2023 China Guidelines for Lipid Management.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death among urban and rural residents in China, and elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for ASCVD. Considering the increasing burden of ASCVD, lipid management is of the utmost importance. In recent years, research on blood lipids has made breakthroughs around the world, hence a revision of China guidelines for lipid management is imperative, especially since the target lipid levels in the general population vary in respect to the risk of ASCVD. The level of LDL-C, which can be regarded as appropriate in a population without frisk factors, can be considered abnormal in people at high risk of developing ASCVD. As a result, the "Guidelines for the prevention and treatment of dyslipidemia" were adapted into the "China Guidelines for Lipid Management" (henceforth referred to as the new guidelines) by an Experts' committee after careful deliberation. The new guidelines still recommend LDL-C as the primary target for lipid control, with CVD risk stratification to determine its target value. These guidelines recommend that moderate intensity statin therapy in adjunct with a heart-healthy lifestyle, be used as an initial line of treatment, followed by cholesterol absorption inhibitors or/and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, as necessary. The new guidelines provide guidance for lipid management across various age groups, from children to the elderly. The aim of these guidelines is to comprehensively improve the management of lipids and promote the prevention and treatment of ASCVD by guiding clinical practice.

2023 Chinese guideline for lipid management.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death among urban and rural residents in China, and elevated low-density lipoprotein cholesterol (LDL-C) is a risk factor for ASCVD. Considering the increasing burden of ASCVD, lipid management is of the utmost importance. In recent years, research on blood lipids has made breakthroughs around the world, hence a revision of Chinese guideline for lipid management is imperative, especially since the target lipid levels in the general population vary in respect to the risk of ASCVD. The level of LDL-C, which can be regarded as appropriate in a population without frisk factors, can be considered abnormal in people at high risk of developing ASCVD. As a result, the "Guidelines for the prevention and treatment of dyslipidemia" were adapted into the "Chinese guideline for Lipid Management" (henceforth referred to as the new guidelines) by an Experts' committee after careful deliberation. The new guidelines still recommend LDL-C as the primary target for lipid control, with cardiovascular disease (CVD) risk stratification to determine its target value. These guidelines recommend that moderate intensity statin therapy in adjunct with a heart-healthy lifestyle, be used as an initial line of treatment, followed by cholesterol absorption inhibitors or/and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, as necessary. The new guidelines provide guidance for lipid management across various age groups, from children to the elderly. The aim of these guidelines is to comprehensively improve the management of lipids and promote the prevention and treatment of ASCVD by guiding clinical practice.

Prevalence and related factors of dyslipidemia among urban adults aged 35 to 79 years in Southwestern China.

This study aimed to investigate the prevalence of dyslipidemia and its related factors among urban adults aged 35 to 79 years in Southwestern China. From September 2013 to March 2014, a multi-stage sampling was conducted, and a total of 10,221 people aged 35-79 years living in Chengdu and Chongqing were included. More than 30 investigators were trained in data collection, including questionnaire, anthropometric measurements and blood biomarkers testing. The prevalence of high triglycerides (≥ 2.3 mmol/L), high total cholesterol (≥ 6.2 mmol/L), high low-density lipoprotein cholesterol (≥ 4.1 mmol/L), low high-density lipoprotein cholesterol (< 1.0 mmol/L), and dyslipidemia were 15.7% (95% confidence interval, 15.0-16.4%), 5.4% (4.9-5.8%), 2.5% (2.2-2.8%), 5.7% (5.3-6.2%), and 27.4% (26.5-28.2%), respectively. The prevalence of dyslipidemia was positively correlated with higher education level, monthly income over 2000 CNY, smoking, hypertension, diabetes, overweight and obesity, and central obesity, and negatively correlated with daily physical exercise. The prevalence of dyslipidemia in Southwestern China is lower than the national average level, with high triglycerides being the most common form of dyslipidemia.

Comparison of the Reductions in LDL-C and Non-HDL-C Induced by the Red Yeast Rice Extract Xuezhikang Between Fasting and Non-fasting States in Patients With Coronary Heart Disease.

