Martha1, Edo Andrew2, Obasohan A Osemwingie2
1 Department of Medicine, Delta State University Teaching Hospital, Oghara, Delta, Nigeria
2 Department of Medicine, University of Benin Teaching Hospital, Benin City, Nigeria
|Date of Web Publication||21-Sep-2013|
Umuerri E Martha
Department of Medicine, Delta State University Teaching Hospital, P.M.B. 07, Oghara, Delta
Source of Support: None, Conflict of Interest: None
Background: Hypertension is a major risk factor for atherosclerosis and by extension lower extremity peripheral artery disease (LEAD). There is however, paucity of data on the prevalence of LEAD among hypertensive patients in Nigeria.
Methods: This study determined the prevalence of LEAD among hypertensive patients attending the hypertension clinic, consultant out-patient department, University of Benin Teaching Hospital, Benin City. It also examined the relationship of certain risk factors known to be associated with atherosclerosis generally. A total of 153 hypertensive patients aged 18 years and above were consecutively enrolled in the study. LEAD was defined as an ankle-brachial index (ABI) <0.9 in either leg using the hand-held Doppler ultrasound scan. The Edinburgh Claudication Questionnaire was administered to determine a history of intermittent claudication, the major symptom of LEAD.
Results: Nearly, 41.8% of the patients had ABI <0.9 in either leg. Among patients with LEAD majority were asymptomatic with a ratio of 1:8 for symptomatic versus asymptomatic disease.
Conclusion: LEAD is common among hypertensive patients, with prevalence of 41.8%. Majority of patients with LEAD were asymptomatic.
Keywords: Ankle-brachial index, atherosclerosis, hypertension, lower extremity peripheral artery disease
|How to cite this article:|
Martha UE, Andrew E, Osemwingie OA. Hypertension and lower extremity peripheral artery disease: An overlooked association. Nig J Cardiol 2013;10:26-30
|How to cite this URL:|
Martha UE, Andrew E, Osemwingie OA. Hypertension and lower extremity peripheral artery disease: An overlooked association. Nig J Cardiol [serial online] 2013 [cited 2019 Jan 23];10:26-30. Available from: http://www.nigjcardiol.org/text.asp?2013/10/1/26/118578
| Introduction|| |
Peripheral vascular disease (PVD) refers to diseases of the blood vessels outside the heart and the brain. Lower extremity peripheral artery disease (LEAD) is the most common form of PVD. LEAD is due mainly to atherosclerosis that leads to narrowing and diminished blood flow to the arteries in the legs. It is one of the components of the cardiovascular disease triad. Others are cerebrovascular disease and coronary artery disease. LEAD, though rarely causes death in itself, serves as an initial marker of cerebrovascular and coronary artery disease as atherosclerosis has been described as a systemic disease. Indeed, it is an evidence of widespread atherosclerosis in other vascular territories. 
The burden of hypertension is enormous world-wide with Nigeria having prevalence of 20%.  Hypertension plays a significant role in the pathogenesis of atherosclerotic vascular disease and has been linked with an increased risk of LEAD. Atherosclerosis is the leading cause of death in the general population in industrialized countries.  A number of other risk factors that are almost identical to other atherosclerotic diseases elsewhere have been identified for LEAD. The presence of many risk factors in a single patient increases the risk for LEAD many folds. In the Basle longitudinal study,  the relative risk for LEAD increased from 2.3 to 3.3 and 6.3 in individuals who had one, two or three respectively of the risk of the following factors: smoking, diabetes, and systolic hypertension.
LEAD is diagnosed by a low ankle-brachial index (ABI), usually <0.9, but the range in the literature varies from <0.80 to <0.97.  It is note-worthy that intermittent claudication is the most common symptomatic manifestation of PVD. The prevalence of LEAD has increased in the African continent from 0% in 1963 in Zimbabwe to 78% in 2000 in Algeria, partly because communities across Africa are becoming more urbanized.  There is however, paucity of data on the prevalence of LEAD among hypertensive patients in Nigeria and the factors associated with its development.
| Materials and Methods|| |
This was a cross-sectional study of 153 hypertensive patients aged 36-92 years who were consecutively recruited from the hypertension clinic, consultant out-patient department, University of Benin Teaching Hospital (UBTH), Benin City, Nigeria between March and August 2009. Hypertensive patients with pitting pedal edema were excluded from the study.
