The Functional Changes of the Perivascular Adipose Tissue in Spontaneously Hypertensive Rats and the Effects of Atorvastatin Therapy

The aim of this study was to examine the function of perivascular adiposa tissue (PVAT) on vascular relaxation response in spontaneously hypertensive rats (SHR) and the modulatory effects of the atorvastatin therapy on the PVAT functions. We investigated the mechanisms of the perivascular adipocyte-derived relaxation factor (PVRF) by using isolated rat's aortic rings and isometric contraction measurements. We found that contraction of the thoracic aorta induced by phenylephrine was significantly attenuated in the presence of PVAT from normotensive Wistar-Kyoto rats (WKY group) or the spontaneously hypertensive rats treated with atorvastatin (SHR-A group, atorvastatin 50mg/kg/day), whereas this effect was not observed in the thoracic aortic rings from the control SHR (SHR group). Transferring the solution incubated with PVAT-intact thoracic aorta to PVAT-free thoracic aorta, it induced a remarkable relaxation response in the WKY but not in the control SHR. Tetraethylammoniumchloride (TEA) could block the above relaxation. It was also shown that the PVRF function was likely, depending on the extracellular [Ca²⁺]; the anti-contractile effect of PVAT could be reduced by the inhibitor of the adenosine triphosphate (ATP)-dependent potassium channels, glibenclamide, and could be reduced by the inhibitor of cyclooxygenase by indomethacin. We thus infer that the PVAT function was distorted in hypertension rats, and the lipid-lowering treatment with atorvastatin could restore the PVAT function. The function of the PVRF may involve the Ca²⁺-activated potassium channels, the ATP-dependent potassium channels in vascular smooth muscle cell (SMC), and the release of PVRF from PVAT may involve prostaglandins (PGs) and the calcium metabolism. These results provide an insight into the pathological mechanisms of hypertension development, and indicate that the PVAT may be a potential new target for the hypertensive therapy.     

Statins and stroke prevention

Over the past decade, statins have been proved to significantly decrease coronary events in the primary and secondary prevention of coronary artery disease. Recent clinical trials have indicated that statins significantly reduce stroke risk in patients with vascular disease. A meta-analysis of randomized trials of statins in combination with other preventive strategies, involving 165,792 individuals, showed that each 1-mmol/l (39 mg/dl) decrease in LDL-cholesterol equates to a reduction in relative risk for stroke of 21.1 (95% CI: 6.3–33.5; p = 0.009). It is not known whether these findings might be due to the cholesterol-reduction effect of statins or to the pleiotropic effects of statins, such as improved endothelial function, decreased platelet aggregability and reduced vascular inflammation. In the secondary prevention of stroke, The Stroke Prevention by Aggressive Reduction of Cholesterol Levels study found that treatment with atorvastatin reduced the risk of recurrent cerebrovascular events in patients with recent stroke or transient ischemic attack but no history of heart disease.     

Extended-release niacin/lovastatin: the first combination product for dyslipidemia

Many clinical studies have demonstrated that lipid-altering drug treatments, including the use of statin and niacin monotherapy, can be effective in the primary and secondary prevention of coronary heart disease, but only in a minority of patients relative to placebo. Since statins and niacin have entirely different mechanisms of action and predominantly different effects on blood lipid levels, the combined use of both a statin and niacin may confer complementary benefits on multiple lipid parameters, produce a more global improvement in lipid blood levels and result in greater reductions in coronary heart disease risk factors than the administration of either agent alone. This may be of particular importance in patients with complex dyslipidemias, such as those with Type 2 diabetes mellitus and metabolic syndrome. This review summarizes the efficacy and safety of extended-release niacin/lovastatin (Advicor^®, Kos Pharmaceuticals Inc.), the first combination product approved for the management of dyslipidemia.     

