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Late prognostic value of flow-mediated dilation in the brachial artery of patients with chest pain

      Several modifiable cardiovascular risk factors such as hypercholesterolemia, smoking, diabetes, hypertension, and hyperhomocysteinemia are associated with impaired endothelium-dependent vasodilation in the preclinical phase of vascular disease.
      • Celermajer D.S.
      • Sorensen K.E.
      • Gooch V.M.
      • Spiegelhalter D.J.
      • Miller O.I.
      • Sullivan I.D.
      • Lloyd J.K.
      • Deanfield J.E.
      Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis.
      ,
      • Celermajer D.S.
      • Sorensen K.E.
      • Georgakopoulos D.
      • Bull C.
      • Thomas O.
      • Robinson J.
      • Deanfield J.E.
      Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults.
      ,
      • Clarkson P.
      • Celermajer D.S.
      • Donald A.E.
      • Sampson M.
      • Sorensen K.E.
      • Adams M.
      • Yue D.K.
      • Betteridge D.J.
      • Deanfield J.E.
      Impaired vascular reactivity in insulin-dependent diabetes mellitus is related to disease duration and low density lipoprotein cholesterol levels.
      ,
      • Panza J.A.
      • Casino P.R.
      • Badar D.M.
      • Quyyumi A.A.
      Effect of increased availability of endothelium-derived nitric oxide precursor on endothelium-dependent vascular relaxation in normal subjects and in patients with essential hypertension.
      ,
      • Woo K.S.
      • Chook P.
      • Lolin Y.I.
      • Cheung A.S.
      • Chan L.T.
      • Sun Y.Y.
      • Sanderson J.E.
      • Metreweli C.
      • Celermajer D.S.
      Hyperhomocyst(e)inemia is a risk factor for arterial endothelial dysfunction in humans.
      We have previously found that endothelial dysfunction is more pronounced in patients with angiographically proved coronary artery disease (CAD) compared with patients with a similar risk factor profile but who have smooth coronary arteries.
      • Neunteufl T.
      • Katzenschlager R.
      • Hassan A.
      • Klaar U.
      • Schwarzacher S.
      • Glogar D.
      • Bauer P.
      • Weidinger F.
      Systemic endothelial dysfunction is related to the extent and severity of coronary artery disease.
      Thus, endothelial dysfunction not only reflects the risk factor burden but also the presence, and perhaps, stages of coronary disease.
      • Neunteufl T.
      • Katzenschlager R.
      • Hassan A.
      • Klaar U.
      • Schwarzacher S.
      • Glogar D.
      • Bauer P.
      • Weidinger F.
      Systemic endothelial dysfunction is related to the extent and severity of coronary artery disease.
      Brachial artery ultrasound, first described by Celermajer et al,
      • Celermajer D.S.
      • Sorensen K.E.
      • Gooch V.M.
      • Spiegelhalter D.J.
      • Miller O.I.
      • Sullivan I.D.
      • Lloyd J.K.
      • Deanfield J.E.
      Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis.
      utilizes high resolution ultrasound to assess flow-mediated dilation (FMD), an endothelium-dependent response,
      • Pohl U.
      • Holtz J.
      • Busse R.
      • Bassenge E.
      Crucial role of endothelium in the vasodilator response to increased flow in vivo.
      ,
      • Holtz J.
      • Förstermann U.
      • Pohl U.
      • Giesler M.
      • Bassenge E.
      Flow-dependent, endothelium-mediated dilation of epicardial coronary arteries in conscious dogs effects of cyclooxygenase inhibition.
      ,
      • Rubanyi G.M.
      • Romero J.C.
      • Vanhoutte P.M.
      Flow-induced release of endothelium-derived relaxing factor.
      which is largely mediated by nitric oxide
      • Joannides R.
      • Haefeli W.E.
      • Linder L.
      • Richard V.
      • Bakkali E.H.
      • Thuillez C.
      • Lüscher T.F.
      Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo.
      and closely related to coronary endothelial function.
      • Anderson T.J.
      • Uehata A.
      • Gerhard M.D.
      • Meredith I.T.
      • Knab S.
      • Delagrange D.
      • Lieberman E.H.
      • Ganz P.
      • Creager M.
      • Yeung A.C.
      • Selwyn A.P.
      Close relation of endothelial function in the human coronary and peripheral circulations.
      Vessel size, age, gender, menstrual cycle, and therapeutic interventions also influence FMD.
      • Celermajer D.S.
      • Sorensen K.E.
      • Gooch V.M.
      • Spiegelhalter D.J.
      • Miller O.I.
      • Sullivan I.D.
      • Lloyd J.K.
      • Deanfield J.E.
      Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis.
      ,
      • Celermajer D.S.
      • Sorensen K.E.
      • Spiegelhalter D.J.
      • Georgakopoulos D.
      • Robinson J.
      • Deanfield J.E.
      Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women.
      ,
      • Hashimoto M.
      • Akishita M.
      • Eto M.
      • Ishikawa M.
      • Kozaki K.
      • Toba K.
      • Sagara Y.
      • Taketani Y.
      • Orimo H.
      • Ouchi Y.
      Modulation of endothelium-dependent flow-mediated dilation of the brachial artery by sex and menstrual cycle.
      Thus, it is difficult to interpret impairment of FMD in patients and it is very questionable whether FMD can be recommended as a screening test for the detection of significant CAD. However, the evaluation of FMD is increasingly used to assess short-term effects of therapeutic interventions on systemic endothelial function.
      • Vogel R.A.
      • Corretti M.C.
      • Plotnick G.D.
      Changes in flow-mediated brachial artery vasoactivity with lowering of desirable cholesterol levels in healthy middle-aged men.
      ,
      • O’Driscoll G.
      • Green D.
      • Taylor R.R.
      Simvastatin, an HMG-coenzyme. A reductase inhibitor, improves endothelial function within 1 month.
      ,
      • Neunteufl T.
      • Kostner K.
      • Katzenschlager R.
      • Zehetgruber M.
      • Maurer G.
      • Weidinger F.
      Additional benefit of vitamin E supplementation to simvastatin therapy on vasoreactivity of the brachial artery of hypercholesterolemic men.
      The present study attempted to assess whether FMD was correlated with prognosis in patients with chest pain who underwent coronary angiography.
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