[Lipoprotein apheresis in patients with familial hypercholesterolemia: a single center research].

Objective: We evaluated the safety and efficacy of lipoprotein apheresis (LA) in patients with familial hypercholesterolemia (FH) who can't reach low-density lipoprotein cholesterol(LDL-C) target goals with the maximal tolerated dose of lipid-lowering agents. Methods: This was a retrospective cross-sectional study. Between February 2015 and November 2019, patients with FH who were admitted in Fuwai hospital and treated with LA were consecutively enrolled. Based on intensive lipid-lowering agents, these patients received LA by double filtration plasma pheresis (DFPP) method. The changes of lipid levels such as LDL-C and lipoprotein(a)[Lp(a)] were compared before and after LA treatment, and the changes of immunoglobulin (Ig) concentration and LA-related adverse effects were also discussed. Results: A total of 115 patients with FH were enrolled in this study, of which 8 cases were homozygous FH and 107 cases were heterozygous FH. The age was (43.9±12.2) years and there were 75 (65.2%) males, and 108 (93.8%) with coronary artery disease. For pre-and immediately after LA treatment, the LDL-C was (5.20±2.94) mmol/L vs. (1.83±1.08) mmol/L, Lp(a) concentration was 428.70(177.00, 829.50)mg/L vs. 148.90(75.90, 317.00) mg/L (P<0.001), with a decrease of 64.2% and 59.8% respectively. The levels of IgG and IgA measured 1 day after LA treatment were both in the normal range and IgM concentration was below the reference value, the reductions of which were 15.1%, 25.0% and 58.7% respectively (P<0.001). Six patients had mild symptoms of nausea, hypotension dyspnea and palpitation, the symptoms were relieved by symptomatic treatment. Conclusion: For patients with FH who do not achieve LDL-C target goal with the maximal tolerated lipid-lowering agents, especially those with elevated Lp(a) levels, LA, which can significantly further reduce LDL-C and Lp(a) levels, is an effective and safe option.

Clinical and genetic characteristics of familial hypercholesterolemia patients with type 2 diabetes.

PURPOSE: Though type 2 diabetes mellitus (T2DM) is an important and independent risk factor for coronary artery disease (CAD) in the general population, the impact of T2DM on CAD in patients with familial hypercholesterolemia (FH) is less understood. Thus, the current study aimed to examine the features of FH patients with T2DM and explore the effects of T2DM on CAD in FH. METHODS: A total of 289 clinical heterozygous FH (HeFH) patients diagnosed with Dutch Lipid Clinic Criteria were consecutively recruited and divided into a T2DM group (n = 58) and non-T2DM group (n = 231). Clinical characteristics and laboratory findings were compared between the two groups. Target exome sequencing was used for gene mutation analysis. RESULTS: HeFH patients with T2DM had significantly higher levels of triglycerides, body mass index and free fatty acids than did non-T2DM patients; moreover, patients with T2DM more frequently exhibited hypertension. However, the spectrum of FH-causing mutations was not significantly different (p = 0.061). Notably, patients with T2DM had higher prevalence of CAD (p = 0.012) and higher Gensini Score (p = 0.002). The regression analysis confirmed that HbA1c was an independent risk factor for both the presence and severity of CAD [OR 2.321 (1.098-4.904), p = 0.027; OR 1.349 (1.032-1.762), p = 0.028, respectively] in patients with HeFH. CONCLUSIONS: Although there were not many differences in the clinical, lipid and genetic aspects of HeFH patients with and without T2DM, T2DM and HbA1c were associated with worse coronary lesions, suggesting that diabetes and the degree of blood glucose control are also important determinants of cardiovascular disease in these patients.

Elevated lipoprotein (a) levels are associated with the presence and severity of coronary artery disease in patients with type 2 diabetes mellitus.

