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Relationship between inter-arm blood pressure differences and future cardiovascular events in coronary artery disease

Tokitsu, Takanori; Yamamoto, Eiichiro; Hirata, Yoshihiro; Fujisue, Koichiro; Sugamura, Koichi; Maeda, Hirofumi; Tsujita, Kenichi; Kaikita, Koichi; Hokimoto, Seiji; Sugiyama, Seigo; Ogawa, Hisao

doi: 10.1097/HJH.0000000000000616
ORIGINAL PAPERS: BP measurement

Objective: Recent studies have shown that inter-arm blood pressure differences (IAD) may be a risk factor for cardiovascular events; however, none have addressed them in patients with coronary artery disease (CAD).

Methods: We measured blood pressure bilaterally with the ankle brachial index (ABI) in 657 patients with suspected CAD and assessed the presence of CAD by coronary angiography, and the severity of coronary atherosclerosis with the Gensini score.

Results: Mean IADs were significantly greater in risk factor matched patients with CAD than in those without it (P = 0.01), whereas Gensini scores were significantly greater in those with high IAD (≥10 mmHg) than in those with low-IAD (P = 0.01) according to cross-sectional analysis. Patients with high IAD had a significantly greater probability of cardiovascular events than those in whom it was low (log-rank test, P < 0.01, mean follow-up range; 827.3 ± 268.1 days). The presence of hypertension, ABI, usage of calcium channel blocker and high IAD were independent predictors of cardiovascular events according to longitudinal analysis (IAD; hazard ratio: 2.90, 95% confidence interval: 1.41–5.94, P < 0.01) in these patients. Patients with high IAD and peripheral artery disease had the highest Gensini scores according to cross-sectional analysis (P < 0.01) and highest probability of cardiovascular events according to longitudinal analysis (log-rank test, P < 0.001).

Conclusion: IADs were increased in CAD patients and correlated with its severity. Greater than 10 mmHg of IAD was independently associated with future cardiovascular events. Assessing IAD by ABI measurement may facilitate risk stratification in CAD patients.

Department of Cardiovascular Medicine, Faculty of Life Sciences, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan

Correspondence to Eiichiro Yamamoto, Department of Cardiovascular Medicine, Faculty of Life Sciences, Graduate School of Medical Science, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan. Tel: +81 96 373 5175; fax: +81 96 362 3256; e-mail: eyamamo@kumamoto-u.ac.jp

Abbreviations: ABI, ankle brachial index; BNP, brain natriuretic peptide; CAD, coronary artery disease; CAG, coronary angiography; CCB, calcium channel blockers; CIs, confidence intervals; eGFR, estimated glomerular filtration rate; IAD, inter-arm blood pressure differences; LVEF, left ventricular ejection fraction; OR, odds ratio; PAD, peripheral artery disease; PWV, pulse wave velocity

Received 25 August, 2014

Revised 30 March, 2015

Accepted 30 March, 2015

Clinical Trial Registration: URL: http://www.umin.ac.jp/ctr/.

Unique identifier: UMIN 000013679.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0

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INTRODUCTION

Hypertension is a well known major risk factor for cardiovascular disease. Recent cohort studies have shown that inter-arm blood pressure differences (IADs) are associated with an increased risk of cardiovascular disease and predict future cardiovascular events [1,2]. In addition, large IAD may indicate the presence of vascular atherosclerotic plaques: several studies have reported that large IADs are associated with subclavian artery stenosis [3,4] and peripheral artery disease (PAD) [5,6]. Therefore, the many societies for hypertension recommend measuring brachial blood pressures bilaterally on the first visit to hypertensive outpatient clinics [7–9].

In many studies, high IADs have been defined as more than 10 mmHg [10]. However, a meta-analysis has shown that the proportion of patients with IAD more than 10 mmHg is very variable (1.4–38%), depending on the backgrounds of enrolled individuals (randomly selected [11–13], hypertensive [1,2,14,15], diabetic [16] and elderly patients [17]). Few studies have investigated IAD in patients with coronary artery disease (CAD); thus, there are no published reports concerning the relationship between severity of CAD and IAD in CAD patients. Aboyans et al. [18] reported a significant correlation between high IAD and high BMI. Although IADs are likely to differ between Asian individuals and those in Europe and North America [18], there are few reports regarding IAD in Japanese patients [11]. Hence, in the present study, we investigated the relationships between IAD in Japanese CAD patients, severity of CAD and occurrence of future cardiovascular events.

