Ankle pressures in UK South Asians with diabetes mellitus: a case control study
- Kirti Kain1,2,
- Michael Brockway1,
- Tasneem Ishfaq1,
- Minnie Merrick1,
- Hadiyah Mahmood1,
- Joseph C Ingoe1,
- Graham Richard Law3,
- Soroush Sohrabi1,2,
- Stephen Wheatcroft1,2,
- D Julian A Scott1,2
- 1Division of Cardiovascular and Diabetes Research, LIGHT, University of Leeds, Leeds, UK
- 2Multidisciplinary Cardiovascular Research Centre, LIGHT, University of Leeds, Leeds, UK
- 3Division of Biostatistics, LIGHT, University of Leeds, Leeds, UK
- Correspondence to Dr Kirti Kain, Division of Cardiovascular and Diabetes Research, LIGHT Labs, University of Leeds, Level 7, Clarendon Way, Leeds LS2 9JT, UK;
- Received 15 October 2012
- Revised 21 December 2012
- Accepted 29 January 2013
- Published Online First 26 February 2013
Objectives To study ethnic differences in ankle pressures in South Asians versus Europeans and in those with and without diabetes mellitus (DM).
Design Case control.
Setting Primary care.
Participants 391(DM=154) South Asian and 252(DM=72) European adults.
Main outcome measures Systolic blood pressure of the left (L) and right (R) brachial, posterior tibial (PT) and dorsalis pedis (DP) arteries were measured using a Doppler probe.
Results In comparison with Europeans, in young South Asians, DM was diagnosed 12 years earlier but pressures were lower, p≤0.0001 for all (RPT (146 vs 157 mm Hg), LPT (143 vs 154 mm Hg), RDP (138 vs 150 mm Hg) and LDP (137 vs 149 mm Hg)). Pack year was greater in Europeans. Odds ratios of cardiovascular disease in relation to ankle pressure were increased in South Asians with ankle brachial index between 0.9 and 1.3 or >1.3. Linear regression in South Asians identified age was an independent predictor of increased pedal pressures, DM of increased RPT and LDP, and sex of LPT and LDP. In Europeans, age was an independent predictor of increased pedal pressures, and sex and pack years were independent predictors of decreased pedal pressures. In South Asians, all ankle pressure and in Europeans, RPT, LPT and LDP were increased in subjects with DM versus without. Ankle pressures and cardiovascular disease in South Asians with DM were similar to those of 10 years older Europeans with DM.
Conclusions South Asians with DM had higher ankle pressures versus without and were similar to 10 years older Europeans with DM. Prospective studies on ankle pressures for development of diabetes or cardiovascular disease are warranted in South Asians.
Ankle brachial index (ABI) is a non-invasive test of peripheral arterial disease. Low ABI (<0.9) indicates peripheral arterial disease and high ABI (>1.3) indicates arterial stiffness and both are associated with subclinical coronary and cerebrovascular atherosclerosis and all-cause and cardiovascular mortality.1 High ABI is associated with diabetes mellitus (DM), chronic kidney disease or ageing1 ,2 and prognosis for cardiovascular outcomes is dependent on coexisting occlusive peripheral arterial disease.3–5 Peripheral arterial pressures often differ between the posterior tibial (PT) and the dorsalis pedis (DP) and between the right and left leg.6 In Europeans, absolute ankle pressures correlate better with peripheral arterial disease than ABI and elevated pressure was identified as an independent predictor of incident coronary heart disease.7 ,8
South Asians suffer from increased mortality from ischaemic heart disease and stroke contributed to by the increased prevalence of DM as compared with Europeans.9 Prevalence of low ABI is strongly associated with smoking and is lower in South Asians as compared with Europeans10 and DM might be increasing ABI in South Asians.11 ,12 Elevated blood pressure is a major risk factor for cardiovascular disease (CVD) yet resting brachial blood pressure is equal or lower in all South Asians than in Europeans13 and association of hypertension with the risk of CVD has been found to be similar in South Asians and Europeans.14
Potential associations between peripheral arterial pressure and CVD remain understudied in South Asians and there are currently no independent ankle pressures datasets. We therefore set out to examine whether absolute ankle pressures are increased with relationship with CVD in South Asians compared with Europeans especially in participants with DM. We anticipated that this information would help to determine whether non-invasive assessment of ankle pressures could be a simple tool to detect South Asian individuals at high risk of CVD.
