title: Lipoprotein (a) levels and apolipoprotein (a) isoform size in patients with subclinical hypothyroidism: effect of treatment with levothyroxine.
abstract: The increased risk for ischemic heart disease (IHD) associated with subclinical hypothyroidism (SH) has been partly attributed to dyslipidemia. There is limited information on the effect of SH on lipoprotein (a) [Lp(a)], which is considered a significant predictor of IHD. Serum Lp(a) levels are predominantly regulated by apolipoprotein [apo(a)] gene polymorphisms. The aim of our study was to evaluate the Lp(a) levels and apo(a) phenotypes in patients with SH compared to healthy controls as well as the influence of levothyroxine substitution therapy on Lp(a) values in relation to the apo(a) isoform size. Lp(a) levels were measured in 69 patients with SH before and after restoration of a euthyroid state and in 83 age- and gender-matched healthy controls. Apo(a) isoform size was determined by sodium dodecyl sulfate (SDS) agarose gel electrophoresis followed by immunoblotting and development via chemiluminescence. Patients with SH exhibited increased Lp(a) levels compared to controls (median value 10.6 mg/dL vs. 6.0 mg/dL, p = 0.003]), but this was not because of differences in the frequencies of apo(a) phenotypes. There was no association between thyrotropin (TSH) and Lp(a) levels in patients with SH. In subjects with either low (LMW; 25 patients and 28 controls) or high (HMW; 44 patients and 55 controls) molecular weight apo(a) isoforms, Lp(a) concentrations were higher in patients than in the control group (median values 26.9 mg/dL vs. 21.8 mg/dL, p = 0.02 for LMW, and 6.0 mg/dL versus 3.3 mg/dL, p < 0.001 for HMW). Levothyroxine treatment resulted in an overall reduction of Lp(a) levels (10.6 mg/dL baseline vs. 8.9 mg/dL posttreatment, p = 0.008]). This effect was mainly evident in patients with LMW apo(a) isoforms associated with high baseline Lp(a) concentrations (median values 26.9 mg/dL vs. 23.2 mg/dL pretreatment and posttreatment, respectively; p = 0.03). In conclusion, even though a causal effect of thyroid dysfunction on Lp(a) was not clearly demonstrated in patients with SH, levothyroxine treatment is beneficial, especially in patients with increased baseline Lp(a) levels and LMW apo(a) isoforms.
authors.affiliation: Department of Internal Medicine, Medical School of Ioannina, Ioannina, Greece.
authors.forename: Haralampos J
authors.initials: HJ
authors.lastname: Milionis
authors.forename: Zoe
authors.initials: Z
authors.lastname: Efstathiadou
authors.forename: Alexandros D
authors.initials: AD
authors.lastname: Tselepis
authors.forename: Eleni T
authors.initials: ET
authors.lastname: Bairaktari
authors.forename: Loukas D
authors.initials: LD
authors.lastname: Tsironis
authors.forename: Agathocles
authors.initials: A
authors.lastname: Tsatsoulis
authors.forename: Moses S
authors.initials: MS
authors.lastname: Elisaf
mesh_terms: D000328:Adult; D000368:Aged; D001054:Apolipoproteins A / Q000097:blood* / Q000737:chemistry*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000097:blood* / Q000188:drug therapy*; D017270:Lipoprotein(a) / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009994:Osmolar Concentration; D020033:Protein Isoforms / Q000097:blood / Q000737:chemistry; D013974:Thyroxine / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001054:Apolipoproteins A; D017270:Lipoprotein(a); D020033:Protein Isoforms; D013974:Thyroxine