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1.
Purpose of Review
There has been confusion following the 2013 American College of Cardiology/American Heart Association (ACC/AHA) Lipid guidelines on the role of non-statin medications for cardiovascular prevention.Recent Findings
Several recent large trials have also now shown that lowering LDL with non-statins reduces cardiovascular events. In ASCVD patients on statins, adding ezetimibe or a PCSK9 inhibitor led to reductions in CV events in the IMPROVE IT, FOURIER, and most recently the ODYSSEY-OUTCOMES trials. Additional novel therapies reducing LDL and other atherogenic lipoproteins are in development during this exciting time in this field.Summary
With recent evidence, the 2017 ACC Expert Consensus Decision pathway calls for initial therapy with statins, monitoring LDL levels, and then adding ezetimibe and/or PCSK9 inhibitors to further lower LDL-C to targets based on the patient’s risk.2.
Ilaria Cavallari Alessia Delli Veneri Ernesto Maddaloni Rosetta Melfi Giuseppe Patti Nicola Napoli Paolo Pozzilli Germano Di Sciascio 《Current diabetes reports》2018,18(12):138
Purpose of the Review
To summarize available evidence regarding lipid-lowering interventions for the prevention of cardiovascular disease in patients with diabetes.Recent Findings
Statins and non-statin therapies that act through upregulation of LDL receptor expression are associated with similar cardiovascular risk reduction per decrease in LDL cholesterol.Summary
In subjects with diabetes, with or without established cardiovascular disease, each 39 mg/dl reduction in LDL cholesterol observed with statins is associated with a 21% relative reduction in the risk of major coronary events at 5 years. Statins remain the first-line lipid-lowering agents for the management of dyslipidemia in individuals with diabetes; however, the addition of non-statin therapies to lower LDL cholesterol, such as ezetimibe and PCSK-9 inhibitors, to maximally tolerated statin therapy is recommended in patients with atherosclerotic cardiovascular disease and baseline LDL cholesterol over 70 mg/dl. Recent data support even lower LDL cholesterol targets (<?55 mg/dl) to further reduce the risk of cardiovascular events especially in subjects with diabetes and documented cardiovascular disease.3.
Purpose of Review
We provide an overview of our current understanding of combination lipid-lowering therapies intended for dyslipidemia treatment and cardiovascular disease prevention. First, we analyze recent statin and non-statin combination therapy guidelines and clinical studies since the publication of 2013 American College of Cardiology Cholesterol Guidelines. Second, we examine the clinical utility of non-statin agents alone and in combination in terms of LDL-C lowering and ASCVD risk reduction.Recent Findings
Medical societies, including the American College of Cardiology (ACC), National Lipid Association (NLA), and American Association of Clinical Endocrinologists (AACE), have released guidelines to address the appropriate use of non-statin therapies. The guidelines incorporated new evidence, including the IMPROVE-IT and FOURIER clinical trials, which demonstrate that the combination of statin therapy with other non-statin agents such as ezetimibe and PCSK9 inhibitors has a significant clinical benefit. Increasing evidence that aggressive low-density lipoprotein cholesterol (LDL-C) lowering leads to lower cardiovascular disease risk supports the need for continued exploration of the role of combination lipid-lowering therapies.Summary
A review of guidelines and clinical trials evaluating non-statin agents illuminates the growing base of evidence and expert opinion supporting the use of combination lipid-lowering therapies. While the majority of clinical trial data utilizes dyslipidemia monotherapy, especially statins, combination therapies represent an opportunity for individualized, patient-centered approach to LDL-C lowering and atherosclerotic cardiovascular disease (ASCVD) risk reduction. The overview provides a perspective on lipid management intended for clinicians who seek additional information and guidance on the use of combination therapies.4.
