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RESEARCH PRODUCT
Lipoprotein(a) Genotype Influences the Clinical Diagnosis of Familial Hypercholesterolemia
Elena OlmastroniMarta GazzottiMaurizio AvernaMarcello ArcaPatrizia TarugiSebastiano CalandraStefano BertoliniAlberico L CatapanoManuela CasulaLaura D'erasmoAngelo Baldassare CefaluAndrea BartuliPaola Sabrina BuonuomoAndrea BensoGuglielmo BeccutiGiacomo BiasucciMaria Elena CapraGianni BioloPierandrea VinciLuca BonanniClaudio BorghiSergio D'addatoAntonio Carlo BossiGiancarla MeregalliAdriana BranchiPaolo CalabròFrancesca CarubbiFabio NascimbeniFrancesco CipolloneMarco BucciNadia CitroniMaria Del BenFrancesco BarattaMassimo FedericiMartina MontagnaClaudio FerriSerena NotargiacomoAnna Maria FiorenzaEmanuela ColomboGiuliana FortunatoMaria Donata Di TarantoAndrea GiaccariSimona MoffaFrancesco GiorginoSergio Di MolfettaOrnella GuardamagnaLuisa De SanctisArcangelo IannuzziRaimondo CavallaroGabriella IannuzzoMarco GentileLorenzo IughettiPatrizia BruzziSalvatore LiaAlessandro LupiGiuseppe MandraffinoArianna ToscanoRossella MarcucciMartina BerteottiLorenzo MaroniFabiana LocatelliTiziana MontalciniGiuliana MombelliSandro MuntoniDavide BalderaGianfranco ParatiAngelina PassaroValerio PecchioliCristina PederivaGiuseppe BanderaliAntonio PipoloDebora D'eliaMatteo PirroVanessa BianconiLivia PisciottaElena FormisanoFrancesco PurrelloRoberto ScicaliElena RepettiElena CantinoElisabetta RinaldiElena SaniRiccardo SarzaniFrancesco SpannellaFrancesco SbranaBeatrice Dal PinoPatrizia SuppressaVeronica CoccoChiara TrentiEmanuele Alberto NegriJosè Pablo WerbaAlessandra RomandiniSabina ZambonAlberto ZambonMaria Grazia ZentiGiulia FainelliFabio PellegattaLiliana GrigoreKatia BonomoEleonora CapattiAda CutoloFabio FimianiSimonetta GenovesiSandro InchiostroChiara PavanelloRoberta PujiaAlon Schaffersubject
cardiovascular risklipoprotein(a).familial hypercholesterolemiadescription
: Background Evidence suggests that LPA risk genotypes are a possible contributor to the clinical diagnosis of familial hypercholesterolemia (FH). This study aimed at determining the prevalence of LPA risk variants in adult individuals with FH enrolled in the Italian LIPIGEN (Lipid Transport Disorders Italian Genetic Network) study, with (FH/M+) or without (FH/M-) a causative genetic variant. Methods and Results An lp(a) [lipoprotein(a)] genetic score was calculated by summing the number risk-increasing alleles inherited at rs3798220 and rs10455872 variants. Overall, in the 4.6% of 1695 patients with clinically diagnosed FH, the phenotype was not explained by a monogenic or polygenic cause but by genotype associated with high lp(a) levels. Among 765 subjects with FH/M- and 930 subjects with FH/M+, 133 (17.4%) and 95 (10.2%) were characterized by 1 copy of either rs10455872 or rs3798220 or 2 copies of either rs10455872 or rs3798220 (lp(a) score ≥1). Subjects with FH/M- also had lower mean levels of pretreatment low-density lipoprotein cholesterol than individuals with FH/M+ (t test for difference in means between FH/M- and FH/M+ groups <0.0001); however, subjects with FH/M- and lp(a) score ≥1 had higher mean (SD) pretreatment low-density lipoprotein cholesterol levels (223.47 [50.40] mg/dL) compared with subjects with FH/M- and lp(a) score=0 (219.38 [54.54] mg/dL for), although not statistically significant. The adjustment of low-density lipoprotein cholesterol levels based on lp(a) concentration reduced from 68% to 42% the proportion of subjects with low-density lipoprotein cholesterol level ≥190 mg/dL (or from 68% to 50%, considering a more conservative formula). Conclusions Our study supports the importance of measuring lp(a) to perform the diagnosis of FH appropriately and to exclude that the observed phenotype is driven by elevated levels of lp(a) before performing the genetic test for FH.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2023-05-16 |