Microvascular Function Contributes to the Relation Between Aortic Stiffness and Cardiovascular Events: The Framingham Heart Study

Circ Cardiovasc Imaging. 2016 Dec;9(12):e004979. doi: 10.1161/CIRCIMAGING.116.004979.


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.

Keywords: arteries; cardiovascular diseases; endothelium; pulse wave analysis; vascular stiffness.

MeSH terms

  • Adult
  • Blood Flow Velocity
  • Brachial Artery / diagnostic imaging
  • Brachial Artery / physiopathology*
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / physiopathology*
  • Carotid Arteries / diagnostic imaging
  • Carotid Arteries / physiopathology*
  • Female
  • Humans
  • Hyperemia / physiopathology
  • Incidence
  • Kaplan-Meier Estimate
  • Male
  • Massachusetts / epidemiology
  • Microcirculation*
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Proportional Hazards Models
  • Pulse Wave Analysis
  • Regional Blood Flow
  • Risk Factors
  • Time Factors
  • Ultrasonography, Doppler
  • Vascular Stiffness*
  • Vasodilation*