李小林
中国医学科学院阜外医院 重症医学科
BACKGROUND:Elevation in small dense low-density lipoprotein (sdLDL) is common in patients with diabetes mellitus (DM), which has already been reported to be associated with incidence of coronary artery disease (CAD). The aim of the present study was to investigate the prognostic value of plasma sdLDL level in patients with stable CAD and DM.METHODS:A total of 4148 consecutive patients with stable CAD were prospectively enrolled into the study and followed up for major cardiovascular events (MACEs) up to 8.5 years. Plasma sdLDL level was measured in each patient by a direct method using automated chemistry analyzer. The patients were subsequently divided into four groups by the quartiles of sdLDL and the association of sdLDL level with MACEs in different status of glucose metabolism [DM, Pre-DM, normal glycaemia regulation (NGR)] was evaluated.RESULTS:A total of 464 MACEs were documented. Both Kaplan-Meier analysis and Cox regression analysis indicated that the patients in quartile 4 but not quartile 2 or 3 of sdLDL level had significantly higher rate of MACEs than that in lowest quartile. When the prognostic value of high sdLDL was assessed in different glucose metabolism status, the results showed that the high sdLDL plus DM was associated with worse outcome after adjustment of confounding risk factors (hazard ratio: 1.83, 95% confident interval: 1.24-2.70, p < 0.05). However, no significant association was observed for high sdLDL plus Pre-DM or NGR.CONCLUSIONS:The present study firstly indicated that elevated levels of plasma sdLDL were associated with increased risk of MACEs among DM patients with proven CAD, suggesting that sdLDL may be useful for CAD risk stratification in DM.
Cardiovascular diabetology 2020
BACKGROUND:The atherogenicity of remnant cholesterol (RC) has been underlined by recent guidelines, which was linked to coronary artery disease (CAD), especially for patients with diabetes mellitus (DM). This study aimed to examine the prognostic value of plasma RC in the patients with CAD under different glucose metabolism status.METHODS:Fasting plasma RC were directly calculated or measured in 4331 patients with CAD. Patients were followed for the occurrence of major adverse cardiovascular events (MACEs) and categorized according to both glucose metabolism status [DM, pre-DM, normoglycemia (NG)] and RC levels. Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals.RESULTS:During a mean follow-up of 5.1 years, 541 (12.5%) MACEs occurred. The risk for MACEs was significantly higher in patients with elevated RC levels after adjustment for potential confounders. No significant difference in MACEs was observed between pre-DM and NG groups (p > 0.05). When stratified by combined status of glucose metabolism and RC, highest levels of calculated and measured RC were significant and independent predictors of developing MACEs in pre-DM (HR: 1.64 and 1.98; both p < 0.05) and DM (HR: 1.62 and 2.05; both p < 0.05). High RC levels were also positively associated with MACEs in patients with uncontrolled DM. .CONCLUSIONS:In this large-scale and long-term follow-up cohort study, data firstly demonstrated that higher RC levels were significantly associated with the worse prognosis in DM and pre-DM patients with CAD, suggesting that RC may be a target for patients with impaired glucose metabolism.
