Erectile dysfunction and statin treatment in high cardiovascular risk patients

Erectile dysfunction (ED) has been associated with risk factors for atherosclerosis. Medications used for atherosclerosis have also been implicated in ED. The aim of this study is to investigate the relationship of erectile function to cardiovascular risk factors and specific drug therapies before and after 6 months of statin therapy. In this prospective observational study, International Index of Erectile Function (IIEF) scores were measured in 93 men attending cardiovascular risk clinics. Cardiovascular risk factors and drug therapies were assessed prior to initiation and after 6 months of statin therapy. Prior to statin therapy, the median IIEF score was 21 (range 0-25), and 57% had impairment of erectile function. After statin therapy, IIEF scores were reduced to 6.5 (range 0-25) (p < 0.001), and 22% experienced new onset ED. Before statin therapy no correlation was observed between IIEF score and any individual cardiovascular risk factor. After 6 months of statin therapy, correlations were observed between lower IIEF scores (r = 0.62; p < 0.001) and age and diabetes and weakly with smoking. Differences in dose, relative efficacy or relative lipophilicity of statin prescribed showed no correlation with change in IIEF score. This study suggests ED following statin therapy is more likely in patients with severe endothelial dysfunction due to established cardiovascular risk factors including age, smoking and diabetes.     

The influence of statin characteristics on their safety and tolerability

The efficacy of the statins for both primary and secondary prevention has now been clearly established in patients across the spectrum of cardiovascular risk. In addition to their primary effect in reducing plasma cholesterol, the statins possess various 'pleiotropic' effects that may contribute to their clinical effectiveness in reducing cardiovascular events, e.g. improvement of endothelial function, reduction of low-density lipoprotein-cholesterol oxidation and stabilisation of atheromatous plaques. Although statins share similar chemical characteristics, they differ significantly in terms of their molecular synthesis, solubility and pharmacokinetic behaviour and metabolism. Side-effects secondary to longterm statin therapy are rare, but rhabdomyolysis may occur when statins are administered together with other drugs that have a direct toxic effect on muscle or which inhibit statin metabolism. Among the various statins, it would appear that fluvastatin has the lowest propensity to interact with other drugs and the least potential to induce myotoxicity.     

Efficacy and safety of ezetimibe coadministered with statins: randomised, placebo-controlled, blinded experience in 2382 patients with primary hypercholesterolemia

We assessed pooled safety and lipid-regulating efficacy data from four similarly designed trials of ezetimibe coadministered with statins in 2382 patients with primary hypercholesterolemia. Patients were randomised to one of the following double-blind treatments for 12 weeks: placebo; ezetimibe 10 mg; statin; or statin + ezetimibe. Statin doses tested were 10, 20, 40 mg/day (atorvastatin, simvastatin, pravastatin or lovastatin) or 80 mg/day (atorvastatin, simvastatin). Treatment with ezetimibe + statin led to significantly greater reductions in low-density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B and increases in HDL-C, compared to statin alone. At each statin dose, treatment with ezetimibe + statin led to a greater LDL-C reduction compared to the next highest statin monotherapy dose. Ezetimibe + statin had a safety profile similar to statin monotherapy. Coadministration of ezetimibe + statin offers a well-tolerated, highly efficacious new treatment strategy for patients with hypercholesterolemia.     

