Inter-arm blood pressure difference: insights into aetiology from the INTERPRESS-IPD collaboration

Talk Code: 
4B.4
Presenter: 
Christopher Clark
Co-authors: 
Fiona C Warren, Kate Boddy, Sinead TJ McDonagh, Sarah Moore, Lyne Cloutier, Rod S Taylor, Angela C Shore, Richard J McManus, Victor Aboyans, John L Campbell
Author institutions: 
University of Exeter College of Medicine & Health, UK. Université du Québec à Trois-Rivières, Canada. Nuffield Department of Primary Care Health Sciences University of Oxford. Deptartment of Cardiology, Dupuytren University Hospital, France

Problem

Differences in systolic blood pressure (BP) between arms are associated with excess mortality and cardiovascular events. Inter-arm difference (IAD) has been attributed to both subclavian stenosis and to arterial stiffening. These conditions share common risk factors but the patho-physiological basis of IAD has not been clearly established. We explored cross-sectional associations of systolic IAD within the large INTERPRESS individual participant data (IPD) Collaboration to gain further insight.

Approach

The INTERPRESS-IPD Collaboration pooled records for 57,434 participants across 24 studies from Europe, North America, East Asia and Africa. Using hierarchical IPD linear regression with random effects for study, we performed univariable and multivariable models, examining cross-sectional associations of IAD with known markers of cardiovascular risk, and with cardiovascular risk scores. IAD was based on a single sequential pair of BP readings. Models were compared using Aikeke’s information criterion (AIC) and likelihood ratios (LR). Analyses were undertaken using Stata v15.0.

Findings

Mean age of participants was 60.3 (Standard deviation 12.5); 47% were female and mean BP was 138.3/80.9 (21.8/11.8). The majority ethnicity was White (69.8%) followed by African American (5.5%) and Hispanic American (3.4%). Based on as single pair of measurements, prevalences of systolic IAD ≥10 mmHg and ≥15 mmHg were 28.2% and 11.1%. Complete case data existed for 43,488 participants from 22 cohorts. Ankle brachial index (ABI) was negatively correlated with IAD: coefficient -0.69mmHg of IAD per 0.1 increment of ABI (-0.74 to -0.65; p<0.001). QRISK2, ASCVD and Framingham cardiovascular risk scores were positively correlated with IAD: coefficients 0.06 (0.06 to 0.07; p<0.001), 0.07 (0.06 to 0.08; p<0.001) and 0.06 (0.05 to 0.06; p<0.001) per 1mmHg increment of IAD respectively.

On multivariable modelling, magnitude of IAD was positively associated with smoking (p=0.04), age (p=0.05), body mass index (p<0.001), systolic BP (p<0.001) and hypertension (p<0.001). IAD was lower for African American (p=0.04) and Hispanic American (p<0.001) participants compared to White ethnicity, and lower for men than women (p=0.02).

Using all available case data the multivariable model was confirmed. Goodness of fit improved on taking account of pre-existing cardiovascular disease (LR p=0.004; n=41,664), with addition of pulse pressure (LR p<0.001; n=33,844) or on adjustment for renal disease (LR p<0.001; n=15,541). AIC was non-discriminatory between models.

Consequences

This large multivariable analysis confirms the independent cross sectional association of systolic IAD with recognised cardiovascular risk markers, and with internationally used cardiovascular risk scores. Findings are consistent with the hypothesis that IAD reflects pathological change in the circulation. The factors correlated with IAD are associated with both arterial stiffening and with occlusive arterial disease; it is likely that both processes make a contribution to the aetiology of IAD. These findings support further hypothesis generation and justify studies aimed to elucidate the full aetiology of IAD.

Submitted by: 
Christopher Clark
Funding acknowledgement: 
This paper presents independent research funded by the National Institute for Health Research (NIHR) under its Research for Patient Benefit (RfPB) Programme (Grant Reference Number PB-PG-0215-36009). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.