Which Components of the Haemodynamic Response to Active Stand Predict Cardiovascular Disease and Mortality? Data From The Irish Longitudinal Study on Ageing

Background An integrated haemodynamic response during standing may serve as an integrative marker of neuro-cardiovascular function. Individual components of both heart rate (HR) and blood pressure (BP) responses to active stand (AS) have been linked with cardiovascular disease (CVD) and mortality. We assessed longitudinal associations between entire HR/BP response curves during AS, incident CVD and mortality over 12 years.

Beat-to-beat measurements of dynamic HR/BP responses to AS were conducted in 4,336 individuals (61.5±8.2 years; 53.7% female). Functional Principal Components Analysis was applied to HR/BP response curves and their association with CVD and mortality assessed. We hypothesised that integrating BP/HR information from the entire haemodynamic response curve may uncover novel associations with both CVD and mortality.

Higher systolic BP (SBP) before AS and blunted recovery of SBP during AS was associated with all-cause mortality over 12-years (Hazard Ratio [HR]: 1.14; 1.04, 1.26; p=0.007). Higher baseline/peak HR and lower HR from 30 seconds post stand onwards were associated with lower mortality due to circulatory causes (HR: 0.78; 0.64, 0.95; p = 0.013). Higher HR throughout AS was associated with mortality from other causes (HR: 1.48; 1.22, 1.80; p<0.001). Findings persisted on robust covariate adjustment.

We observed distinct relationships between HR/BP responses to AS and 12-year incident CVD and mortality. Integrating the entire haemodynamic response may reveal more nuanced relationships between HR/BP responses to AS, CVD and mortality - serving as an integrative marker of neuro-cardiovascular health in midlife and beyond. Competing Interest Statement The authors have declared no competing interest. Funding Statement This work was supported by the SFI US-Ireland Research and Development Partnership (Grant Number 19/US/3615) (RAK, CMcC, BH) and by NIA Biomarker Network seed funding (Grant Number R24 AG054365) (BH). AHD is supported by the Irish Clinical Academic Training (ICAT) Programme, supported by the Wellcome Trust and Health Research Board (Grant Number 203930/B/16/Z), the Health Service Executive, National Doctors Training and Planning, and the Health and Social Care, Research and Development Division, Northern Ireland. TILDA is supported by the Irish Government, the Atlantic Philanthropies, and the Health Research Board. The sponsors played no role in study design, methods, subject recruitment, data collection, analysis, or preparation of the article. 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 TILDA study was approved by the Faculty of Health Sciences Research Ethics Committee at Trinity College Dublin and adhered to the Declaration of Helsinki (REC: 190407). The clinical cohort study was approved by Tallaght University Hospital/St. James's Hospital Joint Research Ethics Committee (REC:2018-08,CA,16) 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. 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 Availability The dataset(s) supporting the conclusions of this article are not publicly available due to data protection regulations but are accessible at TILDA on reasonable request. The procedures to gain access to TILDA data are specified at https://tilda.tcd.ie/data/accessing-data/.