辛伐他汀对一氧化氮缺乏性高血压大鼠早期肾功能的影响

目的 :观察羟甲基戊二酰辅酶A(HMG CoA)还原酶抑制剂辛伐他汀 (Simvastatin)对一氧化氮缺乏性高血压大鼠肾功能的保护作用 ,并探讨其机制。方法 :通过给予一氧化氮合酶抑制剂L NAME制造一氧化氮缺乏性高血压大鼠模型 ,2 4只WKY大鼠随机分为正常对照组 (C组 )、高血压组 (L组 )、辛伐他汀组 (L +S组 )。收集 2 4h尿液测定尿 β2 微球蛋白 (β2 M)、尿蛋白 ,第 8周宰杀收集标本 ,检测血和肾组织中一氧化氮 (NO)、内皮素 (ET 1 )、血管紧张素Ⅱ (AngⅡ )水平。结果 :给予L NAME2周即见血压升高 ,第 8周时显著升高 ,达 (1 76 .5± 3.5 )mmHg。与C组比较 ,L组第 7天和第 8周时尿蛋白及 β2 M形成两个高峰 ,尿蛋白分别为 (4 0 .5± 1 0 .4 6 )mg Lvs 1 5 .2 8± 2 .1 6mg L和 (8.4± 5 .6 2 )g Lvs(1 3.6 5± 3.36 )mg L(P <0 .0 0 1 ) ,尿 β2 M分别为 (0 .5 8± 0 .1 1 )mg Lvs(0 .2 9± 0 .0 6 )mg L和 (0 .6 4± 0 .0 4 )mg Lvs(0 .34± 0 .0 6 )mg L(P <0 .0 1 )。 8周时肾脏局部NO、ET 1及AngⅡ水平均有显著差异 (P <0 .0 5 )。辛伐他汀在不影响血压和血脂条件下 ,减少尿蛋白和尿β2 M排出 ,以第 7天至 2周时最明显 (P <0 .0 5 ) ;使大鼠肾脏局部 ,特别是肾皮质NO水平增高 ,ET 1及AngⅡ水平降低。     

Lipoprotein Lp(a) as predictor of myocardial infarction in comparison to fibrinogen,LDL cholesterol and other risk factors: results from the prospective Göttingen Risk Incidence and Prevalence Study (GRIPS)

Abstract. Based on pathophysiological findings Lp(a) is considered to be a cardiovascular risk factor. The Göttingen Risk Incidence and Prevalence Study (GRIPS) provides the possibility to evaluate this impact of Lp(a) on the basis of a large prospective cohort study. GRIPS included 6002 men, aged 40–59·9 years at baseline. Data of a 5 year follow-up period is now available for > 95% of the study participants. Multivariate logistic regression models for the estimation of MI risk confirm Lp(a) as an important risk factor, ranking fifth behind LDL cholesterol, family history of MI, plasma fibrinogen and HDL cholesterol (inversely related). The GRIPS data strongly support strategies for the identification and treatment of persons at increased MI risk which focus on LDL cholesterol. However, Lp(a) and fibrinogen have to be seriously considered as additional risk factors and should be included in diagnostic panels for the estimation of MI risk.     

Sustained postprandial decrease in plasma levels of LDL cholesterol in patients with type‐2 diabetes mellitus

Objective. Low density lipoprotein cholesterol (LDL‐C) is an independent and modifiable risk factor for development of cardiovascular disease (CVD). Postprandial lipid metabolism has been linked to CVD, but little is known about the postprandial LDL‐C profile in patients with type‐2 diabetes (T2DM). We aimed to study the postprandial levels of LDL‐C in T2DM patients. Material and methods. After an overnight fast, 74 T2DM patients, mean age approximately 60 years, were served a standard fat‐rich meal of 3,515 kJ containing 54?% fat, 13?% protein and 33?% carbohydrates. Only drinking water was allowed postprandially. Blood samples were drawn at times 0 (fasting), 1.5, 3.0, 4.5 and 6.0?h (postprandial). In all samples, LDL‐C was measured with modified beta quantification (separation by ultracentrifugation followed by measurement of infranate high density lipoprotein cholesterol (HLD‐C) using a homogeneous assay). Results. At all postprandial times, levels of LDL‐C showed highly significant (p<0.005) decreases compared to time 0 (mean [95?% CI] maximum change in LDL‐C levels at 3.0?h: ?0.16?mmol/L [?0.12; ?0.20]; p<0.001). Independently of fasting LDL‐C levels and ongoing statin therapy, LDL‐C decreased significantly more in female compared to male patients postprandially (mean [95?% CI] maximum unadjusted change versus time 0 in LDL‐C for men [n = 56] at 3.0?h: ?0.14?mmol/L [?0.19; ?0.10], p<0.001; for women [n = 18] at 4.5?h: ?0.26?mmol/L [?0.35; ?0.18], p<0.001; ?0.14?mmol/L [?0.24; ?0.05], p = 0.005 between genders for the mean [95?% CI] fasting adjusted difference at 4.5?h in the change versus time 0 in LDL‐C; gender by time interaction: p = 0.007 (repeated measures mixed model)). Conclusions. In T2DM patients served a fat‐rich meal, levels of LDL‐C decreased significantly more in women compared to men postprandially, irrespective of fasting levels or ongoing statin therapy. This might have implications in the atherosclerotic process and on any difference in the risk of CVD between genders.     

