Ganoderic acid A (GAA) is one of the major triterpenoids in Ganoderma lucidum (GL). Accumulating evidence has indicated that GAA demonstrates multiple pharmacological effects and exhibits treatment potential for various neurological disorders. Here, the effects and mechanisms of GAA in the treatment of neurological disorders were evaluated and discussed through previous research results. By summarizing previous research results, we found that GAA may play a neuroprotective role through various mechanisms: anti-inflammatory, anti-oxidative stress, anti-apoptosis, protection of nerve cells, and regulation of nerve growth factor. Therefore, GAA is a promising natural neuroprotective agent and this review would contribute to the future development of GAA as a novel clinical candidate drug for treating neurological diseases.

High-density lipoprotein cholesterol (HDL-C) concentration is an independent risk factor for cardiovascular disease. Fibrates are widely used in the management of atherogenic dyslipidemia, principally for their triglyceride-lowering and HDL-C-raising effects. Fibrates may cause paradoxical reductions in HDL-C. These reductions are usually modest, but significant reductions have been observed. The molecular mechanism for these paradoxical reductions remains unexplained despite advances in our understanding of lipid metabolism. This review considers possible mechanisms for this effect, illustrated by a patient with an observed reduction in HDL-C of 88% after introduction of fenofibrate.

To evaluate the effect of statins for erectile dysfunction (ED), a systematic review of the literature was conducted in the Cochrane Library, Embase and PubMed from the inception of each database to June 2013. Only randomized controlled trials (RCTs) comparing treatment for ED with statins were identified. Placebo RCTs with the International Index of Erectile Function (IIEF) as the outcome measure were eligible for meta-analysis. A total of seven RCTs including two statins with a total of 586 patients strictly met our criteria for systematic review and five of them qualified for the meta-analysis. A meta-analysis using a random effects model showed that statins were associated with a significant increase in IIEF-5 scores (mean difference (MD): 3.27; 95% confidential interval (CI):1.51 to 5.02; P < 0.01) and an overall improvement of lipid profiles including total cholesterol (MD: -1.08; 95% CI: -1.68 to -0.48; P < 0.01), low-density lipoprotein (LDL) cholesterol (MD: -1.43; 95% CI: -2.07 to -0.79; P < 0.01), high-density lipoprotein (HDL) cholesterol (MD: 0.24; 95% CI: 0.13 to 0.35; P < 0.01) and triglycerides (TGs) (MD: -0.55; 95% CI: -0.61 to -0.48; P < 0.01). In summary, our study revealed positive consequences of these lipid-lowering drugs on erectile function, especially for nonresponders to phosphodiesterase type 5 inhibitors (PDE5Is). However, it has been reported that statin therapy may reduce levels of testosterone and aggravate symptoms of ED. Therefore, larger, well-designed RCTs are needed to investigate the double-edged role of statins in the treatment of ED.

OBJECTIVE: The aim of this study was to investigate the effectiveness and safety of aggressive statin versus moderate statin therapy on patients with saphenous vein grafts (SVGs) in randomized, controlled trials (RCTs).
METHODS: We searched MEDLINE (1980-June 2012), the Cochrane Controlled Trials Register, EMBASE, Science Citation Index, and PubMed (to June 2012), and found 10 relevant RCTs, including 7 substudy analyses from a Post-CABG trial, and 1 pooled analysis of the PROVE-IT TIMI 22 trial (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Investigators) and A to Z trial. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes; phase Z of the A to Z trial.
RESULTS: A total of 6645 of participants, ages ranging from 21 to 75 years old, were treated with coronary artery bypass graft (CABG) and were followed for 2 to 5 years. Eight studies showed that aggressive statin therapy had lower LDL-C levels and a decrease of 39% in graft atherosclerotic progression, 12% in new occlusions, and 19% in new lesions more than moderate statin therapy. Three reports indicated that aggressive statin therapy lowered the risk of repeated myocardial infarction more than moderate statin therapy for coronary revascularization (95% CI, 0.66-0.95; risk ratio [RR] = 0.80; and 95% CI, 0.66-0.85; RR = 0.75) and lowered the risk of cardiac death as well (95% CI, 0.64-1.08; RR = 0.83). Aggressive statin therapy had safety similar to that of moderate statin therapy except for a slight increase in myopathic events and aminotransferase levels. Seventy percent to 90% of patients took statin treatment as prescribed in long-term.
CONCLUSIONS: Compared with moderate statin therapy, long-term aggressive statin lowered the LDL-C level significantly, further decreased the atherosclerotic progression of SVG, reduced the risks of repeated myocardial infarction and coronary revascularization after CABG, and revealed similar patient compliance and statin-related adverse effects but slightly increased myopathy events and aminotransferase levels.

