Microvascular function contributes to the relation between aortic stiffness and cardiovascular events

Leroy L. Cooper, Joseph N. Palmisano, Emelia J. Benjamin, Martin G. Larson, Ramachandran S. Vasan, Gary F. Mitchell, Naomi M. Hamburg

Research output: Contribution to journalArticlepeer-review

44 Scopus citations


Background - Arterial dysfunction contributes to cardiovascular disease (CVD) progression and clinical events. Inter-relations of aortic stiffness and vasodilator function with incident CVD remain incompletely studied. Methods and Results - We used proportional hazards models to relate individual measures of vascular function to incident CVD in 4547 participants (mean age, 51±11 years; 54% women) in 2 generations of Framingham Heart Study participants. During follow-up (0.02-13.83 years), 232 participants (5%) experienced new-onset CVD events. In multivariable models adjusted for cardiovascular risk factors, both higher carotid-femoral pulse wave velocity (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.07-1.63; P=0.01) and lower hyperemic mean flow velocity (HR, 0.84; 95% CI, 0.71-0.99; P=0.04) were associated significantly with incident CVD, whereas primary pressure wave amplitude (HR, 1.12; 95% CI, 0.99-1.27; P=0.06), baseline brachial diameter (HR, 1.09; 95% CI, 0.90-1.31; P=0.39), and flow-mediated vasodilation (HR, 0.85; 95% CI, 0.69-1.04; P=0.12) were not. In mediation analyses, 8% to 13% of the relation between aortic stiffness and CVD events was mediated by hyperemic mean flow velocity. Conclusions - Our results suggest that associations between aortic stiffness and CVD events are mediated by pathways that include microvascular damage and remodeling.

Original languageEnglish (US)
Article numbere004979
JournalCirculation: Cardiovascular Imaging
Issue number12
StatePublished - Dec 1 2016
Externally publishedYes


  • arteries
  • cardiovascular diseases
  • endothelium
  • pulse wave analysis
  • vascular stiffness

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Radiology Nuclear Medicine and imaging


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