LEAD was diagnosed by an ABI <0.9 in at least one leg. The presence of intermittent claudication was determined using the Edinburgh Claudication Questionnaire. An interviewer-administered questionnaire was used to ascertain demographic data, duration of the hypertension, history of diabetes mellitus and smoking. Anthropometric measurements of weight, height, body mass index (BMI), waist and hip circumference were obtained. The weight was measured in kilograms using the Hospital Health-Care scale ZT-120. The patients were asked to empty their pockets, remove their footwear and any heavy outer clothing and stand upright in the center of the scale. The weight was then recorded to the nearest 0.1 kg. The height in meters was measured using the ZT-120 meter rule. Patients were asked to stand with the back to the meter rule, looking straight on. The hair, if any, was pressed flat and the height recorded to the nearest 0.1 cm. The BMI, defined as patient's weight in kilograms divided by the square of the patient's height in meters, was calculated thereafter. The waist and hip circumference was measured in centimeters using a non-elastic tape measure. The waist circumference (WC) was measured in the horizontal plane at a level mid-way between the lower rib and the iliac crest although the hip circumference was measured at the maximal circumference over the buttocks in the horizontal plane. Both measurements were carried out twice and the average calculated. The waist-hip ratio (WHR) was also calculated.
Blood pressure measurement was obtained using the Accoson® mercury sphygmomanometer, after at least 10 min rest, in the right hand of seated patients on three occasions at an interval of 1 min. The average blood pressure reading was then calculated.
Doppler derived segmental systolic blood pressure (SBP) was recorded using an 8 MHz hand-held Doppler (Summit Doppler Systems® , Inc. Colorado, USA). The brachial systolic pressure in both arms was measured and the higher of the two was used as the reference. A pneumatic cuff was placed on the arm and the Doppler probe placed over the brachial artery to obtain the brachial systolic pressure. Similarly, a pneumatic cuff was placed around the leg just above the medial malleolus and the Doppler probe placed over the dorsalis pedis or the posterior tibial artery (whichever had a better signal). The ankle systolic pressure in both legs was measured. The ABI was calculated as the quotient of the ankle pressure and the higher of the two arm pressures.
Blood samples were obtained for assessment of fasting blood sugar, fasting serum lipid profile - total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), and triglycerides (TG). These were carried out by colorimetry in the chemical pathology laboratory of UBTH, Benin City.
The data obtained from the questionnaire was checked for accuracy. Data were then entered into the computer and analyzed using the Statistical Package for Social Sciences (SPSS) Version 16, IBM Corporation software. The level of significance is set at P<0.05.
| Results|| |
The clinical characteristics of subjects are shown in [Table 1]. There were 50 (32.7%) males and 103 (67.3%) females, with a male to female ratio of 1:2.
Prevalence of LEAD
By history of intermittent claudication
A positive history of intermittent claudication was obtained in 12 out of 153 respondents making the prevalence of LEAD 7.8%.
By Doppler ultrasound
The prevalence of LEAD using Doppler ABI <0.9 in either lower limb was 41.8% (64 out of the 153). The prevalence of LEAD was higher among patients with concomitant diabetes mellitus [Figure 1].
|Figure 1: Prevalence of lower extremity peripheral artery disease diagnosed by ankle-brachial index <0.9. **Hypertensive, *hypertensivediabetic|
Click here to view
LEAD was detected by both history of claudication and Doppler ABI in 8 (5.2%) of the 153 patients studied. Assuming the gold standard for diagnosis of LEAD was by Doppler ABI <0.9, LEAD diagnosed by history of intermittent claudication has a sensitivity, specificity and positive predictive value of 12.5%, 95.5% and 66.7% respectively.
LEAD and other risk factors
The mean age of patients with or without Doppler ABI diagnosed LEAD differ significantly (59.9±1.56 years vs. 55.8±1.04 years; t=2.278, P<0.05).
The proportion of patients with LEAD increased with increasing age. This association was not statistically significant (P=0.05).