Cardiovascular diabetology 2020
BACKGROUND:Recent guidelines highlighted the association between atherosclerosis and triglyceride-enriched lipoproteins in patients with impaired glucose metabolism. However, evidence from prospective studies for long-term prognostic utility of low-density lipoprotein triglyceride (LDL-TG) in real-world patients with prediabetes (Pre-DM) or diabetes mellitus (DM) and coronary artery disease (CAD) is currently not available. The aim of the present study was to evaluate the impact of LDL-TG on major adverse cardiovascular events (MACEs) in patients with stable CAD under different glucose metabolism status.METHODS:A total of 4381 patients with CAD were consecutively enrolled and plasma LDL-TG level was measured by an automated homogeneous assay. They were categorized according to both status of glucose metabolism [DM, Pre-DM, normal glycaemia regulation (NGR)] and tertiles of LDL-TG. All subjects were followed up for the occurrence of MACEs.RESULTS:During a median of 5.1 (interquartile range 3.9 to 5.9) years' follow-up, 507 (11.6%) MACEs occurred. Cubic spline models showed a significant association between LDL-TG and MACEs in DM and Pre-DM but not in NGR. When the combined effect of elevated LDL-TG and glucose disorders was considered for risk stratification, the medium tertile of LDL-TG plus DM, and the highest tertile of LDL-TG plus Pre-DM or plus DM subgroups were associated with significantly higher risk of MACEs after adjustment of confounders including triglyceride [hazard ratios (95% confidence intervals): 1.843 (1.149-2.955), 1.828 (1.165-2.867), 2.212 (1.396-3.507), all p < 0.05]. Moreover, adding LDL-TG into the original model increased the C-statistic from 0.687 to 0.704 (∆C-statistic = 0.016, p = 0.028) and from 0.734 to 0.749 (∆C-statistic = 0.014, p = 0.002) in Pre-DM and DM, respectively.CONCLUSIONS:In this longitudinal cohort study on real-world practice, higher LDL-TG was associated with worse outcomes among Pre-DM and DM patients with stable CAD.
Cardiovascular diabetology 2020
BACKGROUND AND AIMS:Familial hypercholesterolemia (FH) characterized by severe high blood cholesterol levels usually presents an imbalance of systemic oxidative stress (OS). Lipoprotein apheresis (LA), which is the most effective therapy to reduce cholesterol levels, remains unclear in altering OS and scarce in Chinese patient studies. Our study aims to assess the impact of LA on OS status in Chinese patients with FH.METHODS:About 31 patients (22 males, age: 12-69 years) with FH and receiving LA treatment were consecutive enrolled. Free oxygen radicals test (FORT) and free oxygen radicals defense (FORD) values were determined using the free oxygen radical monitor and kit immediately before and after LA, while blood samples were collected to measure plasma lipid levels and hs-CRP by conventional methods. Data were analyzed by paired t test or rank sum test and Spearman-rho correlation analysis.RESULTS:Besides plasma lipid levels, the OS status showed that FORTs were significantly decreased and FORD values significantly enhanced immediately after LA treatment compared with before (both P < .01). In addition, the correlation analysis showed that the removal rates (△%) of TC were positively related to the increased rates (△%) of FORD value (ρ = 0.513, P = .003); LDL-C to FORD (ρ = 0.39, P = .03); Lp(a) to FORD (ρ = 0.473, P = .007); and non-HDL-C to FORD (ρ = 0.46, P = .009). However, no significant difference in hsCRP was found.CONCLUSIONS:The present study indicated, besides effectively lowering plasma lipid levels, LA could significantly improve OS status in Chinese patients with FH.
Journal of clinical laboratory analysis 2020
It has been demonstrated that pitavastatin can significantly reduce low-density lipoprotein (LDL) cholesterol (LDL-C), but its impact on lipoprotein subfractions and oxidized low-density lipoprotein (oxLDL) has not been determined. The aim of the present study was to investigate the potential effects of pitavastatin on subfractions of LDL and high-density lipoprotein (HDL) as well as oxLDL in untreated patients with coronary atherosclerosis (AS). Thirty-six subjects were enrolled in this study. Of them, 18 patients with AS were administered pitavastatin 2 mg/day for 8 weeks and 18 healthy subjects without therapy served as controls. The plasma lipid profile, lipoprotein subfractions and circulating oxLDL were determined at baseline and 8 weeks respectively. The results showed that pitavastatin treatment indeed not only decreased LDL-C, total cholesterol (TC), triglycerides (TG) and apolipoprotein B (ApoB) levels, and increased HDL cholesterol (HDL-C), but also reduced the cholesterol concentration of all of the LDL subfractions and the percentage of intermediate and small LDL subfractions. Meanwhile, pitavastatin could decrease plasma oxLDL levels. Furthermore, a more close correlation was found between oxLDL and LDL-C as well as LDL subfractions after pitavastatin treatment. We concluded that a moderate dose of pitavastatin therapy not only decreases LDL-C and oxLDL concentrations but also improves LDL subfractions in patients with AS.
