Management of diabetic dyslipidemia: An update

Diabetic dyslipidemia is a cluster of lipoprotein abnormalities characterized by increased triglyceride level, decreased high-density lipoprotein-cholesterol levels and increase in small dense low-density lipoprotein(LDL) particles. It is extremely common in type 2 diabetes(T2DM) affecting around 70 % of patients.Diabetic is a significant risk factor for atherosclerotic cardiovascular disease(ASCVD) which is the most common cause of death in the United States and LDL-cholesterol is the number 1 predictor of ASCVD events in T2DM. The purpose of this review is to discuss the pathophysiology and treatment of diabetic dyslipidemia. In this review, we have discussed both nonpharmacological and pharmacological treatment modalities including major treatment trials which have impacted the cardiovascular outcomes in patients with diabetes. Statin therapy is the mainstay of treatment to reduce ASCVD by decreasing LDL-C by 30%-49% or at least 50% depending on risk level. Attractive adjunctive therapies include Ezetimibe which is more cost effective and PCSK9 inhibitors which display potent LDL-cholesterol lowering and ASCVD event reduction. For severe hypertriglyceridemia, to avert the risk of pancreatitis, both fish oil and fenofibrate in concert with diet is the best strategy.     

Lipid-lowering agents in the management of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease(NAFLD) is the most common chronic liver disease in developed countries and is associated not only with increased risk for liver disease-related complications but also with higher cardiovascular morbidity. Accordingly, lipid-lowering agents are frequently considered in these patients to reduce cardiovascular risk. However, there have been concerns regarding the safety of these agents in patients with chronic liver diseases. In the present review, we discuss the safety of lipid-lowering agents in patients with NAFLD as well as their effects on both cardiovascular and liver disease in this population. Accumulating data suggest that statins are safe in patients with NAFLD and that they reduce the increased cardiovascular morbidity of this population. However, it is still unclear whether statins are also useful as a treatment for NAFLD per se, since there are very limited and conflicting data on their effects on liver histology. There is also very scarce evidence regarding the safety and efficacy of other lipid-lowering agents in patients with NAFLD. Randomized controlled studies are needed to evaluate the role of lipid-lowering agents and particularly statins for the prevention of both cardiovascular and liver disease-related complications in this high-risk population.     

CT评价他汀类药物对冠状动脉粥样硬化斑块进展的影响

【】目的 探讨CT在他汀类药物对冠状动脉粥样硬化(CAS)斑块进展效果评价中应用。方法 收集经多排螺旋CT检查发现CAS斑块的220例CHD患者,给予阿托伐他汀钙(10 mg/次,1次/d) 阿司匹林,随访12个月后CT复查斑块情况,根据治疗期间的用药情况分为间断用药组(n=94)、规律用药组(n=126),比较两组血脂改善情况,分析治疗前后斑块体积的变化。结果 治疗后,两组患者的各血脂指标均有不同程度改善,规律用药组TC、LDL-C水平较间断用药组显著降低 (P<0.05);治疗后,规律用药组各种斑块体积均显著缩小,其中低密度斑块体积、斑块总体积均显著小于间断用药组(P<0.05);斑块总体积与TC、LDL-C均呈显著正相关(P<0.05)。结论 他汀类药物能够调节血脂水平,缩小CAS斑块体积;CT可定量、定性评价CAS斑块变化,有效监测他汀类药物的治疗效果。     

Inhibition of cholesterol absorption by HMG-CoA reductase inhibitor

Summary In subjects with familial hypercholesterolemia cholesterol absorption efficiency was insignificantly reduced during a short-term more consistently during longterm pravastatin treatment. A cholesterol feeding had no effect on LDL cholesterol level but reduced absorption efficiency during a long-term lovastatin treatment.     

Vane’s blood-bathed organ technique adapted to examine the endothelial effects of cardiovascular drugs in vivo

This study describes a modification of Vane’s blood-bathed organ technique (BBOT). This new technique consisted of replacing the cascade of contractile smooth muscle organs within the traditional BBOT by a single collagen strip cut from a rabbit’s hind leg tendon. Utilizing the extracorporeal circulation of an anesthetized heparinized mongrel cat or Wistar rat, arterial blood was dripped (1–3 ml min^–1) over a collagen strip. This resulted in a gain in weight of the strip, which was due to the deposition of platelet aggregates and a few blood cells trapped over the strip. Arterial blood that had been used for the superfusion was pumped back into the animal’s venous system. However, when this technique is adapted to human volunteers, the superfusing blood should be discarded. In animal experiments, intravenous injections of a variety of classic fibrinolytic agents (e.g., streptokinase) promoted the formation of platelet thrombi. Nitric oxide donors (e.g., SIN-1) at non-hypotensive doses hardly affected the mass of platelet thrombi deposited over the collagen strip, whereas endogenous prostacyclin (e.g., released from vascular endothelium by bradykinin) or exogenous prostacyclin and its stable analogues (e.g., iloprost) dissipated platelet thrombi as measured by a loss in the weight of the blood superfused collagen strip. This model allowed us to assay numerous drugs for their releasing properties of endogenous prostacyclin from vascular endothelium. These drugs included lipophilic angiotensin converting enzyme inhibitors (ACE-Is), which act in vivo as bradykinin potentiating factors (BPF). Other PGI₂-releasers included statins (e.g., atorvastatin and simvastatin), thienopyridines (e.g., ticlopidine and clopidogrel), a number of thromboxane synthase inhibitors, flavonoids, bradykinin itself, cholinergic M receptor agonists and nicotinic acid derivatives. The thrombolytic actions of lipophilic ACE-Is (e.g., quinapril and perindopril) were prevented by pretreatment with either bradykinin B₂ receptor antagonists (e.g., icatibant) or with endothelial COX-2 inhibitors (e.g., rofecoxib, celecoxib and high dose aspirin). The inhibition of endothelial nitric oxide synthetase (eNOS) by L-NAME hardly blunted the thrombolytic response to ACE-Is. Hence, it can be concluded that many recognized cardiovascular drugs apart from their known basic mechanisms of action, may also behave as releasers of endogenous endothelial prostacyclin. Furthermore, in many instances, this effect may be the primary mechanism of their therapeutic efficacy.     

