Effects of statins on vascular wall: vasomotor function, inflammation, and plaque stability

Clinical trials of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors or statin therapy demonstrate an improvement in cardiovascular end points and coronary stenosis. However, an improvement in cardiovascular end points and coronary stenosis is incompletely explained by the baseline or treated LDL cholesterol level. The beneficial effects of statins on clinical events may involve nonlipid mechanisms that modify endothelial function, smooth muscle cells, and monocyte-macrophage: vasomotor function, inflammatory responses, and plaque stability. Augmented bioactivity of NO by statin therapy either indirectly by its effect on lipoprotein levels and protection of LDL from oxidation, or directly by effects on NO synthesis and release, might account for enhancement of endothelium-dependent vasodilation. Recent experimental and animal studies have demonstrated that statins dose-dependently decrease smooth muscle cells migration and proliferation, independently of their ability to reduce plasma cholesterol. Moreover, statins are able to reduce the in vitro cholesterol accumulation in macrophages and expression of matrix metalloproteinase, resulting in plaque stability. These effects of statins were completely prevented by the addition of mevalonate and partially by all-trans farnesol and all-trans geranylgeraniol, confirming the specific role of isoprenoid metabolites, probably through prenylated proteins, in regulating these cellular events. Statins have been shown to prevent the activation of monocytes into macrophages, inhibit the production of pro-inflammatory cytokines, C-reactive protein, and cellular adhesion molecules. Statins decrease the adhesion of monocyte to endothelial cells. Accordingly, statins exert their cardiovascular benefits through a direct antiatherogenic properties in the arterial wall, beyond their effects on plasma lipids.     

Effects of marijuana smoking on pulmonary function and respiratory complications: a systematic review

BACKGROUND: The relationship between marijuana smoking and pulmonary function or respiratory complications is poorly understood; therefore, we conducted a systematic review of the impact of marijuana smoking on pulmonary function and respiratory complications. METHODS: Studies that evaluated the effect of marijuana smoking on pulmonary function and respiratory complications were selected from the MEDLINE, PsychINFO, and EMBASE databases according to predefined criteria from January 1, 1966, to October 28, 2005. Two independent reviewers extracted data and evaluated study quality based on established criteria. Study results were critically appraised for clinical applicability and research methods. RESULTS: Thirty-four publications met selection criteria. Reports were classified as challenge studies if they examined the association between short-term marijuana use and airway response; other reports were classified as studies of long-term marijuana smoking and pulmonary function or respiratory complications. Eleven of 12 challenge studies found an association between short-term marijuana administration and bronchodilation (eg, increases of 0.15-0.25 L in forced expiratory volume in 1 second). No consistent association was found between long-term marijuana smoking and airflow obstruction measures. All 14 studies that assessed long-term marijuana smoking and respiratory complications noted an association with increased respiratory symptoms, including cough, phlegm, and wheeze (eg, odds ratio, 2.00; 95% confidence interval, 1.32-3.01, for the association between marijuana smoking and cough). Studies were variable in their overall quality (eg, controlling for confounders, including tobacco smoking). CONCLUSIONS: Short-term exposure to marijuana is associated with bronchodilation. Physiologic data were inconclusive regarding an association between long-term marijuana smoking and airflow obstruction measures. Long-term marijuana smoking is associated with increased respiratory symptoms suggestive of obstructive lung disease.     

