-
1.
Central and Brachial Blood Pressures, Statins, and Low-Density Lipoprotein Cholesterol: A Mediation Analysis.
Lamarche, F, Agharazii, M, Nadeau-Fredette, AC, Madore, F, Goupil, R
Hypertension (Dallas, Tex. : 1979). 2018;(3):415-421
Abstract
Central blood pressure may be a better predictor of cardiovascular disease than brachial pressure. Although statins reduce brachial pressure, their impact on central pressure remains unknown. Furthermore, whether this effect is mediated through a decrease in low-density lipoprotein cholesterol (LDL-c) is unknown. This study aims to characterize the association of statins and LDL-c with central and brachial blood pressures and to quantify their respective effects. Of the 20 004 CARTaGENE participants, 16 507 had available central blood pressure, LDL-c, and Framingham risk score. Multivariate analyses were used to evaluate the association between central pressure and LDL-c in subjects with or without statins. The impact of LDL-c on the association between statin and pressure parameters was determined through mediation analyses. LDL-c was positively associated with systolic and diastolic central pressure in nonusers (β=0.077 and 0.106; P<0.001) and in participants with statins for primary (β=0.086 and 0.114; P<0.001) and secondary prevention (β=0.120 and 0.194; P<0.003). Statins as primary prevention were associated with lower central systolic, diastolic, and pulse pressures (-3.0, -1.6, and -1.3 mm Hg; P<0.001). Mediation analyses showed that LDL-c reduction contributed to 15% of central systolic and 44% of central diastolic pressure changes associated with statins and attenuated 22% of the effects on central pulse pressure. Similar results were found with brachial pressure components. In conclusion, reduction of LDL-c was associated with only a fraction of the lower blood pressures in statin user and seemed to be mostly associated with improvement of steady (diastolic) pressure, whereas non-LDL-c-mediated pathways were mostly associated with changes in pulsatile pressure components.
-
2.
Effect of statins and non-statin LDL-lowering medications on cardiovascular outcomes in secondary prevention: a meta-analysis of randomized trials.
Koskinas, KC, Siontis, GCM, Piccolo, R, Mavridis, D, Räber, L, Mach, F, Windecker, S
European heart journal. 2018;(14):1172-1180
-
-
Free full text
-
Abstract
AIMS: Current evidence on dyslipidaemia management has expanded to novel treatments and very low achieved levels of low-density lipoprotein cholesterol (LDL-C). We sought to compare the clinical impact of more-intensive vs. less-intensive LDL-C lowering by means of statins and currently recommended non-statin medications in secondary prevention. METHODS AND RESULTS We searched Medline, EMBASE, and Cochrane databases for randomized controlled trials of statins, ezetimibe, proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, or bile acid sequestrants with >500 patients followed for ≥1 year. We employed random-effects models using risk ratios (RRs) with 95% confidence intervals (CIs) to compare outcomes. We included 19 trials (15 of statins, 3 of PCSK9 inhibitors, and 1 of ezetimibe) with 152 507 patients randomly assigned to more-intensive (n = 76 678) or less-intensive treatment (n = 75 829). More-intensive treatment was associated with 19% relative risk reduction for the primary outcome, major vascular events (MVEs; RR 0.81, 95% CI 0.77-0.86). Risk reduction was greater across higher baseline levels and greater achieved reductions of LDL-C. The clinical benefit was significant across varying types of more-intensive treatment and was consistent for statins (RR 0.81, 95% CI 0.76-0.86) and non-statin agents (PCSK9 inhibitors and ezetimibe; RR 0.85, 95% CI 0.77-0.94) as active (more-intensive) intervention (P-interaction = 0.38). Each 1.0 mmol/L reduction in LDL-C was associated with 19% relative decrease in MVE. Death, cardiovascular death, myocardial infarction, stroke, and coronary revascularization also favoured more-intensive treatment. CONCLUSION Reduction of MVE is proportional to the magnitude of LDL-C lowering across a broad spectrum of on-treatment levels in secondary prevention. Statin intensification and add-on treatment with PCSK9 inhibitors or ezetimibe are associated with significant reduction of cardiovascular morbidity in this very high-risk population.
-
3.
Improving identification and management of familial hypercholesterolaemia in primary care: Pre- and post-intervention study.