This was a cross-sectional study carried out during the period of 2010–2012 of South Asians and Europeans registered at an inner city primary care practice in West Yorkshire, UK. The practice employs an electronic medical database to record consultations, inpatient and outpatient attendances, medical diagnosis, procedures and costs. The study was performed in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology statement.15 Database is updated with all participants’ newly identified data from pharmacy, laboratory, hospitalisation and outpatient diagnosis using standardised criteria.
Local Research Ethics Committee approval (REC reference number 10/H1302/28) was sought for the project and site specific research and development permission was obtained. Recruitment of adults was consecutive from primary care clinics (including diabetes clinics) run by doctors, nurses or healthcare assistants. Potential participants were approached, provided with an information leaflet, nature of the research explained and the opportunity to ask questions for informed decision. All the participants who agreed were asked to sign the consent forms with the information that they could withdraw from the study at any point. Inclusion criteria were participants aged ≥18 years and of South Asian origin (originally from India, Pakistan, Bangladesh or one or more of their grandparents born in one of these countries) or ethnic groups of European origin. Participant's ethnicity was based on electronic medical record data or ascertained from demographic data collected at recruitment which were self-reported, surname assignment and country of birth of grandparents. Exclusion criteria were if they were too ill to participate or were having chemotherapy. Interpreters were available to obtain informed consent from non-English speaking participants. All clinical assessments (ie, medical history and measurements) were performed at the same visit.
A standard questionnaire, which included demographic information including ethnicity, was administered to all participants. History was sought and validated against computerised general practice records.
CVD was defined as previous history of any of the following: myocardial infarction, stroke, transient ischaemic attack, peripheral arterial disease, angioplasty, coronary artery bypass surgery or heart failure. Participants with a diagnosis of DM were identified by review of medical records. History of DM was established according to WHO criteria 1999.16 DM duration, cardiovascular risk factors and complications were recorded. The Edinburgh claudication questionnaire was used to ascertain prevalence of patient-defined intermittent claudication symptoms.17
Detailed smoking habits of participants were obtained by self-reporting, including age of onset and cessation of smoking, and pack year was calculated. Former smokers were defined if they had previously smoked tobacco but had stopped more than 1 year at time of assessment; those who ceased smoking for less than a year were considered as current smokers. An alcohol status was defined by anybody exceeding the recommended limits of no more than 21 units of alcohol per week (or no more than four units in any 1 day) for men and no more than 14 units of alcohol per week (or no more than three units in any 1 day) for women. Hypertension and hyperlipidaemia were defined as either previously diagnosed or currently taking antihypertensive or cholesterol-lowering medications. Information on renal disease classification was also retrieved from the computer. Family history of premature (<55 years of age) CVD in first degree family members was recorded from questionnaire and electronic system. Systolic and diastolic blood pressures were measured after the patient had rested for 5 min using a mercury sphygmomanometer and stethoscope (3M Littmann classic II SE). Height and weight were recorded (to the nearest 0.01 m and kg, respectively) to calculate each participant's body mass index (BMI, calculated as weight (kg)/height2 (m2)). Waist and hip circumferences were measured at the midpoint between the lowest rib and iliac crest and level of the greater trochanters respectively (to nearest cm) to calculate each participant's waist to hip ratio. Participants rested in the supine position for 5 min and blood pressure measurements were taken using appropriately sized cuffs and a handheld continuous wave Doppler instrument (Huntleigh Super Dopplex II, Huntleigh Healthcare, Cardiff, UK) with an 8 MHz probe and a calibrated mercury sphygmomanometer. Brachial systolic blood pressure was taken in both arms by placement of the cuff in the upper arm and measuring the systolic blood pressure by placing the Doppler probe over the brachial artery in the antecubital fossa.18 For ankle systolic blood pressures, the blood pressure cuff was positioned superior to the medial malleolus in each leg. Systolic blood pressure was measured over the DP and PT arteries on right (R) and left (L) limbs. For each blood pressure measurement, the cuff was inflated until the pulse was no longer audible. The cuff was inflated a further 20 mm Hg above the approximate value at which the pulse obliterated then deflated slowly, with the pressure being recorded when the pulse became audible using the Doppler probe again. Trained operators performed all clinical measurements with the same Doppler machine and stethoscope to avoid inter-instrumental errors. The most recent blood test results were obtained from the computer patient records. Blood glucose was measured by glucose oxidase method and cholesterol and triglycerides were done by Hitachi 747 autoanalyser (Boehringer Mannheim, Germany). High density lipoprotein was measured with a Hitachi 717 autoanalyser (Boehringer Mannheim, Germany) after removal of chylomicrons.
