Hypertensive Exposure Markers by MRI in Relation to Cerebral Small Vessel Disease and Cognitive Impairment

R.P. Amier, N. Marcks, A.M. Hooghiemstra, R. Nijveldt, M.A. van Buchem, A. de Roos, G.J. Biessels, L.J. Kappelle, R.J. van Oostenbrugge, R.J. Van der Geest, M.L. Bots, J.P. Greving, W.J. Niessen, M.J.P. van Osch, J. de Bresser, P.M. van de Ven, W.M. Van der Flier, H.P. Brunner-La Rocca, A.C. van Rossum*, Heart-Brain Connection Consortium

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


OBJECTIVES This study sought to investigate the extent of hypertensive exposure as assessed by cardiovascular magnetic resonance imaging (MRI) in relation to cerebral small vessel disease (CSVD) and cognitive impairment, with the aim of understanding the role of hypertension in the early stages of deteriorating brain health.BACKGROUND Preserving brain health into advanced age is one of the great challenges of modern medicine. Hypertension is thought to induce vascular brain injury through exposure of the cerebral microcirculation to increased pressure/pulsatility. Cardiovascular MRI provides markers of (subclinical) hypertensive exposure, such as aortic stiffness by puke wave velocity (PWV), left ventricular (LV) mass index (LVMi), and concentricity by mass-to-volume ratio.METHODS A total of 559 participants from the Heart-Brain Connection Study (431 patients with manifest cardiovascular disease and 128 control participants), age 67.8 +/- 8.8 years, underwent 3.0-T heart-brain MRI and extensive neuropsychological testing. Aortic PWV, LVMi, and LV mass-to-volume ratio were evaluated in relation to presence of CSVD and cognitive impairment. Effect modification by patient group was investigated by interaction terms; results are reported pooled or stratified accordingly.RESULTS Aortic PWV (odds ratio [OR]: 1.17; 95% confidence interval [CI]: 1.05 to 1.30 in patient groups only), LVMi (in carotid occlusive disease, OR: 5.69; 95% CI: 1.63 to 19.87; in other groups, OR: 1.30; 95% CI: 1.05 to 1.62]) and LV mass-to-volume ratio (OR: 1.81; 95% CI: 1.46 to 2.24) were associated with CSVD. Aortic PWV (OR: 1.07; 95% CI: 1.02 to 1.13) and LV mass-to-volume ratio (OR: 1.27; 95% CI: 1.07 to 1.51) were also associated with cognitive impairment. Relations were independent of sociodemographic and cardiac index and mostly persisted after correction for systolic blood pressure or medical history of hypertension. Causal mediation analysis showed significant mediation by presence of CSVD in the relation between hypertensive exposure markers and cognitive impairment.CONCLUSIONS The extent of hypertensive exposure is associated with CSVD and cognitive impairment beyond clinical brood pressure or medical history. The mediating role of CSVD suggests that hypertension may lead to cognitive impairment through the occurrence of CSVD. (C) 2021 Published by Elsevier on behalf of the American College of Cardiology Foundation.
Original languageEnglish
Pages (from-to)176-185
Number of pages10
JournalJACC-Cardiovascular Imaging
Issue number1
Publication statusPublished - 1 Jan 2021


  • association
  • blood-pressure
  • brain
  • cognition
  • dementia
  • left ventricular mass
  • left ventricular mass-to-volume ratio
  • left-ventricular mass
  • performance
  • pulse wave velocity
  • pulse-wave velocity
  • risk-factors
  • stroke
  • vascular brain injury
  • white-matter hyperintensities

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