Weng, S, Kai, J, Tranter, J, Leonardi-Bee, J, Qureshi, N
Atherosclerosis. 2018;:54-60
Abstract
BACKGROUND AND AIMS Familial hypercholesterolaemia (FH) is a major cause of premature heart disease but remains unrecognised in most patients. This study investigated if a systematic primary care-based approach to identify and manage possible FH improves recommended best clinical practice. METHODS Pre- and post-intervention study in six UK general practices (population 45,033), which invited patients with total cholesterol >7.5 mmol/L to be assessed for possible FH. Compliance with national guideline recommendations to identify and manage possible FH (repeat cholesterol; assess family history of heart disease; identify secondary causes and clinical features; reduce total & LDL-cholesterol; statin prescribing; lifestyle advice) was assessed by calculating the absolute difference in measures of care pre- and six months post-intervention. RESULTS The intervention improved best clinical practice in 118 patients consenting to assessment (of 831 eligible patients): repeat cholesterol test (+75.4%, 95% CI 66.9-82.3); family history of heart disease assessed (+35.6%, 95% CI 27.0-44.2); diagnosis of secondary causes (+7.7%, 95% CI 4.1-13.9), examining clinical features (+6.0%, 95% CI 2.9-11.7). For 32 patients diagnosed with possible FH using Simon-Broome criteria, statin prescription significantly improved (18.8%, 95% CI 8.9-35.3), with non-significant mean reductions in cholesterol post-intervention (total: -0.16 mmol/L, 95% CI -0.78-0.46; LDL: -0.12 mmol/L, 95% CI -0.81-0.57). CONCLUSIONS Within six months, this simple primary care intervention improved both identification and management of patients with possible FH, in line with national evidence-based guidelines. Replicating and sustaining this approach across the country could lead to substantial improvement in health outcomes for these individuals with very high cardiovascular risk.
-
4.
Effect of statin therapy on plasma apolipoprotein CIII concentrations: A systematic review and meta-analysis of randomized controlled trials.
Sahebkar, A, Simental-Mendía, LE, Mikhailidis, DP, Pirro, M, Banach, M, Sirtori, CR, Ruscica, M, Reiner, Ž
Journal of clinical lipidology. 2018;(3):801-809
-
-
Free full text
-
Abstract
BACKGROUND Statins are well-established low-density lipoprotein cholesterol-lowering drugs. Elevated apolipoprotein CIII (Apo CIII) levels are associated with elevated triglyceride-rich particles, which are also considered to be a possible risk factor for cardiovascular disease. OBJECTIVE The aim of this meta-analysis of randomized placebo-controlled clinical trials was to assess the effect of statins on Apo CIII concentrations. METHODS Randomized placebo-controlled trials investigating the impact of statin treatment on cholesterol lowering that include lipoprotein measurement were searched in PubMed, MEDLINE, Scopus, Web of Science, and Google Scholar databases (up to July 31, 2017). A random-effects model and generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. A weighted random-effects meta-regression was performed to evaluate the impact of potential confounders on Apo CIII concentrations. RESULTS This meta-analysis of data from 6 randomized placebo-controlled clinical trials (10 statin arms) involving 802 subjects showed that statin therapy significantly decreased circulating Apo CIII concentrations (weighted mean difference [WMD]: -2.71, 95% confidence interval [CI]: -3.74 to -1.68, P < .001; I2: 73.83%). The effect size was robust in the leave-one-out sensitivity analysis and not driven by any single study. Subgroup analysis showed a reduction of Apo CIII concentrations by atorvastatin (WMD: -4.74, 95% CI: -3.74 to -1.68, P = .002; I2: 84.02%), rosuvastatin (WMD: -2.68, 95% CI: -4.52 to -0.84, P = .004; I2: 0%), and lovastatin (WMD: -1.64, 95% CI: -2.22 to -1.07, P < .001; I2: 0%). CONCLUSION This meta-analysis suggests that statin treatment significantly reduces plasma Apo CIII levels.
-
5.
Evaluation of Statin Eligibility, Prescribing Practices, and Therapeutic Responses Using ATP III, ACC/AHA, and NLA Dyslipidemia Treatment Guidelines in a Large Urban Cohort of HIV-Infected Outpatients.
