2023 China Guidelines for Lipid Management / 老年心脏病学杂志（英文版）

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.

Lipoprotein apheresis in patients with familial hypercholesterolemia: a single center research / 中华心血管病杂志

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.

Lipoprotein (a) as a Marker for Predicting the Presence and Severity of Coronary Artery Disease in Untreated Chinese Patients Undergoing Coronary Angiography / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Low-density lipoprotein cholesterol (LDL-C) has been well known as the risk factor of coronary artery disease (CAD). However, the role of lipoprotein (a) [Lp(a)] in the development of CAD is of great interest but still controversial. Thus, we aim to explore the effect of Lp(a) on predicting the presence and severity of CAD in Chinese untreated patients, especially in combination with LDL-C.</p><p><b>METHODS</b>We consecutively recruited 1,980 non-treated patients undergoing coronary angiography, among which 1,162 patients were diagnosed with CAD. Gensini score (GS) was used to assess the severity of CAD. Lp(a) was measured by immunoturbidimetric method.</p><p><b>RESULTS</b>Patients with CAD had higher level of LDL-C and Lp(a) compared with non-CAD (P < 0.05). Multivariable logistic regression revealed that Lp(a) > 205 mg/L (highest tertile) predicted 1.437-fold risk for CAD (95% CI: 1.108-1.865, P = 0.006) and 1.480-fold risk for high GS (95% CI: 1.090-2.009, P = 0.012) respectively. Interestingly, concomitant elevated level of Lp(a) and LDL-C conferred the highest risk for both presence [OR = 1.845, 95% CI: 1.339-2.541, P < 0.001] and severity [OR = 1.736, 95% CI: 1.188-2.538, P = 0.004] of CAD.</p><p><b>CONCLUSION</b>Lipoprotein (a) is a useful marker for predicting the presence and severity of CAD, especially combined with LDL-C.</p>

Correlation Study Between Plasma Level of Pro-protein Convertase Subtilisin Kexin Type 9 and Coronary Artery Calcification / 中国循环杂志

Objective: To investigate the relationship between plasma level of pro-protein convertase subtilisin kexin type9 (PCSK9) and coronary artery calcification (CAC). Methods: A total of 380 consecutive chest pain patients without lipid-lowering therapy were enrolled. All patients received CT scan and coronary artery calcification (CAC) score measurement and were divided into 2 groups: CAC group, n=156 patients with CAC score>0 and Non-CAC group, n=224 patients with CAC score=0. CAC group was further classified in 3 subgroups as CAC score (1-100) subgroup, n=53, CAC score (101-400) subgroup, n=64 and CAC score>400 subgroup, n=39. Clinical data was collected, plasma levels of PCSK9 were measured in all patients and the relationship between PCSK9 and CAC score was investigated. Results: Plasma PCSK9 level in CAC group was higher than Non-CAC group (260.23±69.34) ng/ml vs (205.46±53.21) ng/ml, P<0.001; alone with CAC score increasing, PCSK9 level was elevating accordingly as in CAC score (1-100) subgroup, CAC score (101-400) subgroup and CAC score>400 subgroup, PCSK9 levels were (247.38±72.68) ng/ml, (264.87±57.63) ng/ml and (295.33±69.06) ng/ml respectively, all P<0.05. With adjusted traditional cardiovascular risk factors, multivariate regression analysis confirmed that plasma PCSK9 level was independently related to CAC score (β=0.584, P=0.002). In addition, the optimal cut-off value for PCSK9 predicting CAC was 228.58 ng/ml with sensitivity at 67% and specificity at 71%. Conclusion: Plasma PCSK9 level was related to CAC in chest pain patients without lipid-lowering therapy.

