Triglyseridit ateroskleroosin etiologiassa
Lisätietoa aiheesta
27.10.2020
- Plasman triglyseridit heijastavat aterogeenisten kylomikroniremnanttien, VLDL- (very-low-density lipoprotein) ja IDL- (intermediate-density lipoprotein) fraktioiden lipidimäärää «Krauss RM. Atherogenicity of triglyceride-rich lipoproteins. Am J Cardiol 1998;81:13B-17B »1, ja ennustavat itsenäisesti valtimotaudin vaaraa sekä paastotilanteessa että aterian jälkeen mitattuna «Sarwar N, Danesh J, Eiriksdottir G ym. Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies. Circulation 2007;115:45»2, «Hokanson JE, Austin MA. Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective»3, «Bansal S, Buring JE, Rifai N ym. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. JAMA 2007;298:309-16 »4, «Nordestgaard BG, Benn M, Schnohr P ym. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA 2007;298:299-308 »5. Myös geneettiset tutkimustulokset osoittavat triglyseridipitoisuutta suurentavien geenivarianttien lisäävän valtimotaudin vaaraa «Jørgensen AB, Frikke-Schmidt R, West AS ym. Genetically elevated non-fasting triglycerides and calculated remnant cholesterol as causal risk factors for myocardial infarction. Eur Heart J 2013;34:1826»6, «Do R, Willer CJ, Schmidt EM ym. Common variants associated with plasma triglycerides and risk for coronary artery disease. Nat Genet 2013;45:1345-52 »7.
- Valtimotautia sairastavista potilasta jopa neljäsosalla on suurentunut triglyseridipitoisuus tehokkaasta lipidilääkityksestä huolimatta. Tutkimuksen perusteella tehokkaan statiinihoidon aikana todettu plasman triglyseriditaso ≥ 4 mmol/l suurentaa valtimotaudin riskiä 52 % verrattuna joukkoon, jolla triglyseripitoisuus on < 1 mmol/l «Lawler PR, Kotrri G, Koh M ym. Real-world risk of cardiovascular outcomes associated with hypertriglyceridaemia among individuals with atherosclerotic cardiovascular disease and potential eligibility »13.
- Keskeinen aterogeenisyyden mekanismi näillä triglyseridirikkailla lipiproteiineilla on sama kuin LDL-partikkeleilla eli ne siirtyvät endoteelin läpi verisuonen intimaan, retentoituvat hepariinisulfaatti-glykoproteiinien välityksellä ja aikaansaavat vaahtosolujen muodostumisen kautta ateroomaplakin muodostumisen «Tabas I, Williams KJ, Borén J. Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications. Circulation 2007;116:1832-44 »8.
- Sen vuoksi esimerkiksi eurooppalaisessa hoitosuosituksissa «Catapano AL, Graham I, De Backer G ym. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. Eur Heart J 2016;37:2999-3058 »9 on käytetty ei-HDL-kolesterolipitoisuutta (kokonaiskolesteroli vähennettynä HDL-kolesterolilla) kuvaamaan kaikkien aterogeenisten, apoB:tä sisältävien lipoproteiinien määrää seerumissa «Krauss RM. Atherogenicity of triglyceride-rich lipoproteins. Am J Cardiol 1998;81:13B-17B »1. Ei-HDL-kolesterolin pitoisuus vastaa pääosin LDL-kolesteroliin pohjautuvaa riskinarviota tai jopa ylittää sen valtimotaudin ja kuolemanvaaran ennustajana «Emerging Risk Factors Collaboration., Di Angelantonio E, Gao P ym. Lipid-related markers and cardiovascular disease prediction. JAMA 2012;307:2499-506 »10, «Boekholdt SM, Arsenault BJ, Mora S ym. Association of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins: a meta-a»11, «Robinson JG, Wang S, Jacobson TA. Meta-analysis of comparison of effectiveness of lowering apolipoprotein B versus low-density lipoprotein cholesterol and nonhigh-density lipoprotein cholesterol for c»12. ApoB-pitoisuuden mittaamiseen verrattuna ei-HDL-kolesterolin määrittäminen ei tuo lisäkustannuksia.
- Ainoastaan suuret kylomikronipartikkelit eivät kokonsa vuoksi läpäise verisuonen endoteelia eivätkä siten ole aterogeenisiä.
Kirjallisuutta
- Krauss RM. Atherogenicity of triglyceride-rich lipoproteins. Am J Cardiol 1998;81:13B-17B «PMID: 9526808»PubMed
- Sarwar N, Danesh J, Eiriksdottir G ym. Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies. Circulation 2007;115:450-8 «PMID: 17190864»PubMed
- Hokanson JE, Austin MA. Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk 1996;3:213-9 «PMID: 8836866»PubMed
- Bansal S, Buring JE, Rifai N ym. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. JAMA 2007;298:309-16 «PMID: 17635891»PubMed
- Nordestgaard BG, Benn M, Schnohr P ym. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA 2007;298:299-308 «PMID: 17635890»PubMed
- Jørgensen AB, Frikke-Schmidt R, West AS ym. Genetically elevated non-fasting triglycerides and calculated remnant cholesterol as causal risk factors for myocardial infarction. Eur Heart J 2013;34:1826-33 «PMID: 23248205»PubMed
- Do R, Willer CJ, Schmidt EM ym. Common variants associated with plasma triglycerides and risk for coronary artery disease. Nat Genet 2013;45:1345-52 «PMID: 24097064»PubMed
- Tabas I, Williams KJ, Borén J. Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications. Circulation 2007;116:1832-44 «PMID: 17938300»PubMed
- Catapano AL, Graham I, De Backer G ym. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. Eur Heart J 2016;37:2999-3058 «PMID: 27567407»PubMed
- Emerging Risk Factors Collaboration., Di Angelantonio E, Gao P ym. Lipid-related markers and cardiovascular disease prediction. JAMA 2012;307:2499-506 «PMID: 22797450»PubMed
- Boekholdt SM, Arsenault BJ, Mora S ym. Association of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins: a meta-analysis. JAMA 2012;307:1302-9 «PMID: 22453571»PubMed
- Robinson JG, Wang S, Jacobson TA. Meta-analysis of comparison of effectiveness of lowering apolipoprotein B versus low-density lipoprotein cholesterol and nonhigh-density lipoprotein cholesterol for cardiovascular risk reduction in randomized trials. Am J Cardiol 2012;110:1468-76 «PMID: 22906895»PubMed
- Lawler PR, Kotrri G, Koh M ym. Real-world risk of cardiovascular outcomes associated with hypertriglyceridaemia among individuals with atherosclerotic cardiovascular disease and potential eligibility for emerging therapies. Eur Heart J 2020;41:86-94 «PMID: 31733058»PubMed