Background: Xuezhikang, an extract of red yeast rice, effectively lowers fasting blood lipid levels. However, the influence of Xuezhikang on the non-fasting levels of low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) has not been explored in Chinese patients with coronary heart disease (CHD). Methods: Fifty CHD patients were enrolled and randomly divided into two groups (n = 25 each) to receive 1,200 mg/d of Xuezhikang or a placebo for 6 weeks as routine therapy. Blood lipids were repeatedly measured before and after 6 weeks of treatment at 0, 2, 4, and 6 h after a standard breakfast containing 800 kcal and 50 g of fat. Results: The serum LDL-C levels significantly decreased, from a fasting level of 3.88 mmol/L to non-fasting levels of 2.99, 2.83, and 3.23 mmol/L at 2, 4, and 6 h, respectively, after breakfast (P < 0.05). The serum non-HDL-C level mildly increased from a fasting level of 4.29 mmol/L to non-fasting levels of 4.32, 4.38, and 4.34 mmol/L at 2, 4, and 6 h post-prandially, respectively, and the difference reached statistical significance only at 4 and 6 h after breakfast (P < 0.05). After 6 weeks of Xuezhikang treatment, the patients had significantly lower fasting and non-fasting serum levels of LDL-C and non-HDL-C (P < 0.05) than at pretreatment. The LDL-C levels were reduced by 27.8, 28.1, 26.2, and 25.3% at 0, 2, 4, and 6 h, respectively, and the non-HDL-C levels were reduced by 27.6, 28.7, 29.0, and 28.0% at 0, 2, 4, and 6 h, respectively, after breakfast. No significant difference was found in the percent reductions in the LDL-C and non-HDL-C levels among the four different time-points. Conclusions: Six weeks of Xuezhikang treatment significantly decreased LDL-C and non-HDL-C levels, with similar percent reductions in fasting and non-fasting states in CHD patients, indicating that the percent change in non-fasting LDL-C or non-HDL-C could replace that in the fasting state for evaluation the efficacy of cholesterol control in CHD patients who are unwilling or unable to fast.

Efficacy and safety of coenzyme A versus fenofibrate in patients with hyperlipidemia: a multicenter, double-blind, double-mimic, randomized clinical trial.

Background: We investigated the lipid-lowering efficacy and safety of coenzyme A (CoA) versus fenofibrate in Chinese patients with moderate dyslipidemia.Methods: A total of 417 subjects (aged 18-75 years) diagnosed with moderate dyslipidemia (triglyceride 2.3-6.5 mmol/L) from 13 large cardiovascular centers in China were recruited and randomly divided into a fenofibrate group (n = 207), which received 200 mg of fenofibrate orally once daily, and a CoA group (n = 210), which received 400 mg of CoA orally once a day. Blood lipoproteins, liver and renal function, creatine kinase, and blood glucose were measured at baseline, and after 4 and 8 weeks of treatment.Results: The baseline triglyceride (TG) level in the fenofibrate group and the CoA group was 3.39 ± 0.99 mmol/L and 3.60 ± 1.11 mmol/L, respectively. After treatment for 4 and 8 weeks with fenofibrate, TG was reduced by 31.62% and 33.13%. In the CoA group, TG was reduced by 17.29% and 23.80%. Compared with baseline, total cholesterol (TC) was significantly decreased in both groups after either 4 or 8 weeks of treatment (p < .05). CoA increased high-density lipoprotein cholesterol (HDL-C) after 4 weeks of treatment, whereas it had no significant effect on HDL-C after 8 weeks of treatment. Low-density lipoprotein cholesterol (LDL-C) was not modified in either group. The incidence of side effects was significantly lower in the CoA group compared with the fenofibrate group (p < .05).Conclusions: Compared with fenofibrate, CoA has less effect on reducing plasma TG levels in subjects with moderate dyslipidemia. However, it has fewer adverse effects.

Determination of optimal cut-off points after a high-fat meal corresponding to fasting elevations of triglyceride and remnant cholesterol in Chinese subjects.

