Factor analysis and association of lipid, inflammatory, cardiac and renal biomarkers with creactive protein in cardiovascular risk categorization

Beograd : [S. Ž. Jovičić]

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Medicinske nauke - farmacija - Medicinska biohemija / Medical sciences - Pharmacy - Medical biochemistry

U kliničkoj praksi koristi se nekoliko skorova za procenu rizika od pojave različitih oblika kardiovaskularnih bolesti (KVB) koji se zasnivaju na multivarijabilnim regresionim jednačinama izvedenim iz rezultata praćenja različitih kohortnih grupa. Na osnovu prisustva tradicionalnih faktora rizika [hiperholesterolemija, hipertenzija, pol, starost, porodična istorija KVB, dijabetes i pušenje] definisanim algoritmima se izračunava apsolutni 10-godišnji rizik za koronarnu bolest srca (KBS) na osnovu Framingamskog rizik skora (FRS), 10-godišnji rizik od svih oblika KVB – tzv. „globalni KVB rizik“ (globalni FRS), kao i dugoročni (30-godišnji) rizik za KVB. Ateroskleroza je bolest uslovljena brojnim faktorima koju prati hronična inflamacija niskog intenziteta i dislipidemija. Zahvaljujući velikom broju postojećih dokaza da C-reaktivni protein (CRP) snažno i nezavisno predviđa pojavu kardiovaskularnih komplikacija, primena CRP-a u kliničkoj praksi definisana je od strane nekoliko organizacija. Za proces ateroskleroze karakteristična je hronična inflamacija gde su koncentracije CRP-a u cirkulaciji niže od granice detekcije konvencionalnih testova. Određivanje tako niskih nivoa CRP-a zahteva testove sa većom analitičkom osetljivošću, koji se označavaju kao visoko osetljivi (highsensitivity, hs), a na ovaj način određena koncentracija CRP-a kao „visoko osetljivi CRP“ (hsCRP). Takođe, postoje podaci i o drugim faktorima koji doprinose održavanju inflamacije ili odražavaju intenzitet aterosklerotskih procesa i koji bi mogli da identifikuju doprinos kardiovaskularnom riziku koji ne potiče od tradicionalnih faktora rizika, kao što su mokraćna kiselina, jačina glomerularne filtracije procenjena na osnovu koncentracije kreatinina ili cistatina C (eGFR), amino-terminalni pro-natriuretički peptid 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 biomarkera inflamacije [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), procenjena jačina glomerularne filtracije (eGFR)] i srčane funkcije (NT-proBNP, cTnT), koji bi mogli da unaprede procenu kardiovaskularnog rizika u primarnoj prevenciji. Ispitane su i analitičke karakteristike i klinička efikasnost metode visoke osetljivosti koja se koristila za određivanje hsCRP-a. Faktorskom analizom ispitana je priroda uticaja svakog pojedinačnog biomarkera na kardiovaskularni rizik i eventualna povezanost sa vrednostima hsCRP-a, grupisanje ispitivanih biomarkera povezanih sa aterosklerozom i inflamacijom slabog intenziteta, kao i povezanost dobijenih faktora sa vrednostima hsCRP, kategorizacijom 10-godišnjeg rizika na osnovu FRS i globalnog FRS, kao i sa klasifikacijom 30-godišnjeg rizika...

Several risk score algorithms for cardiovascular risk assessment based on multivariable regression equations derived from different cohorts are being used in clinical 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 in general – „global CVD risk“ using global FRS, and long term (30-year) CVD risk are being calculated. Atherosclerosis is a disease conditioned with multiple factors followed by chronic low-grade inflammation and dyslipidemia. Thanks to substantial evidence that C-reactive protein (CRP) strongly and independently predicts cardiovascular complications, the use of CRP in clinical practice is recommended by several institutions. Atherosclerosis process is characterized with chronic inflammation where circulating CRP concentrations are lower than limit of detection of conventional assays. For measuring such low CRP levels high-sensitivity (hsCRP) assays have been developed. Also, there are evidence of other factors, contributing to and maintaining the intensity of atherosclerotic processes, which might identify cardiovascular risk contribution not originated from traditional risk factors. These are uric acid, estimated glomerular 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 between hsCRP, as the established marker of proaterogenic metabolic state, and other biomarkers of 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), estimated glomerular filtration rate (eGFR)] and cardiac function (NT-proBNP, cTnT), which might promote cardiovascular risk assessment in primary prevention. The analytical performance and clinical efficacy of high sensitivity method used for CRP determination were also evaluated. Using factor analysis, the nature of influence of every single examined biomarker on cardiovascular risk and their possible connection to hsCRP values, also clustering of examined biomarkers associated with atherosclerosis and low-grade inflammation, as well as relations of identified factors with hsCRP values, 10-year risk categorization based on FRS and global FRS, and 30-year risk classification, were analyzed. The examined population were 242 healthy volunteers, 100 men and 142 women, 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 any oral contraceptives, were obtained through questionnaire. Blood pressure was measured prior to venipuncture...

kardiovaskularna bolest, kardiovaskularni rizik, Framingamski rizik skor, C-reaktivni protein, inflamacija, lipidni status, bubrežna funkcija, srčani biomarkeri, faktorska analiza

cardiovascular disease, cardiovascular risk, Framingham risk score, Creactive protein, inflammation, lipid status, renal function, cardiac biomarkers, factor analysis

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