Primary outcome: to study ethnic differences in ankle pressures. Secondary outcomes: (1) Ethnic differences in ankle pressures stratified according to DM status; (2) OR of CVD according to ethnicity stratified by ABI cut-offs.
Continuous variables were analysed using the two independent samples, Mann–Whitney U test and categorical data were cross tabulated and a χ2 test was performed for ethnic differences in ankle pressures and ethnic differences in ankle pressures stratified according to DM status. We carried out multivariable logistic regression analysis with CVD as the dependant variable and reversible cardiovascular risk factors (ie, smoking, hypertension and DM) as independent variables. Linear regression analysis was carried out to identify independent predictors of ankle pressures. Univariate logistic analysis was carried out to study relationship of ankle pressures and CVD at three different clinically useful ABI cut-offs for another secondary outcome. p Values of <0.05 were accepted as significant. All statistical analyses, including logistic regression, were performed with Stata V.12.0 for Windows (StataCorp. 2011. Stata Statistical Software: Release 12. College Station, Texas, USA: StataCorp LP).
We recruited a total of 643 participants, of which 252 were European and 391 were South Asians (84% Pakistani, 15% Indian and 1% Bangladeshi).
South Asians versus Europeans
Demographics, clinical data and absolute arterial pressures of Europeans and South Asians are summarised in table 1. The prevalence of hypertension (p≤0.0001), hyperlipidaemia (p≤0.0001), smoking (p≤0.0001) and prescription of cardiovascular medications (p≤0.0001) was significantly higher in Europeans compared with South Asians. South Asians were younger and had greater waist to hip ratios, higher plasma triglycerides and lower plasma high density lipoprotein cholesterol (HDL) than Europeans. The prevalence of DM was higher in South Asians and was diagnosed at an earlier age than in Europeans. Accordingly, prescriptions of metformin and insulin were more prevalent in South Asians than in Europeans. Arterial pressures at all peripheral sites were lower in South Asians than in Europeans. Across the entire cohort, peripheral arterial pressures tended to be higher in the PT artery than in the DP artery and higher on the right side than left.
Ankle pressures and history of CVD
In European subjects, there were no significant differences in ankle pressures between those with or without a history of CVD (right PT (RPT) 162 vs 154 mm Hg, right DP (RDP) 156 vs 147 mm Hg, left PT (LPT) 156 vs 153 mm Hg) with the exception of left DP (LDP) pressure (154 vs 146 mm Hg, p=0.03). Similarly, in South Asian subjects, there were no significant differences in ankle pressures between those with or without CVD (RPT 151 vs 145 mm Hg, RDP 142 vs 138 mm Hg, LPT 147 vs 142 mm Hg) with the exception of LDP pressure (143 vs 36 mm Hg, p=0.05). ORs of CVD for absolute ankle pressures, stratified according to conventional cut-off points of ABI (ABI<0.9; ABI 0.9–1.3; ABI>1.3), are summarised in table 2. In South Asian subjects, there were significant relationships of ankle pressures with CVD at levels of ABI 0.9–1.3 and ABI>1.3 (table 2).