缺血性脑血管病二级预防他汀类药物应用现况调查

目的:了解北京市部分二级医院缺血性脑血管病二级预防他汀类药物应用现状,为改进缺血性脑血管病二级预防工作提供依据。方法:本研究为现况调查,研究对象为北京市4家二级医院中诊断为急性动脉粥样硬化性脑梗死及短暂性脑缺血发作(TIA)的住院患者,调查患者住院期间以及出院3个月他汀类药物的应用现况。结果:入选患者共458例,其中408例完成了3月随访。住院期间他汀类药物的应用比率为35.6%;出院3月,他汀类药物的用药比率降为22.3%,与住院期间相比有明显差异(p<0.001);而依从性差的原因与患者的性别、经济负担、学历、危险因素的存在与否及脑血管病亚型(脑梗死或TIA)均无明显相关。3月随访发现缺血性脑血管事件发生率为4.9%(20例),冠脉综合征0.5%(2例),且22例血管事件复发患者中仅有9.1%(2例)坚持他汀治疗。结论:北京市部分二级医院脑血管病医生对他汀类调脂药用于缺血性脑血管病二级预防已经有了一定程度的认识,但与卒中降脂指南尚有距离,同时我们应对缺血性脑血管病患者他汀用于缺血性脑血管病二级预防的依从性给予关注。     

早期他汀序贯治疗在行经皮冠状动脉介入治疗冠心病患者中的临床应用

目的评价冠心病行经皮冠状动脉介入治疗（PCI）患者中早期应用阿托伐他汀序贯治疗方法的安全性和有效性。方法170例冠心病患者随机分为序贯治疗组和常规治疗组,每组85例。比较两组基线资料,随访观察治疗前后1周、1个月、3个月、6个月的总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、肝功能、肾功能、肌酸激酶（CK）、超敏C反应蛋白（hsCRP）等生化指标的变化以及不良事件和不良反应的发生情况。结果两组治疗后LDL-C和TC的水平较治疗前均有显著下降（P〈0．05）。两组1周时LDL-C和TC的下降幅度差异有统计学意义（LDL-C：31．2％vs12．5％;TC：29．2％vs13．1％;P〈0．05）,1个月时在原有基础上进一步降低,两组差异有统计学意义（LDL-C：43．0％vs17．6％;TC：41．3％vs22．3％：P〈0．05）。3个月和6个月时,两组间LDL-C和TC变化无统计学差异（P〉0．05）。序贯治疗组1周、1个月、3个月时LDL-C的达标率明显高于常规治疗组（1周：48．2％ vs 25．9％;1个月：77．6％vs60．0％;3个月：81．2％vs68．2％;P〈0．05）。与治疗前相比,两组均可显著降低hs-CRP的水平,序贯治疗组1周和1个月时hs-CRP降低幅度明显大于常规治疗组f序贯治疗组治疗前（8．17±5．69）mg／L,1周时（4．23±2．43）mg／L,1个月时（1．96±0．77）mg／L;常规治疗组治疗前（7．75±4．31）mg／L,1周时（4．87±2．70）mg／L,1个月时（3．21±1．27）mg／L;P＜0．05]。序贯治疗组6个月内主要心血管事件发生率明显低于常规治疗组（5．9％vs15．3％,P〈0．05）,序贯治疗组比常规治疗组风险进一步降低了9．4％。序贯治疗组不良反应轻微,两组不良反应发生率差异无统计学意义（P〉0．05）。结论他汀序贯治疗的疗效和安全性良好,可以明显改善冠心病PCI术患者的临床预后。     

Statin Use in Relation to Intraocular Pressure,Glaucoma, and Ocular Coherence Tomography Parameters in the UK Biobank