Many current guidelines for treating hypertensive patients do not describe in detail a uniform technique for measuring blood pressure in both arms. A recent study by Charmoy et al. [6] showed that unilateral cuff inflation to measure blood pressure can increase the blood pressure values in the contralateral arm; thus, IADs ascertained by sequential measurement of bilateral brachial blood pressures may be greater than those obtained by simultaneous measurement of these blood pressures [19]. Because published meta-analyses employ different kinds of techniques (simultaneous technique or sequential technique) for measuring bilateral blood pressures [20,21], there are disproportionate rates of patients with IAD more than 10 mmHg in these meta-analyses. In the present study, we measured blood pressure in both arms simultaneously by using an an ankle brachial index (ABI) type of device. Our findings clearly demonstrate that high IAD predict future cardiovascular events and correlate with the severity of CAD in Japanese CAD patients.

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MATERIALS AND METHODS

Study participants

We prospectively investigated 1013 consecutive stable patients who had been referred to Kumamoto University hospital between January 2007 and June 2012 and scheduled for hospitalization for coronary angiography (CAG). We recorded the patient's medical histories and relevant clinical characteristics (age, sex, BMI, presence of coronary risk factors, laboratory data, echocardiography data and medications). We excluded 356 patients for the following reasons: chronic heart failure with less than 40% of left ventricular ejection fraction (LVEF) or more than 200 pg/ml of brain natriuretic peptide (BNP) (n = 188), severe valvular disease (n = 98), chronic renal failure on haemodialysis (n = 62), systemic inflammation disease (n = 4) and chronic sequelae of paralysis as a result of old cerebral infarction (n = 4). In all, we enrolled 657 patients to this study (Fig. 1).

FIGURE 1

FIGURE 1

We compared average IAD between patients with and without CAD after risk factor-matching, including number of patients, age and sex, and equal prevalence of hypertension, diabetes mellitus, dyslipidemia and current smoking.

The study protocol conformed to the principles of the Declaration of Helsinki. Written informed consent was obtained from all of participating patients. This study is registered with the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN000013679).

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Measurement of blood pressure and inter-arm blood pressure difference

We measured the IAD simultaneously on admission or in the out-patient clinic just before admission by using an ABI type of device (BP-203RPE II; Omron Colin, Tokyo, Japan). In accordance with the current guidelines of the Japanese Society of Hypertension [9], we used a standard cuff (12–13 cm wide and 35 cm long), but had a larger and a smaller cuff available for large and thin arms, respectively. By automatically controlling the timing of the exhaust and boosting, we measured blood pressures in both arms simultaneously and calculated an average value for blood pressures measured in duplicate. Trained technicians performed all ABI measurements; a detailed description of the procedure follows. They placed sphygmomanometer cuffs on both arms and both ankles, and measured blood pressures in all extremities after 5 min of bed rest in a supine position. We calculated the IAD as the absolute blood pressure difference between the right and left arms, and defined abnormal values as IAD 10 mmHg or more. The ABI for each leg equals the ratio of the higher of the two systolic pressures (posterior tibial or dorsalis pedis) in the leg and the average of the right and left brachial artery pressures, unless there is a discrepancy of at least 10 mmHg in blood pressure between the arms. In such cases, we used the higher reading for the ABI, as described previously [22]. We defined PAD as ABI less than 0.9 in either leg, as reported previously [23].

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The severity and complexity of coronary artery disease

We diagnosed CAD (diameter of stenosis in vessels ≥1.5 mm) in patients with atherosclerotic organic coronary artery stenosis (≥75%) demonstrated by CAG. We calculated Gensini scores to evaluate the severity and complexity of coronary atherosclerosis. The total Gensini score, an index for evaluating the narrowing of the coronary arteries, represents the severity of coronary atherosclerosis and is calculated by the Gensini coronary artery scoring method [24]. After risk factor-matching, we classified CAD patients into two groups, according to Gensini score using a cut-off value of at least 40, as reported previously [25,26].

