Abstract Background Many patients report adverse reactions to, and may not tolerate, statin therapy. These patients may be at increased risk for coronary heart disease (CHD) events and mortality. ...Objectives This study evaluated the risk for recurrent myocardial infarction (MI), CHD events, and all-cause mortality in Medicare beneficiaries with statin intolerance and in those with high adherence to statin therapy. Methods We studied 105,329 Medicare beneficiaries who began a moderate- or high-intensity statin dosage after hospitalization for MI between 2007 and 2013. Statin intolerance was defined as down-titrating statins and initiating ezetimibe therapy, switching from statins to ezetimibe monotherapy, having International Classification of Diseases, 9th revision, diagnostic codes for rhabdomyolysis or an antihyperlipidemic adverse event, followed by statin down-titration or discontinuation, or switching between ≥3 types of statins within 1 year after initiation. High statin adherence over the year following hospital discharge was defined as proportion of days covered ≥80%. Recurrent MI, CHD events (recurrent MI or a coronary revascularization procedure), and mortality were identified from 1 year after hospital discharge through December 2014. Results Overall, 1,741 patients (1.65%) had statin intolerance, and 55,567 patients (52.8%) had high statin adherence. Over a median of 1.9 to 2.3 years of follow-up, there were 4,450 recurrent MIs, 6,250 CHD events, and 14,311 deaths. Compared to beneficiaries with high statin adherence, statin intolerance was associated with a 36% higher rate of recurrent MI (41.1 vs. 30.1 per 1,000 person-years, respectively), a 43% higher rate of CHD events (62.5 vs. 43.8 per 1,000 person-years, respectively), and a 15% lower rate of all-cause mortality (79.9 vs. 94.2 per 1,000 person-years, respectively). The multivariate-adjusted hazard ratios (HR) comparing beneficiaries with statin intolerance versus those with high statin adherence were 1.50 (95% confidence interval CI: 1.30 to 1.73) for recurrent MI, 1.51 (95% CI: 1.34 to 1.70) for CHD events, and 0.96 (95% CI: 0.87 to 1.06) for all-cause mortality. Conclusions Statin intolerance was associated with an increased risk for recurrent MI and CHD events but not all-cause mortality.
Background
Quercetin, the most abundant dietary flavonol, has antioxidant effects in cardiovascular disease, but the evidence regarding its effects on blood pressure (BP) has not been conclusive. We ...assessed the impact of quercetin on BP through a systematic review and meta‐analysis of available randomized controlled trials.
Methods and Results
We searched PUBMED, Cochrane Library, Scopus, and EMBASE up to January 31, 2015 to identify placebo‐controlled randomized controlled trials investigating the effect of quercetin on BP. Meta‐analysis was performed using either a fixed‐effects or random‐effect model according to I2 statistic. Effect size was expressed as weighted mean difference (WMD) and 95% CI. Overall, the impact of quercetin on BP was reported in 7 trials comprising 9 treatment arms (587 patients). The results of the meta‐analysis showed significant reductions both in systolic BP (WMD: −3.04 mm Hg, 95% CI: −5.75, −0.33, P=0.028) and diastolic BP (WMD: −2.63 mm Hg, 95% CI: −3.26, −2.01, P<0.001) following supplementation with quercetin. When the studies were categorized according to the quercetin dose, there was a significant systolic BP and diastolic BP‐reducing effect in randomized controlled trials with doses ≥500 mg/day (WMD: −4.45 mm Hg, 95% CI: −7.70, −1.21, P=0.007 and −2.98 mm Hg, 95% CI: −3.64, −2.31, P<0.001, respectively), and lack of a significant effect for doses <500 mg/day (WMD: −1.59 mm Hg, 95% CI: −4.44, 1.25, P=0.273 and −0.24 mm Hg, 95% CI: −2.00, 1.52, P=0.788, respectively), but indirect comparison tests failed to significant differences between doses.
Conclusions
The results of the meta‐analysis showed a statistically significant effect of quercetin supplementation in the reduction of BP, possibly limited to, or greater with dosages of >500 mg/day. Further studies are necessary to investigate the clinical relevance of these results and the possibility of quercetin application as an add‐on to antihypertensive therapy.
•We aimed to evaluate the efficacy of curcuminoids on parameters of oxidative stress.•7 randomized controlled trials were finally selected for the meta-analysis.•There was a significant increase of ...SOD activities especially for studies ≥6 weeks.•They also significantly reduced lipid peroxides, increased GSH and catalase activity.
