CLINICAL STUDY: RISK FACTORS
Cardiovascular risk factors as determinants of endothelium-dependent and endothelium-independent vascular reactivity in the general population
N. Norman Chan, MB, MRCPa,
Helen M. Colhoun, MD, MFPHM*,a and
Patrick Vallance, PhD, FRCP
a EURODIAB, Department of Epidemiology and Public HealthUniversity College London, London, United Kingdom
Centre for Clinical Pharmacology, University College London, London, United Kingdom
Manuscript received April 17, 2001;
revised manuscript received August 23, 2001,
accepted September 4, 2001.
* Reprint requests and correspondence: Dr. Helen M. Colhoun, EURODIAB, Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, London WC1E 6BT, United Kingdom
Helen{at}public-health.ucl.ac.uk
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 NG-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.
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Abbreviations and Acronyms
| | ACh | = acetylcholine | | BK | = bradykinin | | BMI | = body mass index | | CHD | = coronary heart disease | | FRS | = Framingham risk score | | GTN | = glyceryl trinitrate | | HDL | = high-density lipoprotein | | LDL | = low-density lipoprotein | | L-NMMA | = NG-monomethyl-L-arginine | | NO | = nitric oxide | | PNMR | = proton-nuclear magnetic resonance |
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