-
1.
ACE Inhibitor Benefit to Kidney and Cardiovascular Outcomes for Patients with Non-Dialysis Chronic Kidney Disease Stages 3-5: A Network Meta-Analysis of Randomised Clinical Trials.
Zhang, Y, He, D, Zhang, W, Xing, Y, Guo, Y, Wang, F, Jia, J, Yan, T, Liu, Y, Lin, S
Drugs. 2020;(8):797-811
-
-
Free full text
-
Abstract
BACKGROUND The advantages of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) in reducing risk of cardiovascular events (CVEs) and delaying end-stage kidney disease (ESKD) in patients with chronic kidney disease (CKD) is well-known. However, the efficacy and safety of these agents in non-dialysis CKD stages 3-5 patients are still a controversial issue. METHODS Two investigators (Yaru Zhang and Dandan He) independently searched and identified relevant studies from MEDLINE (from 1950 to October 2018), EMBASE (from 1970 to October 2018), and the Cochrane Library database. Randomised clinical trials in non-dialysis CKD3-5 patients treated with renin-angiotensin system (RAS) inhibitors were included. We used standard criteria (Cochrane risk of bias tool) to assess the inherent risk of bias of trials. We calculated the odds ratio (OR) and 95% confidence interval (CI) for each outcome by random-effects model. A 2-sided p value < 0.05 was considered statistically significant, and all statistical analyses were performed using STATA, version 15.0. This network meta-analysis was undertaken by the frequency model. RESULTS Forty-four randomised clinical trials with 42,319 patients were included in our network meta-analysis. ACEIs monotherapy significantly decreased the odds of kidney events (OR 0.54, 95% CI 0.41-0.73), cardiovascular events (OR 0.73, 95% CI 0.64-0.84), cardiovascular death (OR 0.73, 95% CI 0.63-0.86) and all-cause death (OR 0.77, 95% CI 0.66-0.91) when compared to placebo. According to the cumulative ranking area (SUCRA), ACEI monotherapy had the highest probabilities of their protective effects on outcomes of kidney events (SUCRA 93.3%), cardiovascular events (SUCRA 77.2%), cardiovascular death (SUCRA 86%), and all-cause death (SUCRA 94.1%), even if there were no significant differences between ACEIs and other antihypertensive drugs, including calcium channel blockers (CCBs), β-blockers and diuretics on above outcomes except for kidney events. ARB monotherapy and combination therapy of an ACEI plus an ARB showed no more advantage than CCBs, β-blockers and diuretics in all primary outcomes. In the subgroup of non-dialysis diabetic kidney disease patients, no drugs, including ACEIs or ARBs, significantly lowered the odds of cardiovascular events and all-cause death. However, ACEIs were still better than other antihypertensive drugs including ARBs in all-cause death but not ARBs in cardiovascular events according to the SUCRA. Only ARBs had significant differences in preventing the occurrence of kidney events compared with placebo (OR 0.82, 95% CI 0.72-0.95). Both ACEI/ARB monotherapy and combination therapy had higher odds of hyperkalaemia. ACEIs had 3.81 times higher odds than CCBs (95% CI 1.58-9.20), ARBs had 2.08-5.10 times higher odds than placebo and CCBs and combination therapy of an ACEI and an ARB had 4.80-24.5 times higher odds than all other treatments. Compared with placebo, CCBs and β blockers, ACEI therapy significantly increased the odds of cough (OR 2.90, 95% CI 1.76-4.77; OR 8.21, 95% CI 3.13-21.54 and OR 1.80, 95% CI 1.08-3.00). There were no statistical differences in hypotension among all comparisons except ACEIs versus placebo. CONCLUSIONS Although ACEIs increased the odds of hyperkalaemia, cough and hypotension, they were still superior to ARBs and other antihypertensive drugs and had the highest benefits for the prevention of kidney events, cardiovascular outcomes, cardiovascular death and all-cause mortality in non-dialysis CKD3-5 patients. In patients with advanced diabetic kidney disease, ACEIs were superior to ARBs in lowering risk of all-cause death but not in kidney events and cardiovascular events.