Effects of statins on renal function

This report reviews data on the development of proteinuria in patients with chronic kidney disease who are treated with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) for dyslipidemia. Although subgroup analyses of statin trials have shown cardiovascular benefits in subjects with chronic kidney disease, concern about statin-induced proteinuria remains high. Experimental studies have suggested that the proteinuria seen with statin treatment results from the inhibition of receptor-mediated endocytosis, the likely mechanism of protein uptake in proximal tubular cells. Transient proteinuria may signify little more than the effective inhibition of cholesterol synthesis at this site. The blockade of protein trafficking in tubular cells is thought to reduce inflammation, slow fibrosis, and diminish proteinuria in the long term. Post hoc analyses of large clinical trials in subjects without overt renal disease have generally supported this notion, showing that statins most benefit patients with the greatest baseline renal deficits. Statins have also been shown to preserve glomerular filtration rate and reduce proteinuria in subjects with nondiabetic renal disease. In conclusion, in the absence of prospective, randomized trials in renally impaired patients, the collective evidence indicates that statin therapy may slow the decrease in renal function that generally attends atherosclerotic disease. The incidence of proteinuria with potent statins is only 1% to 2% when these drugs are given in recommended doses. Several large trials are currently under way to examine the safety and efficacy of statins in renally compromised patients at high risk for cardiovascular disease.     

Effects of laparoscopic cholecystectomy on lung function: A systematic review

AIM: To present and integrate findings of studies investigating the effects of laparoscopic cholecystectomy on various aspects of lung function.METHODS: We extensively reviewed literature of the past 24 years concerning the effects of laparoscopic cholecystectomy in comparison to the open procedure on many aspects of lung function including spirometric values, arterial blood gases, respiratory muscle performance and aspects of breathing control, by critically analyzing physiopathologic interpretations and clinically important conclusions. A total of thirty-four articles were used to extract information for the meta-analysis concerning the impact of the laparoscopic procedure on lung function and respiratory physiopathology. The quality of the literature reviewed was evaluated by the number of their citations and the total impact factor of the corresponding journals. A fixed and random effect meta-analysis was used to estimate the pooled standardized mean difference of studied parameters for laparoscopic (LC) and open (OC) procedures. A crude comparison of the two methods using all available information was performed testing the postoperative values expressed as percentages of the preoperative ones using the Mann-Whitney two-sample test.RESULTS: Most of the relevant studies have investigated and compared changes in spirometric parameters.The median percentage and interquartile range (IQR) of preoperative values in forced vital capacity (FVC), forced expiratory volume in 1 s and forced expiratory flow (FEF) at 25%-75% of FVC (FEF_25%-75%) expressed as percentage of their preoperative values 24 h after LC and OC were respectively as follows: [77.6 (73.0, 80.0) L vs 55.4 (50.0, 64.0) L, P < 0.001; 76.0 (72.3, 81.0) L vs 52.5 (50.0, 56.7) L, P < 0.001; and 78.8 (68.8, 80.9) L/s vs 60.0 (36.1, 66.1) L/s, P = 0.005]. Concerning arterial blood gases, partial pressure of oxygen [PaO₂ (kPa)] at 24 or 48 h after surgical treatment showed reductions that were significantly greater in OC compared with LC [LC median 1.0, IQR (0.6, 1.3); OC median 2.4, IQR (1.2, 2.6), P = 0.019]. Fewer studies have investigated the effect of LC on respiratory muscle performance showing less impact of this surgical method on maximal respiratory pressures (P < 0.01); and changes in the control of breathing after LC evidenced by increase in mean inspiratory impedance (P < 0.001) and minimal reduction of duty cycle (P = 0.01) compared with preoperative data.CONCLUSION: Laparoscopic cholecystectomy seems to be associated with less postoperative derangement of lung function compared to the open procedure.     

The association between body composition and foot structure and function: a systematic review

The aim of this systematic review was to investigate the relationship between body composition and foot structure and function. Six electronic databases (Ovid MEDLINE, Ovid EMBASE, Ovid AMED, CINAHL, Scopus and The Cochrane Library) and reference lists from relevant papers were searched on 2 September 2013. Sixteen papers that reported on the association between body composition and foot structure and function met our inclusion criteria and were reviewed. The evidence indicates that obesity is strongly associated with planus (low‐arched) foot posture, pronated dynamic foot function and increased plantar pressures when walking. However, there is limited evidence to support an association between other body composition measures, such as fat mass, with foot structure or function.     