BACKGROUND AND AIMS: The role of lipoprotein (a) [Lp(a)] in coronary artery diseases (CAD) with special clinical background such as type 2 diabetes mellitus (T2DM) has not been fully determined. The aim of the present study was to investigate the relation of Lp(a) to type 2 diabetic patients with or without CAD. METHODS AND RESULTS: A total of 2040 consecutive patients with T2DM who received selective coronary angiography (CAG) due to angina-like chest pain were enrolled. The patients were subsequently divided into CAD and non-CAD groups according to the results of CAG. The severity of CAD was evaluated by the Gensini Score (GS), number of stenotic vessels, and history of myocardial infarction (MI). Data showed that Lp(a) levels were higher in the CAD group than in the non-CAD group (median: 15.00 mg/dL vs. 11.88 mg/dL, P = 0.025). The results from CAD subgroup analysis indicated that the patients with MI, multiple-vessel disease and high GS had higher Lp(a) levels compared with those in their matched subgroups (P < 0.05, respectively). After adjustment for confounders, Lp(a) levels were independently related to the presence and severity of CAD (CAD:OR = 1.564; MI:OR = 1.523; high GS:OR = 1.388; multiple-vessel disease:OR = 1.455; P < 0.05, respectively). CONCLUSION: Elevated Lp(a) levels were independently associated with the presence and severity of CAD in patients with T2DM. More studies are necessary to confirm our findings.

[Prevalence and clinical characteristics of familial hypercholesterolemia among Chinese patients undergoing coronary angiography due to angina-like chest pain].

Objectives: To investigate the prevalence rate and clinical characteristics of familial hypercholesterolemia (FH) in Chinese patients undergoing coronary angiography due to angina-like chest pain. Methods: From March 2011 to December 2016, a total of 9 908 consecutive patients undergoing coronary angiography in Fuwai Hospital due to angina-like chest pain were enrolled. The age of enrolled patients was (56.6±11.1) years old, and 6 782 cases (68.4%) were male. The patients were divided into two groups: FH group (n=271) and non-FH group (n=9 637) according to the Dutch Lipid Clinic Network diagnostic criteria. A retrospective analyze was performed on the baseline features between the two groups including lipids levels, coronary artery disease (CAD) characteristics, and lipids-lowering treatments. Results: In the total cohort, the prevalence of definite/probable FH was 2.7% (271/9 908). The incidence of premature coronary artery disease (PCAD) (women < 60 years old, or men < 55 years old) was higher in patients with FH than that in patients without FH (70.2%(201/271) vs. 44.5% (4 287/9 637); χ(2)=93.738, P<0.001). Patients with FH had higher level of TC and LDL-C when compared with patients without FH ((6.74±2.48) mmol/L vs. (4.15±1.10) mmol/L; (4.53±2.39) mmol/L vs. (2.52±0.97) mmol/L; t=19.403, 22.233, P<0.001, respectively). Additionally, 84.9% (230/271) of FH patients were treated with statin at different intensities, but none of them achieved the LDL-C<2.6 mmol/L. Conclusions: Chinese patients with familial hypercholesterolemia not only showed a high presence of PCAD and higher lipids levels, but also exhibited a low rate of achievement of low-density lipoprotein cholesterol targets despite statin therapy. Our results thus highlight the importance of early diagnosis and intensive treatment of FH patients.

[Prevalence and clinical features of familial hypercholesterolemia in Chinese patients with myocardial infarction].

Objective: To analyze the prevalence and clinical features of familial hypercholesterolemia (FH) in Chinese patients with myocardial infarction (MI). Method: This retrospective study recruited a total of 2 119 consecutive patients (age (56.7±10.9) years old) undergoing coronary angiography with first MI from April 2011 to December 2016. Patients were divided into 2 groups: premature MI (male<55 years old, female<60 years old) and non-premature MI. The diagnosis of FH was established according to Dutch Lipid Clinic Network (DLCN) diagnostic criteria and referred as definite/probable FH in our study. The prevalence and clinical features of FH, including lipid level, MI characteristics and stain therapy, were explored. Multivariable logistic regression analysis was used to assess the predictive value of FH for the presence of premature MI. Results: The prevalence of definite/probable FH was 3.68% (78/2 119) in MI patients and 7.28% (68/934) in premature MI patients. Onset of MI occurred 10 years earlier in patients with definite/probable FH than those without FH ((47.9±9.4) years vs. (58.8±10.7) years, P<0.01). Additionally, we found that the risk of premature MI was significantly and independently increased in definite/probable FH patients (OR=5.32, 95%CI 2.77-10.22, P<0.01). None of FH patients reached the target of LDL-C<1.8 mmol/L under statin therapy. Conclusions: The prevalence of FH in Chinese patients with MI is not rare. Clinically, FH is linked with the early onset of MI.