Purpose of Review
To review the interactions between statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition.Recent Findings
Statins are highly effective for reducing low-density lipoprotein cholesterol (LDL-C) and cardiovascular disease (CVD). However, statins also raise levels of PCSK9, a protein that increases circulating LDL-C levels by increasing LDL-C receptor degradation. Increases in PCSK9 levels also reduce the LDL-C response to statin therapy.Summary
The interactions between statins, PCSK9, LDL-C, and cardiovascular risk are multifaceted and are influenced by genetic, lifestyle, and environmental factors as well as lipid-lowering therapies.5.
Om Ganda 《Current diabetes reports》2018,18(11):126
Purpose of Review
Statins are the most evidence-based therapy to target LDL-C to reduce atherosclerotic events. Yet, many people are unable to achieve adequate reduction in this key atherogenic factor. Moreover, residual risk of cardiovascular events may persist even after “optimal” LDL-C due to elevations in triglyceride-rich lipoproteins. Therefore, additional therapies beyond statins are needed, particularly in patients with diabetes.Recent Findings
Clinical trials with ezetimibe and PCSK9 inhibitors have reported further reductions in cardiovascular events, beyond statins. The latter are particularly effective in lowering LDL-cholesterol and in reducing event rates. However, they are not effective in lowering triglycerides. Currently available fibrates and niacin have not proven effective in combination with statins in clinical trials, while the top line results of the REDUCE-IT trial with EPA, a pure omega-3 fatty acid, reporting 25% relative risk reduction in primary endpoints are of great interest.Summary
Recently approved agents have the promise to improve cardiovascular outcomes beyond statins. Many novel drugs in development have the potential to further improve prognosis.6.
C. Lebherz 《Der Diabetologe》2016,12(2):80-87
Background
Patients with type 2 diabetes are at increased risk of developing cardiovascular diseases and have been shown to greatly benefit from tight control not only of the blood glucose but also of LDL (low density lipoprotein) cholesterol levels.Cardiovascular risk reduction
So far an aggressive treatment regimen with potent statins has been recommended. The IMPROVE IT study caused a paradigm shift in that it showed additional cardiovascular risk reduction if LDL cholesterol was reduced below target levels independent of the pleiotropic statin actions. These effects were even more significant in patients with type 2 diabetes.Conclusions
Therefore even though statins are still first choice, a combination with ezetimibe or the novel PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors is warranted to further reduce cardiovascular risk. As secondary targets, non-HDL (high density lipoprotein) cholesterol or ApoB (apolipoprotein B) levels serve as surrogate markers for atherogenic lipid particles. Depending on the individual lipid levels, combination therapy with fibrates or ω?3 fatty acids might be of benefit.7.
Mosepele Mosepele Onkabetse J. Molefe-Baikai Steven K. Grinspoon Virginia A. Triant 《Current infectious disease reports》2018,20(8):20
Purpose of Review
HIV-infected patients face an increased risk for cardiovascular disease (CVD), estimated at 1.5- to 2-fold as compared to HIV-uninfected persons. This review provides a recent (within preceding 5 years) summary of the role of statin therapy and associated role in CVD risk reduction among HIV-infected patients on anti-retroviral therapy.Recent Findings
Statins remain the preferred agents for reducing risk for CVD among HIV-infected populations based on guidance extrapolated from general population (HIV-uninfected) cholesterol treatment guidelines across different settings globally. However, HIV-infected patients are consistently under prescribed statin therapy when compared to their HIV-uninfected counterparts. The most commonly studied statins in clinical care and small randomized and cohort studies have been rosuvastatin and atorvastatin. Both agents are preferred for their potent lipid-lowering effects and their favorable or neutral pleotropic effects on chronic inflammation, renal function, and hepatic steatosis among others. However, growing experience with the newer glucuronidated pitavastatin suggests that this agent has virtually no adverse drug interactions with ART or effects on glucose metabolism—all marked additional benefits when compared with rosuvastatin and atorvastatin while maintaining comparable anti-lipid effects. Pitavastatin is therefore the statin of choice for the ongoing largest trial (6500 participants) to test the benefits of statin therapy among HIV-infected adults.Summary
Statins are underutilized in the prevention of CVD in HIV-infected populations based on criteria in established cholesterol guidelines. There is a potential role for statin therapy for HIV-infected patients who do not meet guideline criteria which will be further delineated through ongoing clinical trials.8.