Effects of regular cannabis use on neurocognition,brain structure,and function: a systematic review of findings in adults

Background: Cannabis is the most used illicit drug worldwide. The long-standing consequences for the central nervous system associated with frequent cannabis use have not been well delineated and should be determined. Objective: To review recent studies on the effects of regular cannabis use regarding its effects on cognition, brain structure, and function in adults. Methods: A systematic literature review was conducted by performing electronic searches in the PubMed, LILACS, and SciELO databases (2010–2016). The initial search identified 898 records. They were evaluated for relevance according to the inclusion and exclusion criteria and 56 studies were included. Results: The neuropsychological studies provide evidence for subtle cognitive deficits at least 7 days after heavy cannabis use. The structural neuroimaging studies show growing evidence of abnormalities in hippocampus volume and gray matter density of cannabis users relative to controls; however, morphological changes in other brain regions are more controversial. The functional neuroimaging studies suggest an altered pattern of brain activity associated with cannabis use. Conclusion: Although there are several limitations for study comparison and substantial heterogeneity in the findings, the present review suggests that regular cannabis use is associated with mild cognitive changes in addition to structural and functional alterations in the brain in adults. The morphological alterations could ultimately affect brain organization and function, but the associated time course for neuronal recovery as well as the real impact on cognitive functioning remain unknown. Also, it is still unclear whether the identified alterations are as a consequence of or precede cannabis use.     

Effects of sleep deprivation on endothelial function in adult humans: a systematic review

Sleep deprivation is highly prevalent and is associated with increased cardiovascular disease (CVD) morbidity and mortality. Age-related alterations in sleep and chronobiology may exaggerate CVD susceptibility in older individuals. The mechanisms responsible for the association between sleep deprivation and CVD are not fully understood, but endothelial dysfunction may play a central role. Our objective was to conduct a systematic literature review to evaluate the evidence on the effects of sleep deprivation on endothelial function (EF). This review adhered to the PRISMA guidelines and was pre-registered with PROSPERO (#CRD42020192485, 07/24/2020). We searched PubMed, Web of Science, Embase, and Cochrane Library for articles published through May 1, 2020. Eligibility criteria included publication in English and use of well-established EF methodologies in adult humans. Two investigators independently performed the literature search, study selection, data extraction, risk-of-bias assessment, and qualitative data synthesis. Out of 3571 articles identified, 24 articles were included in the systematic review. Main findings include the following: (1) shorter sleep duration is associated with lower macrovascular EF; (2) not sleeping 7–9 h/night is linked with impaired microvascular EF; (3) sleep restriction impairs micro- and macrovascular EF; (4) acute total sleep deprivation impairs micro- and macrovascular EF but data on macrovascular EF are less consistent; and (5) shift work impairs macrovascular EF. In conclusion, sleep deprivation impairs EF, which may explain the link between insufficient sleep and CVD. Future investigations should fully elucidate the underlying mechanisms and develop strategies to combat the adverse endothelial effects of sleep deprivation across the lifespan.

     

Effects of statins on renal function after aortic cross clamping during major vascular surgery

Ischemic reperfusion injury is an important cause of renal dysfunction after major vascular surgery and increases postoperative morbidity and mortality. The aim of the present study was to assess the effect of statins on renal function in patients at high risk for renal dysfunction, that is, those who underwent suprarenal aortic cross clamping-declamping. Seventy-seven patients (28 statin users, 57 men; mean age 69 +/- 8 years) with normal preoperative renal function requiring suprarenal aortic cross clamping-declamping during vascular surgery from 1995 to 2005 were studied. Creatinine levels were obtained before surgery and on days 1, 2, 3, 7, and 30 after surgery. An analysis-of-variance model for repeated measurements was applied to compare creatinine levels between statin users and nonusers, with adjustment for clamping time and blood loss. There were no differences in baseline clinical characteristics, preoperative creatinine levels (0.93 vs 0.96 mg/dl, p = 0.59), and glomerular filtration rate (79 vs 73 ml/min, p = 0.1). Postoperative creatinine levels during the 30 days after surgery were significantly lower in statin users than in nonusers (analysis-of-variance p <0.01, 1.17 vs 1.98 mg/dl). Postoperative hemodialysis was required (temporarily) in 7 patients (9.1%), all statin nonusers. These findings suggest an association between statin use and preserved renal function after suprarenal aortic clamping.     