BACKGROUND: Postprandial high triglyceride (HTG), marking elevated level of remnant cholesterol (RC), is an independent risk factor of coronary heart disease (CHD). The postprandial cut-off points for HTG and high RC (HRC) after a daily meal are recommended as 2.0 mmol/L and 0.9 mmol/L, respectively, by the European Atherosclerosis Society (EAS), while those after a high-fat meal in Chinese subjects were not explored. METHODS: Ninety subjects, including 60 CHD patients (CHD group) and 30 non-CHD controls (CON group), were enrolled in this study. Serum levels of blood lipids, including calculated RC, were monitored at 0, 2, 4 and 6 h after a high-fat meal with 800 kcal and 50 g fat. Analysis of c-statistic was used to determine the cut-off points for postprandial HTG and HRC. RESULTS: Postprandial levels of triglyceride (TG) and RC significantly increased and peaked at 4 h after a high-fat meal in two groups, although those in CHD group were significantly higher (P < 0.05). The optimal cut-off point to predict HTG at 4 h corresponding to fasting TG ≥ 1.7 mmol/L was 3.12 mmol/L, and that to predict HRC at 4 h corresponding to fasting RC ≥ 0.8 mmol/L was 1.36 mmol/L. According to the new cut-off points, the omissive diagnosis rates of postprandial HTG and HRC decreased obviously. CONCLUSION: The cut-off points of postprandial HTG and HRC in Chinese subjects after a high-fat meal were higher than those after a daily meal recommended by the EAS, indicating that specific cut-off points should be determined after a certain high-fat meal.

The Benefits and Risks of Statin Therapy in Ischemic Stroke: A Review of the Literature.

Statins are effective cholesterol-lowering drugs for reducing the risks of mortality and morbidity of cardiovascular diseases. Increasing evidence has shown that statin use is associated with a significant beneficial effect in patients with ischemic stroke. Both pre-stroke and post-stroke statin use has been found to be beneficial in ischemic stroke. Furthermore, good adherence is associated with a better clinical outcome, and statin withdrawal is associated with a poor functional outcome in patients with ischemic stroke. High-intensity statin therapy is advocated for the treatment of ischemic stroke. However, there are concerns regarding the adverse effects associated with statin use in ischemic stroke such as intracranial hemorrhage. In this review, we summarize the beneficial effect of statin use in ischemic stroke and discuss the potential risks associated with statin therapy.

miR-122 promotes hepatic lipogenesis via inhibiting the LKB1/AMPK pathway by targeting Sirt1 in non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common hepatic disease with an increasing prevalence but an unclear aetiology. This study aimed to investigate the functional implications of microRNA-122 (miR-122) in the pathogenesis of NAFLD and the possible molecular mechanisms. METHODS: Both in vitro and in vivo models of NAFLD were generated by treating HepG2 and Huh-7 cells with free fatty acids (FFA) and by feeding mice a high-fat diet (HFD), respectively. HE and Oil Red O staining were used to examine liver tissue morphology and lipid deposition, respectively. Immunohistochemical (IHC) staining was used to examine Sirt1 expression in liver tissues. qRT-PCR and Western blotting were employed to measure the expression of miR-122, Sirt1, and proteins involved in lipogenesis and the AMPK pathway. Enzyme-linked immunosorbent assay (ELISA) was used to quantify triglyceride (TG) levels in HepG2 and Huh-7 cells and in liver tissues. The interaction between miR-122 and the Sirt1 gene was further examined by a dual luciferase reporter assay and RNA-immunoprecipitation (RIP). RESULTS: NAFLD hepatic tissues and FFA-treated HepG2 and Huh-7 cells presented excess lipid production and TG secretion, accompanied by miR-122 upregulation, Sirt1 downregulation, and potentiated lipogenesis-related genes. miR-122 suppressed Sirt1 expression via binding to its 3'-untranslated region (UTR). Knockdown of miR-122 effectively mitigated excessive lipid production and suppressed the expression of lipogenic genes in FFA-treated HepG2 and Huh-7 cells via upregulating Sirt1. Furthermore, miR-122 knockdown activated the LKB1/AMPK signalling pathway. CONCLUSION: The inhibition of miR-122 protects hepatocytes from lipid metabolic disorders such as NAFLD and suppresses lipogenesis via elevating Sirt1 and activating the AMPK pathway. These data support miR-122 as a promising biomarker and drug target for NAFLD.

[Stored autologous blood transfusion does not increase recurrence of prostate cancer after radical prostatectomy: A preliminary study].