[Status of intra-aortic balloon pump application and related factors in Chinese patients with acute myocardial infarction].

Objective: To investigate the current status of application of intra-aortic balloon pump(IABP) and analyze the factors which might impact the application of IABP in patients with acute myocardial infarction complicated with cardiac shock in China. Methods: In China Acute Myocardial Infarction (CAMI) Registry,a nationwide, multicenter(107 hospitals), prospective study, 26 592 patients with acute myocardial infarction were enrolled consecutively between January 1, 2013 and September 30, 2014. After excluding of 30 cases due to missing important data,26 562 cases were analyzed.The application status of IABP was analyzed and multivariate logistic regression analysis was performed to determine the factors related to IABP application. Results: A total of 785(3.0%) patients with acute myocardial infarction received IABP implantation, and 381(49.9%) patients belonged to preventive application of IABP before primary percutaneous coronary intervention,and 6(0.8%) patients were complicated with mechanical complications.There were 118(15.0%) patients with cardiac shock received IABP implantation, which accounted for 12.0%(118/984) of all patients with cardiac shock.Multivariate logistic regression analysis showed that the clinical independent factors of the decision of IABP insertion included dyslipidemia (OR=2.858, 95%CI 1.397-5.846, P=0.004),left ventricular ejection fraction (OR=0.977, 95%CI 0.961-0.994, P=0.009),usage of dopamine (OR=2.817, 95%CI 1.495-5.308, P=0.001), left main disease (OR=2.817, 95%CI 1.495-5.308, P=0.001), GRACE score (OR=1.006, 95%CI 1.000-1.011, P=0.034), receiving primary percutaneous coronary intervention (OR=4.508, 95%CI 1.673-12.146, P=0.003), teritiary hospitals (OR=2.562, 95%CI 1.498-4.384, P=0.001), and higher education of the patients (OR=2.183, 95%CI 1.056-4.509, P=0.016). Conclusions: Among the Chinese acute myocardial infarction patients who received IABP implantation, nearly half application of IABP are preventive implantation before primary percutaneous coronary intervention. Only a few patients complicated with cardiac shock received IABP insertion. The clinical conditions, grade of hospitals, degree of education impact the decision of IABP insertion for the patients with acute myocardial infarction. Clinical Trial Registry National Institutes of Health, NCT018746.

[Study on the reliability of CardioChek PA for measuring lipid profile].

OBJECTIVE: To evaluate the clinical correlation between the CardioChek PA analyzer (CCPA) and a clinical laboratory reference method to use for screening program purposes. METHODS: Fasting blood samples were collected on 325 patients (age: 23-86 years). One venous sample was collected using a serum tube for the evaluation on a Beckman reference analyzer. A second venous sample was collected in a lithium heparin tube and was evaluated on the CCPA analyzer. Linear regression analyses and Bland-Altman method were performed for each measured analyte: total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), triglycerides (TG) and low density lipoprotein-cholesterol (LDL-C). RESULTS: Our results demonstrated a good clinical agreement for TC, HDL-C, TG and LDL-C(97.0%, 92.9%, 92.4% and 83.7%)in comparison with the CCPA to the reference analyzer. The correlation coefficients were 0.875, 0.813, 0.910, 0.864, respectively. P values all < 0.001. There was no significant difference in the detection rate of hyperlipidemia in TC, HDL-C and LDL-C. CONCLUSION: We have identified the pre-analytic phase as an important step to guarantee the quality of results and indicated that the CCPA is a reliable lipid point-of-care testing system that can be used for the application of clinical screening anywhere.

Analysis of the association between plasma PCSK9 and Lp(a) in Han Chinese.