Effects of cereal fiber on bowel function: A systematic review of intervention trials

AIM: To comprehensively review and quantitatively summarize results from intervention studies that examined the effects of intact cereal dietary fiber on parameters of bowel function. METHODS: A systematic literature search was conducted using Pub Med and EMBASE. Supplementary literature searches included screening reference lists from relevant studies and reviews. Eligible outcomes were stool wet and dry weight, percentage water in stools, stool frequency and consistency, and total transit time. Weighted regression analyses generated mean change(± SD) in these measures per g/d of dietary fiber. RESULTS: Sixty-five intervention studies among generally healthy populations were identified. A quantitative examination of the effects of non-wheat sources of intact cereal dietary fibers was not possible due to an insufficient number of studies. Weighted regression analyses demonstrated that each extra g/d of wheat fiber increased total stool weight by 3.7 ± 0.09 g/d(P 0.0001; 95%CI: 3.50-3.84), dry stool weight by 0.75 ± 0.03 g/d(P 0.0001; 95%CI: 0.69-0.82), and stool frequency by 0.004 ± 0.002 times/d(P = 0.0346; 95%CI: 0.0003-0.0078). Transittime decreased by 0.78 ± 0.13 h per additional g/d(P 0.0001; 95%CI: 0.53-1.04) of wheat fiber among those with an initial transit time greater than 48 h.CONCLUSION: Wheat dietary fiber, and predominately wheat bran dietary fiber, improves measures of bowel function.     

Effects of exercise training on endothelial function in individuals with hypertension: a systematic review with meta-analysis

A slight increase (1%) in endothelial function is associated with reduction of cardiovascular risks by 13% in individuals with cardiovascular disease risk, including those with hypertension. Thus, we conducted a systematic review and meta-analysis to assess the efficacy of exercise training on endothelial function in individuals with hypertension.We included randomized clinical trials (RCTs) with adult participants diagnosed with hypertension undergoing exercise training (≥4 weeks), and the primary outcome was endothelial function, measured by flow-mediated dilatation (FMD). Five studies comprising a total of 362 participants (252 exercise and 110 controls; 59.3 years old, ranged from 52.0 to 67.2 years) were included in the meta-analysis. The pooled mean estimate indicated increased FMD after exercise training of 1.45 (P = .001), and 95% confidence interval ?0.11 to 3.00 compared with control comparators. The studies were characterized by significant heterogeneity (χ² = 23.34, P < .001, I² = 70%). The present results are consistent with the notion that aerobic exercise training elicits favorable adaptations in endothelial function in individuals with hypertension. However, more studies are needed to make more definitive conclusions.     

Circulating calcium concentrations,vascular disease and mortality: a systematic review