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Follow-up and cardiovascular events

Patients were followed up prospectively at our outpatient clinics until November 2013 or until the occurrence of cardiovascular events. Cardiovascular events were defined as cardiovascular death, nonfatal myocardial infarction, unstable angina pectoris, coronary revascularization for a new diagnosis of angina or in-stent restenosis, nonfatal ischemic stroke or hospitalization for heart failure decompensation. A new diagnosis of PAD was not considered a cardiovascular event for the purposes of this study. Cardiovascular death was defined as death caused by myocardial infarction (within 28 days of occurrence), heart failure or documented sudden death without identified noncardiovascular causes. A diagnosis of myocardial infarction was made by detection of rises or falls in cardiac biomarkers (plasma creatine kinase-MB or cardiac troponin-T) above the 99th percentile of the upper limit of normal together with evidence of myocardial ischemia in the form of at least one of the following: ECG changes (new ST-T changes, left bundle branch block or pathological Q wave) or imaging evidence of new loss of viable myocardium or new regional wall motion abnormality. A diagnosis of unstable angina pectoris was made in patients with new or accelerating symptoms of myocardial ischemia accompanied by new ischemic ST-T-wave changes in their ECGs. Coronary revascularization was defined as coronary artery bypass grafting or percutaneous coronary intervention (PCI) driven by a positive functional ischemia study (on exercise testing, fractional flow reserve and/or nuclear imaging), ischemic symptoms and coronary artery stenosis ≥ 75% narrowing of the arterial diameter. A diagnosis of ischemic stroke required both neurological symptoms and radiological evidence, excluding intracranial haemorrhage. A diagnosis of hospitalization for heart failure decompensation was made in patients admitted with symptoms typical of heart failure and with objective evidence of worsening heart failure requiring intravenous drug administration [27].

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Blood sampling

Blood tests (for plasma BNP and other biochemical markers) were performed early in the morning in our hospital laboratory after patients had fasted. Renal function was determined from the estimated glomerular filtration rate (eGFR; ml/min per 1.73 m2), which was calculated using the equation recommended by the Japanese Society of Nephrology [28].

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Echocardiography

All patients underwent two-dimensional transthoracic echocardiography performed by blinded cardiac sonographers according to the current guidelines [29]. We used commercially available, ultrasonic cardiogram systems (Vivid-7; GE-Vingmed Ultrasound A.S., Horton, Norway and Aplio XG; Toshiba, Tokyo, Japan). LVEF was measured by the biplane modified Simpson method.

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Statistical analysis

We used SPSS 17.0 software (SPSS Inc., Chicago, Illinois, USA) for statistical processing. Nonmanually distributed data are expressed as the median (25–75%). We considered a P value of less than 0.05 statistically significant. We assessed differences between the two groups with the Fisher exact test for categorical variables and with Student's unpaired t-test or the Mann–Whitney U test, as appropriate, for differences in continuous variables. Differences between multiple means were determined by one-way analysis of variance (ANOVA), and the Turkey or Dunnett posthoc analysis was used to determine differences between individual means. We used propensity score matching to match risk factors in patients with or without CAD and low or high Gensini score in CAD patients. Independent variables included in the propensity score model were age, sex, proportion of hypertension, diabetes mellitus, dyslipidemia and current smoking, SBP in both arms, mean IAD, DBP in both arms, ABI, pulse wave velocity (PWV), BMI, eGFR (ml/min per 1.73 m2), ln-BNP, LVEF and the use of calcium channel blockers (CCBs) and β-blockers, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers and diuretics. We evaluated clinical variables significantly associated with CAD according to simple logistic regression analysis and several factors previously reported as affecting CAD by multivariable logistic regression analysis. We calculated the cumulative cardiovascular event incidence with the Kaplan–Meier method and compared cardiovascular event incidence by the log-rank test. We used Cox proportional hazard models to estimate cardiovascular event hazard ratios and their 95% confidence intervals (CIs) in the CAD patients by simple and multivariable analysis with forced inclusion models.

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RESULTS

Baseline characteristics of risk factor matched patients with and without coronary artery disease

We performed CAG on the 657 enrolled stable patients to determine the presence and severity of CAD, and 407 of them had CAD. Those with CAD had a significantly higher prevalence of various coronary risk factors (higher age, P < 0.01; male sex, P < 0.01; past smoking, P < 0.01; hypertension, P < 0.01; diabetes mellitus, P < 0.01; and dyslipidemia, P < 0.01) than non-CAD patients according to cross-sectional analysis (Table 1). To investigate whether increases in IAD are simply attributable to the presence of CAD, we categorized patients into risk factor matched groups with (n = 159) and without CAD (n = 159) by using propensity score matching (Table 2). The mean IAD was significantly higher in the risk factor matched patients with CAD than in those without it according to cross-sectional analysis (4.0 ± 5.3 vs. 2.8 ± 2.4 mmHg, P = 0.01, Fig. 2).

