0
selected
-
1.
High-Sensitivity C-Reactive Protein Combined with Low-Density Lipoprotein Cholesterol as the Targets of Statin Therapy in Patients with Acute Coronary Syndrome.
Fang, M, Qian, Q, Zhao, Z, Zhu, L, Su, J, Li, X
International heart journal. 2018;(2):300-306
Abstract
To investigate the combination of high-sensitivity C-reactive protein (hs-CRP) and Low-density lipoprotein (LDL)-C as the targets for statin treatment in patients with acute coronary syndrome (ACS). This single-center, prospective, randomized study was performed in 400 patients treated with atorvastatin 40 mg/day for 1 month and then with atorvastatin 20 mg/day as maintenance. The patients were randomized to the LDL group (LDL-C target of < 2.07 mmol/L according to the Chinese dyslipidemia guidelines) and to the LDL-CRP group (LDL-C target of < 2.07 mmol/L and hs-CRP target of < 3 mg/L). The patients were followed up for major adverse cardiac events (MACE) at 6, 12, and 18 months. The two groups had similar baseline characteristics and 391 patients completed the follow-up. No differences were found in LDL-C between the two groups, but a difference was found in hs-CRP at 12 and 18 months. There was a significant difference in revascularization (8.7% versus 3.6%, P = 0.04) and MACE (16.8% versus 9.7%; P = 0.04) between the LDL and LDL-CRP groups at 18 months. Compared to LDL-C as the single target, targeting both LDL-C and hs-CRP by statin therapy in patients with ACS could further reduce the incidence of MACE and the residual cardiovascular risk.
-
2.
Prescription of statins at discharge and 1-year risk of major clinical outcomes among acute coronary syndromes patients with extremely low LDL-cholesterol in clinical pathways for acute coronary syndromes studies.
Sun, Y, Xie, G, Patel, A, Li, S, Zhao, W, Yang, X, Wu, T, Li, M, Li, X, Du, X, et al
Clinical cardiology. 2018;(9):1192-1200
Abstract
OBJECTIVE The aim of this study was to investigate statin description on discharge and the benefit on the long-term outcomes in acute coronary syndromes (ACS) patients with very low baseline LDL-cholesterol (LDL-c). METHODS This is a post-hoc analysis of 3374 ACS patients who were discharged alive and had baseline LDL-c levels below 70 mg/dL (1.8 mmol/L). The propensity score of using statin was estimated with a multivariable Logistic model including patient's demography, social economic status, cardiovascular risk factors, subtype of the diagnosis, and treatments received during hospitalization and current LDL-c level. The risk of major adverse cardiovascular events (MACEs) was compared between patients received and not-received statin with Cox-regression models adjusting for the propensity score plus other factors. A sensitivity analysis was done in propensity score matched patients. RESULTS Compared with nonstatin group, the incidence of MACE at 12 months after discharge was lower in the statin group (11.1% vs 5.8%; P < 0.001). The propensity score plus other factors-adjusted hazard ratios for MACEs was significant (0.58; 95% CI: 0.39, 0.87). The effect showed a significant dose-response relationship (P for trend = 0.02). The results in analyses with propensity-score matched participants were in consistent with above findings. Analyses on total mortality in 12 months showed similar results. CONCLUSIONS Among ACS survivors with a very low baseline LDL-c, low to moderate intensity statin therapy was associated significantly with lower risk of MACEs and total mortality at 12 months. The results suggested that ACS survivors should take statin regardless of the baseline of LDL-c.
-
3.
Impact of matrix metalloproteinase 9 rs3918242 genetic variant on lipid-lowering efficacy of simvastatin therapy in Chinese patients with coronary heart disease.
Xu, Y, Wang, Y, Zhi, J, Qi, L, Zhang, T, Li, X
BMC pharmacology & toxicology. 2017;(1):28
Abstract
BACKGROUND Genetic variation of matrix metalloproteinase 9 (MMP-9) gene polymorphism has been suggested to modulate coronary heart diseases (CHD), yet the underlying mechanisms are not well understood. METHODS We investigated the association of MMP9 rs3918242 single nucleotide polymorphism with inflammation and lipid-lowering efficacy after simvastatin treatment in Chinese patients with CHD. Fasting serum lipid profile and plasma inflammatory mediators were determined at baseline in 264 patients with CHD and 186 healthy control subjects, and after HMG-CoA reductase inhibitor simvastatin treatment (20 mg/day) for 12 weeks in CHD subjects. RESULTS We found that plasma MMP-9, TNF-α and IL-10 levels were significantly elevated in patients with CHD compared to control subjects before treatment. The plasma MMP9 in CHD patients carrying rs3918242 CC, CT and TT genotypes were comparable. Interestingly, CHD patients carrying TT genotype had significantly higher level of triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) than those carrying CC genotype (P <0.05). Simvastatin treatment significantly reduced LDL-C, TG and plasma inflammatory mediator levels in CHD patients. The reduction of LDL-C upon simvastatin therapy was significantly greater in patients carrying TT genotype than those carrying CC genotype (P <0.05). CONCLUSIONS MMP9 rs3918242 TT genotype is associated with elevated serum TG and LDL-C, and enhanced LDL-C-lowering response upon simvastatin treatment in Chinese patients with CHD. CLINICAL TRIAL REGISTRATION This study was retrospectively registered at Chinese Clinical Trial Registry (Registration number: ChiCTR-ROC-17010971 ) on March 23rd 2017.
-
4.
Rooted in risk: genetic predisposition for low-density lipoprotein cholesterol level associates with diminished low-density lipoprotein cholesterol response to statin treatment.
Smit, RA, Postmus, I, Trompet, S, Barnes, MR, Warren, H, Arsenault, BJ, Chasman, DI, Cupples, LA, Hitman, GA, Krauss, RM, et al
Pharmacogenomics. 2016;(15):1621-1628
-
-
Free full text
-
Abstract
AIMS: To utilize previously reported lead SNPs for low-density lipoprotein cholesterol (LDL-c) levels to find additional loci of importance to statin response, and examine whether genetic predisposition to LDL-c levels associates with differential statin response. METHODS We investigated effects on statin response of 59 LDL-c SNPs, by combining summary level statistics from the Global Lipids Genetics and Genomic Investigation of Statin Therapy consortia. RESULTS Lead SNPs for APOE, SORT1 and NPC1L1 were associated with a decreased LDL-c response to statin treatment, as was overall genetic predisposition for increased LDL-c levels as quantified with 59 SNPs, with a 5.4% smaller statin response per standard deviation increase in genetically raised LDL-c levels. CONCLUSION Genetic predisposition for increased LDL-c level may decrease efficacy of statin therapy.
-
5.
Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins.
Postmus, I, Trompet, S, Deshmukh, HA, Barnes, MR, Li, X, Warren, HR, Chasman, DI, Zhou, K, Arsenault, BJ, Donnelly, LA, et al
Nature communications. 2014;:5068
Abstract
Statins effectively lower LDL cholesterol levels in large studies and the observed interindividual response variability may be partially explained by genetic variation. Here we perform a pharmacogenetic meta-analysis of genome-wide association studies (GWAS) in studies addressing the LDL cholesterol response to statins, including up to 18,596 statin-treated subjects. We validate the most promising signals in a further 22,318 statin recipients and identify two loci, SORT1/CELSR2/PSRC1 and SLCO1B1, not previously identified in GWAS. Moreover, we confirm the previously described associations with APOE and LPA. Our findings advance the understanding of the pharmacogenetic architecture of statin response.