Inter-arm systolic blood pressure differences, relations with future vascular events and mortality in patients with and without manifest vascular disease

Abstract

Background

Inter-arm systolic blood pressure difference (SBPD) is an easily obtained patient characteristic which relates to vascular disease. We aimed to identify determinants of large inter-arm SBPD and to investigate the relation between inter-arm SBPD and vascular events in patients with and without manifest vascular disease.

Methods

In a cohort of 7344 patients with manifest vascular disease or vascular risk factors alone enrolled in the Second Manifestations of ARTerial disease (SMART) study, single bilateral non-simultaneous blood pressure measurements were performed. Logistic and Cox regression was used to identify determinants of large inter-arm SBPD (≥ 15 mm Hg) and to investigate the relation between inter-arm SBPD and vascular events (composite of non-fatal myocardial infarction, stroke, and vascular mortality) and all-cause mortality.

Results

In all patients the median inter-arm SBPD was 7 mm Hg (IQR 3–11) and 1182 (16%) patients had inter-arm SBPD ≥ 15 mm Hg. Higher age, higher systolic blood pressure, diabetes mellitus, peripheral artery disease, carotid artery stenosis, higher carotid intima-media thickness, and lower ankle-brachial indices were related to large inter-arm SBPD (≥ 15 mm Hg). Each 5 mm Hg increase in inter-arm SBPD was related to a 12% higher risk of vascular events in patients without manifest vascular disease (HR 1.12; 95% CI 1.00–1.27), whereas no relation was apparent in patients with manifest vascular disease (HR 0.98; 95% CI 0.93–1.04, interaction p-value 0.036). Inter-arm SBPD was not related to all-cause mortality (HR 1.05; 95% CI 0.93–1.19).

Conclusions

Inter-arm SBPD relates to a higher risk of vascular events in patients without manifest vascular disease, whereas this relation is not apparent in patients with manifest vascular disease.

Introduction

Peripheral artery disease (PAD) significantly contributes to the total burden of vascular disease as it is related to high risks of vascular morbidity and mortality [1], [2]. Although PAD most often presents as an atherosclerotic disease of the leg arteries, atherosclerotic changes in the arteries of the upper limbs occur as well [3]. Inter-arm systolic blood pressure difference (SBPD) reflects subclavian stenosis which in most cases is caused by atherosclerosis in the upper limb arteries [4]. In rare cases there may be another origin such as arteritis, fibromuscular dysplasia, arterial injuries or arterial dissection [5], [6], [7]. International hypertension guidelines stress the importance of bilateral blood pressure measurement and state that large inter-arm SBPD is an indicator of elevated vascular risk [8], [9]. Indeed, high inter-arm SBPD (> 15 mm Hg) relates to an approximately 1.6-fold risk of cardiovascular mortality [4], [10]. Although the association of inter-arm SBPD with atherosclerotic stenosis of the upper arm arteries is generally acknowledged, little is known about the precise determinants of a large inter-arm SBPD.

Several epidemiological studies indicate that large inter-arm SBPD confers a higher risk for (cardiovascular) mortality and relates to the presence of cardiovascular risk factors, PAD of the lower extremities, and cerebrovascular disease [4], [10], [11], [12], [13], [14]. Previous studies mostly used cut off values (≥ 10, ≥ 15 or ≥ 20 mm Hg) to investigate the relation between inter-arm SBPD and prevalent vascular disease, while a continuous approach could provide more precise information [10], [11]. A small prospective cohort study of 230 patients with hypertension with a median follow-up of 9.8 years shows that each 1 mm Hg increase in inter-arm SBPD relates to future cardiovascular events (HR 1.04; 95% CI 1.02–1.07) [15]. Also, a larger community-based prospective cohort including 3390 participants shows that each standard deviation increase in inter-arm SBPD relates to cardiovascular events (HR 1.07; 95% CI 1.00–1.14) [14]. Nevertheless, evidence on the relation in patients with manifestations of vascular disease is scarce [10], [11].

The presence of clinical manifest vascular disease might influence the relation between inter-arm SBPD and vascular events. Patients with clinical manifest vascular disease are at higher risk for vascular events than patients without clinical manifestations of vascular disease. Therefore the relation between inter-arm SBPD and vascular risk might be different in patients with and without clinical manifest vascular disease.

The aim of the present study is to identify determinants of high inter-arm SBPD and to investigate the relation between inter-arm SBPD and vascular events and all-cause mortality in patients with and without clinical manifest vascular disease.