ENDOTHELIUM-DEPENDENT DILATATION IS IMPAIRED IN YOUNG HEALTHY-SUBJECTS WITH A FAMILY HISTORY OF PREMATURE CORONARY-DISEASE

Background A family history of premature coronary artery disease (CAD) in a first-degree relative is an independent risk: factor for coronar y disease. Both genetic and environmental influences are likely to be responsible and map interact, but their relative Importance is unclear . Methods and Results We studied endothelial function in 50 first-degr ee relatives (31 men, 19 women; mean age, 25+/-8 years) of patients (m en less than or equal to 45years, women less than or equal to 55years) with proven CAD. All subjects were well, lifelong nonsmokers. not dia betic, and not hypertensive and took no medications. Using high-resolu tion external vascular ultrasound, we measured brachial artery diamete r at rest and In response to reactive hyperemia (with Increased flow c ausing an endothelium-dependent vasodilatation) and to sublingual glyc eryltrinitrate (GTN, an endothelium-independent dilator). Vascular res ponses were compared with those of 50 healthy control subjects matched for age and sex. Flow-mediated dilatation (FMD) was impaired in the F amily history group (4.9+/-4.6% versus 8.3+/-3.5% in control subjects, P<.005). In contrast, GTN caused dilatation in all subjects (family h istory, 17.1+/-8.8%; control subjects, 19.0+/-6.3%; P=NS): suggesting that reduced FMD was due to endothelial dysfunction. When the family h istory subjects were subdivided. those found to have a serum cholester ol >4.2 mmol/L (group A, n=10) had mildly impaired FMD compared with c ontrol subjects (5.5+/-5.1% versus 8.3+/-3.5%). In others whose affect ed relative had coronary risk factors (group B, n=24), FMD was also on ly slightly reduced (6.2+/-4.8% versus 8.3 +/- 3.5%). In contrast, sub jects with no risk factors and whose affected relative had a normal ca rdiovascular risk factor profile (group C, n=16) had markedly impaired FMD (2.9+/-3.7% versus 8.3+/-3.5%). Although ANOVA of the three famil y history subgroups did not reach statistical significance (F=2.55, P= .09), pairwise analysis showed that FMD in group C was significantly i mpaired compared with group B (P=.026). Conclusions Healthy young adul ts with a family history of premature coronary disease may have impair ed endothelium-dependent dilatation, even in the absence of other card iovascular risk factors. Those subjects, who were free of risk factors and whose affected first-degree relative was free of risk factors, ha d the most impaired endothelial function, suggesting a genetic influen ce on early arterial physiology that may be relevant to later clinical disease.