PURPOSE: It has been reported that proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors can significantly reduce lipoprotein(a) [Lp(a)], and the mechanism for Lp(a) reduction remains unclear. Recently an interesting clinical research with a small sample showed a positive correlation between plasma PCSK9 and Lp(a) levels in diabetes. Here we aimed to use a relatively large sample to investigate whether such an association exists in Han Chinese. METHODS: A total of 783 inpatients were consecutively enrolled and composed of 172 patients with type 2 diabetes mellitus (T2DM) and 611 non-T2DM subjects. Plasma PCSK9 level was measured by ELISA, and its association with Lp(a) was assayed by Spearman's correlation and multiple regression. Clinical and biochemical parameters were determined in all subjects studied. RESULTS: No significant differences in PCSK9 and Lp(a) levels were found between T2DM and non-T2DM patients. PCSK9 level was not related to Lp(a) level either in T2DM or non-T2DM group in bivariate correlation and multiple linear regression analysis. Additionally, no association between the levels of PCSK9 and Lp(a) was found in well, poorly controlled T2DM patients or in T2DM patients with or without coronary artery disease (CAD). Besides, no difference was found among the PCSK9 values across tertiles of Lp(a) level. CONCLUSION: We found no association of plasma PCSK9 levels with Lp(a) level in Han Chinese with or without T2DM, suggesting that Lp(a) reduction by PCSK9 inhibitors may not be achieved simply through PCSK9 pathway at least in Chinese.

A prospective comparative study of kyphoplasty using the Jack vertebral dilator and balloon kyphoplasty for the treatment of osteoporotic vertebral compression fractures.

This study prospectively compared the efficacy of kyphoplasty using a Jack vertebral dilator and balloon kyphoplasty to treat osteoporotic compression fractures between T10 and L5. Between 2004 and 2009, two groups of 55 patients each underwent vertebral dilator kyphoplasty and balloon kyphoplasty, respectively. Pain, function, the Cobb angle, and the anterior and middle height of the vertebral body were assessed before and after operation. Leakage of bone cement was recorded. The post-operative change in the Cobb angle was significantly greater in the dilator kyphoplasty group than in the balloon kyphoplasty group (-9.51 degrees (sd 2.56) vs -7.78 degrees (sd 1.19), p < 0.001)). Leakage of cement was less in the dilator kyphoplasty group. No other significant differences were found in the two groups after operation, and both procedures gave equally satisfactory results in terms of all other variables assessed. No serious complications occurred in either group. These findings suggest that vertebral dilator kyphoplasty can facilitate better correction of kyphotic deformity and may ultimately be a safer procedure in reducing leakage of bone cement.

Direct evidence of oxidized gold on supported gold catalysts.

Supported gold catalysts have drawn worldwide interest due to the novel properties and potential applications in industries. However, the origin of the catalytic activity in gold nanoparticles is still not well understood. In this study, time-of-flight secondary ion mass spectroscopy (TOF-SIMS) has been applied to investigate the nature of gold in Au (1.3 wt %)/gamma-Al2O3 and Au (2.8 wt %)/TiO2 catalysts prepared by the deposition-precipitation method. The SIMS spectrum of the supported gold catalysts presented AuO-, AuO2-, and AuOH- ion clusters. These measurements show direct evidence for oxidized gold on supported gold catalysts and may be helpful to gaining better understanding of the origin of the catalytic activity.

New evidence on the earliest human presence at high northern latitudes in northeast Asia.

The timing of early human dispersal to Asia is a central issue in the study of human evolution. Excavations in predominantly lacustrine sediments at Majuangou, Nihewan basin, north China, uncovered four layers of indisputable hominin stone tools. Here we report magnetostratigraphic results that constrain the age of the four artefact layers to an interval of nearly 340,000 yr between the Olduvai subchron and the Cobb Mountain event. The lowest layer, about 1.66 million years old (Myr), provides the oldest record of stone-tool processing of animal tissues in east Asia. The highest layer, at about 1.32 Myr, correlates with the stone tool layer at Xiaochangliang, previously considered the oldest archaeological site in this region. The findings at Majuangou indicate that the oldest known human presence in northeast Asia at 40 degrees N is only slightly younger than that in western Asia. This result implies that a long yet rapid migration from Africa, possibly initiated during a phase of warm climate, enabled early human populations to inhabit northern latitudes of east Asia over a prolonged period.