-
2.
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Alirocumab in Healthy Chinese Subjects: A Randomized, Double-Blind, Placebo-Controlled, Ascending Single-Dose Study.
Li, H, Wei, Y, Yang, Z, Zhang, S, Xu, X, Shuai, M, Vitse, O, Wu, Y, Baccara-Dinet, MT, Zhang, Y, et al
American journal of cardiovascular drugs : drugs, devices, and other interventions. 2020;(5):489-503
-
-
Free full text
-
Abstract
BACKGROUND The addition of alirocumab (a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 [PCSK9]) to background statin therapy provides significant incremental low-density lipoprotein cholesterol (LDL-C) lowering and cardiovascular event risk reduction. OBJECTIVES Our objectives were to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses of alirocumab in healthy Chinese subjects. METHODS In this double-blind, placebo-controlled, phase I study, 35 Chinese subjects (aged 21-45 years) with baseline LDL-C > 100 mg/dL (2.59 mmol/L) were randomized to receive a single 1 mL subcutaneous injection of alirocumab 75, 150, or 300 mg, or placebo, and followed up for ~ 12 weeks. RESULTS Treatment-emergent adverse events, most frequently nasal congestion and dry throat, were reported in three of seven or eight subjects in each alirocumab dose group (two of seven in the placebo group). One patient receiving alirocumab 300 mg had a mild local injection-site reaction. No alirocumab recipients demonstrated antidrug antibodies. Maximum alirocumab serum concentrations (6-34 mg/dL) occurred at a median of 3-7 days across the dose groups. Maximum mean LDL-C reductions from baseline were observed on days 8, 15, and 22 with alirocumab 75 (55.3%), 150 (63.7%), and 300 mg (73.7%), respectively. Mean free PCSK9 levels were reduced to below the lower limit of quantification within 4 h of dosing. Total cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B were reduced with alirocumab. CONCLUSIONS In Chinese subjects, alirocumab 75, 150, and 300 mg was safe and well-tolerated. Pharmacokinetic/pharmacodynamic parameters, including clinically meaningful reductions in LDL-C and other lipids/lipoproteins, were consistent with data from Japanese and Western populations. Clinicaltrials.gov identifier: NCT02979015.
-
3.
Serum magnesium, mortality, and cardiovascular disease in chronic kidney disease and end-stage renal disease patients: a systematic review and meta-analysis.
Xiong, J, He, T, Wang, M, Nie, L, Zhang, Y, Wang, Y, Huang, Y, Feng, B, Zhang, J, Zhao, J
Journal of nephrology. 2019;(5):791-802
Abstract
BACKGROUND Previous studies reported that magnesium deficiency was associated with vascular calcifications, atherosclerosis and cardiovascular disease, which might play an independent pathogenic role in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. However, the results of these studies were somewhat underpowered and inconclusive. METHODS Literature was identified by searching PubMed, EMBASE, Web of Science and the Cochrane Central Register of Controlled Trials (CENTRAL). We included studies that investigated the association between serum magnesium with mortality risk in CKD and ESRD patients. Unadjusted and adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) were pooled. RESULTS Twenty studies involving 200,934 participants were included, and the results showed that there was a strong association between hypomagnesemia and the risk of all-cause mortality in patients with CKD and ESRD (HR 1.32; 95% CI 1.19-1.47; p < 0.00001) (hypomagnesemia vs. normal magnesium or hypermagnesemia) after multivariable adjusted. On the contrary, hypermagnesemia was inversely associated with all-cause mortality in patients with CKD and ESRD (HR 0.86; 95% CI 0.79-0.94; p = 0.001) (per unit increase). Moreover, a significant association between hypermagnesemia and decreased risk of cardiovascular mortality was observed (HR 0.71; 95% CI 053-0.97, p = 0.03) in the adjusted model. In addition, subgroup analysis found that hypomagnesemia was strongly associated with increased all-cause mortality in hemodialysis patients (HR 1.29; 95% CI 1.12-1.50; p = 0.0005) (hypomagnesemia vs. normal magnesium or hypermagnesemia). CONCLUSIONS Our results indicate that hypomagnesemia is significantly associated with cardiovascular and all-cause mortality in patients with CKD and ESRD. Further studies evaluating benefits of magnesium correction in CKD and dialysis patients with hypomagnesemia should be performed.
