Visit-to-visit blood pressure variability and the risk of stroke in the Netherlands: A population-based cohort study

Alis Heshmatollah, Yuan Ma, Lana Fani, Peter J. Koudstaal, M. Arfan Ikram*, M. Kamran Ikram

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Background Apart from blood pressure level itself, variation in blood pressure has been implicated in the development of stroke in subgroups at high cardiovascular risk. We determined the associa tion between visit-to-visit blood pressure variability and stroke risk in the general population taking into account the size and direction of variation and several time intervals prior to stroke diagnosis. Methods and findings From 1990 to 2016, we included 9,958 stroke-free participants of the population-based Rot terdam Study in the Netherlands. This is a prospective cohort study including participants aged 45 years and older. Systolic blood pressure (SBP) variability was calculated as absolute SBP difference divided by mean SBP over 2 sequential visits (median 4.6 years apart). Directional SBP variability was defined as SBP difference over 2 visits divided by mean SBP. Using time-varying Cox proportional hazards models adjusted for age, sex, mean SBP, and cardiovascular risk factors, hazard ratios (HRs) for stroke up to January 2016 were estimated per SD increase and in tertiles of variability. We also conducted analyses with 3-, 6-, and 9-year intervals between variability measurement and stroke assessment. These analyses were repeated for diastolic blood pressure (DBP). The mean age of the study population was 67.4 ± 8.2 years and 5,776 (58.0%) were women. During a median fo low-up of 10.1 years, 971 (9.8%) participants had a stroke, including 641 ischemic, 89 hem orrhagic, and 241 unspecified strokes. SBP variability was associated with an increased ris of hemorrhagic stroke (HR per SD 1.27, 95% CI 1.05–1.54, p = 0.02) and unspecified strok (HR per SD 1.21, 95% CI 1.09–1.34, p < 0.001). The associations were stronger for all stroke subtypes with longer time intervals; the HR for any stroke was 1.29 (95% CI 1.21–1.36, p < 0.001) at 3 years, 1.47 (95% CI 1.35–1.59, p < 0.001) at 6 years, and 1.38 (95%C 1.24–1.51, p < 0.001) at 9 years. For DBP variability, we found an association with unspecified stroke risk. Both the rise and fall of SBP and the fall of DBP were associated with an increased risk for unspecified stroke. Limitations of the study include that, due to an average interval of 4 years between visits, our findings may not be generalizable to blood pressure variability over shorter periods. Conclusions In this population-based study, we found that visit-to-visit blood pressure variation was associated with an increased risk of unspecified and hemorrhagic stroke, independent of direction of variation or mean blood pressure.

Original languageEnglish
Article numbere1003942
JournalPLoS Medicine
Issue number3
Publication statusPublished - 17 Mar 2022

Bibliographical note

Funding: The Rotterdam Study is supported by the Erasmus MC University Medical Center and Erasmus University Rotterdam; The Netherlands Organization for Scientific Research (NWO); The Netherlands Organization for Health Research and Development (ZonMw); The Research Institute for Diseases in the Elderly (RIDE); The Netherlands Genomics Initiative (NGI); the Ministry of Education, Culture and Science; The Ministry of Health, Welfare and Sports; the European Commission (DG XII); and The Municipality of Rotterdam. Funding was not based on specific award or grant numbers. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright: © 2022 Heshmatollah et al.


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