OBJECTIVE: To analyze the association of stored autologous blood transfusion (SABT) with tumor recurrence in PCa patients after radical prostatectomy and explore the application of SABT in this surgical procedure. METHODS: Forty-five PCa patients underwent radical prostatectomy in our hospital in recent five years, of whom, 20 received SABT (group A) and the other 25 allogeneic blood transfusion (group B) intraoperatively. After surgery, we followed up the patients regularly for 3－66 months by examination of the levels of total PSA (tPSA) and free PSA (fPSA), digital rectal examination (DRE), and MRI to observe the biochemical recurrence of the tumor. We compared the data obtained between the two groups of patients. RESULTS: In group A, 8 cases were in stages T1a－T1b and 12 in stages T2a－T2c, and in group B, 14 cases were in stages T1a－T1b and 11 in stages T2a－T2c. The volume of transfused blood was 800 ml in group A and 400－1 200 ml in group B. No statistically significant differences were observed between the two groups in the operation time, intraoperative blood loss or postoperative Gleason scores (P > 0.05), nor in the tPSA level or the results of DRE and MRI at 12, 24, 36, 48 and over 48 months (P > 0.05). CONCLUSIONS: SABT is safe for PCa patients undergoing radical prostatectomy and does not increase the tumor recurrence rate after surgery.

Inhibitory Effects of Simvastatin on Oxidized Low-Density Lipoprotein-Induced Endoplasmic Reticulum Stress and Apoptosis in Vascular Endothelial Cells.

BACKGROUND: Oxidized low-density lipoprotein (ox-LDL)-induced oxidative stress and endothelial apoptosis are essential for atherosclerosis. Our previous study has shown that ox-LDL-induced apoptosis is mediated by the protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic translation initiation factor 2α-subunit (eIF2α)/CCAAT/enhancer-binding protein homologous protein (CHOP) endoplasmic reticulum (ER) stress pathway in endothelial cells. Statins are cholesterol-lowering drugs that exert pleiotropic effects including suppression of oxidative stress. This study aimed to explore the roles of simvastatin on ox-LDL-induced ER stress and apoptosis in endothelial cells. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with simvastatin (0.1, 0.5, or 2.5 µmol/L) or DEVD-CHO (selective inhibitor of caspase-3, 100 µmol/L) for 1 h before the addition of ox-LDL (100 µg/ml) and then incubated for 24 h, and untreated cells were used as a control group. Apoptosis, expression of PERK, phosphorylation of eIF2α, CHOP mRNA level, and caspase-3 activity were measured. Comparisons among multiple groups were performed with one-way analysis of variance (ANOVA) followed by post hoc pairwise comparisons using Tukey's tests. A value of P < 0.05 was considered statistically significant. RESULTS: Exposure of HUVECs to ox-LDL resulted in a significant increase in apoptosis (31.9% vs. 4.9%, P < 0.05). Simvastatin (0.1, 0.5, and 2.5 µmol/L) led to a suppression of ox-LDL-induced apoptosis (28.0%, 24.7%, and 13.8%, F = 15.039, all P < 0.05, compared with control group). Ox-LDL significantly increased the expression of PERK (499.5%, P < 0.05) and phosphorylation of eIF2α (451.6%, P < 0.05), if both of which in the control groups were considered as 100%. Simvastatin treatment (0.1, 0.5, and 2.5 µmol/L) blunted ox-LDL-induced expression of PERK (407.8%, 339.1%, and 187.5%, F = 10.121, all P < 0.05, compared with control group) and phosphorylation of eIF2α (407.8%, 339.1%, 187.5%, F = 11.430, all P < 0.05, compared with control group). In contrast, DEVD-CHO treatment had no significant effect on ox-LDL-induced expression of PERK (486.4%) and phosphorylation of eIF2α (418.8%). Exposure of HUVECs to ox-LDL also markedly induced caspase-3 activity together with increased CHOP mRNA level; these effects were inhibited by simvastatin treatment. CONCLUSIONS: This study suggested that simvastatin could inhibit ox-LDL-induced ER stress and apoptosis in vascular endothelial cells.

Whole exome sequencing identifies a novel mutation (c.333 + 2T > C) of TNNI3K in a Chinese family with dilated cardiomyopathy and cardiac conduction disease.

Dilated Cardiomyopathy (DCM) and cardiac conduction disease (CCD) are two kinds if diseases that can induce heart failure, syncope and even sudden cardiac death (SCD). DCM patients can experience CCD at the same time. In recent research, some disease-causing genes and variants have been identified in patients with DCM and CCD, such as Alpha-Actinin-2 and TNNI3 Interacting Kinase (TNNI3K). In this study, we employed whole-exome sequencing (WES) to explore the potential causative genes in a Chinese family with DCM and CCD. A novel splice site mutation (c.333 + 2 T > C) of TNNI3K was identified and co-segregated with the affected family members. This novel mutation was also absent in 200 healthy local controls and predicted to be disease-causing by Mutationtaster. The splice site mutation (c.333 + 2 T > C) may result in a premature stop codon in exon 4 of the TNNI3K gene and can induce nonsense-mediated mRNA decay. Real-time qPCR also confirmed that the level of TNNI3K mRNA expression was decreased significantly compared with the controls, which may lead to myocardial structural disorder and arrhythmia. In this study we reported the third novel mutation of TNNI3K in DCM and CCD patients which further supported the important role of TNNI3K in heart development and expanded the spectrum of TNNI3K mutations. The results may contribute to the genetic diagnosis and counseling of families with DCM and CCD.