The aim of the meta-analysis was to evaluate the efficacy of purified curcuminoids supplementation on plasma activities of superoxide dismutase (SOD), catalase and glutathione (GSH) and lipid peroxides as parameters of oxidative stress. Seven randomized controlled trials were finally selected for the meta-analysis. There was a significant increase of serum SOD activities after curcuminoids supplementation (weighted mean difference WMD: 1.15 U/mL, 95% confidence interval CI: 0.49–1.82, p = 0.0007). In a subgroup analysis, no significant effects was observed in the subset of studies administering curcuminoids for <6 weeks (WMD: 0.75 U/mL, 95%CI: −0.56–2.05, p = 0.26), but a significant increase of SOD activities was found with supplementation duration ≥6 weeks (WMD: 1.46 U/mL, 95%CI: 0.60–2.32, p = 0.0009). The curcuminoids significantly reduced serum lipid peroxides (WMD: −6.35 nmol/mL, 95%CI: −11.06 to −1.64, p = 0.008), increased GSH concentrations (WMD: 5.39 µg/mL, 95%CI: 1.17–9.60, p = 0.01), and catalase activity (WMD: 51.78 U/mL, 95%CI: 15.71–87.85, p = 0.005). This meta-analysis showed a significant effect of curcuminoids in elevating serum SOD and catalase activities, GSH concentrations, and reduction of serum lipid peroxides.
Statins are the most common drugs administered for patients with cardiovascular disease. However, due to statin-associated muscle symptoms, adherence to statin therapy is challenging in clinical ...practice. Certain nutraceuticals, such as red yeast rice, bergamot, berberine, artichoke, soluble fiber, and plant sterols and stanols alone or in combination with each other, as well as with ezetimibe, might be considered as an alternative or add-on therapy to statins, although there is still insufficient evidence available with respect to long-term safety and effectiveness on cardiovascular disease prevention and treatment. These nutraceuticals could exert significant lipid-lowering activity and might present multiple non–lipid-lowering actions, including improvement of endothelial dysfunction and arterial stiffness, as well as anti-inflammatory and antioxidative properties. The aim of this expert opinion paper is to provide the first attempt at recommendation on the management of statin intolerance through the use of nutraceuticals with particular attention on those with effective low-density lipoprotein cholesterol reduction.
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The study aims to investigate the effect of argan oil on plasma lipid concentrations through a systematic review of the literature and a meta‐analysis of available randomized controlled trials. ...Randomized controlled trials that investigated the impact of at least 2 weeks of supplementation with argan oil on plasma/serum concentrations of at least 1 of the main lipid parameters were eligible for inclusion. Effect size was expressed as the weighted mean difference (WMD) and 95% confidence interval (95% CI). Meta‐analysis of data from 5 eligible trials with 292 participants showed a significant reduction in plasma concentrations of total cholesterol (WMD: −16.85 mg/dl, 95% CI −25.10, −8.60, p < .001), low‐density lipoprotein cholesterol (WMD: −11.67 mg/dl, 95% CI −17.32, −6.01, p < .001), and triglycerides (WMD: −13.69 mg/dl, 95% CI −25.80, −1.58, p = .027) after supplementation with argan oil compared with control treatment, and plasma concentrations of high‐density lipoprotein cholesterol (WMD: 4.14 mg/dl, 95% CI 0.86, 7.41, p = .013) were found to be increased. Argan oil supplementation reduces total cholesterol, low‐density lipoprotein cholesterol, and triglycerides and increases high‐density lipoprotein cholesterol levels. Additionally, larger clinical trials are needed to assess the impact of argan oil supplementation on other indices of cardiometabolic risk and on the risk of cardiovascular outcomes.
Statin discontinuation—a problem to be solved Statin discontinuation may concern the patients with complete statin intolerance, as well as patients with cancer, palliative care patients, patients ...with cachexia, but also elderly patients, and primary CV prevention individuals, in which the risk of statin‐related side effects (mainly associated with new‐onset diabetes) might exceed the benefits (especially with subjects with risk factors of diabetes well adhered to non‐pharmacological therapy). ...elderly patients, particularly those over the age of 75 years (or 80+), have not been properly investigated in RCTs evaluating lipid‐lowering therapy. ...the available data on the efficacy and safety of statin therapy in elderly patients (especially without diagnosed CAD) are still very limited. According to the International Lipid Expert Panel Position Paper, there are very detailed recommendations on how to use statins in elderly patients in order to be the most effective in case of CV prevention as well as to reduce the risk of statin‐related side effects: (i) statin therapy should be started when clinically appropriate, especially if the benefits on CVD prevention outweigh potential risks; (ii) discontinuation of statin therapy should be recommended in case of severe illness, major surgery or major trauma until the person recovers. There are also single studies investigating the impact of statin discontinuation on the reduced risk of drug‐related side effects and QOL improvement, especially in patients with cancer with the limited life expectancy. ...it needs to be emphasized that the available data are not sufficient to draw any direct conclusions or recommendations, and any reduction in the statin dose or discontinuation should be balanced with the increased risk of CV events.