A critical appraisal and recommendation synthesis of delirium clinical practice guidelines relevant to the care of older adults in the emergency department: An umbrella review

Rationale

Older adults are at high risk of developing delirium in the emergency department (ED); however, it is often missed or undertreated. Improving ED delirium care is challenging in part due to a lack of standards to guide best practice. Clinical practice guidelines (CPGs) translate evidence into recommendations to improve practice.

Aim

To critically appraise and synthesize CPG recommendations for delirium care relevant to older ED patients.

Methods

We conducted an umbrella review to retrieve relevant CPGs. Quality of the CPGs and their recommendations were critically appraised using the Appraisal of Guidelines, Research, and Evaluation (AGREE)-II; and Appraisal of Guidelines Research and Evaluation—Recommendations Excellence (AGREE-REX) instruments. A threshold of 70% or greater in the AGREE-II Rigour of Development domain was used to define high-quality CPGs. Delirium recommendations from CPGs meeting this threshold were included in the synthesis and narrative analysis.

Results

AGREE-II Rigour of Development scores ranged from 37% to 83%, with 5 of 10 CPGs meeting the predefined threshold. AGREE-REX overall calculated scores ranged from 44% to 80%. Recommendations were grouped into screening, diagnosis, risk reduction, and management. Although none of the included CPGs were ED-specific, many recommendations incorporated evidence from this setting. There was agreement that screening for nonmodifiable risk factors is important to define high-risk populations, and those at risk should be screened for delirium. The ‘4A's Test’ was the recommended tool to use in the ED specifically. Multicomponent strategies were recommended for delirium risk reduction, and for its management if it occurs. The only area of disagreement was for the short-term use of antipsychotic medication in urgent situations.

Conclusion

This is the first known review of delirium CPGs including a critical appraisal and synthesis of recommendations. Researchers and policymakers can use this synthesis to inform future improvement efforts and research in the ED.

Registration

This study has been registered in the Open Science Framework registries: https://doi.org/10.17605/OSF.IO/TG7S6OSF.IO/TG7S6 .     

The relationship of TFPI, Lp(a), and oxidized LDL antibody levels in patients with coronary artery disease

OBJECTIVES: The aim of the present study was to determine and correlate tissue factor pathway inhibitor (TFPI), lipoprotein (a) (Lp(a)), oxidized low-density lipoprotein (LDL) antibody (oLAB), and thiobarbituric acid reactive substances (TBARS; as a marker of lipid peroxidation) levels in patients with coronary artery disease (CAD) and in a control group. DESIGN AND METHODS: Peripheral blood samples from patients with coronary heart disease were provided by the Department of Cardiology. Serum oLAB, Lp(a), plasma total TFPI, and plasma-free TFPI levels were determined by ELISA. Serum TBARS levels were determined by a spectrophotometric method using thiobarbituric acid. RESULTS: The CAD and the control group were matched for age and sex. Serum Lp(a), oLAB, and plasma total TFPI levels in patients with coronary heart disease were found to be significantly higher than in the control group (P < 0.001). But there was no difference in plasma-free TFPI levels between patients with CAD and the control group (P > 0.05). In patients with single (P < 0.05), double, and triple vessel (P < 0.01) disease, the mean serum Lp(a) levels were significantly higher than in the control group. On the other hand, in patients with single vessel disease (P < 0.05), double vessel disease (P < 0.05), and triple vessel disease (P < 0.001), plasma total TFPI levels were found to be significantly higher than in the control group. We also found a significant positive correlation (r = 0.28, P < 0.05) between serum Lp(a) and plasma total TFPI levels in CAD. In the patient group, TBARS, total cholesterol, triglyceride (TRG), and LDL cholesterol levels were found to be significantly higher than those in the control group. In addition, high-density lipoprotein (HDL) cholesterol levels were found to be significantly lower than the control group. CONCLUSIONS: These results suggest that elevated plasma levels of total TFPI, Lp(a), and oLAB may be useful diagnostic and monitoring markers in patients with CAD.