Prevalence and risk factors associated with hypertension in the Chinese Qiang population.

Our aim is to investigate the prevalence and risk factors associated with hypertension among the Chinese Qiang population. From September 2012 to March 2013, a cross-sectional study was conducted in urban and rural communities of the Qiang population using multistage cluster sampling. A total of 2676 people aged above 20 years were enrolled in the analysis. Standardized mercury sphygmomanometer was used to measure the blood pressure twice after a 10-minute seated rest, and the average blood pressure was obtained. The hypertension prevalence among the population aged above 20 years was 13.9%, and age-standardized prevalence was 12.3%. Male and female prevalence of hypertension, as well as the prevalence in urban and rural areas, all increased with age. There were no significant differences between males and females and between urban and rural residents. Among hypertensive patients, 44.2% were aware of their hypertension, 38.0% were undergoing antihypertensive treatment, but only 10.5% achieved blood pressure control. Multivariate logistic regression analysis showed that the risk factors of hypertension included age, low income, overweight and obesity, family history of hypertension. The prevalence of hypertension in Chinese Qiang adults is significantly lower than the national level. Awareness, treatment, and control rates of hypertension were low in the Qiang population. Thus, hypertension-related health knowledge should be more aggressively delivered to improve public awareness and the capacity of community health services should be strengthened.

Xuezhikang contributes to greater triglyceride reduction than simvastatin in hypertriglyceridemia rats by up-regulating apolipoprotein A5 via the PPARα signaling pathway.

Xuezhikang (XZK), an extract of Chinese red yeast rice, is recommended as an optimal choice for patients with coronary heart disease (CHD) with markedly elevated triglyceride (TG) levels. This study was designed to compare the hypotriglyceridemic effects between XZK and simvastatin. The role of apolipoprotein A5 (apoA5), a key regulator of TG metabolism and a target gene of peroxisome proliferator-activated receptor α (PPARα), was to be identified in XZK-related hypotriglyceridemic actions. For these goals, hypertriglyceridemia of rats was induced by a high-fructose diet. In order to investigate the hypotriglyceridemic effects of XZK and simvastatin on these animals based on an equivalent low-density lipoprotein cholesterol (LDL-C) lowering power, we titrated their doses (XZK 80 mg/kg/d versus simvastatin 1 mg/kg/d) according to plasma LDL-C reduction of rats. Similarly, we titrated the target doses of the two agents (XZK 500 µg/ml versus simvastatin 10 µM) according to hepatocyte LDL receptor expressions, and then compared the effects of the two agents on TG and apoA5 of hepatocytes in vitro. Our results showed that XZK (80 mg/kg/d) had higher hypotriglyceridemic performance than simvastatin (1 mg/kg/d) on these animals albeit their equivalent LDL-C lowering power. Higher plasma apoA5 levels and hepatic apoA5 expressions were observed in rats treated with XZK (80 mg/kg/d) than simvastatin (1 mg/kg/d). Further, XZK (80 mg/kg/d) contributed to higher hepatic PPARα expressions of rats than simvastatin (1 mg/kg/d). Although the two agents led to an equivalent up-regulation of LDL receptors of hepatocytes, more TG reduction and apoA5 elevation were detected in hepatocytes treated with XZK (500 µg/ml) than simvastatin (10 µM). However, PPARα knockdown eliminated the above effects of XZK on hepatocytes. Therefore, our study indicates that XZK has greater hypotriglyceridemic performance than simvastatin in the setting of an equivalent LDL-C lowering power, which is attributed to more apoA5 up-regulation by this agent via the PPARα signaling pathway.

Apolipoprotein A5 regulates intracellular triglyceride metabolism in adipocytes.