Impact of Smoking Status on Lipoprotein Subfractions: Data from an Untreated Chinese Cohort / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Cigarette smoking is one of the established risk factors of atherosclerotic cardiovascular disease, however, its impact on lipids is not completely understood, especially in the Chinese population. Therefore, this study evaluated the impact of smoking status (non, former, and current smoking) on the distribution of lipoprotein subfractions in untreated patients with angina-like chest pain.</p><p><b>METHODS</b>A total of 877 patients were consecutively enrolled and divided into nonsmoking (n = 518), former smoking (n = 103), and current smoking (n = 256) groups. Both low- and high-density lipoprotein cholesterol (LDL-C and HDL-C) subfractions were measured using the Quantimetrix Lipoprint System. The distributions of lipoprotein subfractions were evaluated among the groups.</p><p><b>RESULTS</b>Compared with nonsmoking subjects, the current smoking group had significantly lower large/medium HDL-C (both P < 0.001) concentration and large HDL subfraction percentage but higher small HDL-C and medium LDL-C concentrations as well as medium LDL subfraction percentage. Importantly, former smoking subjects showed elevated levels of large HDL-C concentration, large HDL particle percentage, and mean LDL particle size and attenuation in small HDL/LDL percentages and small LDL-C concentration, but these levels did not reach the optimal status compared with those of the non-smoking group (data not shown).</p><p><b>CONCLUSION</b>Smoking has an adverse impact on the lipoprotein subfractions, presented as lower large HDL particles besides higher small HDL and medium LDL particles, whereas smoking cessation could reverse these change to a certain degree.</p>

Plasma apoCIII Levels in Relation to Inflammatory Traits and Metabolic Syndrome in Patients not Treated with Lipid-lowering Drugs Undergoing Coronary Angiography / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Assessment of the comprehensive relationship among apolipoprotein CIII (apoCIII) levels, inflammation, and metabolic disorders is rare.</p><p><b>METHODS</b>A total of 1455 consecutive patients not treated with lipid-lowering drugs and undergoing coronary angiography were enrolled in this cross-sectional study. A mediation analysis was used to detect the underlying role of apoCIII in the association of inflammation with metabolic syndrome (MetS).</p><p><b>RESULTS</b>Patients with MetS showed higher levels of apoCIII [95.1 (73.1-131.4) vs. 81.7 (58.6-112.4) μg/mL, P < 0.001] and inflammatory markers [high sensitivity C-reactive protein, 1.7 (0.8-3.4) vs. 1.1 (0.5-2.2) mg/L; white blood cell count, (6.48 ± 1.68) vs. (6.11 ± 1.67) × 109/L]. The levels of apoCIII and inflammatory markers increased with the number of metabolic risk components (all P < 0.001). Furthermore, apoCIII levels were associated with virtually all individual MetS risk factors and inflammatory markers (all P < 0.05). Importantly, the prevalence of MetS in each metabolic disorder rose as apoCIII levels increased (all P < 0.05). Mediation analysis showed that apoCIII partially mediated the effect of inflammation on MetS independently from triglycerides.</p><p><b>CONCLUSION</b>Plasma apoCIII levels were significantly associated with the development and severity of MetS, and a role of apoCIII in the effect of inflammation on the development of MetS was identified.</p>

Circulating MicroRNAs as Novel Diagnostic Biomarkers for Very Early-onset (≤40 years) Coronary Artery Disease / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>Very early-onset coronary artery disease (CAD) is a great challenge in cardiovascular medicine throughout the world, especially regarding its early diagnosis. This study explored whether circulating microRNAs (miRNAs) could be used as potential biomarkers for patients with very early-onset CAD.</p><p><b>METHODS</b>We performed an initial screening of miRNA expression using RNA isolated from 20 patients with angiographically documented very early-onset CAD and 20 age- and sex-matched normal controls. For further confirmation, we prospectively examined the miRNAs selected from 40 patients with very early-onset CAD and 40 angiography-normal controls.</p><p><b>RESULTS</b>A total of 22 overexpressed miRNAs and 22 underexpressed miRNAs were detected in the initial screening. RT-qPCR analysis of the miRNAs obtained from the initial screening revealed that four miRNAs including miR-196-5p, miR-3163-3p, miR-145-3p, and miR-190a-5p exhibited significantly decreased expression in patients compared with that in controls (P<0.05). The areas under the receiver operating characteristic curve for these miRNAs were 0.824 (95% CI, 0.731-0.917; P<0.001), 0.758 (95% CI, 0.651-0.864; P<0.001), 0.753 (95% CI, 0.643-0.863; P<0.001), and 0.782 (95% CI, 0.680-0.884; P<0.001), respectively, in the validation set.</p><p><b>CONCLUSION</b>To our knowledge, this is an advanced study to report about four serum miRNAs (miR-196-5p, miR-3163-3p, miR-145-3p, and miR-190a-5p) that could be used as novel biomarkers for the diagnosis of very early-onset CAD.</p>