Karen M. Goldstein Leah L. Zullig Lori A. Bastian Hayden B. Bosworth 《Current atherosclerosis reports》2016,18(11):63
Purpose of Review
Cardiovascular disease (CVD) continues to be the leading cause of death for men and women in the USA. Statins have contributed significantly to noted declines in cardiovascular-related mortality in the last decade; however, the benefit of statins is inequitable across genders. Women continue to be less likely to take statins and to meet target LDL goals than men. As a possible contributing factor to this disparity, we explore the evidence for gender-based differences in provision of, and adherence to statins.Recent Findings
Compared with men, women are less likely to adhere to statins. Potential reasons for this gender difference in use of statins can be observed across all phases of adherence including both intentional and unintentional non-adherence. Notable gender-specific contributing factors for statin non-adherence include decreased provider and patient awareness of CVD risk among women, higher risk of statin intolerance among women, and competing demands associated with family caregiving responsibilities. Similar to limitations in the broader CVD literature, there is inadequate inclusion of gender-specific analyses in statin-related trials.Summary
Gender-based disparities in statin adherence can be linked to both provider level, psychosocial, and medication intolerance factors. Interventions designed to improve statin adherence should take gender-specific challenges into consideration such as women being older at the time of increased CVD risk, higher rates of statin intolerance, and potentially greater caregiving responsibilities.9.
Purpose
Besides the lipid-lowering properties, statins are thought to have anti-inflammatory effects and it has been shown that statins directly attenuate the inflammatory stress response after surgical trauma. The aim of the study was to examine the association between preoperative statin use and 30-day mortality as well as postoperative complications after curative-intended surgery for colorectal cancer.Methods
The study was a Danish nationwide register-based observational study. A total of 29,352 patients undergoing surgery for colorectal cancer between January 1, 2003, and December 31, 2012, were included in the study. At the time of surgery, 5961 were registered as statin users. The outcomes were 30-day mortality and risk of postoperative complications.Results
The adjusted hazard ratio of 30-day mortality was 0.91 (95 CI 0.80–1.04, P?=?0.16) among statin users compared with the non-statin group. There was no difference between the two groups regarding the risk of infectious complications (sepsis, anastomotic leakage, pneumonia) (odds ratio 0.95, 95% CI 0.86–1.05, P?=?0.31). For other postoperative complications (cardiovascular events, stroke, renal failure, respiratory insufficiency, and thromboembolic events), there was no significant difference between the two groups (odds ratio 0.89, 95% CI 0.78–1.01, P?=?0.06).Conclusion
The study did not show an improved 30-day survival after surgery for colorectal cancer in patients treated with statins in the year preceding surgery. No overall association with the risk of postoperative complications was shown.10.
Purpose of Review
Assessing the cardiovascular risk associated with hypertriglyceridemia can be challenging due to frequent confounding conditions such as hypertension, diabetes mellitus, and hyperlipidemia. We sought to quantify this risk by examining several meta-analyses as well as subgroup analyses of previously published major randomized controlled trials that focused on the treatment of hyperlipidemia.Recent Findings
Recent trials measuring the effects of PCSK9 inhibitors such as evolocumab and alirocumab on cardiovascular outcomes have demonstrated a high degree of residual cardiovascular risk even after profound reductions in low-density-lipoprotein cholesterol (LDL-C).Summary
Despite optimization of LDL-C through the use of statins, PCSK9 inhibitors and adjunctive therapies such as ezetimibe, bile acid sequestrants and niacin, residual cardiovascular risk remains significant. Several ongoing trials are assessing the efficacy of pemafibrate and omega-3 fatty acids for the treatment of hypertriglyceridemia and their effects on major cardiovascular outcomes.11.