It has previously been demonstrated that apolipoprotein A5 (apoA5) can be internalized by human adipocytes and significantly decreases intracellular triglyceride content. In the present study, endocytosis of apoA5 by adipocytes under different conditions, and the underlying mechanism by which apoA5 regulates cellular triglyceride storage, was investigated. The results revealed that the apoA5 protein was detected in human subcutaneous abdominal adipose tissues. In addition, the uptake of apoA5 was attenuated in human obese adipose tissues and in cultured adipocytes with hypertrophy or insulin resistance. Low­density lipoprotein receptor protein 1 (LRP1) knockdown in adipocytes resulted in a decrease in internalized apoA5 content, suggesting that LRP1 serves a role in apoA5 uptake. Treatment of adipocytes with apoA5 decreased the expression of the lipid droplet­associated proteins such as cidec and perilipin. ApoA5­treated adipocytes demonstrated an increase in lipolysis activity and expression of uncoupling protein 1, which is the molecular effector of thermogenesis in brown adipocytes. These results suggested that decreased triglyceride accumulation in adipocytes induced by apoA5 may be associated with enhanced lipolysis and energy expenditure, which may result from reduced expression of cidec and perilipin. In conclusion, the present study demonstrated a novel role of apoA5 in regulating the intracellular triglyceride metabolism of adipocytes. The results of the present study suggested that apoA5 may serve as a potential therapeutic target for the treatment of obesity and its related disorders.

Risk factors associated with atherogenic dyslipidemia in the presence of optimal statin therapy.

BACKGROUND: This study investigated the prevalence of atherogenic dyslipidemia (AD) in Chinese outpatients whose low-density lipoprotein cholesterol (LDL-C) levels reached the goals with statin monotherapy and evaluated the characteristics of these patients. METHODS: An analysis of the Dyslipidemia International Survey-China study that was carried out at 122 hospitals in China. Among patients reaching their LDL-C goals, the presence of AD was defined as triglyceride levels ≥1.7mmol/L and/or low levels of high-density lipoprotein cholesterol (men: <1.0mmol/L; women: <1.3mmol/L). RESULTS: 22,039 patients receiving statin monotherapy were analyzed. According to the American National Cholesterol Education Program Adult Treatment Panel III, 13,088 patients reached LDL-C goals, and 7134 patients of them had AD. Age, male gender, BMI, sedentary lifestyle, diabetes mellitus, ischemic cerebrovascular disease, serum uric acid levels, and fasting plasma glucose (all P<0.05) were independently associated with AD. Based on the Chinese guideline for the management of dyslipidemia, 13,551 patients reached LDL-C goals, and 7719 patients of them had AD. Age, male gender, BMI, sedentary lifestyle, coronary heart disease, serum uric acid levels, and fasting plasma glucose (all P<0.05) were independently associated with AD. The intensity of statin therapy did not affect the prevalence of AD. CONCLUSION: There was a high prevalence of AD in Chinese patients with optimal statin treatment. Some risk factors associated with AD were identified, but these factors were slightly different according to two criteria/guidelines. The intensity of statin therapy did not reduce the prevalence of AD. A combination lipid therapy may be more suitable for Chinese patients.

Combined use of metformin and atorvastatin attenuates atherosclerosis in rabbits fed a high-cholesterol diet.

Statins are widely used to reduce cardiovascular risk. Unfortunately, some patients still experience cardiovascular events though prescribed with high-intensity statins. Metformin, an anti-diabetic drug, was reported to possess anti-atherosclerotic effects. Therefore, the experiments were designed to evaluate whether combined use of metformin and atorvastatin can achieve additional benefits. In rabbits fed a high-cholesterol diet, we evaluated the effects of the combination therapy on atherosclerotic plaques, lipid profiles, blood glucose levels, liver and kidney functions. Effects of combination therapy on cholesterol efflux and the expression of related transporters were studied in vitro. Our results showed that the combination therapy induced a more significant decrease in atherosclerotic lesion area than atorvastatin without additional lipid-lowering effect. The combination therapy significantly increased the percentage of large high-density lipoprotein subfraction. The intravenous glucose tolerance test showed that atorvastatin-treated rabbits had an increased area under the curve for time-dependent glucose levels after a bolus injection of glucose, which was completely reversed by metformin treatment. In cultured macrophages, co-treatment with metformin and atorvastatin promoted cholesterol efflux and up-regulated expression of ATP-binding cassette transporters A1 and G1. Taken together, our results suggest that atorvastatin/metformin combination therapy may achieve additional anti-atherosclerotic benefits likely through increasing cholesterol efflux in macrophages.

