Plasma homocysteine levels are related to medium-term venous graft degeneration in coronary artery bypass graft patients

Add ess o co espondence: Emília Balogh, MD, Nyék u. 69., 4032 Deb ecen, Hunga y Ins i u e o Ca diology, Clinical Cen e, Uni e si y o Deb ecen, Deb ecen-Hunga y Phone: +00 36 30 6226822 Fax: +36 14576600 E-mail: balo[email p o ec ed] Accep ed Da e: 15.01.2016 A ailable Online Da e: ©Copy igh 2016 by Tu kish Socie y o Ca diology - A ailable online a www.ana oljca diol.com DOI:10.14744/Ana olJCa diol.2016.6738 UNCORRECTED PROOF O iginal In es iga ion Emília Balogh, Tamás Ma os*, And ea Da agó, Kálmán Csapó 1 , Béla He czegh 2 , Balázs Nyul 3 , Is án Czu iga, Zsuzsanna Be eczky**, Is án Édes, Zsol Kőszegi Ins i u e o Ca diology, *Depa men o Ca diac Su ge y,**Clinical Resea ch Cen e, Clinical Cen e, Uni e si y o Deb ecen, Deb ecen- Hunga y 1 Depa men o Ca diology, Bo sod Coun y Hospi al, Miskolc- Hunga y 2 Depa men o Ca diology, Géza He ényi Coun y Hospi al and Ou pa ien Cen e, Szolnok- Hunga y 3 Facul y o In o ma ics Uni e si y o Deb ecen, Deb ecen- Hunga y Plasma homocys eine le els a e ela ed o medium- e m enous g a degene a ion in co ona y a e y bypass g a pa ien s In oduc ion A e ial and enous condui s ha e been used o co ona y a e y bypass g a ing (CABG) o alle ia e se ious myoca dial ischemia. Saphenous enous g a s (SVGs) ha e been e i ied o ca y a highe isk o de eloping accele a ed g a disease in- duced by he edi a y, en i onmen al, o sys emic o local ac o s in complex in e ac ions (1, 2). I is known ha shea s ess and local blood low a ec g a pa ency (3). Despi e he imp o e- men o su gical echniques and expe iences, CABG s ill poses a challenge in seconda y ca dio ascula p e en ion. Holis ic isk s a i ica ion is o en unwo kable o incomple ely es ablished, o managing como bidi ies p o es ine ec i e (2). The aim o ou in es iga ion was o map he isk ac o s o ch onic SVG disease in ela ion o he indi idual—on bo h pe pa ien and pe g a basis. Ou in es iga ion ocused on homo- cys eine (Hcy), a sul u -con aining amino acid o med du ing he me abolism o me hionine. I s associa ion wi h a he oscle o ic lesions o na i e essels was published by McCully in he ea ly 1960s (4). In he las hal cen u y, se e al clinical and expe imen al s udies ha e cla i ied ha ele a ed blood Hcy le els a e ela ed o a he oscle o ic disease (5, 6). Howe e , ials in es iga ing he e ec o he lowe ing o Hcy le els yielded con o e sial esul s conce ning isk educ ion in ca dio ascula pa ien s (7, 8). Fu - he mo e, only e y limi ed da a a e a ailable ega ding he e ec o Hcy on medium- and long- e m enous g a pa ency (9, 10). Objec i e: Saphenous enous g a s (SVGs) a e es ablished choices o co ona y a e y bypass g a ing (CABG); howe e , hei lumen pa ency is limi ed. Ou goal was o in es iga e he isk ac o s o SVG degene a ion. Me hods: Se en y- i e pa ien s (mean age, 57.5±10.4 yea s) wi h 133 SVG condui s who had ca diac ca he e iza ion ≥1 yea a e CABG we e selec ed; ollow-up pe iod was 67.6±36.8 mon hs. Pa ien s we e di