Familial hypercholesterolemia (FH) is an inherited disorder of lipid metabolism characterized by significant elevation of low-density lipoprotein cholesterol, increasing the risk of atherosclerotic cardiovascular disease and causing serious consequences for FH patients and the whole society. The development of molecular biotechnology is crucial for screening, diagnosing, and treating patients with FH. This paper systematically summarizes how the development of genetic testing technologies, particularly next-generation sequencing, has improved the accuracy of diagnosis and efficiency of genetic screening for FH, while also introducing many variations of unknown significance. In contrast to pharmacotherapy, transgenic technology and gene editing technology offer the potential to rectify the molecular aberration within the patient's physiological system, holding promise for eradicating FH at the molecular level. However, preliminary results have shown that patients could suffer from side-effects, such as liver damage, and long-term follow-up is needed to clarify the efficacy of these technologies. Therefore, this article reviews the latest advances in molecular biotechnology, including genetic testing technology and gene therapy technology, in the diagnosis and treatment of FH, aiming to provide new perspectives for FH related research.
Lipoprotein (a) [Lp (a) ] is significantly related to atherosclerotic cardiovascular disease (ASCVD), but it is unclear whether clinical agents that lower Lp (a) can reduce the risk of ASCVD. Here, we systematically reviewed the structure, function, genetic characteristics and detection status of Lp (a), discussed the relationship of Lp (a) with ASCVD, aortic valve stenosis and other cardiovascular diseases, and summarized new advance of Lp (a) -lowering therapies. The structural composition of Lp (a) indicates that Lp (a) may promote atherosclerosis, inhibit fibrinolytic reaction and promote inflammation. Multiple evidence from genetic studies and epidemiological studies supports that Lp (a) is significantly associated with an increased risk of ASCVD and major adverse cardiovascular events. In addition, Lp (a) is also associated with other cardiovascular diseases such as aortic valve stenosis. At present, several emerging drugs that lower Lp (a) are in clinical trials and may further reduce residual cardiovascular risk. This paper hopes to offer new thought for the study of Lp (a), and provide a basis for the monitoring and management of blood lipids.
Familial hypercholesterolemia (FH) is an autosomal dominant inherited disorder characterized by severe hypercholesterolemia and significantly elevated levels of serum low-density lipoprotein cholesterol (LDL-C). Patients with FH are at an increased risk of premature atherosclerotic cardiovascular disease, and early detection and treatment can improve their survival rates.
This study aims to explore the clinical value and significance of screening for FH among patients with hypercholesterolemia in community populations.
During the period from July to December 2023, a total of 164 patients diagnosed with hyperlipidemia and exhibiting LDL-C levels ≥4.90 mmol/L underwent gene sequencing at Department of Cardiology, the Affiliated Suzhou Hospital of Nanjing Medical University and its 5 community health centers within the medical alliance. Based on quartile intervals of LDL-C levels, the patients were stratified into four groups: Q1 group (LDL-C ≤5.10 mmol/L, n=43), Q2 group (5.10 mmol/L≤LDL-C≤5.32 mmol/L, n=40), Q3 group (5.32 mmol/L≤LDL-C≤5.67 mmol/L, n=41), and Q4 group (LDL-C≥5.67 mmol/L, n=40). Baseline data and laboratory test results of the patients were collected.
A total of 164 patients with hypercholesterolemia were included, with a prevalence of awareness of dyslipidemia at 39.02% (64/164), and 21.95% (36/164) of the patients had previously taken lipid-lowering medications. The comparison of total cholesterol (TC) and LDL-C among Q1 to Q4 groups showed statistically significant differences (P<0.05). Physical examinations of the patients in all groups revealed no tendon xanthomas or corneal arcus, but one case in Q4 had a family history of premature coronary heart disease. The comparison of Dutch Clinical Lipid Network criteria scores and the proportion of suspected FH among Q1 to Q4 groups showed statistically significant differences (P<0.05). The main results of genetic sequencing in all groups were the diagnosis of FH, with a detection rate of FH gene mutations at 14.6% (24/164), including LDL receptor (LDLR) mutations accounting for 11.0% (18/164), apolipoprotein B (ApoB) mutations accounting for 3.1% (5/164), and proprotein convertase subtilisin/kexin type 9 (PCSK9) mutations accounting for 0.6% (1/164). The comparison of FH gene mutation detection rates, pathogenic, likely pathogenic, heterozygous genotypes, and LDLR proportions among Q1 to Q4 groups showed statistically significant differences (P<0.05). The secondary results of genetic sequencing, defined as suspected FH and other primary lipid metabolism abnormalities, showed a mutation rate of 70.12% (115/164). The comparison of secondary results of genetic sequencing among Q1 to Q4 groups showed no statistically significant differences (P>0.05) .
