(Circulation. 1997;96:3378-3383.)
© 1997 American Heart Association, Inc.
Articles |
Endothelium-Dependent Dilatation Is Impaired in Young Healthy Subjects With a Family History of Premature Coronary Disease
From the Cardiothoracic Unit, Great Ormond Street Hospital for Children NHS Trust, London, UK, and the Department of Cardiology, Royal Prince Alfred Hospital, Camperdown, Australia (D.S.C.).
Correspondence to John E. Deanfield, Cardiothoracic Unit, Great Ormond Street Hospital for Children NHS Trust, Great Ormond St, London WC1N 3JH, UK.
Background A family history of premature coronary artery disease (CAD) in a first-degree relative is an independent risk factor for coronary disease. Both genetic and environmental influences are likely to be responsible and may interact, but their relative importance is unclear.
Methods and Results We studied endothelial
function in 50 first-degree relatives (31 men, 19 women; mean age,
25±8 years) of patients (men 
45years, women 55years) with proven
CAD. All subjects were well, lifelong nonsmokers, not diabetic, and not
hypertensive and took no medications. Using high-resolution external
vascular ultrasound, we measured brachial artery diameter at rest and
in response to reactive hyperemia (with increased flow causing
an endothelium-dependent vasodilatation) and to
sublingual glyceryltrinitrate (GTN, an
endothelium-independent dilator). Vascular responses
were compared with those of 50 healthy control subjects matched for age
and sex. Flow-mediated dilatation (FMD) was impaired in the family
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 history, 17.1±8.8%; control subjects, 19.0±6.3%;
P=NS), suggesting that reduced FMD was due to
endothelial dysfunction. When the family history
subjects were subdivided, those found to have a serum
cholesterol >4.2 mmol/L (group A, n=10) had mildly
impaired FMD compared with control subjects (5.5±5.1% versus
8.3±3.5%). In others whose affected relative had coronary
risk factors (group B, n=24), FMD was also only slightly reduced
(6.2±4.8% versus 8.3±3.5%). In contrast, subjects with no risk
factors and whose affected relative had a normal
cardiovascular 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 family history subgroups did not reach statistical
significance (F=2.55, P=.09), pairwise analysis
showed that FMD in group C was significantly impaired compared with
group B (P=.026).
Conclusions Healthy young adults with a family history of premature coronary disease may have impaired endothelium-dependent dilatation, even in the absence of other cardiovascular risk factors. Those subjects, who were free of risk factors and whose affected first-degree relative was free of risk factors, had the most impaired endothelial function, suggesting a genetic influence on early arterial physiology that may be relevant to later clinical disease.
Key Words: endothelium • family history • ultrasonics • genetics • risk factors
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