TABLE 1

TABLE 1

TABLE 2

TABLE 2

FIGURE 2

FIGURE 2

To examine differences in distribution of IAD, the patients were divided into six groups according to their IAD (0–1, 2–3, 4–5, 6–7, 8–9 and ≥10 mmHg). The proportion of risk factor matched patients without CAD with each of these IAD were 37.1, 33.3, 18.2, 6.9, 3.1 and 1.3%, respectively (Fig. 3). By contrast, the proportions of risk factor matched CAD patients with each IAD were 28.3, 35.2, 14.5, 8.8, 6.9 and 6.3%, respectively (Fig. 3). Thus, patients with CAD had a higher proportion of IAD of more than 6 mmHg than those without CAD (P = 0.01).

FIGURE 3

FIGURE 3

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Differences in clinical characteristics between coronary artery disease patients with low vs. high inter-arm blood pressure difference

We allocated CAD patients into two groups (high-IAD and low-IAD), the cut-off value being 10 mmHg in accordance with the findings of a previous study [8]. BMI and Gensini scores were significantly higher in those with high-IAD than in those with low- IAD (P < 0.01 and P = 0.01, respectively), whereas bilateral ABI, eGFR and the proportion of men were significantly lower in those with high-IAD than in those with low-IAD according to cross-sectional analysis (P < 0.01, P = 0.04 and P < 0.01, respectively) (Table 3).

TABLE 3

TABLE 3

The IADs were significantly higher in CAD patients with high-Gensini scores (n = 120) than in those with low-Gensini scores (n = 120) after risk factor matching (cut-off value 40, as previously reported [25,26]) (4.7 ± 4.4 vs. 3.5 ± 2.9 mmHg, respectively, P = 0.02) (Table 4, Fig. 4). Furthermore, mean Gensini scores were significantly higher in CAD patients with high-IAD than in those with low-IAD (41.1 ± 28.5 vs. 60.9 ± 28.3, respectively, P < 0.01) (Table 3).

TABLE 4

TABLE 4

FIGURE 4

FIGURE 4

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Relationship between presence of inter-arm blood pressure difference and other coronary risk factors

Simple logistic regression analysis demonstrated that male sex, BMI, ABI, Gensini score and eGFR were significantly correlated with the presence of IAD. According to multivariate logistic regression analysis with factors found to be significant by simple regression, male sex [odds ratio (OR), 0.36; 95% CI, 0.15–0.82; P = 0.02], BMI (OR, 1.17; 95% CI, 1.07–1.29; P < 0.01), ABI (OR, 0.05; 95% CI, 0.01–0.33; P < 0.01) and Gensini score (OR, 1.02; 95% CI, 1.01–1.03; P < 0.01) were independently and significantly associated with the presence of IAD according to cross-sectional analysis (Table 5). According to multivariate logistic regression analysis with previously reported coronary risk factors, male sex (OR, 0.39; 95% CI, 0.18–0.87; P = 0.02) and BMI (OR, 1.19; 95% CI, 1.08–1.32; P < 0.01) were also independently and significantly associated with the presence of IAD (Table 5).

TABLE 5

TABLE 5

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Cardiovascular events during follow-up

Data from 407 patients with CAD were available for analysing cardiovascular events. The duration of follow-up was 90–1000 days (mean 827.3 ± 268.1 days). During follow-up, 61 cardiovascular events were recorded in patients with CAD; details are summarized in Table 6. Total cardiovascular events, nonfatal myocardial infarction and PCI were significantly more numerous in CAD patients with high-IAD than in those with low-IAD (P < 0.01, P < 0.01 and P = 0.03, respectively). Kaplan–Meier analysis showed that CAD patients with high-IAD [IAD ≥10 mmHg, n = 29 (higher in right arm; n = 18, higher in left arm; n = 11)] had a higher probability of cardiovascular events than those with low-IAD according to longitudinal analysis (IAD <10 mmHg, n = 378) (log-rank test, P < 0.01, Fig. 5).

