Significance of heterogenity in endothel-dependent vasodilatation occurrence in healthy individuals with or without coronary risk factors

Abstract

Background/Aim. Brachial artery flow-mediated dilation (FMD) is extensively used for non-invasive assessment of endothelial function. Traditionally, FMD is calculated as a percent change of arterial diameter from the baseline value at an arbitrary time point after cuff deflation (usually 60 seconds). Considerable individual differences in brachial artery temporal response to hyperemic stimulus have been observed, potentially influenced by the presence of atherosclerotic risk factors (RF). The importance of such differences for the evaluation of endothelial function has not been well established. The aim of the stady was to determine the time course of maximal brachial artery endothelium- dependent dilation in healthy adults with and without RF, to explore the correlation of RF with brachial artery temporal response and to evaluate the importance of individual differences in temporal response for the assessment of endothelial function. Methods. A total of 115 healthy volunteers were included in the study. Out of them, 58 had no RF (26 men, mean age 44 ? 14 years) and 57 had at least one RF (29 men, mean age 45 ? 14 years). High-resolution color Doppler vascular ultrasound was used for brachial artery imaging. To determine maximal arterial diameter after cuff deflation and the time-point of maximal vasodilation off-line sequential measurements were performed every 10 seconds from 0 to 240 seconds after cuff release. True maximal FMD value was calculated as a percent change of the true maximal diameter from the baseline, and compared with FMD value calculated assuming that every participant reached maximal dilation at 60 seconds post cuff deflation (FMD60). Correlation of different RF with brachial artery temporal response was assessed. Results. A maximal brachial artery endothelium-dependent vasodilation occurred from 30-120 seconds after cuff release, and the mean time of endothelium-dependent dilation was 68 ? 20 seconds. Individuals without RF had faster endothelium-dependent dilation (mean time 62 ? 17 seconds), and a shorter timespan (30 to 100 seconds), than participants with RF (mean time 75 ? 21 seconds, time-span 40 to 120 seconds) (p < 0.001). Time when the maximal endotheliumdependent dilation occurred was independently associated with age, serum lipid fractions (total cholesterol, LDL and HDL cholesterol), smoking, physical activity and C-reactive protein. True maximal FMD value in the whole group (6.7 ? 3.0%) was significantly higher (p < 0.001) than FMD60 (5.2 ? 3.5%). The same results were demonstrated for individuals with RF (4.9 ? 1.7% vs 3.1 ? 2.3%, p < 0.001) and without RF (8.4 ? 2.9% vs 7.2 ? 3.2%, p < 0.05). Conclusion. The temporal response of endothelium- dependent dilation is influenced by the presence of coronary FR and individually heterogeneous. When calculated according to the commonly used approach, i.e. 60 seconds after cuff deflation, FMD is significantly lower than the true maximal FMD. The routinely used measurement time-points for FMD assessment may not be adequate for the detection of true peak vasodilation in individual persons. More precise evaluation of endothelial function can be achieved with sequential measurement of arterial diameter after hyperemic stimulus.Uvod/Cilj. Dilatacija brahijalne arterije, izazvana protokom (flow-mediated dilation - FMD), ima siroku primenu za neinvazivno odredjivanje funkcije endotela. Tradicionalno, FMD izracunava se kao procenat promene precnika arterije od pocetne vrednosti u proizvoljno vreme posle popustanja poveske (obicno 60 sekundi). Primecene su znacajne individualne razlike u vremenskoj reakciji brahijalne arterije na hiperemijske stimulanse, moguce zbog prisustva aterosklerotskih faktora rizika (FR). Uloga ovih razlika u odredjivanju funkcije endotela nije, medjutim, dovoljno utvrdjena. Cilj ove studije bio je da se utvrdi opseg vremena nastanka maksimalne endotel-zavisne dilatacije brahijalne arterije kod zdravih osoba sa i bez koronarnih FR, povezanost FR sa brzinom dilatacije i znacaj individualnih razlika u brzini dilatacije za procenu endotelne funkcije. Metode. U ovu studiju bilo je ukljuceno 115 zdravih dobrovoljaca, 58 bez FR i 57 sa bar jednim FR. Vaskularnim ultrazvukom, merenjem precnika arterije na 10 s, od 0 do 240 s od izazivanja hiperemijskog stimulusa, odredjeni su vreme maksimalne dilatacije i realna vrednost FMD. Ispitana je korelacija vremena maksimalne dilatacije i prisutnih FR. Poredjenjem realne vrednosti FMD sa vrednoscu koja se izracunava pod pretpostavkom da dilatacija uvek nastaje u 60. s (FMD60), ispitan je znacaj individualnih razlika u brzini dilatacije. Rezultati. Srednje vreme maskimalne endotel-zavisne dilatacije bilo je 68 ? 20 s, opseg od 30 - 120 s. Dilatacija je nastajala brze (62 ? 17 s) i u kracem opsegu (30-100 s) kod osoba bez FR u odnosu na osobe sa FR (75 ? 21 s, opseg 40 - 120 s) (p < 0,001). Nadjena je znacajna korelacija izmedju brzine dilatacije i starosti, vrednosti lipidnih frakcija, pusenja, fizicke aktivnosti i C-reaktivnog proteina. Realna srednja vrednost FMD (6,7 ? 3,0%) bila je visa (p < 0,001) u odnosu na FMD60 (5,2 ? 3,5%), sto vazi i za osobe bez FR (8,4 ? 2,9% vs 7,2 ? 3,2%, p < 0,05), kao i one sa FR (4,9 ? 1,7% vs 3,1 ? 2,3%, p < 0,001). Zakljucak. Kod zdravih osoba sa umerenim kardiovaskularnim rizikom postoji vremenska heterogenost endotel-zavisne dilatacije, zavisna od FR, koja utice na tacnost FMD metode. Sekvencijalno merenje unutrasnjeg precnik arterije i odredjivanje realne vrednosti FMD omogucava precizniju procenu funkcije endotela.