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Abstract: Despite progress in treatment, elevated levels of low-density lipoprotein cholesterol (LDL-C) and lipoprotein (a) (Lp(a)), represent a significant part of the residual risk. Both are associated with inflammation and the coagulation fibrinolytic system. The purpose of our research was to evaluate the effect of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) on lipid parameters and indicators of inflammation, coagulation and fibrinolysis. We included 100 post myocardial infarction (MI) patients with insufficiently controlled LDL-C values despite the maximum dose of statin, and highly elevated Lp(a). Patients received alirocumab or evolocumab (150 mg sc or 140 mg sc every two weeks, respectively), or placebo for 6 months. In patients receiving PCSK9i, a significant decrease in total cholesterol (TC), LDL-C, triglycerides (TG) and Lp(a), and an increase in high density lipoprotein cholesterol (p < 0.001 for all) was found. Before treatment, the concentrations of TC, LDL-C and TG correlated with the concentrations of thrombin activatable fibrinolysis inhibitor (r = 0.41, p < 0.001; r = 0.353, p < 0.001; r = 0.311, p = 0.003, respectively), and plasminogen activator inhibitor-1 (r = 0.302, p = 0.007; r = 0.218, p = 0.049; r = 0.278; p = 0.013, respectively). The concentrations of TC and LDL-C correlated with overall fibrinolytic potential (r = −0.220, p = 0.034; r = −0.207, p = 0.047, respectively). The concentration of TG was related to the concentration of interleukin 6 (r = 0.290, p = 0.004) and interleukin 8 (r = 0.332, p = 0.001). No correlations between Lp(a) and inflammatory or hemostatic variables were found. No associations were found after treatment. Our results show that inflammatory cytokines and fibrinolytic parameters are related to LDL-C and not Lp(a) in post-MI patients before and with neither of them following PCSK9i treatment.
Keywords: inflammation, hemostasis, PCSK9 inhibitors, LDL cholesterol, lipoprotein (a)
Published in DiRROS: 08.06.2026; Views: 182; Downloads: 173
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Abstract: Background: Evidence suggests statins may influence cognition in Alzheimer's disease (AD), but specific use patterns in AD patients remain unclear. Objective: To identify factors influencing statin use in AD and explore associations between statins, cholesterol, and cognition, evaluated with Mini-Mental State Examination (MMSE) at dementia diagnosis. Methods: A cross-sectional study using data from the Swedish Registry for Dementia and Cognitive Disorders (SveDem) and Stockholm Creatinine Measurements (SCREAM) from 2007 to 2018. Multivariable logistic regression examined associations between baseline characteristics and statin use, while linear regression analyzed relationships between statins, cholesterol levels, and MMSE scores. Results: We included 3074 AD patients (mean age 78.1 years; 59.4% women), of whom 1028 used statins (79.6% simvastatin, 20.4% atorvastatin). Patients with diabetes mellitus, ischemic heart disease, or stroke had greater odds of receiving statins. Older patients had slightly lower odds of receiving any statin at baseline (simvastatin use OR 0.98, 95% CI 0.97–0.99). Simvastatin users had 0.53 points higher MMSE on average at baseline compared to non-users of statins (se 0.23, p = 0.021). Higher low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) levels were associated with higher MMSE in non-users of statins, but not in statin users. Conclusions: Younger AD patients and those with cardiovascular disease were more likely to use statins. Simvastatin use was linked to higher cognitive scores at diagnosis. In non-users, higher LDL-C, TC, and HDL-C levels correlated with better baseline cognitive scores. Longitudinal studies are needed to investigate the effects of statins on cognitive decline in AD.
Keywords: Alzheimer's disease, cholesterol, dementia, drug repurposing, mini-mental state examination
Published in DiRROS: 15.04.2026; Views: 306; Downloads: 139
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Abstract: Background and aims Thyroid hormones regulate lipoprotein metabolism—primarily by up-regulating the LDL receptor. Whether TSH relates to LDL-C in hypercholesterolemic children, and whether this depends on familial hypercholesterolemia (FH) status or the underlying defective gene, is uncertain. We evaluated TSH–lipid associations in prepubertal children and tested effect modification by FH status and, within FH, by gene with a pathogenic variant (LDLR vs APOB). Methods We performed a cross-sectional study of prepubertal children referred to the Slovenian national tertiary center through the universal FH screening program or cascade screening. Eligibility required concurrent TSH and fasting lipid measurement and completed genetic testing (pathogenic/likely pathogenic variants in LDLR/APOB/PCSK9 vs polygenic hypercholesterolemia). Results Among 738 children, 182 (24.7%) were FH-positive (LDLR 132; APOB 50). In the pooled cohort, TSH did not correlate with age or lipids (all p≥0.050). After sex stratification, TSH correlated with triglycerides only in males (ρ=0.156; p=0.012). In FH-positive children, TSH correlated with total cholesterol, LDL-cholesterol, and ApoB (ρ≈0.184–0.207; all p<0.050), with no associations in FH-negative children. Interaction testing confirmed effect modification by FH (TSH×FH β=0.141 mmol/L per mIU/L, p=0.023). Within FH-positive children, a positive TSH–LDL-C slope was seen in LDLR carriers (β=0.237, p=0.004) but not in APOB carriers (β=−0.065, p=0.655). Conclusions TSH was positively associated with LDL-C only in FH due to LDLR variants, not in APOB carriers. These findings suggest that genetic background may shape hormonal sensitivity, and that attention to thyroid status could be particularly relevant in LDLR-FH.