ided in o 3 g oups acco ding o angiog aphic s a us a ollow up [in ac : <20% (n=23); na owed: 20–99% (n=24); and occluded (n=28)]. Baseline clinical condi ions we e e alua ed in ela ion o ollow-up angiog aphy. As onse da e o ch onic o al occlusions is usually unce ain, hey a ise ypically om h ombo ic lesions; hus, hei alue in e alua ion is limi ed. Resul s: The e we e no signi ican di e ences be ween he 3 g oups in clinical pa ame e s. Linea co ela ion analysis ound signi ican (p<0.01) posi i e connec ion o SVG disease (luminal diame e educ ion 20–99%) wi h C- eac i e p o ein (CRP) and homocys eine (Hcy), as well as be ween CRP and Hcy. Mul iple eg ession analysis showed plasma Hcy le el o be signi ican ly ela ed o g a diame e educ ion no malized o ime elapsed un il angiog aphy in na owed g a s: 1 μmol/L inc ease o Hcy was associa ed wi h 0.053%/mon h dec ease in lumen diame e (p<0.01; R2=0.428); ex apola ing: +10 μmol/L highe Hcy le el du ing 5 yea s is associa ed wi h 32.1% lumen educ ion. Conclusion: Medium- o long- e m SVG degene a ion is ela ed o ele a ed plasma o al Hcy in pa ien s wi h sub-occlusi e g a s enosis, while in cases wi h in ac SVGs, he bene icial local low condi ions may p o ec he g a s om degene a ion. (Ana ol J Ca diol 2016; 16: 000-00) Keywo ds: homocys eine, saphenous ein g a disease ABSTRACT Balogh e al. Homocys eine and enous g a degene a ion Ana ol J Ca diol 2016; 16: 000-000 DOI:10.14744/Ana olJCa diol.2016.6738 Me hods The p esen s udy was based on e ospec i e da a col- lec ed om ou clinical da abase be ween 2001 and 2013. The scien i ic plan had p e iously been submi ed o and app o ed by he Ins i u ional E hics Commi ee. All de ails po en ially e- ealing he iden i y o he subjec s we e handled acco ding o he ICH GCP guidelines and au ho i y egula ions. Da a we e collec ed om 75 SVG ecipien s (aged ≥30 yea s) who had ≥1 ca diac ca he e iza ion because o symp oms o co ona y a e y disease (CAD) a leas 1 yea a e CABG. Pa ien s <1 yea a - e CABG we e excluded o a oid conside ing echnical ailu e Table 1. Pe iope a i e clinical cha ac e is ics o pa ien s in subg oups pe ollow-up s a us (n=75) Pe pa ien * Va iable In ac a Na owedb Occludedc P To al no. o pa ien s n=75; 23 24 28 – Age, yea s, (mean±SD) 59.4±10.2 53.5±8.8 59.1±10.1 NS Male, n, (%) 13 (56.5) 22 (91.7) 19 (67.8) NS Diabe es†, n, (%) 9 (39.1) 3 (12.5) 14 (50.0) NS Hype ension††, n, (%) 16 (69.5) 16 (66.7) 21 (75.0) NS Hype lipidemia‡, n, (%) 17 (73.9) 19 (79.2) 26 (92.8) NS Myoca dial in a c ion, n, (%) 14 (60.8) 15 (62.5) 20 (71.4) NS S oke, n, (%) 2 (8.7) 2 (8.3) 3 (10.7) NS Pe iphe al ascula disease, n, (%) 7 (30.4) 3 (12.5) 9 (32.1) NS Smoking#, n, (%) 3 (13.0) 5 (20.8) 7 (25.0) NS EF, (%, mean±SD) 52.6±9.5 48.6±10.0 48.0±10.7 NS Sys olic blood p essu e, mm Hg, (mean±SD) 136.1±16.8 136.7±14.9 133.8±13.0 NS Dias olic blood p essu e, mm Hg, (mean±SD) 80.9±12.5 83.1±10.8 79.6±5.9 NS C ea inine, μmol/L, mean±SD) 85.7±15.3 88.4±20.4 87.7±17.3 NS HDL, mmol/L, (mean±SD) 1.1±0.2 1.0±0.2 1.1±0.3 NS LDL, mmol/L, (mean±SD) 