In community populations with hypercholesterolemia and LDL-C ≥ 4.9 mmol/L, the rate of FH gene mutations is relatively high, and the rate of other primary (genetic) lipid metabolism gene mutations is also high. Screening for FH among patients with hypercholesterolemia in community populations has significant clinical importance and value.
Statins are the cornerstone of lipid-lowering therapy and moderate-dose statin therapy is the preferred treatment strategy for lipid management in the Chinese population. Despite the widely recognized efficacy of statins in reducing cholesterol levels and preventing cardiovascular diseases, there are significant differences in treatment responses among patients from different ethnic groups.
To explore the differences in therapeutic efficacy between Han and Uyghur patients under moderate-dose statin therapy to guide the formulation of individualized treatment plans.
A total of 780 patients diagnosed with atherosclerotic cardiovascular disease (ASCVD) by coronary angiography at the First Affiliated Hospital of Xinjiang Medical University's Cardiac Center from 2012 to 2022 were included in the study. Baseline data and laboratory examination results of the patients were collected.
A total of 780 ASCVD patients were included, with 408 Han and 372 Uyghur patients. The mean age and gender composition of the two groups were statistically significant (P<0.05). Prior to statin therapy, Han patients had higher levels of total bilirubin (Tbil), albumin (ALB), glycated hemoglobin (HbA1c), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and proportions of hypertriglyceridemia and hypercholesterolemia compared to Uyghur patients. Conversely, Han patients had lower levels of alanine aminotransferase (ALT), hypoalphalipoproteinemia, hypoapolipoproteinemia A1, and hyperlipoproteinemia a compared to Uyghur patients (P<0.05). After statin therapy, Han patients had higher levels of Tbil, aspartate aminotransferase, ALB, HbA1c, HDL-C, ApoA1, and lower levels of ALT, TC, low-density lipoprotein cholesterol (LDL-C), ApoB, hypoalphalipoproteinemia, hypoapolipoproteinemia A1, and hyperapolipoproteinemia B compared to Uyghur patients (P<0.05). After medium-dose statin therapy, the reduction levels of TC, HDL-C, LDL-C, and ApoB in Han patients were higher than those in Uyghurs (P<0.05) ; the reduction levels of TC, LDL-C, and ApoB were higher in Han patients than those in Uyghurs, and the increase level of HDL-C was lower in Han patients than those in Uyghurs (P<0.05). Patients were categorized into sensitive group (n=124), resistant group (n=104), and Intermediate group (n=552) based on the reduction in LDL-C. The resistant group consisted of 42 Han and 62 Uyghur patients, the sensitive group of 78 Han and 46 Uyghur patients, and the intermediate group of 288 Han and 264 Uyghur patients. The distribution of ethnicities among the three groups was statistically significant (χ2=11.511, P=0.030) .
Han patients showed a significantly better lipid-lowering effect following moderate-dose statin therapy compared to Uyghur patients. Uyghur patients may require more frequent monitoring of lipid levels and consideration of increased statin dosage or early combination with other lipid-lowering drugs to improve therapeutic efficacy.
Cardiovascular disease, mainly atherosclerotic cardiovascular disease, is the first cause of death for urban and rural residents in China. Low density lipoprotein cholesterol is the pathogenic risk factor of ASCVD.
By establishing a new outpatient model for blood lipid management, to analyze the awareness rate of abnormal blood lipids in patients before and after the establishment of the new model, the proportion of rational drug use, patient compliance, and medication compliance rate.
From September 1, 2023 to February 28, 2024, has established a comprehensive outpatient model for managing blood lipid abnormalities based on scientific research projects by integrating medical resources. The model takes the outpatient service of "patients with dyslipidemia" as the carrier, and collaborates with specialized doctors and general practitioners to standardize the management of dyslipidemia patients, optimize the consultation and follow-up process, effectively screen the population with dyslipidemia, diagnose hyperlipidemia patients, and provide correct treatment methods.
The model of patients with dyslipidemia included in the management of chronic diseases has shifted from a dispersed model to a comprehensive, standardized, and centralized management of lipid management outpatient services, and the number of patients managed has significantly increased compared to before. The proportion of standardized medication for first-time patients in our blood lipid management outpatient department has increased from 25.3% (147/580) to 30.3% (242/798), the proportion of adherence to medication has increased from 32.7% (190/580) to 41.6% (332/798), and the compliance rate of medication has increased from 15.8% (92/580) to 22.5% (180/798) (P<0.05) .
Through the implementation of the "comprehensive and specialized" prevention and treatment model, the number of patients with dyslipidemia included in chronic disease management has significantly increased, and the proportion of standardized medication, medication compliance, and medication compliance rate have been improved. The model not only cultivates talents while implementing scientific research projects, but also enhances the research capabilities and professional service levels of general practitioners, graduate students, and regulatory trainees.