eNOS T-786C polymorphism affects atorvastatin-induced changes in erythrocyte membrane fluidity

Purpose  Statins have pleiotropic effects, including endothelial nitric oxide synthase (eNOS) upregulation and increased nitric oxide formation, which can be modulated by a genetic polymorphism in the promoter region of the eNOS gene (T-786C). Here, we report our investigation of whether this polymorphism modulates the effects of atorvastatin on the fluidity of erythrocyte membranes. Methods  We genotyped 200 healthy subjects (males, 18–60 years of age) and then randomly selected 15 of these with the TT genotype and 15 with the CC genotype to receive placebo or atorvastatin (10 mg/day oral administration) for 14 days. Cell membrane fluidity was evaluated by electron paramagnetic resonance (EPR) and spin-labeling method. The EPR spectra were registered on a VARIAN-E4 spectrometer. Thiobarbituric acid-reactive species (TBA-RS) and plasma membrane cholesterol were determined in the erythrocytes. Results  Atorvastatin reduced membrane fluidity in CC subjects (P < 0.05) but not in those with the TT genotype (P > 0.05). While no significant differences were found in plasma membrane cholesterol concentrations, higher TBA-RS concentrations were found in the CC subjects than in the TT subjects (P < 0.05). Conclusions  These findings suggest that a short treatment with atorvastatin is disadvantageous to subjects with the CC genotype for the T-786C polymorphism compared to those with TT genotype, at least in terms of the hemorheological properties of erythrocytes.     

Statins and prostate cancer: molecular and clinical aspects

The field of the potential applications of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) beyond their unambiguous cardiovascular beneficial effects is steadily increasing. In this regard, statins have also been shown to possess anti-inflammatory, immunomodulatory, antioxidant and growth inhibitory properties. Regarding their role in carcinogenesis, both preclinical and clinical studies report conflicting results. Intriguingly, accumulating evidence suggests that statins may relate to decreased prostate cancer incidence and recurrence risk. However, data from clinical studies seem to be still weak and are confounded by several factors. Nonetheless, preclinical data suggest that statins might exert a chemopreventive role against prostate cancer by inhibiting the proliferation and inducing apoptosis of prostate cancer cells and also inhibiting angiogenesis, inflammation and metastasis. Cholesterol lowering as well as statin pleiotropy through inhibition of the synthesis of isoprenoids have both been implicated in their anticancer properties. In this review, we discuss the preclinical and clinical evidence supporting the preventive or potentially harmful effects of statins on prostate tumourigenesis and conclude that statins should not be recommended for the prevention of prostate cancer development or progression based on the current data.     

急性期抗血小板及调脂治疗对缺血性卒中患者预后影响的前瞻性随访研究

目的：探讨缺血性卒中患者急性期抗血小板、调脂治疗与预后的关系。方法：收集自2007年1月～2008年5月在卒中单元病房住院治疗的1016例急性缺血性脑卒中患者,男630例,女386例,平均年龄64．54±11．60岁。根据是否服用抗血小板的药物和是否应用他汀类调脂药进行分组,分别分为使用组和未使用组。应用N1HSS评分了解各组入院时、随访3月和随访12月后的神经功能缺损程度,根据改良Rankin评分（mRs）评价各组患者预后、复发率和病死率的差异。结果：缺血性脑卒中男性患者发病年龄较女性患者早（P〈0．001）。其中使用抗血小板治疗927例,随访3月及12月抗血小板治疗组神经功能缺损程度较术使用者轻,NIHSS评分比较有显著性差异（P〈0．05）,使用抗血小板治疗组改善明显（P〈0．05）,预后不良发生率和病死率均较术使用背低（P〈0．001）,然而,复发率在两组之间比较无差异（P〉0．05）。同样,使用他汀类调脂药者随访3月和随访12月的病死率和预后不良发生率均低于未使用组（P〈0．001）,但复发率在两组之间比较无差异（P〉0．05）。结论：使用抗血小板药及他汀类调脂药将能改善患者预后,明显降低缺血性卒中患者的预后不良的发生率和病死率。