TABLE 6

TABLE 6

FIGURE 5

FIGURE 5

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Cox proportional hazard analysis of cardiovascular events

Univariate Cox hazard analysis identified eight variables as significant predictors (age, hypertension, ABI, the presence of IAD more than 10 mmHg, Gensini score, eGFR and use of CCB and diuretics, Table 7). Because there was a significant internal correlation between age and eGFR and PWV, eGFR and PWV were excluded from multivariate Cox hazard analysis. Multivariate Cox hazard analysis, including predictors identified as significant by simple Cox hazard analysis and various established coronary risk factors, identified hypertension (hazard ratio, 3.26; 95% CI, 1.26–8.44; P = 0.02), ABI (hazard ratio, 0.25; 95% CI, 0.07–0.91; P = 0.04), presence of IAD (hazard ratio, 2.90; 95% CI, 1.45–5.94; P < 0.01) and use of CCB (hazard ratio, 0.42; 95% CI, 0.25–0.71; P < 0.01) as significant and independent predictors of future cardiovascular events according to longitudinal analysis (Table 7).

TABLE 7

TABLE 7

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Gensini scores and Kaplan–Meier analysis in coronary artery disease patients stratified by a combination of inter-arm blood pressure difference and ankle brachial index values

We further stratified CAD patients according to IAD and ABI values into the following four groups: normal (IAD <10 mmHg and ABI >0.9, n: 326), low-IAD with PAD (IAD <10 mmHg and ABI ≤0.9, n: 52), high-IAD without PAD (IAD ≥10 mmHg and ABI >0.9, n: 17) and high-IAD with PAD (IAD ≥10 mmHg and ABI ≤0.9, n: 12). Of these groups, the high-IAD with PAD group had the severest CAD assessed by Gensini score among above-mentioned four groups (Fig. 6a). Compared with the normal group, Kaplan–Meier analysis showed that the groups with normal IAD with PAD and with high-IAD without PAD had significantly higher probabilities of cardiovascular events. Furthermore, the high-IAD with PAD group had the highest probability of cardiovascular events of all these groups (log-rank test, P < 0.01) (Fig. 6b).

FIGURE 6

FIGURE 6

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DISCUSSION

This study showed the following: IADs are significantly higher in patients with CAD than in those without CAD according to cross-sectional analysis; CAD is significantly more severe in CAD patients with high-IAD than in those with low-IAD according to cross-sectional subgroup analysis; high BMI is independently and significantly associated with the presence of IAD according to cross-sectional subgroup analysis; the presence of IAD more than 10 mmHg is a significant and independent predictor of future cardiovascular events according to longitudinal analysis; and patients with high-IAD with PAD have the highest probability of cardiovascular events according to an analysis of a combination of IAD and ABI values according to longitudinal analysis.

In a number of previous cohort studies, IADs were determined by measuring blood pressure in each arms sequentially, not simultaneously. However, as described previously, unilateral cuff inflation to measure blood pressure increases the blood pressure values in the contralateral arm [4]; thus, sequential measurement of blood pressure in each arms with one sphygmomanometer is not accurate. Consequently, in recent studies, IAD has been measured simultaneously with an automatic oscillometric device [30]; IADs in recent reports have differed widely from those cited in earlier reports. Therefore, it is preferable to measure blood pressure simultaneously in both arms to gain accurate IAD [19,20]. We therefore measured IAD simultaneously by using an ABI type of device in this study.

Some previous studies have reported that IAD reflects systemic atherosclerotic changes and that IAD more than 15 mmHg denotes significant stenosis in one subclavian artery, indicating severe PAD [4,18]. However, because there are reportedly ethnic variations in human atherogenic properties [31,32], the distribution of IAD in Asians possibly differs from that in Europeans and North Americans. In support of this contention, a recent study from China demonstrated that the mean IAD was significantly less in a sample of over 3000 elderly Chinese than those reported for Europeans and North Americans [33]. In the present study, the mean IAD in Japanese patients without CAD was also less than those cited in meta-analyses from Western countries; CAD patients with high-IAD also had significantly higher BMI than those with low-IAD, as previously reported [18,34,35]. Asians have relatively low BMIs, which may explain why fewer Asian than European and North American individuals have high IAD.

To the best of our knowledge, no studies have investigated associations between IAD and the presence and severity of CAD as assessed by CAG. In the present study, the IADs were significantly greater in Japanese patients with CAD than in those without CAD. Furthermore, CAD patients with high-IAD had more severe coronary arterial atherosclerosis, as indicated by Gensini scores more than 40. This is the first study to report a significant association between IAD and the presence and severity of CAD. Furthermore, we found that CAD patients with high-IAD (>10 mmHg) had a poorer prognosis than those with low-IAD (<10 mmHg). Thus, IAD more than 10 mmHg might be a significant predictor of future cardiovascular events in Japanese CAD patients. Coronary revascularization by PCI and unstable angina pectoris were the main causes of cardiovascular events in the present study (Table 6). This suggests that high IAD is more predictive of coronary-related events than of other vascular-related events in patients with CAD.