Lane B. Benes Daniel J. Brandt Eric J. Brandt Michael H. Davidson 《Current cardiology reports》2018,20(12):138
Purpose of the Review
To summarize advances in genomic medicine and anticipated future directions to improve cardiovascular risk reduction.Recent Findings
Mendelian randomization and genome-wide association studies have given significant insights into the role of genetics in dyslipidemia and cardiovascular disease (CVD), with over 160 gene loci found to be associated with coronary artery disease to date. This has enabled the creation of genetic risk scores that have demonstrated improved risk prediction when added to clinical markers of CVD risk.Summary
Incorporation of genomic data into clinical patient care is on the horizon. Genomic medicine is expected to offer improved risk assessment, determination of targeted treatment strategies, and improved detection of lipid disorders causal to CVD development.12.
Purpose of Review
The increased cardiovascular disease (CVD) risk in subjects with type 2 diabetes (T2D) is well established. This review collates the available evidence and assesses the shared genetic background between T2D and CVD: the causal contribution of common risk factors to T2D and CVD and how genetics can be used to improve drug development and clinical outcomes.Recent Findings
Large-scale genome-wide association studies (GWAS) of T2D and CVD support a shared genetic background but minimal individual locus overlap.Summary
Mendelian randomisation (MR) analyses show that T2D is causal for CVD, but GWAS of CVD, T2D and their common risk factors provided limited evidence for individual locus overlap. Distinct but functionally related pathways were enriched for CVD and T2D genetic associations reflecting the lack of locus overlap and providing some explanation for the variable associations of common risk factors with CVD and T2D from MR analyses.13.
Purpose of the Review
In the present review, we will discuss the evidence and the mechanisms underlying the complex interplay between obesity, mineralocorticoid receptor activation, and cardiovascular dysfunction with special emphasis on the pathogenesis of cardiovascular disease (CVD) in obese and insulin-resistant females.Recent Findings
Since the initial isolation of aldosterone in 1953 and the cloning of the mineralocorticoid receptor (MR) decades later, our understanding has expanded tremendously regarding their involvement in the pathogenesis of CVD. Recent results from both pre-clinical and clinical studies support a close correlation between increase adiposity and enhanced aldosterone production (MR activation).Summary
Importantly, insulin resistance and obese females are more prone to the deleterious cardiovascular effects of MR activation, and enhanced MR activation in females has emerged as an important causative event in the genesis of a more severe CVD in diabetic women. Different clinical trials have been completed examining the effect of MR blockade in subjects with CVD. Despite its important beneficial mortality impact, side effects are frequent and a newer MR antagonist, finerenone, with less risk of hyperkalemia is currently being tested in large clinical trials.14.
Purpose of Review
We briefly introduce the concept and use of cardiovascular disease (CVD) risk scores and review the methodology for CVD risk score development and validation in patients with diabetes. We also discuss CVD risk scores for diabetic patients that have been developed in different countries.Recent Findings
Patients with diabetes have a gradient of CVD risk that needs to be accurately assessed. Numerous CVD risk scores for diabetic patients have been created in various settings. The methods to develop risk scores are highly diverse and each choice has its own pros and cons. A well-constructed risk score for diabetic patients may be advocated by guidelines and adopted by healthcare providers to help determine preventive strategies. New risk factors are being investigated in order to improve the predictive accuracy of current risk scores.Summary
A suitable CVD risk score for the diabetes population should be accurate, low-cost, and beneficial to outcome. While the performance (accuracy) has all been internally validated, validation on external populations is still needed. Cost-effectiveness and clinical trials demonstrating improvement in outcomes are limited and should be the target of future research.15.