Keywords: TSH, low-density lipoprotein cholesterol, familial hypercholesterolemia, LDLR, APOB, subclinical hypothyroidism
Published in DiRROS: 16.03.2026; Views: 477; Downloads: 433
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Abstract: Background: MicroRNAs (miRNAs) are involved in the synthesis of proprotein convertase subtilisin–kexin type 9 (PCSK9), one of the regulators of low-density lipoprotein cholesterol (LDL-C) metabolism, and are directly involved in the atherosclerotic process. The aim of this study was to verify whether treatment with PCSK9 inhibitors (PCSK9i) and changes in the expression of miRNAs involved in PCSK9 metabolism are associated with arterial wall properties in stable post-myocardial infarction (MI) patients with insufficiently regulated LDL-C levels and significantly increased Lp(a) levels. Methods: Ninety-five patients after MI were enrolled and randomized to a placebo (N = 31) or PCSK9i group (N = 64). The treatment group received subcutaneous alirocumab 150 mg or evolocumab 140 mg, every 2 weeks. Blood for biochemical and epigenetic analysis was taken and ultrasound measurements of flow-mediated dilation of brachial artery (FMD), carotid intima–media thickness (c-IMT) and pulse wave velocity (PWV) were performed initially and after 6 months of treatment. The expression of the selected 5 miRNAs (miR-191-5p, miR-224-5p, miR-337-3p, miR-483-5p, and miR-552-3p) was quantified using quantitative polymerase chain reaction. Results: A decrease in c-IMT was associated with a decrease in the expression of miR-337-3p (ρ = 0.329; p = 0.010) and miR-483-5p (ρ = 0.324; p = 0.012). We did not detect any associations between miRNA changes and FMD or PWV. Conclusions: Our results suggest that changes in the selected miRNAs are associated with changes in the morphological properties of the arterial wall. We have shown that the decrease in miR-483-5p expression present a good indicator of the regression of morphological atherosclerotic change. The trial registration: The study is registered with CinicalTrials under the number NCT04613167, date of registration November 2nd, 2020. Approval for this study was obtained from the National Medical Ethics Committee of the Republic of Slovenia (reference number: KME 0120-357/2018/8).
Keywords: miRNA, endothelial function, PCSK9 inhibitors, myocardial infarction, low-density lipoprotein cholesterol
Published in DiRROS: 18.02.2026; Views: 575; Downloads: 324
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Abstract: Background and aims: Sex differences in cholesterol levels are well documented in adults and adolescents, but limited data exist for prepubertal children. This study aimed to evaluate innate sex differences in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels among prepubertal children, both in the general population and among those with familial hypercholesterolemia (FH). Methods: This cross-sectional study used data from Slovenia’s Universal FH Screening Program. Two populationbased random samples of children undergoing routine cholesterol screening at age 5 years were included from 2014 (N = 3412) and 2023 (N = 4182). In addition, a referred cohort from the Slovenian Hypercholesterolemia Registry (n = 1160, aged <10 years) who underwent genetic testing was analyzed. Results: In both the 2014 and 2023 cohorts, girls had significantly higher TC levels than boys (median difference: 0.10–0.11 mmol/L; p < 0.05). Among FH-negative children in the Registry, girls had on average 0.14 mmol/L higher TC and 0.13 mmol/L higher LDL-C than boys (both p < 0.05). No sex differences were observed in FHpositive children (p = 0.83 for TC; p = 0.82 for LDL-C). In the overall Registry cohort, after adjusting for FH status, girls had 0.11 mmol/L higher TC and 0.10 mmol/L higher LDL-C (both p < 0.05). Conclusion: Prepubertal girls have modestly higher TC and LDL-C than boys, a difference not observed in prepubertal FH-positive children, suggesting that the presence of a pathogenic FH variant may override innate physiological differences in lipid metabolism. These findings support universal early cholesterol screening and suggest that sex-specific reference values may improve early cardiovascular risk assessment in prepubertal FHnegative children.
Keywords: sex differences, prepubertal children, total cholesterol, low-density lipoprotein cholesterol, familial hypercholesterolemia
Published in DiRROS: 17.11.2025; Views: 788; Downloads: 444
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