Lipoprotein(a) kao misteriozni čimbenik kardiovaskularne bolesti

master's thesis

• Title (english): Lipoprotein(a) as a Mysterious Factor for Cardiovascular Disease
• Author: Matko Zelić
• Mentor: Ivan Pećin (mentor)
• Committee member: Tina Dušek (predsjednik povjerenstva)
• Committee member: Boško Skorić (član povjerenstva)
• Committee member: Ivan Pećin (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2024-07-12, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine

Abstract

Lipoprotein(a) je molekula slična LDL-u, za koju je specifičan dodatak glikoproteina apolipoproteina(a). Apo(a) vrlo je polimorfan glikoprotein te interindividualne razlike u molekularnoj masi njegovih izoformi, koje su posljedica genske varijabilnosti na LPA lokusu, uvjetuju veliku varijabilnost serumske koncentracije Lp(a). Serumska je koncentracija Lp(a), stoga, pretežno (>90%) genski uvjetovana. Kauzalna veza između visoke serumske koncentracije Lp(a) i aterosklerotske kardiovaskularne bolesti te stenoze aortalne valvule dobro je utvrđena obiljem genskih dokaza. Iako se nekoć tako smatralo, danas znamo da Lp(a) nije čimbenik rizika za vensku tromboemboliju. Prema sadašnjim definicijama, oko 20% opće populacije ima visoku koncentraciju Lp(a) i za te ljude on predstavlja veoma značajan čimbenik rizika. Mjerenje serumske koncentracije Lp(a) preporučuje se učiniti barem jednom u životu, po mogućnosti prilikom izrade prvog lipidograma. Budući da je koncentracija Lp(a) poprilično stabilna tijekom cijelog odraslog života, u odsustvu specifičnih terapija za snižavanje njegove koncentracije ponovna mjerenja nisu potrebna. Kod pojedinaca s visokom koncentracijom Lp(a) preporučuje se inkorporirati ga u procjenu ukupnog rizika te u skladu s time kontrolirati druge čimbenike rizika. Iako trenutno nema odobrene specifične terapije za snižavanje koncentracije Lp(a), u razvoju je više lijekova koji pokazuju vrlo obećavajuće rezultate. Od toga su za dva nova lijeka u tijeku studije faze 3, koje proučavaju njihov učinak na kardiovaskularni rizik u pojedinaca s visokom koncentracijom Lp(a).

Abstract (english)

Lipoprotein(a) is an LDL-like molecule that contains a specific glicoprotein moiety apolipoprotein(a). Apo(a) is a very polymorphic glicoprotein and the interindividual differences in the molecular mass of its isoforms, which are themselves a consequence of genetic variability of the LPA locus, are the cause of high variability of Lp(a) serum concentration. The serum concentration of Lp(a) is, therefore, mainly (>90%) genetically determined. The causal association between high Lp(a) serum concentration and atherosclerotic cardiovascular disease and aortic valve stenosis is well established with abundant genetic evidence. Although it was once considered so, today we know that Lp(a) is not a risk factor for venous thromboembolism. According to current definitions, around 20% of the general population has a high Lp(a) concentration and for those people that is a highly significant risk factor. Measurement of serum Lp(a) concentration is recommended to be performed at least once in a lifetime, preferably alongside the first lipid profile. Considering that Lp(a) concentration is quite stable during the course of adult life, in the absence of specific Lp(a)-lowering therapy repeat measurements are not necessary. In individuals with high Lp(a) concentration it is recommmended that Lp(a) be incorporated into overall risk estimation and that other risk factors be managed accordingly. Although currently there are no approved specific Lp(a)-lowering therapies, several drugs are now being developed with very promising results. Of those, phase 3 trials are ongoing for two new drugs and they are studying their effect on cardiovascular risk in individuals with high Lp(a) concentrations.

• Keywords: lipoprotein(a); apolipoprotein(a); aterosklerotska kardiovaskularna bolest; stenoza aortalne valvule; kardiovaskularni rizik
• Keywords (english): lipoprotein(a); apolipoprotein(a); atherosclerotic cardiovascular disease; aortic valve stenosis; cardiovascular risk
• Language: croatian
• URN:NBN: urn:nbn:hr:105:235454
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-06-25 10:41:00