Michael M. Hoffmann 《Current cardiology reports》2018,20(7):56
Purpose of Review
Today, statins are the first choice to lower LDL cholesterol and concomitantly the risk of atherosclerotic cardiovascular disease. There is a significant minority of statin-treated patients who are more susceptible to occasionally serious side effects that may increase morbidity and lead to compliance problems or the discontinuation of therapy. This review addresses the question of whether genetics can provide meaningful insights into the risk of statin side effects or therapy success.Recent Findings
The use of genome-wide association studies has significantly reduced the number of predictive genetic markers for statin effects, and the isolated effect of the surviving markers is low; more promising are approaches to stratify patients with genetic risk scores.Summary
Patients reveal a pronounced individual response to the administration of statins. The idea of being able to adequately describe this variability with single genetic markers has failed, genetic risk scores will be the method of choice.16.
Leslie Cho Michael Rocco David Colquhoun David Sullivan Robert S. Rosenson Ricardo Dent Allen Xue Rob Scott Scott M. Wasserman Erik Stroes 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》2016,30(3):297-304
Purpose
Recent evidence suggests that statin intolerance may be more common than reported in randomized trials. However, the statin-intolerant population is not well characterized. The goal of this report is to characterize the population enrolled in the phase 3 Goal Achievement after Utilizing an anti-PCSK9 antibody in Statin Intolerant Subjects Study (GAUSS-2; NCT 01763905).Methods
GAUSS-2 compared evolocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9) to ezetimibe in hypercholesterolemic patients who discontinued statin therapy due to statin-associated muscle symptoms (SAMS). GAUSS-2 was a 12-week, double-blind, placebo-controlled, randomized study that enrolled patients with elevated LDL-C who were either not on a statin or able to tolerate only a low-dose due to SAMS. Patients had received ≥2 statins and were unable to tolerate any statin dose or increase in dose above a specified weekly dose due to SAMS.Results
Three hundred seven patients (mean [SD] age, 62 [10] years; 54 % males) were randomized 2:1 (evolocumab:ezetimibe). Mean (SD) LDL-C was 4.99 (1.51) mmol/L. Patients had used ≥2 (100 %), ≥3 (55 %), or ≥4 (21 %) statins. Coronary artery disease was present in 29 % of patients. Statin-intolerant symptoms were myalgia in 80 % of patients, weakness in 39 %, and more serious complications in 20 %. In 98 % of patients, SAMS interfered with normal daily activity; in 52 %, symptoms precluded moderate exertion.Conclusion
Evaluation of the GAUSS-2 trial population of statin-intolerant patients demonstrates that most patients were high risk with severely elevated LDL-C and many had statin-associated muscle symptoms that interfered with their quality of life.17.
M. Regina Castro Gyorgy Simon Stephen S. Cha Barbara P. Yawn L. Joseph MeltonIII Pedro J. Caraballo 《Journal of general internal medicine》2016,31(5):502-508
BACKGROUND
The association between the use of statins and the risk of diabetes and increased mortality within the same population has been a source of controversy, and may underestimate the value of statins for patients at risk.OBJECTIVE
We aimed to assess whether statin use increases the risk of developing diabetes or affects overall mortality among normoglycemic patients and patients with impaired fasting glucose (IFG).DESIGN AND PARTICIPANTS
Observational cohort study of 13,508 normoglycemic patients (n?=?4460; 33 % taking statins) and 4563 IFG patients (n?=?1865; 41 % taking statin) among residents of Olmsted County, Minnesota, with clinical data in the Mayo Clinic electronic medical record and at least one outpatient fasting glucose test between 1999 and 2004. Demographics, vital signs, tobacco use, laboratory results, medications and comorbidities were obtained by electronic search for the period 1999–2004. Results were analyzed by Cox proportional hazards models, and the risk of incident diabetes and mortality were analyzed by survival curves using the Kaplan–Meier method.MAIN MEASURES
The main endpoints were new clinical diagnosis of diabetes mellitus and total mortality.KEY RESULTS
After a mean of 6 years of follow-up, statin use was found to be associated with an increased risk of incident diabetes in the normoglycemic (HR 1.19; 95 % CI, 1.05 to 1.35; p?=?0.007) and IFG groups (HR 1.24; 95%CI, 1.11 to 1.38; p?=?0.0001). At the same time, overall mortality decreased in both normoglycemic (HR 0.70; 95 % CI, 0.66 to 0.80; p?<?0.0001) and IFG patients (HR 0.77, 95 % CI, 0.64 to 0.91; p?=?0.0029) with statin use.CONCLUSION
In general, recommendations for statin use should not be affected by concerns over an increased risk of developing diabetes, since the benefit of reduced mortality clearly outweighs this small (19–24 %) risk.18.
