PCSK9 binds to the LDL receptor, promoting degradation and thus elevating plasma LDL-C levels. Lipid- and inflammation-related markers, such as lipoprotein(a), PCSK9, and high-sensitivity C-reactive protein (hsCRP), play key roles in modulating atherosclerotic cardiovascular diseases, as indicated by genetic studies and clinical outcomes. Interestingly, the physical signs vary based on the severity of hypercholesterolemia and CAD, even in subjects with the same LDL receptor gene defect. It has been postulated that TX/CA and atherosclerosis have similar pathogenic processes, featuring the accumulation of lipids in perivascular or avascular tissues such as the tendon sheath and corneal limbus. The presence of physical signs (TX and/or CA) is the major criterion for the clinical diagnosis of heterozygous FH (HeFH). FH is mainly caused by pathological mutations, such as LDL receptor ( LDLR), apolipoprotein B ( APOB), and proprotein convertase subtilisin/kexin type 9 ( PCSK9). Physical signs were associated with genotypes and phenotypes, and worse outcomes in patients with HeFH, suggesting that these signs may help in risk stratification in these patients.įamilial hypercholesterolemia (FH) is a genetic lipoprotein disorder characterized by an elevated plasma low-density lipoprotein cholesterol (LDL-C) level, deposition of cholesterol in extravascular tissues such as tendon xanthomas (TX) and corneal arcus (CA), and an increased risk of premature coronary artery disease (CAD). Patients with physical signs and mutation positivity had threefold higher risks of CVEs (adjusted hazard ratio 3.34, 95% confidence interval 1.04–10.72, p = 0.024). Over an average follow-up of 3.7 years, the incidence of CVEs was significantly higher in patients with TX/CA (log-rank p < 0.001). Patients with physical signs had significantly higher low-density lipoprotein cholesterol levels higher PCSK9 or hsCRP concentrations more LDLR positive mutations and higher prevalence of high tertiles of Gensini, SYNTAX and Jeopardy scores as well as coronary artery calcium scores than did those without. Laboratory markers (proprotein convertase subtilisin/kexin type 9, lipoprotein(a) and high-sensitivity C-reactive protein ), computed tomography angiography, coronary angiography, and follow-up for CVEs were performed.
LDLR, APOB, and PCSK9 genes were screened in 523 HeFH patients, and patients with TX/CA (n = 50) were 1:4 propensity score-matched to patients without TX/CA (n = 200) to adjust for age and sex. This study aimed to examine the association of TX/CA with genetic mutation, lipid- and inflammation-related markers, the severity of coronary stenosis or calcification, and cardiovascular events (CVEs) in patients with HeFH. Although the presence of physical signs, are associated with the risk of coronary artery disease in patients with heterozygous familial hypercholesterolemia (HeFH), their relationship with genotypes and clinical characteristics has not been fully determined.
0 kommentar(er)