3.1±0.6 3.4±0.9 3.3±0.6 NS To al-choles e ol, mmol/L, (mean±SD) 5.1±0.7 5.3±1.0 5.4±0.8 NS TG, mmol/L, (mean±SD) 1.9±0.7 2.0±1.6 2.2±1.4 NS Lipop o ein(a), nmol/L, (mean±SD) 421.4±590.4 494.6±514.7 521.9±593.1 NS CRP, mg/L, (mean±SD) 5.1±4.7 5.5±5.0 4.5±3.6 NS Homocys eine, μmol/L, (mean±SD) 15.9±7.6 16.0±15.2 15.1±4.7 NS Fola e, nmol/L, (mean±SD) 13.9±7.6 11.0±4.3 12.2±3.6 NS Vi amin B12, pmol/L, (mean±SD) 232.6±129.0 251.1±111.2 248.2±103.4 NS Follow up ime, mon h, (mean±SD) 70.1±33.5 74,6±39.1 64.1±38.9 NS A ec ed g a s, n, (%) – – – NS o LAD 7 (30.4) 7 (29.2) 8 (28.6) NS o CX 9 (39.2) 16 (66.6) 14 (50.0) NS o RCA 7 (30.4) 1 (4.2) 6 (21.4) NS Indica ion o pos CABG co ona y angiog aphy – – – NS S able angina, n, (%) 15 (65.2) 15 (62.5) 20 (71.5) NS Uns able angina, n, (%) 4 (17.4) 8 (33.3) 5 (17.8) NS Acu e co ona y synd ome, n, (%) 1 (4.3) 1 (4.2) 0 (0.0) NS O he s, n, (%) 3 (13.0) 0 (0.0) 3 (10.7) NS *Ranking: pa ien s wi h >1 SVG we e classi ied acco ding o hei mos se e e g a ’s s a us. De ini ions: In ac : <20% SVG lumen diame e educ ion; Na owed: Be ween 20% and 99% SVG lumen diame e educ ion; and Occluded: SVG wi h closed lumen. CABG - co ona y a e y bypass g a ing; Chol - choles e ol; CRP-C - eac i e p o ein; CX - ci cum lex co o- na y a e y; EF - ejec ion ac ion; Hcy - homocys eine; HDL - high-densi y lipop o ein; LAD - le an e io descending co ona y a e y; LDL - low-densi y lipop o ein; NS - no signi ican ; RCA - igh co ona y a e y; SVG - saphenous enous g a ; TG - iglyce ide and p ema u e h ombosis as a di e en mani es a ion o SVG disease. Pa ien s wi h enal dys unc ion (se um c ea inine >160 μmol/L), known his o y o diabe ic ke oacidosis, le en icula ejec ion ac ion ≤35%, o in e ened SVGs we e also excluded. The ollowing pe i-CABG clinical pa ame e s we e collec ed: demog aphic cha ac e is ics; medical his o y (e.g., onse o CAD, p e ious MI, s oke) and his o y o ca dio ascula isk ac o s (e.g., hype ension, diabe es, hype lipidemia); smoking his o y and smoking s a us; CAD- ela ed d ug he apy; sys olic and dia- s olic blood p essu e; le en icula ejec ion ac ion (EF); and le els o plasma Hcy, LDL-choles e ol, HDL-choles e ol, o al choles e ol, iglyce ides, apo-AI, apo-B, c ea inine, high-sensi- i i y C- eac i e p o ein, ola e, and i amin B12. Blood pa am- e e s we e de e mined by s anda d labo a o y echniques us- ing alida ed me hods. As ega ds CABG, he numbe o enous condui s, loca ion, hos co ona y pa ame e s, p e ious co ona y in e en ions, and da a o epea ca diac ca he e iza ion we e documen ed. Co ona y angiog aphies we e pe o med using he s anda d echnique acco ding o he accep ed guidelines wi h Philips In eg is X- ay equipmen (In u is Sui e Viewe Li e 1.0; Philips, The Ne he lands). Baseline SVG s a us a CABG was deemed as in ac . Follow-up co ona y angiog ams we e indica ed in he case o clinical symp oms. The diagnosis o SVG disease was based on independen judgemen o epea co ona y angiog a- phies by 2 expe ca diologis s; SVGs we e classi ied acco d- ing o hei lumen s a us (diame e