Jea Young Min Marie R. Griffin Adriana M. Hung Carlos G. Grijalva Robert A. Greevy Xulei Liu Tom Elasy Christianne L. Roumie 《Journal of general internal medicine》2016,31(6):638-646
BACKGROUND
Type 2 diabetes patients often initiate treatment with a sulfonylurea and subsequently intensify their therapy with insulin. However, information on optimal treatment regimens for these patients is limited.OBJECTIVE
To compare risk of cardiovascular disease (CVD) and hypoglycemia between sulfonylurea initiators who switch to or add insulin.DESIGN
This was a retrospective cohort assembled using national Veterans Health Administration (VHA), Medicare, and National Death Index databases.PARTICIPANTS
Veterans who initiated diabetes treatment with a sulfonylurea between 2001 and 2008 and intensified their regimen with insulin were followed through 2011.MAIN MEASURES
The association between insulin versus sulfonylurea?+?insulin and time to CVD or hypoglycemia were evaluated using Cox proportional hazard models in a 1:1 propensity score-matched cohort. CVD included hospitalization for acute myocardial infarction or stroke, or cardiovascular mortality. Hypoglycemia included hospitalizations or emergency visits for hypoglycemia, or outpatient blood glucose measurements <60 mg/dL. Subgroups included age < 65 and ≥ 65 years and estimated glomerular filtration rate ≥ 60 and < 60 ml/min.KEY FINDINGS
There were 1646 and 3728 sulfonylurea monotherapy initiators who switched to insulin monotherapy or added insulin, respectively. The 1596 propensity score-matched patients in each group had similar baseline characteristics at insulin initiation. The rate of CVD per 1000 person-years among insulin versus sulfonylurea?+?insulin users were 49.3 and 56.0, respectively [hazard ratio (HR) 0.85, 95 % confidence interval (CI) 0.64, 1.12]. Rates of first and recurrent hypoglycemia events per 1000 person-years were 74.0 and 100.0 among insulin users compared to 78.9 and 116.8 among sulfonylurea plus insulin users, yielding HR (95 % CI) of 0.94 (0.76, 1.16) and 0.87 (0.69, 1.10), respectively. Subgroup analysis results were consistent with the main findings.CONCLUSIONS
Compared to sulfonylurea users who added insulin, those who switched to insulin alone had numerically lower CVD and hypoglycemia events, but these differences in risk were not statistically significant.19.
Purpose of Review
We review recent epidemiological and clinical studies investigating the consumption of tree nuts and peanuts and cardiovascular disease (CVD) mortality as well as CVD risk factors.Recent Findings
A greater consumption of tree nuts and peanuts is associated with a reduced risk of CVD mortality, as well as lower CVD events. Furthermore, risk factors associated with the development of CVD such as dyslipidemia, impaired vascular function, and hypertension are improved with regular tree nut and peanut consumption through a range of mechanism associated with their nutrient-rich profiles. There is weak inconsistent evidence for an effect of nut consumption on inflammation. There is emerging evidence that consuming tree nuts reduces the incidence of non-alcoholic fatty liver disease (NAFLD) and promotes diversity of gut microbiota, which in turn may improve CVD outcomes.Summary
Evidence for CVD prevention is strong for some varieties of tree nuts, particularly walnuts, and length of supplementation and dose are important factors for consideration with recommendations.20.
Lisandro D. Colantonio Shia T. Kent Lei Huang Ligong Chen Keri L. Monda Maria-Corina Serban Angelika Manthripragada Meredith L. Kilgore Robert S. Rosenson Paul Muntner 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》2016,30(5):525-533