Measurement of ABI is the gold standard for diagnosing PAD easily and noninvasively, and many previous reports have shown that ABI less than 0.9 is significantly correlated with the occurrence of future cardiovascular events [36–38]. Therefore, we used a combination of ABI and IAD values to further examine the prognosis of CAD patients and found that those with high-IAD and low-ABI (IAD ≥10 mmHg and ABI ≤0.9), indicating complicated PAD, had the highest probability of cardiovascular events among all CAD patients. These results indicate that ABI measurement, especially in CAD patients, is a profoundly significant noninvasive means of identifying patients with complicated polyvascular disease who have poor prognoses.

The present study demonstrated that the usage of CCB was one of the significant and independent predictors of future cardiovascular events in CAD patients (Table 7). In high-IAD or PAD patients, furthermore, the proportion of using CCB was significantly lower in patients with cardiovascular events despite same levels of blood pressure between CAD patients with or without cardiovascular events (data not shown). Hence, CCB could be one of the most promising drugs for decreasing not only blood pressure but also IAD. Moreover, vascular protective drugs such as CCB have the potential of decreasing IAD, and inhibition of CAD and cardiovascular events.

Our study has several limitations. First, it was a one-centre design with relatively few patients. Even so, IADs in CAD patients were closely correlated with the severity of CAD. Further large multicentre studies involving larger numbers of patients are required to determine the importance of IAD in CAD patients. Second, the present study was aimed at patients with CAD, all of whom take a variety of cardiovascular agents, including various antihypertensive drugs. In a population-based prospective cohort study conducted in Japan [11], mean IAD values and mean SBP in 1090 individuals drawn from the general population were higher than those in the non-CAD patients in our study. Furthermore, a recent study has reported that IAD may be detected less frequently in patients whose SBP has been reduced by antihypertensive therapy [39]. Thus, there may have been selection biases because patients enrolled in this study were taking more antihypertensive agents than the general population and IAD values in CAD patients could have been influenced by their medications. Third, we found no relationship between IAD and brachial-ankle PWV (baPWV) values in CAD patients, although several studies have demonstrated significant associations between IAD, baPWV and carotid-femoral PWV [35]. The values of baPWV generally tend to be underestimated in patients with very low-ABI because in patients with peripheral artery stenosis, pulse waves are poorly transmitted to the posterior tibial artery. The values of baPWV in CAD patients in the present study could be inaccurate because of strong and significant association of CAD with the presence of PAD. Finally, in the present study, we measured blood pressure in a supine position by ABI form device, whereas standard blood pressure measurements are made in a seated position. Blood pressure is generally higher in the supine position than the seated position. However, we consider that measuring blood pressure in a seated rather than supine position would not have affected our findings because IAD values derived from simultaneous bilateral blood pressure measurements would be affected to the same degree whatever the individual's positions. Although many previous studies have reported measuring IAD with ABI form devises in the supine position [33,34], differences in IAD attributable to the individual's position have not been thoroughly investigated. Further investigation is needed to examine the impact of the individual's position on IAD and blood pressure measurements.

However, despite these limitations, our study provides the first evidence for the diagnostic and prognostic significance of IAD in CAD patients. Simultaneous measurement of IAD by using an ABI type of device may provide clinical benefits in enabling risk stratification in patients with CAD. A large-scale, multicentre trial is warranted to further examine the clinical significance of IAD in patients with CAD.

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ACKNOWLEDGEMENTS

The authors are grateful to Ayuko Tateishi of the Department of Cardiovascular Medicine, Faculty of Life Sciences, Kumamoto University, for her skilful technical assistance.

This work was supported in part by Grants-in Aid for Scientific Research (No. B24790770 to E.Y.) from the Japanese Ministry of Education, Culture, Sports, Science and Technology.

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Conflicts of interest

All authors have no potential conflicts to disclose.

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Reviewer's Summary Evaluation Reviewer 2

This article confirms that high inter-arm blood pressure differences are associated with coronary artery disease. The strengths of this paper are the number of patients (n = 667) and the utilisation of the Gensini score for the cross-sectional analysis and the follow-up of these patients (longitudinal analysis). It is regrettable that the blood pressure measurements have been performed only in supine position which may create an evaluation bias.

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Keywords:

cardiovascular events; coronary artery disease; follow-up study; inter-arm blood pressure differences; peripheral artery disease

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