s enosis; %) a epea co o- na y angiog aphy. By excluding co ona y angiog aphies wi hin 12 mon hs a e CABG, i was possible o clea ly dis inguish echnical ailu e o p ema u e h ombosis caused sho - e m SVG degene a ions. Ou app oach ensu ed ime p opo ional e alua ion o g a s by no malizing he change o diame e ac- co ding o he ime elapsed du ing ollow-up. In his way, he selec ion bias could no a ec he obse ed ela ions and e- lec ed he “ eal-li e” complexi y o g a degene a ion whe e he same pa hophysiological condi ions may esul in di e en mani es a ions o SVG disease in di e en g a s o he same pa ien . G a s we e g aded as in ac wi h a <20% lumen diam- e e educ ion simila o la ge ascula ials (11, 12); na owed, be ween 20% and 99%; o occluded (closed lumen). Based on p e ious obse a ions ha ch onic occlusions o en a ise om h ombo ic lesions (13, 14) wi h unde ined onse da e, occluded SVGs we e no used o compa ison. SVG condui s we e e alua ed bo h pe pa ien and pe g a le el. Pa ien s ha ing >1 SVG wi h di e en luminal diame e s a us a ollow-up we e g aded acco ding o he mo e se e e Balogh e al. Homocys eine and enous g a degene a ion Ana ol J Ca diol 2016; 16: 000-000 DOI:10.14744/Ana olJCa diol.2016.6738 Table 2. Rela ionship o known o po en ial isk ac o s o SVG disease in “in ac ” and “na owed” SVG pa ien g oup (n=47) SVG na owing (%)/mon h Age C ea inine HDL LDL TG CRP Hcy Folic acid Vi B12 EF SVG na owing (%)/mon h Age 0.148 0.320 C ea inine 0.231 -0.017 0.118 0.907 HDL 0.252 -0.082 -0.009 0.091 0.586 0.951 LDL -0.028 -0.053 0.098 -0.157 0.850 0.721 0.514 0.297 TG -0.002 -0.132 0.091 -0.336* -0.092 0.989 0.377 0.543 0.022 0.538 CRP 0.483** 0.122 0.159 0.002 0.214 0.036 0.0001 0.437 0.310 0.988 0.168 0.816 Hcy 0.752** 0.248 0.268 0.248 -0.092 0.015 0.509** 0.0001 0.093 0.068 0.096 0.539 0.923 0.0001 Folic acid -0.052 -0.117 0.166 0.188 -0.187 -0.205 -0.109 -0.012 0.730 0.438 0.270 0.216 0.213 0.171 0.492 0.935 Vi B12 -0.254 -0.235 -0.074 0.083 -0.191 -0.128 -0.167 -0.253 0.443** 0.730 0.117 0.627 0.586 0.204 0.398 0.289 0.090 0.0002 EF -0.055 0.134 -0.279 0.073 -0.163 -0.056 -0.048 0.020 -0.075 -0.70 0.713 0.371 0.057 0.628 0.273 0.709 0.762 0.895 0.621 0.645 Me hod o analysis: Pea son co ela ion analysis. The - alue is shown abo e; P- alue is shown below in he cells. Signi icance is ma ked by bold le e and as e isk (*): *P<0.05; **P<0.01. SVGs we e classi ied as acco ding o hei luminal diame e s a us a epea co ona y angiog aphy as in ac wi h ≤20% and na owed wi h a luminal diame e na owing be- ween >20% and 99%. CRP-C - eac i e p o ein; EF - ejec ion ac ion; Hcy - homocys eine; HDL - high-densi y lipop o ein; LDL - low-densi y lipop o ein; SVG - saphenous enous g a ; TG - iglyce ide; i B12 - i amin B12 Balogh e al. Homocys eine and enous g a degene a ion Ana ol J Ca diol 2016; 16: 000-000 DOI:10.14744/Ana olJCa diol.2016.6738 g a ’s s a us classi ying hem in o 1 o he 3 abo e-men ioned pa ien g oups, and absolu e alues o luminal diame e educ- ion we e a e aged. Condui s wi h any kind o in e en ion we