There were more female than male patients with LEAD (45% vs. 36% respectively). The association between sex and the prevalence of LEAD diagnosed by Doppler ABI was not however, statistically significant (χ2 =1.037, P=0.308).
History of diabetes mellitus was obtained in 33 (21.6%) of the patients. The proportion of patients with LEAD diagnosed by Doppler ABI was higher among hypertensive patients with concomitant history of diabetes (19 out of 33 vs. 45 out of 120 for hypertensive-diabetic and hypertensive-only sub-groups, respectively). This association was statistically significant (χ2 =4.287, P=0.038).
More than 80% of the patients in the study population had never smoked. The association between cigarette smoking and the prevalence of LEAD in this study was not statistically significant.
The mean BMI, WC, and WHR were higher among patients with LEAD than those without LEAD though the difference was not statistically significant [Table 2].
|Table 2: Relationship between anthropometric measurements and LEAD diagnosed by Doppler ABI|
Click here to view
Serum lipid profile levels did not differ significantly among patients with and without LEAD [Table 3].
|Table 3: Relationship between laboratory parameters and LEAD diagnosed by Doppler ABI|
Click here to view
Multiple regression analysis was used to explore the relationship between the Doppler ABI and factors associated with development of LEAD. The independent factors were age, duration of hypertension, BMI, WHR, SBP, diastolic blood pressure (DBP), heart rate, TC, HDL, LDL, TG, TC/HDL ratio, and fasting blood sugar. The multiple regression of Doppler ABI on the combined influence of these factors was not significant (P>0.05). However, the regression of right limb Doppler ABI on SBP, DBP, LDL and TC was significant (P<0.05) and these factors still retained their significance even without the composite effect of the other factors [Figure 2]. The regression of left limb Doppler ABI on DBP and LDL though significant (P<0.05), this significant relationship was found to have been enhanced by the composite effects of the other parameters.
|Figure 2: Scatter graph of right Doppler ankle-brachial index and low density lipoprotein, total cholesterol, diastolic blood pressure, systolic blood pressure|
Click here to view
| Discussion|| |
This study has demonstrated that LEAD is common among adult hypertensive patients in Nigeria. The prevalence of LEAD was higher with Doppler ABI compared with a history of intermittent claudication (41.8% vs. 7.8%). This is in keeping with the internationally held view that ABI is the better screening tool for PVD.  Out of the 64 patients with LEAD by Doppler ABI in this study only 8 were symptomatic, making the ratio of symptomatic to asymptomatic LEAD 1:8. This is not surprising as most patients with PVD are asymptomatic.  The Rotterdam population study  as well as the PARTNERS study  reported a ratio of 1:8 for symptomatic versus asymptomatic PVD. This is similar to what was obtained in this study. The low sensitivity (12.5%) of history of claudication in the diagnosis of LEAD further buttresses the fact that it is, in isolation, an inadequate tool for diagnosis of LEAD. However, this diagnostic tool has a high specificity (95.5%) and may allow for a presumptive diagnosis, especially among patients with significant risk factors such as hypertension and diabetes mellitus.
There was a significant association between the diabetes mellitus and LEAD in this study. The prevalence of LEAD was 57.6% in the hypertensive-diabetic sub-group compared to 37.5% in the hypertensive only sub-group. This finding is consonant with the fact that the presence of multiple risk factors increases the risk for LEAD many fold. Obasohan et al.  had earlier shown that concomitance of hypertension with diabetes mellitus synergistically worsens cardiovascular risk and is associated with much higher cardiovascular risk than either disease alone, in terms of the prevalence, and aggregation of risk factors.
The prevalence of LEAD increased with age in this study. The prevalence of LEAD was highest in patients aged 70 years and above. The relationship between age and LEAD in this study agrees with earlier reports that the prevalence of LEAD increases with age. , The finding that more females than males had LEAD in this study is similar to the report of the Rotterdam study.  The Framingham study also showed that more females than males were at risk of PVD.  Gender; however, did not significantly influence the prevalence of LEAD in this study as in some other studies that showed that the prevalence of intermittent claudication was a commoner in men. 