Levy, ME, Greenberg, AE, Magnus, M, Younes, N, Castel, A
AIDS patient care and STDs. 2018;(2):58-69
-
-
Free full text
-
Abstract
Statin coverage has been examined among HIV-infected patients using Adult Treatment Panel III (ATP III) and American College of Cardiology/American Heart Association (ACC/AHA) guidelines, although not with newer National Lipid Association (NLA) guidelines. We investigated statin eligibility, prescribing practices, and therapeutic responses using these three guidelines. Sociodemographic, clinical, and laboratory data were collected between 2011 and 2016 for HIV-infected outpatients enrolled in the DC Cohort, a multi-center, prospective, observational study in Washington, DC. This analysis included patients aged ≥21 years receiving primary care at their HIV clinic site with ≥1 cholesterol result available. Of 3312 patients (median age 52; 79% black), 52% were eligible for statins based on ≥1 guideline, including 45% (NLA), 40% (ACC/AHA), and 30% (ATP III). Using each guideline, 49% (NLA), 56% (ACC/AHA), and 73% (ATP III) of eligible patients were prescribed statins. Predictors of new prescriptions included older age (aHR = 1.16 [1.08-1.26]/5 years), body mass index ≥30 (aHR = 1.50 [1.07-2.11]), and diabetes (aHR = 1.35 [1.03-1.79]). Hepatitis C coinfection was inversely associated with statin prescriptions (aHR = 0.67 [0.45-1.00]). Among 216 patients with available cholesterol results pre-/post-prescription, 53% achieved their NLA cholesterol goal after 6 months. Hepatitis C coinfection was positively associated (aHR = 1.87 [1.06-3.32]), and depression (aHR = 0.56 [0.35-0.92]) and protease inhibitor use (aHR = 0.61 [0.40-0.93]) were inversely associated, with NLA goal achievement. Half of patients were eligible for statins based on current US guidelines, with the highest proportion eligible based on NLA guidelines, yet, fewer received prescriptions and achieved treatment goals. Greater compliance with recommended statin prescribing practices may reduce cardiovascular disease risk among HIV-infected individuals.
-
6.
Recent Developments in the Role of Coenzyme Q10 for Coronary Heart Disease: a Systematic Review.
Ayers, J, Cook, J, Koenig, RA, Sisson, EM, Dixon, DL
Current atherosclerosis reports. 2018;(6):29
Abstract
PURPOSE OF REVIEW This review examines recent randomized clinical trials evaluating the role of coenzyme Q10 (CoQ10) in the management of coronary heart disease. RECENT FINDINGS CoQ10 is one of the most commonly used dietary supplements in the USA. Due to its antioxidant and anti-inflammatory effects, CoQ10 has been studied extensively for possible use in managing coronary heart disease. One of the most common applications of CoQ10 is to mitigate statin-associated muscle symptoms (SAMS) based on the theory that SAMS are caused by statin depletion of CoQ10 in the muscle. Although previous studies of CoQ10 for SAMS have produced mixed results, CoQ10 appears to be safe. Because CoQ10 is a cofactor in the generation of adenosine triphosphate, supplementation has also recently been studied in patients with heart failure, which is inherently an energy deprived state. The Q-SYMBIO trial found that CoQ10 supplementation in patients with heart failure not only improved functional capacity, but also significantly reduced cardiovascular events and mortality. Despite these positive findings, a larger prospective trial is warranted to support routine use of CoQ10. Less impressive are the effects of CoQ10 on specific cardiovascular risk factors such as blood pressure, dyslipidemia, and glycemic control. Current evidence does not support routine use of CoQ10 in patients with coronary heart disease. Additional studies are warranted to fully determine the benefit of CoQ10 in patients with heart failure before including it in guideline-directed medical therapy.
-
7.
Does Treating Vascular Risk Factors Prevent Dementia and Alzheimer's Disease? A Systematic Review and Meta-Analysis.
Larsson, SC, Markus, HS
Journal of Alzheimer's disease : JAD. 2018;(2):657-668
Abstract
BACKGROUND Epidemiological evidence has associated Alzheimer's disease (AD) with vascular risk factors (VRFs), but whether treatment of VRFs reduces the incidence of dementia and AD is uncertain. OBJECTIVE To conduct a systematic review and meta-analysis to summarize available data on the impact of treatment of VRFs on dementia and AD incidence. METHODS Pertinent studies published until 1 January 2018 were identified from PubMed. Both randomized controlled trials (RCT) and prospective studies that investigated the impact of treatment of VRFs on dementia or AD incidence were included. RESULTS Eight RCTs and 52 prospective studies were identified. Antihypertensive treatment was associated with a non-significant reduced risk of dementia in RCTs (n = 5; relative risk [RR], 0.84; 95% confidence interval [CI], 0.69-1.02) and prospective studies (n = 3; RR, 0.77; 95% CI, 0.58-1.01) and with reduced AD risk in prospective studies (n = 5; RR = 0.78; 95% CI, 0.66-0.91). In prospective studies, treatment of hyperlipidemia with statins, but not nonstatin lipid-lowering agents, was associated with reduced risk of dementia (n = 17; RR, 0.77; 95% CI, 0.63-0.95) and AD (n = 13; RR, 0.86; 95% CI, 0.80-0.92). The single RCT on statins and dementia incidence showed no association. Data from one RCT and six prospective studies did not support a beneficial impact of antidiabetic drugs or insulin therapy on dementia risk. CONCLUSION Current evidence indicates that antihypertensives and statins might reduce the incidence of dementia and AD. Further trials to determine the effect of VRF on AD are needed.
