{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:07:54Z","timestamp":1787504874149,"version":"build-2736575974"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[1997,11,18]]},"abstract":"<jats:p>\n                    <jats:italic>Background<\/jats:italic>\n                    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.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Methods and Results<\/jats:italic>\n                    We studied endothelial function in 50 first-degree relatives (31 men, 19 women; mean age, 25\u00b18 years) of patients (men \u226445years, women \u226455years) 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\u00b14.6% versus 8.3\u00b13.5% in control subjects,\n                    <jats:italic>P<\/jats:italic>\n                    &lt;.005). In contrast, GTN caused dilatation in all subjects (family history, 17.1\u00b18.8%; control subjects, 19.0\u00b16.3%;\n                    <jats:italic>P<\/jats:italic>\n                    =NS), suggesting that reduced FMD was due to endothelial dysfunction. When the family history subjects were subdivided, those found to have a serum cholesterol &gt;4.2 mmol\/L (group A, n=10) had mildly impaired FMD compared with control subjects (5.5\u00b15.1% versus 8.3\u00b13.5%). In others whose affected relative had coronary risk factors (group B, n=24), FMD was also only slightly reduced (6.2\u00b14.8% versus 8.3\u00b13.5%). 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\u00b13.7% versus 8.3\u00b13.5%). Although ANOVA of the three family history subgroups did not reach statistical significance (F=2.55,\n                    <jats:italic>P<\/jats:italic>\n                    =.09), pairwise analysis showed that FMD in group C was significantly impaired compared with group B (\n                    <jats:italic>P<\/jats:italic>\n                    =.026).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Conclusions<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1161\/01.cir.96.10.3378","type":"journal-article","created":{"date-parts":[[2012,6,11]],"date-time":"2012-06-11T20:41:02Z","timestamp":1339447262000},"page":"3378-3383","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":171,"title":["Endothelium-Dependent Dilatation Is Impaired in Young Healthy Subjects With a Family History of Premature Coronary Disease"],"prefix":"10.1161","volume":"96","author":[{"given":"Peter","family":"Clarkson","sequence":"first","affiliation":[{"name":"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.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Celermajer","sequence":"additional","affiliation":[{"name":"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.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda J.","family":"Powe","sequence":"additional","affiliation":[{"name":"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.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann E.","family":"Donald","sequence":"additional","affiliation":[{"name":"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.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald M. 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