Higher long-term visit-to-visit blood pressure variability is associated with severe cerebral small vessel disease in the general population

Background Long-term blood pressure (BP) variability is related to several diseases, but its impact on cerebral small vessel disease (cSVD) is uncertain. The study explored the relationship between BP variability, total cSVD burden, and its typical features. Method The study involved 1284 participants from the Kailuan cohort. From 2006 to 2022, systolic BP (SBP), diastolic BP (DBP), and pulse pressure (PP) variability were calculated as low, middle, or high. Magnetic resonance imaging was used to identify white matter hyperintensities (WMH), lacunae (LA), cerebral microbleeds (CMBs), and visible perivascular spaces (PVS). The burden of cSVD was defined as non, mild, moderate, or severe. Logistic regression was used to estimate the odds ratio (OR) and confidence interval (CI). Results High SBP variability was associated with moderate cSVD burden (OR=1.89, 95% CI: 1.09-3.29) and PVS (OR= 1.62, 95%CI: 1.10-2.39). The DBP was associated with LA (OR=1.74, 95%CI: 1.06-2.84). The PP showed obvious risk effects on moderate/severe cSVD burden (OR= 1.99, 95%CI: 1.17-3.41; OR=2.49, 1.34-4.63). These associations were modified by age and hypertension status. In the young adults (age<60 years old), only high PP variability associated with severe cSVD burden (OR=3.33, 95%CI: 1.31-8.44), LA (OR=3.02, 95%CI: 1.31-6.93), and PVS (OR=1.86, 95%CI: 1.20-2.88). The risk effect of SBP and PP variability on cSVD burden was only significant in the participants with hypertension. Conclusion High long-term BP variability, especially in combination with hypertension, is a risk factor for total cSVD burden, LA, and PVS. it is crucial to pay attention to PP variability in young adults. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial The Medical Ethics Committee of Kailuan General Hospital has approved both the Kailuan Study and META-KLS (IRB Number: 2008 No.1 and 2021002, respectively). These two cohort studies were registered online (ChiCTR2000029767 on [chictr.org.cn][1] and [NCT05453877][2] on [Clinicaltrials.gov][3], respectively). Informed consent was obtained from all participants included in the study. ### Funding Statement This work was supported by the Beijing Municipal Administration of Hospitals Incubating Program (PX2022001), the National Natural Science Foundation of China (grant numbers: 82272072,61931013), and Beijing Scholars Program (grant number: [2015] 160). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Medical Ethics Committee of Kailuan General Hospital I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as [ClinicalTrials.gov][4]. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data are available on reasonable request from the corresponding author at [cjr.wzhch@vip.163.com][5]. * Abbreviations: (cSVD) : Cerebral small vessel disease (WMHs) : white matter hyperintensities (LA) : lacunae of presumed vascular origin (CMBs) : cerebral microbleeds (PVS) : visible perivascular spaces (MR) : magnetic resonance (BP) : blood pressure (SBP) : systolic blood pressure (DBP) : diastolic blood pressure (PP) : pulse pressure (META-KLS) : multi-modality medical imaging study [1]: http://chictr.org.cn [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT05453877&atom=%2Fmedrxiv%2Fearly%2F2024%2F01%2F04%2F2024.01.02.24300738.atom [3]: http://Clinicaltrials.gov [4]: http://ClinicalTrials.gov [5]: http://cjr.wzhch@vip.163.com