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The effects of improved metabolic risk factors on bone turnover markers after 12 weeks of simvastatin treatment with or without exercise.
Jiang, J, Boyle, LJ, Mikus, CR, Oberlin, DJ, Fletcher, JA, Thyfault, JP, Hinton, PS
Metabolism: clinical and experimental. 2014;(11):1398-408
Abstract
OBJECTIVE Emerging evidence supports an association between metabolic risk factors and bone turnover. Statins and exercise independently improve metabolic risk factors; however whether improvements in metabolic risk factor affects bone turnover is unknown. The purpose of the present study was to: 1) evaluate the relationship between metabolic risk factors and bone turnover; and 2) determine if improvements in metabolic risk factors after 12 weeks of statin treatment, exercise or the combination affect bone turnover. METHODS Fifty participants with ≥2 metabolic syndrome defining characteristics were randomly assigned to one of three groups: statin (STAT: simvastatin, 40 mg/day), exercise (EX: brisk walking and/or slow jogging, 45 minutes/day, 5 days/week), or the combination (STAT+EX). Body composition and whole body bone mineral density were measured with dual energy X-ray absorptiometry. Serum markers of bone formation (bone specific alkaline phosphatase, BAP; osteocalcin, OC), resorption (C-terminal peptide of type I collagen, CTX) and metabolic risk factors were determined. Two-factor (time, group) repeated-measures ANCOVA was used to examine changes of metabolic risk factors and bone turnover. General linear models were used to determine the effect of pre-treatment metabolic risk factors on post-treatment bone turnover marker outcomes. RESULTS Participants with ≥4 metabolic syndrome defining characteristics had lower pre-treatment OC than those with 3 or fewer. OC was negatively correlated with glucose, and CTX was positively correlated with cholesterol. STAT or STAT+EX lowered total and LDL cholesterol. The OC to CTX ratio decreased in all groups with no other significant changes in bone turnover. Higher pre-treatment insulin or body fat predicted a greater CTX reduction and a greater BAP/CTX increase. CONCLUSION Metabolic risk factors were negatively associated with bone turnover markers. Short-term statin treatment with or without exercise lowered cholesterol and all treatments had a small effect on bone turnover.
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Simvastatin impairs exercise training adaptations.
Mikus, CR, Boyle, LJ, Borengasser, SJ, Oberlin, DJ, Naples, SP, Fletcher, J, Meers, GM, Ruebel, M, Laughlin, MH, Dellsperger, KC, et al
Journal of the American College of Cardiology. 2013;(8):709-14
Abstract
OBJECTIVES This study sought to determine if simvastatin impairs exercise training adaptations. BACKGROUND Statins are commonly prescribed in combination with therapeutic lifestyle changes, including exercise, to reduce cardiovascular disease risk in patients with metabolic syndrome. Statin use has been linked to skeletal muscle myopathy and impaired mitochondrial function, but it is unclear whether statin use alters adaptations to exercise training. METHODS This study examined the effects of simvastatin on changes in cardiorespiratory fitness and skeletal muscle mitochondrial content in response to aerobic exercise training. Sedentary overweight or obese adults with at least 2 metabolic syndrome risk factors (defined according to National Cholesterol Education Panel Adult Treatment Panel III criteria) were randomized to 12 weeks of aerobic exercise training or to exercise in combination with simvastatin (40 mg/day). The primary outcomes were cardiorespiratory fitness and skeletal muscle (vastus lateralis) mitochondrial content (citrate synthase enzyme activity). RESULTS Thirty-seven participants (exercise plus statins: n = 18; exercise only: n = 19) completed the study. Cardiorespiratory fitness increased by 10% (p < 0.05) in response to exercise training alone, but was blunted by the addition of simvastatin resulting in only a 1.5% increase (p < 0.005 for group by time interaction). Similarly, skeletal muscle citrate synthase activity increased by 13% in the exercise-only group (p < 0.05), but decreased by 4.5% in the simvastatin-plus-exercise group (p < 0.05 for group-by-time interaction). CONCLUSIONS Simvastatin attenuates increases in cardiorespiratory fitness and skeletal muscle mitochondrial content when combined with exercise training in overweight or obese patients at risk of the metabolic syndrome. (Exercise, Statins, and the Metabolic Syndrome; NCT01700530).
