Faktorska analiza i povezanost lipidnih, inflamatornih, srčanih i bubrežnih biomarkera sa C-reaktivnim proteinom u kategorizaciji kardiovaskularnog rizika

Abstract

U kliničkoj praksi koristi se nekoliko skorova za procenu rizika od pojaverazličitih oblika kardiovaskularnih bolesti (KVB) koji se zasnivaju na multivarijabilnimregresionim jednačinama izvedenim iz rezultata praćenja različitih kohortnih grupa. Naosnovu prisustva tradicionalnih faktora rizika [hiperholesterolemija, hipertenzija, pol,starost, porodična istorija KVB, dijabetes i pušenje] definisanim algoritmima seizračunava apsolutni 10-godišnji rizik za koronarnu bolest srca (KBS) na osnovuFramingamskog rizik skora (FRS), 10-godišnji rizik od svih oblika KVB – tzv. „globalniKVB rizik“ (globalni FRS), kao i dugoročni (30-godišnji) rizik za KVB.Ateroskleroza je bolest uslovljena brojnim faktorima koju prati hroničnainflamacija niskog intenziteta i dislipidemija. Zahvaljujući velikom broju postojećihdokaza da C-reaktivni protein (CRP) snažno i nezavisno predviđa pojavukardiovaskularnih komplikacija, primena CRP-a u kliničkoj praksi definisana je odstrane nekoliko organizacija. Za proces ateroskleroze karakteristična je hroničnainflamacija gde su koncentracije CRP-a u cirkulaciji niže od granice detekcijekonvencionalnih testova. Određivanje tako niskih nivoa CRP-a zahteva testove savećom analitičkom osetljivošću, koji se označavaju kao visoko osetljivi (highsensitivity,hs), a na ovaj način određena koncentracija CRP-a kao „visoko osetljiviCRP“ (hsCRP). Takođe, postoje podaci i o drugim faktorima koji doprinose održavanjuinflamacije ili odražavaju intenzitet aterosklerotskih procesa i koji bi mogli daidentifikuju doprinos kardiovaskularnom riziku koji ne potiče od tradicionalnih faktorarizika, kao što su mokraćna kiselina, jačina glomerularne filtracije procenjena na osnovukoncentracije kreatinina ili cistatina C (eGFR), amino-terminalni pro-natriuretičkipeptid tipa B (NT-proBNP), srčani troponin (cTn).Cilj rada bio je da se ispita da li postoji povezanost između hsCRP-a,ustanovljenog biomarkera proaterogenog metaboličkog stanja, i drugih biomarkerainflamacije [serumski amiloid A (SAA), fibrinogen, α1-kiseli glikoprotein (A1AGP),haptoglobin, C3 i C4 komponente komplementa), metabolizma lipida [ukupan, HDL,non-HDL i LDL holesterol, trigliceridi, apolipoprotein A-I (apo A-I), apolipoprotein B(apo B), lipoprotein (a) (Lp(a))], bubrežne [kreatinin, cistatin C (Cys-C), procenjenajačina glomerularne filtracije (eGFR)] i srčane funkcije (NT-proBNP, cTnT), koji bimogli da unaprede procenu kardiovaskularnog rizika u primarnoj prevenciji. Ispitane sui analitičke karakteristike i klinička efikasnost metode visoke osetljivosti koja sekoristila za određivanje hsCRP-a. Faktorskom analizom ispitana je priroda uticajasvakog pojedinačnog biomarkera na kardiovaskularni rizik i eventualna povezanost savrednostima hsCRP-a, grupisanje ispitivanih biomarkera povezanih sa aterosklerozom iinflamacijom slabog intenziteta, kao i povezanost dobijenih faktora sa vrednostimahsCRP, kategorizacijom 10-godišnjeg rizika na osnovu FRS i globalnog FRS, kao i saklasifikacijom 30-godišnjeg rizika...

Several risk score algorithms for cardiovascular risk assessment based onmultivariable regression equations derived from different cohorts are being used inclinical practice. According to presence of traditional risk factors [hypercholesterolemia,hypertension, gender, age, family history of premature cardiovascular disease (CVD),diabetes and cigarette smoking], absolute 10-year risk for coronary heart disease (CHD)according to Framingham risk score (FRS), 10-year risk for cardiovascular disease ingeneral – „global CVD risk“ using global FRS, and long term (30-year) CVD risk arebeing calculated.Atherosclerosis is a disease conditioned with multiple factors followed bychronic low-grade inflammation and dyslipidemia. Thanks to substantial evidence thatC-reactive protein (CRP) strongly and independently predicts cardiovascularcomplications, the use of CRP in clinical practice is recommended by severalinstitutions. Atherosclerosis process is characterized with chronic inflammation wherecirculating CRP concentrations are lower than limit of detection of conventional assays.For measuring such low CRP levels high-sensitivity (hsCRP) assays have beendeveloped. Also, there are evidence of other factors, contributing to and maintaining theintensity of atherosclerotic processes, which might identify cardiovascular riskcontribution not originated from traditional risk factors. These are uric acid, estimatedglomerular filtration rate (eGFR) based on creatinine or cystatin C, amino-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac troponin (cTn).The aim of this study was to examine whether there is association betweenhsCRP, as the established marker of proaterogenic metabolic state, and other biomarkersof inflammation [serum amyloid A (SAA), fibrinogen, α1-acid glycoprotein (A1AGP),haptoglobin, C3 and C4 complement components), lipid metabolism [total, HDL, non-HDL and LDL cholesterol, triglycerides, apolipoprotein A-I (apo A-I), apolipoprotein B(apo B), lipoprotein (a) (Lp(a))], renal [creatinine, cystatin C (Cys-S), estimatedglomerular filtration rate (eGFR)] and cardiac function (NT-proBNP, cTnT), whichmight promote cardiovascular risk assessment in primary prevention. The analyticalperformance and clinical efficacy of high sensitivity method used for CRPdetermination were also evaluated. Using factor analysis, the nature of influence ofevery single examined biomarker on cardiovascular risk and their possible connection tohsCRP values, also clustering of examined biomarkers associated with atherosclerosisand low-grade inflammation, as well as relations of identified factors with hsCRPvalues, 10-year risk categorization based on FRS and global FRS, and 30-year riskclassification, were analyzed.The examined population were 242 healthy volunteers, 100 men and 142women, 20–80 years old. They were free of diabetes mellitus and of any known cardiac,renal, hepatic and rheumatic disease, and were not taking any prescribed medication.Information about their age, smoking habits, body weight and height, physical activity, family history of CVD, aspirin intake and, in case of women, if they were taking anyoral contraceptives, were obtained through questionnaire. Blood pressure was measuredprior to venipuncture...