BACKGROUND: Statins are the treatment of choice for lowering LDL-C levels and reducing cardiovascular events. They have a remarkable safety profile, although some patients do not tolerate them. The aim of the study was to summarize the existing data on non-every day statin administration regimens.
METHODS: We searched the MEDLINE databases to identify articles on non-every day statin administration, published between 1990 and January 2010. All publications regardless of methodology, design, size, or language were included. Data extracted included study design, duration and aims, type of statin, therapeutic regimen, patient characteristics, effectiveness, tolerability, and costs.
RESULTS: The 21 retrieved articles were characterized by small sample size, short follow up period, and a preponderance of males and \"primary\" prevention cases. Several lacked randomization or a control group. The heterogeneity of the study groups, medications, doses, design and aims precluded a pooled or meta-analysis. The most reported and effective regimens were atorvastatin and rosuvastatin on alternate days. These regimens, with or without other lipid lowering agents, were well tolerated even among subjects with previous statin intolerance, and produced meaningful cost savings. Nevertheless, the effectiveness of these regimens on cardiovascular events was not clarified.
CONCLUSIONS: Atorvastatin or rosuvastatin on alternate days might be considered for patients who are intolerant to statin therapy. Further studies are needed to evaluate the effect of these regimens on cardiovascular events.

Fibrates activate peroxisome proliferator activated receptor α and exert beneficial effects on triglycerides, high-density lipoprotein cholesterol, and low density lipoprotein subspecies. Fenofibric acid (FA) has been studied in a large number of patients with mixed dyslipidemia, combined with a low- or moderate-dose statin. The combination of FA with simvastatin, atorvastatin and rosuvastatin resulted in greater improvement of the overall lipid profile compared with the corresponding statin dose. The long-term efficacy of FA combined with low- or moderate- dose statin has been demonstrated in a wide range of patients, including patients with type 2 diabetes mellitus, metabolic syndrome, or elderly subjects. The FA and statin combination seems to be a reasonable option to further reduce cardiovascular risk in high-risk populations, although trials examining cardiovascular disease events are missing.

Patients with dyslipidemia receive a cardiovascular benefit from lowering low-density lipoprotein cholesterol (LDL-C). Atorvastatin is currently one of the most effective approved medications for lowering LDL-C, and has been shown to significantly reduce cardiovascular risk in many patient groups. However, even with substantial lowering of LDL-C with atorvastatin, patients still have a residual risk for coronary heart disease. Elevated triglyceride levels and low high-density lipoprotein cholesterol (HDL-C) levels may contribute to this risk. Approved medications targeting these secondary lipid parameters include fibrates, omega-3 fatty acids, and niacin. Among these medications, niacin provides the optimal increase in HDL-C levels and has efficacy similar to the other medications in lowering triglyceride levels. However, there are challenges to adherence with niacin treatment. The most common challenge during niacin treatment is flushing, although it typically decreases with ongoing use and can be ameliorated by pretreatment with aspirin and counseling by the prescriber. A combination of atorvastatin and niacin may provide more complete normalization of the lipid profile and increased cardiovascular benefits. A literature review of the PubMed and Embase databases was conducted for clinical studies that reported on the lipid-modifying efficacy of the atorvastatin plus niacin combination. Identified studies involved patients at risk for coronary heart disease and patients with established coronary heart disease. Overall, the studies were small but indicated that atorvastatin in combination with niacin was efficacious in normalizing lipid parameters. Larger lipid studies as well as studies evaluating cardiovascular outcomes during atorvastatin plus niacin treatment are warranted.