Patients who were currently smoking cigarette tended to have the highest prevalence of LEAD compared with non-smokers and passive smokers though it did not reach statistical significance. In this study; however, there was no statistically significant association between the cigarette smoking and LEAD. This differs from earlier reports by Kannel and Shurtleff  and Balkau et al.  in which cigarette smoking was the most important risk factor after advanced age for PVD. In Africa and indeed Nigeria with a low smoking prevalence (6%), which is considerably lower than in Caucasians and where most individuals only smoked in their youthful days, lack of association between LEAD and cigarette smoking is therefore, not surprising.
| Conclusion|| |
This study has shown that LEAD is common in Nigerian hypertensive patients. It occurred in 41.8% of hypertensive patients. Majority of patients with LEAD were asymptomatic. Therefore, reliance on symptoms alone could lead to under-diagnosis of LEAD. The diagnosis of LEAD, whether symptomatic or not, is greatly enhanced by ABI estimation as clearly shown in this study and other studies around the world.
| References|| |
|1.||Bennett PC, Silverman S, Gill PS, Lip GY. Ethnicity and peripheral artery disease. QJM 2009;102:3-16. |
|2.||Onwubere B, Kadiri S, editors. Guidelines for the Management of Hypertension in Nigeria. Enugu: Ezu Books Ltd.; 2005. |
|3.||Caralis DG, Bakris GL. Clinical Hypertension and Vascular Diseases: Lower Extremity Arterial Disease. New Jersey: Humana Press; 2005. E-ISBN1-59259-881-6. |
|4.||Da Silva A, Widmer LK, Ziegler HW, Nissen C, Schweizer W. The Basle longitudinal study: Report on the relation of initial glucose level to baseline ECG abnormalities, peripheral artery disease, and subsequent mortality. J Chronic Dis 1979;32:797-803. |
|5.||Weitz JI, Byrne J, Clagett GP, Farkouh ME, Porter JM, Sackett DL, et al. Diagnosis and treatment of chronic arterial insufficiency of the lower extremities: A critical review. Circulation 1996;94:3026-49. |
|6.||Abbas ZG, Archibald LK. Epidemiology of the diabetic foot in Africa. Med Sci Monit 2005;11:RA262-70. |
|7.||American Diabetes Association. Peripheral arterial disease in people with diabetes. Diabetes Care 2003;26:3333-41. |
|8.||Leng GC, Fowkes FG. The Edinburgh Claudication Questionnaire: An improved version of the WHO/Rose Questionnaire for use in epidemiological surveys. J Clin Epidemiol 1992;45:1101-9. |
|9.||Meijer WT, Hoes AW, Rutgers D, Bots ML, Hofman A, Grobbee DE. Peripheral arterial disease in the elderly: The Rotterdam study. Arterioscler Thromb Vasc Biol 1998;18:185-92. |
|10.||Hirsch AT, Criqui MH, Treat-Jacobson D, Regensteiner JG, Creager MA, Olin JW, et al. Peripheral arterial disease detection, awareness, and treatment in primary care. JAMA 2001;286:1317-24. |
|11.||Obasohan AO, Okokhere PO, Omoraka FE. Cardiovascular risk factors in Nigerian patients with concomitant hypertension and diabetes mellitus. High Blood Press 1999;8:163-6. |
|12.||Vogt MT, Cauley JA, Newman AB, Kuller LH, Hulley SB. Decreased ankle/arm blood pressure index and mortality in elderly women. JAMA 1993;270:465-9. |
|13.||Murabito JM, D'Agostino RB, Silbershatz H, Wilson WF. Intermittent claudication. A risk profile from The Framingham heart study. Circulation 1997;96:44-9. |
|14.||Kannel WB, McGee DL. Update on some epidemiologic features of intermittent claudication: The Framingham study. J Am Geriatr Soc 1985;33:13-8. |
|15.||Reunanen A, Takkunen H, Aromaa A. Prevalence of intermittent claudication and its effect on mortality. Acta Med Scand 1982;211:249-56. |
|16.||Kannel WB, Shurtleff D. The Framingham study. Cigarettes and the development of intermittent claudication. Geriatrics 1973;28:61-8. |
|17.||Balkau B, Vray M, Eschwege E. Epidemiology of peripheral arterial disease. J Cardiovasc Pharmacol 1994;23:S8-16. |
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]