Current medical science 2020
BACKGROUND:Previous studies have clearly demonstrated that XueZhiKang (XZK), an extract of cholestin, can decrease low-density lipoprotein cholesterol (LDL-C) and cardiovascular events. However, the mechanism of the effects of XZK on atherosclerosis (AS) in humans has been reported less frequently. In the present study, we investigated the impact of XZK on lipoprotein subfractions, oxidized LDL (oxLDL), and interleukin-6 (IL-6).METHODS:From October 2015 to July 2016, 40 subjects were enrolled in this study. Of them, 20 subjects with dyslipidemia received XZK 1200 mg/day for 8 weeks (XZK group); 20 additional healthy subjects who did not receive therapy acted as controls. The plasma lipoprotein subfractions, oxLDL, and IL-6 were examined at baseline and again at 8 weeks.RESULTS:Data showed that XZK could significantly decrease not only plasma LDL-C levels (87.26 ± 24.45 vs. 123.34 ± 23.99, P < 0.001), total cholesterol (4.14 ± 0.87 vs. 5.08 ± 1.03, P < 0.001), triglycerides (0.95 ± 0.38 vs. 1.55 ± 0.61, P < 0.05), and apolipoprotein B (1.70 ± 0.35 vs. 1.81 ± 0.72, P < 0.05), but also oxLDL (36.36 ± 5.31 vs. 49.20 ± 15.01, P < 0.05) and IL-6 (8.50 ± 7.40 vs. 10.40 ± 9.49, P < 0.05). At the same time, XZK reduced the concentration of small LDL-C (1.78 ± 2.17 vs. 6.33 ± 7.78, P < 0.05) and the percentage of the small LDL subfraction (1.09 ± 1.12 vs. 3.07 ± 3.09, P < 0.05).CONCLUSIONS:Treatment with 1200 mg/day XZK for 8 weeks significantly decreased the atherogenic small LDL subfraction and reduced oxidative stress and inflammatory markers, in addition to affecting the lipid profile, suggesting multiple beneficial effects in coronary artery disease.
Chronic diseases and translational medicine 2018
Familial hypercholesterolemia (FH) is one of the most common causes of premature myocardial infarction (MI). However, The patterns of FH remained unrecognized in clinical care, especially in very young patients (VYPs, ≤35 years) with MI. The present study enrolled a total of 1,093 VYPs (≤35 years) presenting a first MI. Clinical diagnosis of FH was made using Dutch Lipid Clinic Network criteria. Coronary severity was assessed by Gensini score (GS). Patients were followed for a median of 40-months with cardiac death, stroke, MI, post-discharge revascularization or unstable angina as primary endpoints. The detected rates of definite/probable FH were 6.5%. The prevalence reached up to 10.3% in patients ≤25 years. The FH had similar levels of comorbidities but was younger, more likely to be very high risk (VHR) and had higher GS (p < 0.05) than unlikely FH. Notably, the FH on prior lipid-lowering medication presented a lower GS compared to those untreated. Differences in event rates were similar in FH as unlikely FH (11.8% vs. 8.1%, adjusted hazard ratio 1.35 [0.64-2.86], p = 0.434) but patients on treatment improved outcome (6.5% vs. 10.5%, adjusted hazard ratio 0.35[0.13-0.95], p = 0.039). The early identification and treatment might be critical to reduce cardiovascular risk in VYPs with MI.