-
4.
Serum apolipoproteins and apolipoprotein-defined lipoprotein subclasses: a hypothesis-generating prospective study of cardiovascular events in T1D.
Basu, A, Bebu, I, Jenkins, AJ, Stoner, JA, Zhang, Y, Klein, RL, Lopes-Virella, MF, Garvey, WT, Budoff, MJ, Alaupovic, P, et al
Journal of lipid research. 2019;(8):1432-1439
Abstract
APOB, APOC3, and APOE and apolipoprotein-defined lipoprotein subclasses (ADLSs; based on qualitative apolipoprotein complement) have been associated with dyslipidemia and CVD. Our main objective was to define associations of serum apolipoproteins and ADLSs with "any CVD" and "major atherosclerotic cardiovascular events" (MACEs) in a prospective study of T1D. Serum apolipoproteins and ADLSs (14 biomarkers in total) were measured in sera (obtained between 1997 and 2000) from a subset (n = 465) of the Epidemiology of Diabetes Interventions and Complications cohort. Prospective associations of "any CVD" (myocardial infarction, stroke, confirmed angina, silent myocardial infarction, revascularization, or congestive heart failure) and MACEs (fatal or nonfatal myocardial infarction or stroke), over 5,943 and 6,180 patient-years follow-up, respectively, were investigated using Cox proportional hazards models that were unadjusted and adjusted for risk factors. During 15 years of follow-up, 50 "any CVD" events and 24 MACEs occurred. Nominally significant positive univariate associations with "any CVD" were APOB, APOC3 and its subfractions [heparin precipitate, heparin-soluble (HS)], and ADLS-defined Lp-B. In adjusted analyses, APOC3-HS remained nominally significant. Nominally significant positive univariate associations with MACEs were APOC3 and its subfractions and Lp-B:C; those with total APOC3 and APOC3-HS persisted in adjusted analyses. However, these associations did not reach significance after adjusting for multiple testing. There were no significant associations of APOA1, APOA2, APOE, or other ADLSs with either "any CVD" or MACEs. These hypothesis-generating data suggest that total serum APOC3 and APOC3 in HDL are potentially important predictive biomarkers for any CVD and MACEs in adults with T1D.
-
5.
Traditional Chinese Medicine for Cardiovascular Disease: Evidence and Potential Mechanisms.
Hao, P, Jiang, F, Cheng, J, Ma, L, Zhang, Y, Zhao, Y
Journal of the American College of Cardiology. 2017;(24):2952-2966
Abstract
Traditional Chinese medicine (TCM) has more than 2,000 years of history and has gained widespread clinical applications. However, the explicit role of TCM in preventing and treating cardiovascular disease remains unclear due to a lack of sound scientific evidence. Currently available randomized controlled trials on TCM are flawed, with small sample sizes and diverse outcomes, making it difficult to draw definite conclusions about the actual benefits and harms of TCM. Here, we systematically assessed the efficacy and safety of TCM for cardiovascular disease, as well as the pharmacological effects of active TCM ingredients on the cardiovascular system and potential mechanisms. Results indicate that TCM might be used as a complementary and alternative approach to the primary and secondary prevention of cardiovascular disease. However, further rigorously designed randomized controlled trials are warranted to assess the effect of TCM on long-term hard endpoints in patients with cardiovascular disease.
-
6.
Analysis of Lipoprotein Subfractions in 920 Patients With and Without Type 2 Diabetes.