PurposeThe purpose of this study was to evaluate the relationship between statin use and glaucoma-related traits.MethodsIn a cross-sectional study, we included 118,153 UK Biobank participants with data on statin use and corneal-compensated IOP. In addition, we included 192,283 participants (8982 cases) with data on glaucoma status. After excluding participants with neurodegenerative diseases, 41,638 participants with macular retinal nerve fiber layer thickness (mRNFL) and 41,547 participants with macular ganglion cell inner plexiform layer thickness (mGCIPL) were available for analysis. We examined associations of statin use with IOP, mRNFL, mGCIPL, and glaucoma status utilizing multivariable-adjusted regression models. We assessed whether a glaucoma polygenic risk score (PRS) modified associations. We performed Mendelian randomization (MR) experiments to investigate associations with various glaucoma-related outcomes.ResultsStatin users had higher unadjusted mean IOP ± SD than nonusers, but in a multivariable-adjusted model, IOP did not differ by statin use (difference = 0.05 mm Hg, 95% confidence interval [CI] = −0.02 to 0.13, P = 0.17). Similarly, statin use was not associated with prevalent glaucoma (odds ratio [OR] = 1.05, 95% CI = 0.98 to 1.13). Statin use was weakly associated with thinner mRNFL (difference = −0.15 microns, 95% CI = −0.28 to −0.01, P = 0.03) but not with mGCIPL thickness (difference = −0.12 microns, 95% CI = −0.29 to 0.05, P = 0.17). No association was modified by the glaucoma PRS (P_interaction ≥ 0.16). MR experiments showed no evidence for a causal association between the cholesterol-altering effect of statins and several glaucoma traits (inverse weighted variance P ≥ 0.14).ConclusionsWe found no evidence of a protective association between statin use and glaucoma or related traits after adjusting for key confounders.     

Decrease of hemostatic cardiovascular risk factors by aggressive vs. conventional atorvastatin treatment in patients with Type 2 diabetes mellitus

Summary.  Background : Patients with Type 2 diabetes mellitus have increased levels of hemostatic risk variables for cardiovascular disease, such as fibrinogen, von Willebrand factor (VWF), factor (F)VIIa, d -dimer and plasminogen activator inhibitor-1 (PAI-1). Objectives : To evaluate the effect of aggressive vs. standard dose atorvastatin on hemostatic cardiovascular risk factors in patients with Type 2 diabetes mellitus. Patients and methods : The effect of 30 weeks of treatment with atorvastatin 10 and 80 mg on hemostatic cardiovascular risk factors was assessed in a randomized double-blind placebo-controlled trial on 217 patients with Type 2 diabetes mellitus and dyslipidemia. Results and conclusions : Atorvastatin 10 and 80 mg dose-dependently reduced d -dimer (7.4% and 8.5%, respectively, P for trend = 0.004) and PAI-1 antigen levels (9.0% and 18%, respectively, P for trend = 0.021). Levels of fibrinogen, VWF, tissue-type plasminogen activator and FVIIa were not influenced by atorvastatin. In conclusion, in patients with Type 2 diabetes mellitus, atorvastatin dose-dependently improved the levels of the hemostatic risk variables d -dimer and PAI-1.     

In vitro inhibitory effects of atorvastatin on cardiac fibroblasts: implications for ventricular remodelling

1. Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors (statins) reduce mortality after myocardial infarction (MI). Although this may be predominantly due to their known anti-ischaemic actions, these drugs are known to have other beneficial effects. 2. Because pathological deposition of extracellular matrix (ECM) material is a key component of remodelling after MI, we sought to determine whether atorvastatin could inhibit ECM production in vitro. 3. The addition of atorvastatin to rat cardiac fibroblasts stimulated with either transforming growth factor (TGF)-beta1 (TGF-beta1) or angiotensin (Ang) II reduced collagen synthesis in a dose-dependent manner (3.7-fold reduction (95% confidence interval (CI) 1.8-15; P < 0.01) and 5.3-fold reduction (95% CI 1.8-7.7; P < 0.01), respectively, compared with stimulant alone). Similar observations were made in human cardiac fibroblast cell culture. Atorvastatin also dose-dependently reduced TGF-beta1 and AngII-induced increases in alpha(I)-procollagen mRNA (P < 0.01 for both), as well as gene expression of the profibrotic peptide connective tissue growth factor. 4. Atorvastatin appears to directly inhibit collagen production by cardiac fibroblasts. This antifibrotic action may contribute to the antiremodelling effect of statins.