Linear regression analyses were performed with pedal pressures as dependant variables and age, sex, pack year history and DM as covariates. In South Asians, age was identified as an independent predictor of increased pedal pressures. DM was a significant predictor for RPT and LDP, sex was associated with LPT and LDP. In Europeans, age was also identified as an independent predictor of increased pedal pressures. Sex and smoker pack years were significant predictors for lower pressures at all four peripheral arterial sites.
Demographics and clinical data according to diabetes status in South Asians and Europeans
Demographic, clinical data and absolute peripheral arterial pressures stratified according to DM status in Europeans and South Asians are presented in table 3. Participants with DM were older than those without DM in both Europeans and South Asians. South Asians with DM were 10 years younger than Europeans with DM. BMI and waist to hip ratio were higher and hypertension and hyperlipidaemia more prevalent in participants with DM in both groups. DM was associated with an increased prevalence of CVD in South Asians but not Europeans. In Europeans, only RPT, LPT and LDP were increased in participants with DM (figure 1). However, in South Asians all the ankle pressures were markedly increased in those with DM (figure 1). Pressures in the PT artery and on right side tended to be higher than DP and left side pressures in participants with DM. There were no differences in smoking pack years in both groups. After adjustment for age, the differences in pedal pressures disappeared between those with or without DM in both groups.
European controls versus South Asian controls
On comparison of variables between European controls versus South Asian controls, age, sex, hypertension history, CVD, hyperlipidaemia, pack years history, all brachial and pedal pressures and all treatments were significantly different (table 3).
Europeans with diabetes versus South Asians with diabetes
On comparison of Europeans with DM versus South Asian with DM, age, waist to hip ratio, RDP, hypertension history and pack years of smoking were significantly different. There were no differences in treatments, three pedal pressures and in CVD. On logistic regression analysis after adjustment for the above factors, only age, waist to hip ratio and pack years were significantly different in Europeans versus South Asians. The pressures remained similar.
In our sample of primary care clinic attendees, we have demonstrated that age of diagnosis of DM is 12 years earlier in South Asians and three out of four ankle pressures in participants with DM are similar to 10 years older Europeans with DM. Ankle pressures are markedly increased in South Asians with DM as compared with those without DM. Ankle pressures correlate to pack years in Europeans and DM mellitus in South Asians.
Elevated ankle pressures without increased brachial pressures have been associated with increased cardiovascular deaths and death from any cause in Europeans.19 It is postulated that raised ankle pressures due to arterial stiffness precede occlusive vascular disease in the lower limbs.20 Medial calcification in DM in Europeans is associated with fourfold increased risk of lower extremity amputation and twofold cardiovascular mortality.21 ,22 There are no accepted normal reference ranges for ankle pressures in South Asians and so potential associations were studied using ankle pressure as a continuous variable to increase the power of the study. In 1991, calcification of the lower-extremity arteries was considered if ankle pressure was more than 100 mm Hg higher than brachial pressure23 but now an ankle pressures of >175 mm Hg is considered to be a marker.20 Ankle pressures in South Asians with DM are higher than those without but were similar to those in older Europeans with DM and could be because the DM is diagnosed at a younger age and high blood glucose predisposes South Asians to medial artery stiffness and calcification earlier or to a greater extent than it does occlusive disease in lower limbs potentially due to different haemodynamics or wave reflection.24 Two previous studies support this interpretation. Chaturvedi et al found intima media thickness and plaque to be less in the lower limbs of South Asians and lower prevalence of low ABI compared with Europeans even after adjustment for smoking and systolic blood pressure which is adverse in Europeans. Lipids, visceral obesity, insulin and glycaemic status which is more adverse in South Asians did not account for ethnic differences.12 Young apparently healthy South Asians matched for smoking, BMI, fasting glucose, lipid profile and brachial pressures to Europeans have been observed to have markedly increased augmentation index and augmented pressure after adjustment for diastolic blood pressure and heart rate suggesting that arterial stiffness and increased wave reflection contribute to their increased cardiovascular risk.25 Arterial stiffening is also increased in insulin resistance and South Asians are more insulin resistant than Europeans. It is probable that South Asians due to premature mortality from heart disease or stroke may not be living long enough to develop