Zhao, X, Zhang, HW, Zhang, Y, Li, S, Xu, RX, Sun, J, Zhu, CG, Wu, NQ, Gao, Y, Guo, YL, et al
Heart, lung & circulation. 2017;(3):211-218
Abstract
BACKGROUND It has been demonstrated that diabetic dyslipidaemia is the chief bridge between diabetes and incremental risk of cardiovascular disease in patients with diabetes. However, the characteristics of lipoprotein subfractions distribution in patients with type 2 diabetes (T2D) have not been fully investigated. The aim of present study was to evaluate the distributions of lipoprotein subfractions in T2D patients. METHODS A total of 920 patients, who have not received lipid-lowering drug treatment previously, were consecutively enrolled in this study. Based on the evidence of diabetes, patients were divided into T2D group (n=204) and non-T2D group (n=716). Both low- and high-density lipoprotein cholesterol (LDL- and HDL-C) subfractions were analysed using the Quantimetrix Lipoprint System. The distributions of lipoprotein subfractions were evaluated in patients with and without T2D. RESULTS Compared with non-T2D individuals, the T2D group manifested significantly lower large HDL-C concentration/HDL subfraction percentage, smaller mean LDL particle size but higher small HDL-C and LDL-C concentrations as well as small HDL and LDL subfraction percentages. Moreover, the data indicated that the small HDL-C/ LDL-C concentrations, the small and large HDL subfraction percentages along with the mean LDL particle size were independently related to the existence of T2D (95% CI=1.009-1.067, p=0.009; 95% CI=0.938-0.983, p=0.001; 95% CI=1.023-1.135, p=0.005; 95% CI= 1.005-1.048, p=0.014; 95% CI=0.940-0.999, p=0.040; respectively) assessed by logistic regression analysis. CONCLUSIONS The present study indicated that the changes of lipid profile in patients with T2D are characterised by abnormal distributions of lipoprotein subfractions apart from clinically atherogenic dyslipidaemia.
-
7.
Nut consumption and risk of type 2 diabetes, cardiovascular disease, and all-cause mortality: a systematic review and meta-analysis.
Luo, C, Zhang, Y, Ding, Y, Shan, Z, Chen, S, Yu, M, Hu, FB, Liu, L
The American journal of clinical nutrition. 2014;(1):256-69
-
-
Free full text
-
Abstract
BACKGROUND Epidemiologic studies have shown inverse associations between nut consumption and diabetes, cardiovascular disease (CVD), and all-cause mortality, but results have not been consistent. OBJECTIVE We assessed the relation between nut intake and incidence of type 2 diabetes, CVD, and all-cause mortality. DESIGN We searched PubMed and EMBASE for all prospective cohort studies published up to March 2013 with RRs and 95% CIs for outcomes of interest. A random-effects model was used to pool risk estimates across studies. RESULTS In 31 reports from 18 prospective studies, there were 12,655 type 2 diabetes, 8862 CVD, 6623 ischemic heart disease (IHD), 6487 stroke, and 48,818 mortality cases. The RR for each incremental serving per day of nut intake was 0.80 (95% CI: 0.69, 0.94) for type 2 diabetes without adjustment for body mass index; with adjustment, the association was attenuated [RR: 1.03; 95% CI: 0.91, 1.16; NS]. In the multivariable-adjusted model, pooled RRs (95% CIs) for each serving per day of nut consumption were 0.72 (0.64, 0.81) for IHD, 0.71 (0.59, 0.85) for CVD, and 0.83 (0.76, 0.91) for all-cause mortality. Pooled RRs (95% CIs) for the comparison of extreme quantiles of nut intake were 1.00 (0.84, 1.19; NS) for type 2 diabetes, 0.66 (0.55, 0.78) for IHD, 0.70 (0.60, 0.81) for CVD, 0.91 (0.81, 1.02; NS) for stroke, and 0.85 (0.79, 0.91) for all-cause mortality. CONCLUSIONS Our meta-analysis indicates that nut intake is inversely associated with IHD, overall CVD, and all-cause mortality but not significantly associated with diabetes and stroke. The inverse association between the consumption of nuts and diabetes was attenuated after adjustment for body mass index. These findings support recommendations to include nuts as part of a healthy dietary pattern for the prevention of chronic diseases.