Associations between serum calcium and vascular disease have been reported, but the consistency of these findings is unknown. We conducted a systematic review to determine whether circulating calcium concentrations are associated with risks of cardiovascular disease and death in normocalcaemic populations. We conducted PubMed searches up to 18 December 2014 and scrutinized reference lists of papers. Eligible studies related serum calcium to mortality or cardiovascular events in humans. A follow‐up of at least one year was required for longitudinal studies. Studies in populations selected on the basis of renal disease or abnormal serum calcium were excluded. Two investigators performed independent data extraction. The results were tabulated and, where possible, meta‐analysed. Five of 11 studies reported a statistically significant positive association between serum calcium and mortality. Meta‐analysis of eight of these studies showed a hazard ratio of death of 1.13 (1.09, 1.18) per standard deviation of serum calcium. Eight of 13 studies reported a statistically significant positive association between serum calcium and cardiovascular disease. Meta‐analysis of eight studies showed a hazard ratio of cardiovascular disease of 1.08 (1.04, 1.13) per standard deviation of serum calcium. For two studies reporting odds ratios, the pooled odds ratio per standard deviation was 1.22 (1.11, 1.32). When hazard ratios adjusted for cardiovascular risk factors were meta‐analysed, the pooled hazard ratio was 1.04 (1.01, 1.08). Other studies demonstrated associations between serum calcium and stroke and between serum calcium and direct measurements of arterial disease and calcification. These observational data indicate that serum calcium is associated with vascular disease and death, but they cannot determine causality.     

溶栓前使用他汀类药物对缺血性卒中静脉溶栓疗效的系统评价

目的系统评价缺血性卒中急性期静脉溶栓前使用他汀类药物对患者的疗效和安全性。方法计算机检索Pub Med、EMbase、Web of Science和Cochrane Library等数据库,并辅以手工和其他检索,收集关于静脉溶栓前他汀类药物使用对缺血性卒中急性期静脉溶栓患者的疗效和安全性的研究,检索时间截至2016年4月。由两名研究者按照纳入与排除标准独立筛选文献、提取资料和评价纳入研究的方法学质量后,采用Rev Man 5.3软件进行统计学分析。结果共纳入12个队列研究,包括9 237例患者。他汀类药物使用对缺血性卒中静脉溶栓与近期预后无关(3个月改良Rankin量表评分≤2分:OR=1.05,95%CI:0.93~1.18,P=0.47)或呈负相关(3个月改良Rankin量表评分≤1分:OR=0.82,95%CI:0.73~0.92,P0.01);与症状性颅内出血呈正相关(OR=1.46,95%CI:1.17~1.82,P0.01);与病死率无关(OR=1.16,95%CI:0.79~1.71,P=0.44)。结论溶栓前使用他汀类药物可能导致急性缺血性卒中患者溶栓后出血等不良反应,并且可能导致卒中患者溶栓后3个月预后不良。     

贝特类调脂药物预防心脑血管疾病的系统评价

目的研究吉非罗齐、非诺贝特和苯扎贝特3种贝特类药物对心、脑血管事件的作用。方法系统性检索Cochrane图书馆临床对照试验数据库（CCTR2011年第4期）、MEDLINE（1950-2011）、EMBase（1950-2011）,并纳入所有对比3种贝特类药物（吉非罗齐、非诺贝特和苯扎贝特）与安慰剂或空白组预防心脑血管疾病随访时间不少于1年的随机对照试验。由两名评价员独立评价文献质量、提取资料并交叉核对,而后采用MetaAnalystbeta3．13软件进行荟萃分析。结果研究最终纳入11项随机对照试验。与安慰剂或空白对照组相比,吉非罗齐、非诺贝特、苯扎贝特3种贝特类药物对全因死亡率和脑卒中均无明显影响,其全因死亡率风险比（95％可信区间）[RR（95％CI）]分别为0．985（0．830-1．169）、1．023（0．905-1．155）、0．948（0．837-1．073）,脑卒中RR（95％CI）分别为0．765（0．548-1．067）、0．865（0．646-1．158）、1．056（0．772-1．081）。3种贝特类药物均能显著降低患者非致死性心肌梗死发生率,其RR（95％CI）分别为0．776（0．646-0．931）、0．833（0．717-0．968）、0．752（0．591-0．958）。此外,吉非罗齐和非诺贝特与安慰剂相比均可显著降低10％-20％的全部心血管事件,而3种贝特类药物对肿瘤发生率和肿瘤归因死亡率均不具有显著作用。结论与安慰剂相比,贝特类药物可以显著降低心肌梗死等心血管事件的风险,但对全因死亡率和肿瘤的发生率没有显著影响。     