The genetic spectrum of familial hypercholesterolemia in the central south region of China.

BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is the most common and severe autosomal dominant lipid metabolism dysfunction, which causes xanthoma, atherosclerosis and coronary heart disease. Earlier studies showed that mutations in LDLR, APOB and PCSK9 cause FH. Although more than 75% of the population in Europe has been scrutinized for FH-causing mutations, the genetic diagnosis proportion among Chinese people remains very low (less than 0.5%). The aim of this study was to perform a survey and mutation detection among the Chinese population. METHODS: 219 FH patients from the central south region of China were enrolled. After extracting DNA from circulating lymphocytes, we used direct DNA sequencing to screen each exon of LDLR, APOB and PCSK9. All detected variants were predicted by Mutationtaster, Polyphen-2 and SIFT to assess their effects. RESULTS: In total, 43 mutations were identified from 158 FH patients. Among them, 11 novel mutations were found, including seven LDLR mutations, two APOB mutations and two PCSK9 mutations. Moreover, five common mutations in LDLR were detected. We geographically marked their distributions on the map of China. CONCLUSIONS: The spectrum of FH-causing mutations in the Chinese population is refined and expanded. Along with future studies, our study provides the necessary data as the foundation for the characterization of the allele frequency distribution in the Chinese population. The identification of more LDLR, APOB and PCSK9 novel mutations may expand the spectrum of FH-causing mutations and contribute to the genetic diagnosis and counseling of FH patients.

Prevalence of diabetes and unrecognized diabetes in hypertensive patients aged 40 to 79 years in southwest China.

This study aimed to assess the prevalence of diabetes and unrecognized diabetes in hypertensive patients aged 40 to 79 years in Southwest China. From September 2013 to March 2014, a cross-sectional survey was conducted in 4021 hypertensive patients aged 40 to 79 years living in Chengdu and Chongqing, China. Fasting plasma glucose (FPG) and 2h plasma glucose (2-hPG) in an oral glucose-tolerance test (OGTT) were used for assessments. Whether the patients previously had diabetes (DM) was determined by their own reports. The survey was carried out by the same questionnaire for all respondents. DM prevalence was 32.0% in hypertensive patients aged 40 to 79 years in Southwest China, with the rates of 29.6% and 33.5% in men and women, respectively (P<0.001). DM prevalence increased with age age and body-mass index. DM prevalence rates were 16.9%, 24.7%, 38.2% and 41.9% in hypertensive patients aged 40-49, 50-59, 60-69 and over 70, respectively. DM prevalence were 30.6%, 27.9%, 37.1%, and 37.4%, for BMI<18.5, 18.5-24.9, 25.0-29.9, and ≥30, respectively. Prevalence of unrecognized DM were 20.8% in hypertensive patients aged 40 to 79 years in Southwest China. Using only fasting blood glucose testing without OGTT would have resulted in 65.0% of missed DM diagnosis in these newly diagnosed patients. The prevalence of DM and unrecognized DM were high in hypertensive patients aged 40 to 79 years in Southwest China.These findings indicate that hypertensive patients aged 40 to 79 years should regularly submit to community-based OGTT screening for timely DM diagnosis.

Mutation detection in Chinese patients with familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is the first molecularly and clinically characterized genetic disease of lipid metabolism. It is an autosomal dominant disorder with significantly elevated levels of total cholesterol and low density of lipoprotein cholesterol in serum, which would lead to extensive xanthomas and premature coronary heart disease. Mutations in low density lipoprotein receptor (LDLR), proprotein convertase subtilisin/kexin type 9 and Apo lipoprotein B-100 (APOB) have been identified to be the underlying cause of this disease. METHODS: Genetic testing and reports of the mutations in the Chinese population are still limited. In this study, 11 unrelated Chinese FH families were enrolled to detect the candidate gene variants by DNA direct sequencing. RESULTS AND CONCLUSION: We identified 12 mutations (11 in LDLR and one in APOB) in ten FH families. Three novel LDLR mutations (c.516C>A/p.D172E, c.1720C>A/p.R574S and c.760C>T/p.Q254X) were identified and co-segregated with the affected individuals in the families. Our discoveries not only further supports the significant role of LDLR in FH, but also expands the spectrum of LDLR mutations. These new insights will contribute to the genetic diagnosis and counseling of FH patients.