Cardiovascular risk factors as determinants of endothelium-dependent and endothelium-independent vascular reactivity in the general population

J Am Coll Cardiol. 2001 Dec;38(7):1814-20. doi: 10.1016/s0735-1097(01)01669-2.


Objectives: We examined to what extent the variation in risk factors for coronary heart disease (CHD) and the Framingham risk score (FRS) explain the variation in vascular reactivity in adults aged 30 to 53 years.

Background: The role of risk factors in determining vascular reactivity in the general population has not been quantified.

Methods: Risk factors for CHD were measured, and the FRS was calculated in 69 healthy volunteers. Lipoprotein particle size was measured using proton-nuclear magnetic resonance spectroscopy. Forearm plethysmography was used to assess blood flow responses to acetylcholine (ACh), bradykinin (BK), glyceryl trinitrate (GTN), noradrenaline and N(G)-monomethyl-L-arginine (L-NMMA).

Results: Lower ACh and BK responses were associated with a higher body mass index (BMI), a higher total cholesterol to high-density lipoprotein (HDL) cholesterol ratio, lower HDL cholesterol and a cigarette smoking habit (all p < 0.05). Higher low-density lipoprotein (LDL) cholesterol was also associated with a lower BK response (p = 0.001). A decreased GTN response was associated with a higher BMI and total cholesterol to HDL cholesterol ratio (both p < 0.05). A decreased L-NMMA response was associated with a smoking habit (p < 0.001). Lipoprotein particle sizes did not independently predict any vascular response. A high FRS was associated with a reduced response to ACh (p = 0.07), BK (p = 0.003) and L-NMMA (p = 0.003), and the relationship was stronger in women than in men. Altogether, risk factors explained 13%, 9%, 8% and 15% of the response to ACh, BK, GTN and L-NMMA, respectively.

Conclusions: Lipids, BMI and smoking are important determinants of vascular reactivity. The FRS is predictive of agonist-stimulated, endothelium-dependent vasodilation and basal NO release. However, much of the variation in the vascular responses to these drugs, at this age, remains unexplained.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Body Mass Index
  • Cholesterol / blood
  • Cohort Studies
  • Coronary Circulation / physiology*
  • Coronary Disease / etiology
  • Coronary Disease / physiopathology*
  • Endothelium, Vascular / physiopathology*
  • Female
  • Humans
  • Lipoproteins / blood
  • Male
  • Middle Aged
  • Risk Factors
  • Smoking / adverse effects
  • Vascular Resistance / physiology*


  • Lipoproteins
  • Cholesterol