-
8.
Impact of statin-ezetimibe combination on coronary atheroma plaque in patients with and without chronic kidney disease - Sub-analysis of PRECISE-IVUS trial.
Fujisue, K, Nagamatsu, S, Shimomura, H, Yamashita, T, Nakao, K, Nakamura, S, Ishihara, M, Matsui, K, Yamamoto, N, Koide, S, et al
International journal of cardiology. 2018;:23-26
Abstract
BACKGROUND Chronic kidney disease (CKD) deteriorates the prognosis of patients undergoing percutaneous coronary intervention (PCI). Because coronary artery disease (CAD) is the major cause of death in CKD patients, cardiovascular risk reduction has been clinically important in CKD. We hypothesized intensive lipid-lowering with statin/ezetimibe attenuated coronary atherosclerotic development even in patients with CKD. METHODS In the prospective, randomized, controlled, multicenter PRECISE-IVUS trial, 246 patients undergoing intravascular ultrasound (IVUS)-guided PCI were randomly assigned to receive atorvastatin/ezetimibe combination or atorvastatin alone (the dosage of atorvastatin was up-titrated to achieve the level of low-density lipoprotein cholesterol < 70 mg/dL). Serial volumetric IVUS findings obtained at baseline and 9-12 month follow-up to quantify the coronary plaque response in 202 patients were compared stratified by the presence or absence of CKD. RESULTS CKD was observed in 52 patients (26%) among 202 enrolled patients. Compared with the non-CKD group, the CKD group was significantly older (71.5 ± 8.6 years vs. 64.4 ± 9.6 years, P < 0.001) with similar prevalence of comorbid coronary risk factors and lipid profiles. Similar to the non-CKD group (-1.4 [-2.8 to -0.1]% vs. -0.2 [-1.7 to 1.0]%, P = 0.002), the atorvastatin/ezetimibe combination significantly reduced ∆PAV compared with atorvastatin alone even in the CKD group (-2.6 [-5.6 to -0.4]% vs. -0.9 [-2.4 to 0.2]%, P = 0.04). CONCLUSIONS As with non-CKD, intensive lipid-lowering therapy with atorvastatin/ezetimibe demonstrated stronger coronary plaque regression effect even in patients with CKD compared with atorvastatin monotherapy. TRIAL REGISTRATION NCT01043380 (ClinicalTrials.gov).
-
9.
Statins: a new approach to combat temozolomide chemoresistance in glioblastoma.
Shojaei, S, Alizadeh, J, Thliveris, J, Koleini, N, Kardami, E, Hatch, GM, Xu, F, Hombach-Klonisch, S, Klonisch, T, Ghavami, S
Journal of investigative medicine : the official publication of the American Federation for Clinical Research. 2018;(8):1083-1087
Abstract
Patients with glioblastoma multiforme (GBM) have an average life expectancy of approximately 15 months. Recently, statins have emerged as a potential adjuvant cancer therapy due to their ability to inhibit cell proliferation and induce apoptosis in many types of cancer. The exact mechanisms that mediate the inhibitory actions of statins in cancer cells are largely unknown. The purpose of this proceeding paper is to discuss some of the known anticancer effects of statins, while focusing on GBM therapy that includes adjunct therapy of statins with chemotherapeutic agents.
-
10.
Statin-Associated Muscle Disease: Advances in Diagnosis and Management.
Taylor, BA, Thompson, PD
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics. 2018;(4):1006-1017
-
-
Free full text
-
Abstract
Since the first approval of lovastatin in 1987, hydroxy-methyl-glutaryl CoA (HMG CoA) reductase inhibitors, or statins, have been effective and widely popular cholesterol-lowering agents with substantial benefits for the prevention and treatment of cardiovascular disease. Not all patients can tolerate these drugs, however, and statin intolerance is most frequently associated with a range of side effects directed toward skeletal muscle, termed statin-associated muscle symptoms or SAMS. SAMS are particularly difficult to treat because there are no validated biomarkers or tests that can be used to confirm patient self-reports of SAMS, and a number of patients who report SAMS have non-specific muscle pain not attributable to statin therapy. This review summarizes the most recent evidence related to diagnosis and management of SAMS. First, the range of skeletal muscle side effects associated with statin therapy is described. Second, data regarding the incidence and prevalence of SAMS, the most frequently experienced muscle side effect, are presented. Third, the most promising new techniques to confirm diagnosis of SAMS are explored. Finally, the most effective strategies for the clinical management of SAMS are summarized. Better diagnostic and treatment strategies for SAMS will increase the number of patients using these life-saving statins, thereby increasing statin adherence and reducing the costs of avoidable cardiovascular events.