e excluded. We complemen ed e alua ion a pe g a le el as well. This way, by ha ing an inc eased i em o da a abou SVGs, s onge con idence o he s a is ical analysis was achie ed. Ca ego ical a iables a e epo ed as pe cen ages, while con inuous a iables a e epo ed as mean±s anda d de ia ion (SD). The Kolmogo o –Smi no es was used o es he no - mali y o pa ame e s. The equali y o da a o pa ien g oups was es ed by analysis o a iance (ANOVA). The e ec o ele a ed Hcy on he isk o SVG degene a ion was analyzed by s epwise o wa d linea eg ession analysis, wi h a p alue signi icance le el o <0.05. Analyses we e pe o med using he S a is ical Package o he Social Sciences (IBM SPSS S a is ics so wa e 20.0.0), USA. Resul s Mean ollow up ime was ≥5 yea s (67.6±36.8 mon hs). The elapsed ime un il ollow-up co ona y angiog aphy did no di e be ween he 3 g oups. Clinical cha ac e is ics and labo a o y indings ega ding di e en pa ien g oups a e lis ed in Table 1. Mean pa ien age was 57.5±10.4 yea s, eason o pos -CABG epea co ona y angiog aphy was p ima ily s able angina, and mo e han wo- hi ds o pa ien s showed ascula signs o SVG disease (s enosis/occlusion). Demog aphics, medical his o y, indica ion o epea co ona y angiog aphy, clinical pa ame e s, and isk ac o s did no di e signi ican ly be ween he g oups acco ding o ANOVA. The po en ial connec ion among clinical and angiog aphy pa ame e s we e e alua ed in in ac and na owed g oups by uni a ia e co ela ion analysis (Table 2). A signi ican posi i e co ela ion was ound be ween he ollowing pa ame e s: CRP and SVG disease (luminal diame e educ ion; %/mon h; p<0.01), Hcy and SVG disease (p<0.01), CRP and Hcy (p<0.01), as well as i amin B12 and olic acid (p<0.01); while a signi ican (p<0.05) bu nega i e co ela ion was seen be ween iglyce ides and HDL- choles e ol. As pa ien s wi h enal ailu e we e no included, ele a ed c ea inine alues (>160 mmol/L) could be excluded as con ounde s o inc eased Hcy le els. By s epwise o wa d mul i a ia e linea eg ession analysis (Table 3, Fig. 1), only Hcy was associa ed independen ly and sig- ni ican ly wi h SVG disease; a 1 μmol/L inc ease in Hcy le el was associa ed wi h a 0.053% inc ease in lumen diame e educ ion/ mon h (R2=0.428; p<0.01), based on he co esponding pa ien co ona y angiog ams. Theo e ically, his means ha +10 μmol/L inc ease o Hcy le el could be esponsible o +32.1% luminal e- duc ion in SVG wi hin 5 yea s. A ep esen a i e case o a CABG pa ien wi h enous g a degene a ion is shown in Figu e 2 (a-c). Discussion In his s udy, he pa ency a e was obse ed h oughou he 5.6-yea ollow-up o be 74.4%, which was simila o p e iously published esul s bu highe han ha epo ed by Sabik (15) (65%) and less han ha eco ded by Haywa d (16) (86%) and Collins (17) (86.4%). Ha is (18) has ound an associa ion be ween plas- ma Hcy and LDL le els in 77 CAD pa ien s 2 yea s a e CABG. Ou esul s could no con i m his, al hough we highligh he po- en ial ole o ce ain ac o s in medium- e m SVG degene a ion in con as wi h sho - e m g a occlusions. Ou esul s o