Head-to-head comparison of fibrates versus statins for elevation of circulating adiponectin concentrations: a systematic review and meta-analysis

BackgroundElevation of adiponectin levels is a potential therapeutic tool against cardiovascular and metabolic diseases. Clinical evidence suggests differences between fibrates and statins in improving circulating concentrations of adiponectin.AimTo compare the efficacy of fibrates vs. statins on circulating concentrations of adiponectin by meta-analysis of randomized head-to-head trials.MethodsA systematic literature search of Medline was conducted to identify randomized head-to-head comparative trials investigating the efficacy of fibrates vs. statins on circulating levels of adiponectin. Inverse variance-weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated for net changes in adiponectin concentrations using a random-effects model. Random-effects meta-regression was performed to assess the effect of putative moderators on adiponectin levels.ResultsSix trials with a total of 326 subjects (166 in the fibrate and 160 in the statin group) met the eligibility criteria and were selected for this meta-analysis. The estimated effect size for fibrate versus statin therapy was 0.42 μg/mL (95% CI: ? 0.34–1.17). This effect size was robust in the leave-one-out sensitivity analysis and not sensitive to any single study. Meta-regression indicated a borderline significant association between duration of treatment and the effect of fibrates vs. statins on adiponectin concentrations (slope: ? 0.20; 95% CI: ? 0.41–0.01; p = 0.06). However, baseline body mass index, glucose and lipid levels did not predict the effect of fibrate vs. statin therapy on circulating adiponectin concentrations (p > 0.05).ConclusionsMonotherapy with either fibrates or statins has comparable effects on circulating concentrations of adiponectin. Thus, differential effects of statins and fibrates on the occurrence of cardiovascular events may not be attributed to the corresponding changes in adiponectin levels.     

Effects of zinc supplementation on diabetes mellitus: a systematic review and meta-analysis

ABSTRACT: The number of people with diabetes and pre-diabetes are exponentially increasing. Studies on humans have shown the beneficial effects of Zinc supplementation in patients with diabetes. The present study aims to systematically evaluate the literature and meta-analyze the effects of Zinc supplementation on diabetes. A systematic review of published studies reporting the effects of Zinc supplementations on diabetes mellitus was undertaken. The literature search was conducted in the following databases; PubMed, Web of Science and SciVerse Scopus. A meta-analysis of studies examining the effects of Zinc supplementation on clinical and biochemical parameters in patients with diabetes was performed. The total number of articles included in the present review is 25, which included 3 studies on type-1 diabetes and 22 studies on type-2 diabetes. There were 12 studies comparing the effects of Zinc supplementation on fasting blood glucose in patients with type-2 diabetes. The pooled mean difference in fasting blood glucose between Zinc supplemented and placebo groups was 18.13mg/dl (95%CI:33.85,2.41; p<0.05). 2-h post-prandial blood sugar also shows a similar distinct reduction in (34.87mg/dl [95%CI:75.44; 5.69]) the Zinc treated group. The reduction in HbA1c was 0.54% (95%CI:0.86;0.21) in the Zinc treated group. There were 8 studies comparing the effects of Zinc supplementation on lipid parameters in patients with type-2 diabetes. The pooled mean difference for total cholesterol between Zinc supplemented and placebo groups was 32.37mg/dl (95%CI:57.39,7.35; p<0.05). Low-density lipoprotein cholesterol also showed a similar distinct reduction in the Zinc treated group, the pooled mean difference from random effects analysis was 11.19mg/dl (95%CI:21.14,1.25; p<0.05). Studies have also shown a significant reduction in systolic and diastolic blood pressures after Zinc supplementation. This first comprehensive systematic review and meta-analysis on the effects of Zinc supplementation in patients with diabetes demonstrates that Zinc supplementation has beneficial effects on glycaemic control and promotes healthy lipid parameters. Further studies are required to identify the exact biological mechanisms responsible for these results.