Effects of Hedan Tablet () on lipid profile, proprotein convertase subtilisin/kexin type 9 and high-density lipoprotein subfractions in patients with hyperlipidemia: A primary study / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effects of Hedan Tablet () on serum lipid profile, proprotein convertase subtilisin/kexin type 9 (PSCK9) and high-density lipoprotein (HDL) subfractions in patients with hyperlipidemia.</p><p><b>METHODS</b>Thirty-seven patients with hyperlipidemia were randomized to treatment with Hedan Tablet 4.38 g/day as Hedan group (18 cases) or placebo (19 cases) as control group for 8 weeks. The lipid profile, PCSK9 and HDL subfractions were determined at day 0 and week 8 in both groups respectively.</p><p><b>RESULTS</b>Hedan treatment for 8 weeks mildly decreased serum low-density lipoprotein cholesterol (LDL-C) levels, while no changes were found in total cholesterol (TC), triglycerides (TG) and PCSK9 concentrations. Furthermore, Hedan treatment increased the concentration of large high-density lipoprotein cholesterol (HDL-C) and the percentage of large HDL subfraction, while decreased the concentration of small HDL-C and the percentage of small HDL subfraction without changing serum HDL-C levels in patients with hyperlipidemia.</p><p><b>CONCLUSION</b>Hedan treatment of 4.38 g per day for 8 weeks could confer a favorable effects on serum LDL-C concentration as well as HDL subfractions.</p>

Correlation of red cell distribution width with the severity of coronary artery disease: a large Chinese cohort study from a single center / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It has been reported that increased red blood cell width (RDW) is a marker associated with the presence and adverse outcomes of various cardiovascular diseases. The aim of the present study was prospectively evaluate the severity of coronary artery disease (CAD) and RDW in a large Chinese cohort.</p><p><b>METHODS</b>A total of 677 consecutive individuals who underwent coronary angiography due to the presence of angina-like chest pain and/or positive treadmill exercise test were enrolled in this study. All patients received coronary angiography and were then divided into two groups based on the results of coronary angiography (CAD group (n = 499) and control group (n = 178)). The clinical information including classical CAD risk factors and RDW were analyzed to identify their relationship to CAD. The severity of CAD was evaluated by Gensini score and its relationship with RDW was also analyzed.</p><p><b>RESULTS</b>Patients with angiographic CAD had significantly elevated RDW levels compared with controls ((12.95 ± 0.77)% vs. (12.73 ± 0.83)%, P = 0.001). There was a significant positive correlation between RDW and the Gensini score (r = 0.37, P < 0.001). In multivariate Logistic regression analysis, RDW was demonstrated to be an independent predictor for both angiographic CAD (OR = 1.34, 95%CI: 1.02 - 1.77, P < 0.05) and for a higher Gensini score (> 13, OR = 2.23, 95%CI: 1.62 - 3.08, P < 0.001). In a receiver operating characteristic (ROC) curve analysis, an RDW value of 12.85% was identified as an effective cut-point in predicting the presence or absence of CAD with a sensitivity of 50.0% and a specificity of 65.2%.</p><p><b>CONCLUSION</b>RDW is associated with both presence of CAD and the severity of coronary stenosis, suggesting that it might be a readily available marker for the prediction of CAD and its severity.</p>