lipid pa ame e s we e in line wi h p e ious clinical obse a ions ha a ema kable p opo ion o high- isk CAD pa ien s do no achie e hei he apeu ic goals (19). Despi e he ac ha ou pa ien pop- ula ion ecei ed s anda d s a in he apy, he o al-choles e ol le els did no di e signi ican ly be ween pa ien g oups. S a in ea men may slow down he a he oscle o ic p ocess in SVGs independen ly om he achie ed o al-choles e ol le el, which can be explained by he pleio opic e ec o s a ins (20). Table 3. P edic o s o SVG p og ession (dependen a iable) in na owed g a g oup (n=37) Va iable Coe icien P Age 0.036 0.813 LDL 0.250 0.073 HDL 0.066 0.686 Tg 0.027 0.851 Chol 0.206 0.138 C ea inine 0.158 0.276 EF -0.157 0.272 CRP 0.098 0.537 HCy 0.053 p<0.01 Vi B12 0.075 0.632 R2=0.428; Adjus ed R2=0.409 Me hod: mul iple eg ession analysis; R2=0.428; Adjus ed R2=0.409; P og ession=SVG diame e lumen educ ion (%) a ollow-up pe elapsed ime (mon hs). SVG was classi ied as na owed showing 20–99% lumen diame e educ ion a ollow-up; Chol - choles e in; CRP - c- eac i e p o ein; EF - ejec ion ac ion; Hcy - homocys eine; HDL - high-densi y lipop o ein; LDL - low-densi y lipop o ein; SVG - saphenous enous g a ; Tg - iglyce ide; i B12 - i amin B12 SVG p og ession (%/mon h) 6.00 5.00 4.00 3.00 2.00 1.00 .00.00 20.00 40.00 60.00 80.00 100.00 Hcys (μmol/L) Figu e 1. ??????????????????????????????????????????????????????? Linea Obse ed I is o be no ed ha he lack o gene al olic acid/ i amin B supplemen a ion in g ain p oduc s o ca dio ascula p e en ion in Hunga y can be a po en ial cause o he ela i ely ele a ed plasma Hcy and low olic acid and i amin B12 le els in he s udy popula ion. Resul s o he uni a ia e co ela ion analysis sug- ges ed a co ela ion be ween CRP and he ime p opo ional ex en o SVG disease ( =0.483; p<0.01) as well as be ween CRP and Hcy ( =0.509; p<0.01) in SVG disease. The CRP–Hcy connec- ion has been ecen ly in es iga ed in an animal model by Pang e al. (21). They ound ha Hcy can ini ia e an in lamma o y e- sponse by s imula ing CRP p oduc ion. In line wi h ou indings, human and expe imen al da a we e published abou he ole o CRP in he in he pa hogenesis o SVG disease (22, 23). Howe e , o he esul s o Aue (24) o F iso and colleagues (25) in CAD pa ien s did no ind associa ion be ween he ele a ed hs-CRP le el and o al plasma Hcy. Ou conclusion was simila o Shammas’s (26) obse a ions in 77 pa ien s a e 2 yea s ha plasma Hcy is an independen p ognos ic ac o o medium- e m pos -CABG g a degene a- ion. Among he known isk ac o s o CAD, clinical and expe i- men al s udies ha e con i med a posi i e impac o Hcy on CAD (6, 27), bu only ew on SVG degene a ion (26). Con a y o Rodi- ono ’s (28) obse a ion ha Hcy is only a bys ande in CAD, ou esul s suppo he opinion ha Hcy plays an ac i e ole in SVG p og ession. Gi elli e al. (29) obse ed simila esul s in 350 CAD pa ien s a e a mean ollow-up o 4.8 yea s; Hcy was an impo - an and independen p ognos ic ac o o mo ali y a e CABG. Fu he mo e, as ing Hcy le el co ela ed posi i ely wi h CRP. I was p