IMPORTANCE: Studies have shown that both high and low blood pressure (BP) may play a role in the etiology of brain atrophy. High BP in midlife has been associated with more brain atrophy later in life, whereas studies in older populations have shown a relation between low BP and more brain atrophy. Yet, prospective evidence is limited, and the relation remains unclear in patients with manifest arterial disease.

OBJECTIVE: To examine the associations of baseline BP and change in BP over time with progression of brain atrophy.

DESIGN: The Secondary Manifestations of ARTerial disease-Magnetic Resonance (SMART-MR) Study is a prospective cohort study with baseline measurements in 2001-2005 and follow-up measurements in 2006-2009. The mean follow-up time was 3.9 years.

SETTING: University Medical Center Utrecht, the Netherlands.

PARTICIPANTS: A total of 663 patients (mean [SD] age, 57 [9] years; 81% male) with coronary artery disease, cerebrovascular disease, peripheral artery disease, or abdominal aortic aneurysm were included.

MAIN OUTCOMES AND MEASURES: Using automated segmentation at baseline and follow-up, change in brain parenchymal fraction, cortical gray matter fraction, and ventricular fraction (%ICV) were quantified as indicators of progression of global, cortical, and subcortical brain atrophy.

RESULTS: Multivariable adjusted regression analysis showed that patients with lower baseline diastolic BP (DBP) or mean arterial pressure had more progression of subcortical atrophy. The mean differences in the change in ventricular fraction between low and high DBP was 0.07% (95% CI, 0.01-0.14) and between low and high mean arterial pressure was 0.05% (95% CI, 0.00-0.10). Furthermore, in patients with higher baseline BP (DBP, mean arterial pressure, or systolic BP), those with declining BP levels over time had less progression of subcortical atrophy compared with those with rising BP levels.

CONCLUSIONS AND RELEVANCE: In patients with manifest arterial disease, low baseline DBP was associated with more progression of subcortical atrophy, irrespective of the BP course during follow-up. Furthermore, in patients with higher baseline BP, declining BP levels over time were associated with less progression of subcortical atrophy. This could imply that BP lowering is beneficial in patients with higher BP levels, but caution should be taken with further BP lowering in patients who already have a low DBP.

Original languageEnglish
Pages (from-to)1046-1053
Number of pages8
JournalJAMA Neurology
Issue number8
Publication statusPublished - Aug 2013


  • Adult
  • Aged
  • Atrophy
  • Blood Pressure
  • Brain
  • Cerebral Cortex
  • Cohort Studies
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Netherlands
  • Prospective Studies
  • Vascular Diseases
  • Comparative Study
  • Journal Article
  • Research Support, Non-U.S. Gov't


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