occlusive peripheral arterial disease or in mild forms of occlusive disease ankle pressure may be normal at rest because of adequate collateral flow around occlusive lesions. Response of different vascular beds to DM as a risk factor might be different in different ethnic groups. Although lower extremity atherosclerosis often affects major proximal arteries or is diffuse there might be regional differences in occlusive disease in South Asians. Although smoking affects proximal arteries more than distal arteries, the increased prevalence of smoking in Europeans probably explains the significant association of all ankle pressures with the best measure of exposure of smoking: the pack years in Europeans but not in South Asians.11 Moreover, pack years decreases ankle pressures. There were a small percentage of smokers in South Asians and so this study was not able to detect the effect or maybe the pack years as a risk factor for vascular disease in South Asians is not significant. Nonetheless, it is suggested that South Asians should stop smoking as well. Hypertension was associated with all ankle pressures in both ethnic groups as expected because it is a major risk factor for vascular disease.26 ,27
DM was associated with a substantially increased prevalence of CVD in South Asians but not in Europeans. In South Asians, ankle pressures were significantly higher at all peripheral arterial sites in those with DM, even though use of drugs for hypertension was more prevalent in this group. Generally participants are put on medications when considered to have high cardiovascular risk and therefore South Asians were at an increased risk only after diagnosis of DM. CVD was significantly increased in South Asians with DM and possibly insulin resistance plays a crucial role in its development as compared with other risk factors like smoking or hypertension which had more effect in Europeans. It is possible that hypertension and its contribution to significant CVD in South Asians was more prevalent secondary to DM/insulin resistance unlike in Europeans where it was much increased in participants without DM. In Europeans ABI rather than ankle pressures have been studied and found to have U shaped relationship with CVD in the Cardiovascular Health Study. After adjustment for potential confounders, ABI measurements <0.9 and >1.40 were associated with higher cardiovascular mortality risk compared with the referent group (ABI 1.11–1.20).28 It is possible that the relationship is applicable to South Asians as well.
Because of the relative limited size of this study, the differences identified need to be interpreted with caution and verified in larger prospective studies. We did not use a measure of subclinical occlusive vascular disease or medial sclerosis to verify our hypothesis, which may have led to an underestimation of CVD by residual confounding.
We have shown that changes in ankle pressures which are one of the earliest signs of adverse changes in the arteries without indexing to brachial pressures are higher in South Asians with DM. Further longitudinal studies are needed to study the relation of low and high ankle pressures with a measure of medial arterial stiffness and occlusion in lower limbs in South Asians. The results might contribute for higher ankle pressures to be used in non-invasive prediction models for DM in young South Asians.
What is already known on this subject
Abnormally low and high ankle brachial index (ratio of ankle pressure and brachial pressure) in Europeans is associated with cardiovascular disease.
The relative association of hypertension (brachial pressures) with the risk of developing cardiovascular disease has been found to be similar in South Asians and Europeans.
South Asians have lower prevalence of low ankle pressures and therefore might have increased prevalence of higher ankle pressures; hence this study was undertaken.
What this study adds
Our study suggests that ankle pressures are similar in South Asians with diabetes mellitus compared with older Europeans with diabetes mellitus.
Prospective studies might clarify whether higher ankle pressures in participants without diabetes mellitus in South Asians develop more diabetes mellitus and cardiovascular disease in future.
This will feed into practice of carrying out non-invasive measurement of ankle pressures and incorporating in prediction models for South Asians.
We are grateful to all the participants and healthcare staff at Kensington Street Surgery and Bradford PCT for their help in conducting this study.
Contributors KK contributed to conception and design, analysis and interpretation of data, drafting the article and revising it critically for important intellectual content. GL contributed to analysis and interpretation of data. JI, MM, MB, HM and TI contributed to acquisition of data or analysis and interpretation of data. SW, DJAS and SS contributed to revising the article critically for important intellectual content. KK and DJAS gave final approval of the version to be published.
Funding University of Leeds; no External Source of Funding.
Competing interests None.
Ethics approval Yorkshire Research Ethics Committee.
Provenance and peer review Not commissioned; internally peer reviewed.