e iously published by esea che s, e.g., by Chong e al (3) ha shea s ess in essels induces compensa o y mechanisms in endo helial cells, hus causing local asodila o y elease o ni ic oxide and p os aglandins and inhibi ion o cons ic ing ac- o s (e.g., endo helin). This can bene icially a ec neu ophil ad- hesion and smoo h muscle cell p oli e a ion. S udy limi a ions Limi a ions o he s udy include i s e ospec i e and obse a- ional na u e. Ideally, he ques ion o how sys emic and local isk ac o s (e.g., Hcy) a ec medium- and long- e m SVG p og es- sion should be add essed op imally in p ospec i e andomized ials. The numbe o pa ien s en olled in his s udy was ela i ely low. We acknowledge ha lack o baseline SVG angiog aphy is a majo limi a ion o his s udy. S a us was eco ded by co ona y angiog aphy, bu he easonable assump ion was made ha he g a s we e in ac a he ime o CABG. Repea co ona y angio- g ams we e indica ed by clinical symp oms; he e o e, he e- quency o SVG disease migh ha e been o e es ima ed as com- pa ed o p ospec i e angiog aphy s udies. Whe e a single pa ien had ≥2 SVG condui s wi h di e en lumen s a us a ollow-up, hey we e anked acco ding o he mo e se e e g a ’s s a us o classi ica ion in o he g oup wi h in ac o na owed o occluded SVG g a s. Ou pe pa ien ap- p oach equi ed he a e aging o he s enosis o he g a s in he na owed g oup. Exclusion o ollow-up co ona y angiog aphies wi hin 12 mon hs pos -CABG educed he s udy popula ion bu allowed he di e en ia ion be ween sho - e m and ch onic SVG disease de elopmen . The possibili y o esidual con ounding ac o s in mani es a ion is p esumable. Conclusion This s udy e ealed u he de ails ega ding ac o s o g a disease in CABG pa ien s. The long- e m SVG degene a ion shows co ela ion wi h he ele a ed plasma o al Hcy in pa ien s wi h sub-occlusi e g a s enosis, while in cases wi h in ac SVGs, he bene icial local low condi ions may p o ec he g a s om degene a ion. The eby in ensi y o elemen s can change by indi iduals making assessmen o hei eal in ol emen di icul . Balogh e al. Homocys eine and enous g a degene a ion Ana ol J Ca diol 2016; 16: 000-000 DOI:10.14744/Ana olJCa diol.2016.6738 Figu e 2. ??????????????????????????????????????????????????????? ??????????????????????????????????????????????????????? a b c Balogh e al. Homocys eine and enous g a degene a ion Ana ol J Ca diol 2016; 16: 000-000 DOI:10.14744/Ana olJCa diol.2016.6738 Ele a ed plasma o al Hcy le el should dese e a en ion in SVG pa ien s ega ding medium- e m p og ession as Hcy seems o be associa ed wi h ch onic SVG s enosis. Ou da a can be a p omo - e o u he esea ch o op imize p e en ion. We conclude ha wide-scope isk managemen is an impo an objec i e o CABG pa ien s o long- e m success o hei su gical ea men in CAD. Con lic o in e es : None decla ed. Pee - e iew: Ex e nally pee - e iewed. 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PLoS ONE 2006; 1: e83. Balogh e al. Homocys eine and enous g a degene a ion Ana ol J Ca diol 2016; 16: 000-000 DOI:10.14744/Ana olJCa diol.2016.6738