Scientific reports 2018
Background Plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) has been reported to be related to several risk factors and diseases such as inflammatory markers and coronary artery disease. The aim of present study was to investigate whether plasma PCSK9 concentration was associated with coronary artery calcification. Methods A total of 403 consecutive untreated patients with angina-like chest pain, who received electron beam computed tomography, were enrolled and a coronary artery calcification score (CACS) was also measured. The baseline clinical characteristics were collected and blood sample was taken after 12-h fasting. The plasma PCSK9 concentrations were determined by ELISA in all patients, and the relationship between plasma PCSK9 concentrations and CACS was investigated. Results Patients with coronary artery calcification (CACS > 0) had significant higher plasma PCSK9 concentrations compared with those (CACS = 0) without coronary artery calcification (258.58 ± 69.53 ng/mL vs. 202.53 ± 52.17 ng/mL, P < 0.001). Patients with highest PCSK9 concentrations had the highest CACS. Multivariable linear regression analysis suggested that PCSK9 was independently associated with coronary artery calcification ( P = 0.002) after adjusting for traditional cardiovascular risk factors. Furthermore, the area under the curve for the plasma PCSK9 concentration in predicting coronary artery calcification was 0.736 (95% CI: 0.687-0.785, P < 0.001), with a sensitivity of 66% and specificity of 70%. Conclusion A positive association between plasma PCSK9 concentration and coronary artery calcification in untreated patients with angina-like chest pain was observed in our study, suggesting that further investigation may be needed in order to confirm our primary findings and explore the clinical implications.
Annals of clinical biochemistry 2018
OBJECTIVES:Although previous studies have demonstrated the relationship between ABO blood groups and cardiovascular disease, the association of ABO blood type with spontaneous recanalization (SR) in patients with acute myocardial infarction (AMI) has not been previously investigated.METHODS:We performed an initial exploratory study on the association of ABO blood groups with the presence of SR in 1209 patients with AMI. They were divided into two groups according to the thrombolysis in myocardial infarction (TIMI) grades: no-SR group (TIMI 0-1, n = 442) and SR group (TIMI 2-3, n = 767). To confirm our primary findings, data from a second AMI population (n = 200) was analyzed.RESULTS:In the initial data, SR group had a significantly higher percentage of blood type O and a lower percentage of blood type A compared to the no-SR group. Multivariate logistic regression analysis showed that blood type O was positively associated with SR (odds ratio: 1.40, 95% confidence interval: 1.05-1.87, p = .02), and this finding was confirmed in our second population.CONCLUSION:The present study demonstrates that blood type O was independently and positively associated with an open culprit artery in patients with AMI, suggesting that the ABO blood type is not only associated with the susceptibility to coronary artery disease but also to spontaneous reperfusion in AMI patients.
Scandinavian cardiovascular journal : SCJ 2017
Fibrinogen (Fib) is a useful marker for predicting the severity of coronary artery disease (CAD) in adult population. However, whether Fib can be a predictor for the presence and severity of CAD in very young MI patients (≤35 years old) remains to be determined. A total of 418 males from 61,863 patients with MI who were under 35 years old were sequentially recruited in our study. The patients were divided into two main groups and three subgroups according to coronary angiograph and Gensini score (GS) system: no coronary artery stenosis (group A), the results of the coronary artery stenosis (group B); low GS, intermediate GS and high GS. Data indicated that Fib, body mass index, current smoking, white blood cell count (WBCC) and GS were significantly higher in group B than those in group A (all P < 0.01). Moreover, there were significant differences in Fib, mean age, diabetes mellitus, family history of CAD, WBCC, left ventricular ejection fraction, and GS between high GS and low GS subgroups (all P < 0.01). A positive correlation between Fib levels and GS was found (r = 0.242, p < 0.001). Receiver operating characteristics curve analysis demonstrated that the best cut-off level of Fib predicting the severity of coronary stenosis was 3.475g/L (sensitivity 64%; specificity 70%) and the area under the curve was 0.656. Fib was also independently associated with high GS (OR=2.173, 95%CI 1.011-4.670, P = 0.047) after adjusting for potential confounders. In conclusion, Fib is significantly related to the presence and severity of coronary stenosis in male patients with MI under 35 years old.
Oncotarget 2017