Body mass index and prognosis in patients with systolic heart failure / 中华心血管病杂志

<p><b>OBJECTIVE</b>In individuals without cardiovascular disease, elevated body mass index (BMI) is associated with an increased risk of death. However, in patients with certain chronic diseases, including heart failure, low BMI has been associated with increased mortality. We investigated the association between BMI and prognosis in patients with systolic HF.</p><p><b>METHOD</b>Follow-up was made on 540 patients (mean age 58.53 years, 84.2% men) with systolic HF (LVEF < or = 45%) and association between BMI and adverse cardiac events was analyzed.</p><p><b>RESULTS</b>During a median follow-up of 24 months, 92 patients died including 87 cases of cardiac death and 92 patients were rehospitalized. Compared with patients with BMI higher than 28.0 kg/m(2), patients in lower BMI categories (BMI < or = 18.5 kg/m(2) and > or = 18.5 kg/m(2) < 24.0 kg/m(2)) had a graded increase in the all cause death rate [5.44 (1.78 - 16.66), 4.30 (1.71 - 10.82)], cardiac death rate [OR(95%CI): 5.42 (1.77 - 16.59), 4.00 (1.59 - 10.10)], HF death rate [8.94 (2.37 - 33.74), 4.97 (1.52 - 16.20)] and MACE rate [2.10 (1.09 - 4.07), 1.79 (1.14 - 2.82)]. After adjustment for age, gender, LVEF and NYHA grade using cox regression analysis, BMI categories still significantly associated with all cause death rate (OR = 0.77, P < 0.05), cardiac death rate (OR = 0.78, P < 0.05) and HF death rate (OR = 0.79, P < 0.05).</p><p><b>CONCLUSION</b>In patients with systolic heart failure, lower BMI was an independent predictor of increased all cause death rate, cardiac death rate and HF death rate.</p>

Association between single nucleotide polymorphisms of matrix metalloproteinase-3 gene and the severity of coronary atherosclerosis in patients with coronary artery disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the association between the severity of coronary arteries in patients with coronary artery disease and the single nucleotide polymorphisms of MMP-3 gene.</p><p><b>METHODS</b>One thousand and three hundred seventy-one patients with coronary artery disease (CAD) diagnosed by coronary angiography and six hundred and ninety-five healthy controls without CAD were enrolled in this study. The SNPs of -1612 5A/6A, -376C/G, Glu45Lys of MMP-3 were genotyped by restriction fragment length polymorphism analysis (RFLP) in all subjects. Univariate analysis was applied to measure the association of the single nucleotide polymorphisms with the severity of coronary arteries.</p><p><b>RESULTS</b>The minor allele frequency of -1612 5A/6A was 0.189, 0.185, 0.183 and 0.152 (P < 0.05 vs. non-CAD control and single stenosis), the minor allele frequency of -376C/G was 0.311, 0.329, 0.326 and 0.325, and the minor allele frequency of Glu45Lys was 0.367, 0.423, 0.417 and 0.405 in non-CAD control, CAD patients with single, two and three vessels stenosis, respectively. 5A allele frequency is significant lower in the group with three vessels stenosis than in non-CAD control and CAD patients with single vessel stenosis (OR = 0.74, P = 0.04). The 5A/5A and 5A/6A genotypes frequency is significant lower in the group with three vessels stenosis than in the non-CAD group and CAD patients with single vessel stenosis (OR = 0.74, P = 0.04).</p><p><b>CONCLUSIONS</b>The single nucleotide polymorphism of -1612 5A/6A of MMP-3 gene may be associated with the severity of coronary atherosclerosis in the Chinese Han patients with coronary artery disease, and the 5A allele might therefore, play a protective role on the progression of coronary atherosclerosis.</p>