👤 Farigol Hakem Zadeh

Familial hypercholesterolemia (FH) is a co-dominantly inherited condition that leads to enhanced risk of atherosclerotic cardiovascular disease (ASCVD). The Montreal FH Score (MFHS), Combined FH Score (CFHS), and FH Risk Score (FHRS) are strongly associated with ASCVD events in patients with heterozygous FH (HeFH). In this study, the association between these risk scores and prevalent ASCVD was evaluated among Australian patients with HeFH. We collected clinical data from 655 adult patients with genetically confirmed HeFH (87% with LDLR, 11% with APOB, and 2% with PCSK9 or APOE p.Leu167del variants). Logistic regression was used to assess the association between risk scores and prevalence of ASCVD. Receiver operating characteristic curve analysis was used to evaluate the discriminatory ability of the risk scores. We identified 153 patients with a history of ASCVD events. A 1-unit increase in the MFHS, CFHS, and FHRS was associated with 16%, 18%, and 14% increase in the odds of ASCVD, respectively. Patients with high (greater than the median) MFHS (≥ 25), CFHS (≥ 26), and FHRS (≥ 31) had 9.7-fold, 9.1-fold, and 13.4-fold greater odds of ASCVD compared with those with low scores. The area under the receiver operating characteristic curve for MFHS, CFHS, and FHRS were 0.808 (95% confidence interval [CI], 0.772-0.844), 0.821 (95% CI, 0.785-0.856), and 0.818 (95% CI, 0.782-0.854), respectively, indicating excellent discriminatory ability, with the area under the receiver operating characteristic curve for CFHS being significantly higher than for the MFHS (P = 0.014). The MFHS, CFHS, and FHRS were strongly associated with an increase in the prevalence of ASCVD, with excellent discriminatory ability in identifying ASCVD in Australian patients with HeFH. Show less

Dyslipidemia, characterized by abnormal lipid levels in the blood, significantly escalates the risk of atherosclerotic cardiovascular disease and requires effective treatment strategies. While existing therapies can be effective, long-term adherence is often challenging. There has been an interest in developing enduring and more efficient solutions. In this context, gene editing, particularly clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology, emerges as a groundbreaking approach, offering potential long-term control of dyslipidemia by directly modifying gene expression. This review delves into the mechanistic insights of various gene-editing tools. We comprehensively analyze various pre-clinical and clinical studies, evaluating the safety, efficacy, and therapeutic implications of gene editing in dyslipidemia management. Key genetic targets, such as low-density lipoprotein receptor ( Show less