Abstract The review provides an up-to-date summary of the findings on the lipid-lowering effects of the most important nutraceuticals and functional foods. Based on the current knowledge, ...nutraceuticals might exert significant lipid-lowering, and their use has several advantages – they have natural origins and are mainly extracted from natural products, they are mostly safe and very well tolerated and their use is supported by the findings from randomizded controlled trials and meta-analyses, finally the lipid-lowering effect of most nutraceuticals is multimechanistic, what makes them potential candidates for improving the effects of current lipid-lowering drugs when used in combination. However, still a number of important questions need to be addressed, including whether longer durations of therapy would result in a better response, and what is the the safety profile of nutraceuticals, especially at doses higher than those consumed in an average diet. In addition, data regarding the impact of nutraceuticals supplementation on the incidence of cardiovascular outcomes are lacking, and it is not clear if additional lipid lowering by nutraceuticals can modify the residual cardiovascular risk that remains following statin therapy.
Abstract
In recent years, there has been growing interest in the possible use of nutraceuticals to improve and optimize dyslipidemia control and therapy. Based on the data from available studies, ...nutraceuticals might help patients obtain theraputic lipid goals and reduce cardiovascular residual risk. Some nutraceuticals have essential lipid-lowering properties confirmed in studies; some might also have possible positive effects on nonlipid cardiovascular risk factors and have been shown to improve early markers of vascular health such as endothelial function and pulse wave velocity. However, the clinical evidence supporting the use of a single lipid-lowering nutraceutical or a combination of them is largely variable and, for many of the nutraceuticals, the evidence is very limited and, therefore, often debatable. The purpose of this position paper is to provide consensus-based recommendations for the optimal use of lipid-lowering nutraceuticals to manage dyslipidemia in patients who are still not on statin therapy, patients who are on statin or combination therapy but have not achieved lipid goals, and patients with statin intolerance. This statement is intended for physicians and other healthcare professionals engaged in the diagnosis and management of patients with lipid disorders, especially in the primary care setting.
Currently, experimental and clinical evidences showed that polyphenols-rich natural products, like nutraceuticals and food supplements, may offer unique treatment modalities in type 2 diabetes ...mellitus (DM), due to their biological properties. Natural products modulate the carbohydrate metabolism by various mechanisms, such as restoring beta-cells integrity and physiology, enhancing insulin releasing activity, and the glucose using. Sea buckthorn berries, red grapes, bilberries, chokeberries and popular drinks like cocoa, coffee and green tea are all rich in polyphenols and may decrease the insulin response, offer in g a natural alternative of treatment in diabetes. Therefore, researches are now focused on potential efficacies of different types of polyphenols, including flavonoids, phenolic acids, lignans, anthocyans and stilbenes. Animal and human studies showed that polyphenols modulate carbohydrate and lipid metabolism, decrease glycemia and insulin resistance, increase lipid metabolism and optimize oxidative stress and inflammatory processes. It is important to understand the proper dose and duration of supplementation with polyphenols-rich extracts in order to guide effective therapeutic interventions in diabetic patients.
Summary Background & aims The impact of Spirulina supplementation on plasma lipid concentrations has not been conclusively studied. Therefore the aim of the meta-analysis was to assess the effect of ...Spirulina supplementation on plasma lipid concentrations. Methods We searched PubMed and Scopus (up to July 03, 2015) to identify randomized controlled trials (RCTs) that investigate the effect Spirulina supplementation on plasma lipid concentrations. Meta-analysis and meta-regression were performed using random-effects models. Results Random-effect meta-analysis of data from 7 RCTs showed a significant effect of supplementation with spirulina in reducing plasma concentrations of total cholesterol (WMD: −46.76 mg/dL, 95% CI: −67.31 to −26.22, p < 0.001), LDL-C (WMD: −41.32 mg/dL, 95% CI: −60.62 to −22.03, p < 0.001) and triglycerides (WMD: −44.23 mg/dL, 95% CI: −50.22 to −38.24, p < 0.001), and elevating those of HDL-C (WMD: 6.06 mg/dL, 95% CI: 2.37–9.76, p = 0.001). The impact of spirulina on plasma concentrations of total cholesterol (slope: −1.32; 95% CI: −8.58 to 5.93; p = 0.720), LDL-C (slope: −1.01; 95% CI: −8.03 to 6.02; p = 0.778), triglycerides (slope: −1.39; 95% CI: −4.26 to 1.48; p = 0.342) and HDL-C (slope: 1.79, 95% CI: −0.48 to 4.05; p = 0.122) was independent of administered dose. Regarding duration of supplementation with Spirulina, significant associations were found with changes in plasma concentrations of total cholesterol (slope: −1.77; 95% CI: −3.48 to −0.07; p = 0.042), LDL-C (slope: −1.73; 95% CI: −3.40 to −0.06; p = 0.042) HDL-C (slope: 0.91; 95% CI: 0.68–1.14; p < 0.001) and triglycerides (slope: −1.39; 95% CI: −2.28 to −0.50; p = 0.002). Conclusions This meta-analysis showed a significant effect of supplementation with Spirulina in reducing plasma concentrations of total cholesterol, LDL-C, triglycerides and elevating those of HDL-C.
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