Several case reports and studies suggest that partially thrombosed large and giant aneurysms are potential sources of distal embolic events. However, there are limited data on small thrombosed aneurysms as a possible cause of ischemic events. Three patients are reported who presented with acute ischemic stroke and in whom the initial imaging studies showed a small (<10 mm), unruptured, partially thrombosed aneurysm. In each case, the aneurysm location was confirmed by a conventional angiogram. In all cases, the aneurysms were found on the proximal middle cerebral artery, in the territory corresponding to the clinical symptoms of the stroke. The mechanism of middle cerebral artery embolic event was thought to be related to the thrombus within the aneurysm, causing subsequent embolization into distal related vascular territory. Two of these patients had craniotomy for aneurysm clipping; one was managed conservatively with medical therapy alone. Thrombosis of small, unruptured intracranial aneurysms should be considered as a possible cause of acute-onset stroke symptoms in patients with acute ischemic stroke. It is under-recognized in the current literature, and no guidelines currently exist for medical or surgical treatment of such aneurysms. Medical management is often decided on an individual basis. Surgical treatment mostly involves aneurysmal clipping rather than coiling.

Statin therapy in patients with cardiovascular disease is associated with reduced incidence of stroke. The Stroke Prevention by Aggressive Reduction of Cholesterol Levels (SPARCL) trial showed daily treatment with 80 mg of atorvastatin in patients with a recent stroke or transient ischemic attack (TIA) reduced the incidence of fatal or nonfatal stroke by 16%. Several post hoc analyses of different subgroups followed the SPARCL study. They have not revealed any significant differences when patients were sorted by age, sex, presence of carotid disease or type of stroke, with the exception of intracranial hemorrhage as the entry event. Lower low-density lipoprotein cholesterol levels in addition to possible neuroprotective mechanisms due to atorvastatin treatment correlate with improved risk reduction. Although not predefined subgroups and subject to an insufficient power, these post hoc studies have generated new clinical questions. However, clinicians should avoid denying therapy based on such subgroup analysis. At this point, the best evidence powerfully demonstrates stroke and TIA patients should be prescribed high dose statin therapy for secondary stroke prevention.

Amlodipine/atorvastatin (Caduet) is a single-tablet, fixed-dose combination of the dihydropyridine calcium channel antagonist amlodipine and the HMG-CoA reductase inhibitor atorvastatin. The bioavailability of amlodipine and atorvastatin with a single-tablet, fixed-dose amlodipine/atorvastatin combination was not significantly different to that with coadministered separate amlodipine and atorvastatin tablets. In well controlled clinical trials in patients with hypertension and dyslipidaemia, once-daily amlodipine and atorvastatin (administered as the single-tablet, fixed-dose combination or coadministered as two separate tablets) effectively reduced systolic BP (SBP) and low-density lipoprotein cholesterol (LDL-C) levels, and enabled more patients to achieve BP and LDL-C goals than single-agent or placebo therapy. There was no modification of the effect of amlodipine on SBP when administered in combination with atorvastatin and there was no modification of the effect of atorvastatin on LDL-C when administered in combination with amlodipine. In noncomparative, titration-to-goal, open-label \'real-world\' trials, the single-tablet, fixed-dose combination of amlodipine/atorvastatin enabled patients with hypertension and dyslipidaemia to achieve both BP and LDL-C goals. Administration of a single tablet of amlodipine/atorvastatin, compared with coadministration of these agents as two separate tablets, improved patient adherence, according to a retrospective study that utilized prescription refill rates from a large US insurance database. Data from the large, randomized, double-blind, placebo-controlled ASCOT-LLA trial also demonstrated that the combination of amlodipine-based therapy and atorvastatin was effective in preventing cardiovascular (CV) endpoints in hypertensive patients at risk of CV disease (CVD). In summary, amlodipine/atorvastatin offers a convenient and effective approach to improving adherence and managing CV risk in hypertensive patients with dyslipidaemia or at risk of CVD.