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The efficacy and safety of ezetimibe/simvastatin combination compared with intensified lipid-lowering treatment strategies in diabetic subjects with and without metabolic syndrome.
Jimenez, JG, Rosen, JB, Pirags, V, Massaad, R, Hanson, ME, Brudi, P, Triscari, J
Diabetes, obesity & metabolism. 2013;(6):513-22
Abstract
AIMS: The objective was to assess the consistency of effect of switching to ezetimibe/simvastatin 10/20 mg versus doubling the baseline statin dose (to simvastatin 40 mg or atorvastatin 20 mg) or switching to rosuvastatin 10 mg across subgroups of subjects with (n = 617) and without (n = 191) metabolic syndrome (MetS). METHODS This was a post hoc analysis of a randomized, double-blind, 6-week study of adults 18-79 years with cardiovascular disease and diabetes mellitus with low-density lipoprotein cholesterol (LDL-C) ≥70 and ≤160 mg/dl. The percent change in LDL-C and other lipids was estimated within each subgroup separately. Safety and tolerability were assessed. RESULTS In subjects with MetS, percent changes in LDL-C and other lipids were greater with ezetimibe/simvastatin versus doubling baseline statin or numerically greater versus switching to rosuvastatin, except high-density lipoprotein cholesterol and apolipoprotein (Apo) AI (mean percent changes in LDL-C were: -22.49% ezetimibe/simvastatin, -9.64% doubled baseline statin and -19.20% rosuvastatin). In subjects without MetS, percent changes in LDL-C, total cholesterol and Apo B were greater with ezetimibe/simvastatin versus doubling baseline statin or numerically greater versus switching to rosuvastatin (mean percent changes in LDL-C were: -25.14% ezetimibe/simvastatin, -4.75% doubled baseline statin and -19.75% rosuvastatin). Safety profiles were generally similar. CONCLUSION These results showed that switching to ezetimibe/simvastatin 10/20 mg was more effective at reducing LDL-C, total cholesterol and Apo B versus doubling the baseline statin dose to simvastatin 40 mg or atorvastatin 20 mg or switching to rosuvastatin 10 mg regardless of MetS status. These results were generally similar to those of the full cohort.
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Comparison of the effects of atorvastatin and simvastatin in women with polycystic ovary syndrome: A prospective, randomized study.
Kaya, C, Pabuccu, R, Cengiz, SD, Dünder, I
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2010;(3):161-6
Abstract
UNLABELLED Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism, insulin resistance (IR), and chronic inflammation. Simvastatin improves endocrine/clinical aspects of PCOS and decreases systemic inflammation in PCOS. There have been no comparative studies carried out regarding the effects of different statin treatment in PCOS. We aimed to assess the effects of two different statin treatments on various metabolic, endocrine, oxidative and inflammatory factors in PCOS. DESIGN Prospective, randomized clinical trial METHODS Sixty-four (64) women with PCOS were included in the study. Group 1 had (atorvastatin, 20lmg daily; n=32) or group 2 had (simvastatin, 20l mg daily n=32). The metabolic, endocrine, inflammatory and oxidative profiles were evaluated. RESULTS Group 1 resulted in a significant reduction in the HOMA index and fasting insulin (-26.9+/-9.6%, -26.2+/-10.8%, P<0.01, respectively).CRP levels decreased by 63.6+/-15.9% in group 1 (P<0.01), whereas in the group 2 it decreased by 34.6+/-10.7% (P<0.05). Serum levels of LH declined by 19.1+/-4.5% (P<0.05) in the group 1 and by 39.3+/-11.9% (P<0.01) in the group 2. FAI decreased by -20+/-9.9% in group 1 (P<0.05) and it decreased by -38.7+/-13.8% in the group 2 (P<0.01). MDA levels decreased by 32.6+/-9.6% in group 1 (P<0.05), whereas in the group 2 it decreased by 30.3+/-10.9% (P<0.01). HOMA index and fasting insulin showed a reduction but not reached statistically significance in the group 2 (8.3+/-1.9%, 3.0+/-0.8%, P>0.05, respectively). CONCLUSION Both the statins are effective in reducing inflammation, hyperandrogenemia, oxidative stress and metabolic parameters. While atorvastatin has more noticeable effects on fasting insulin and insulin sensitivity, simvastatin has a dominant effect on total T in PCOS women.
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Reduction of cardiovascular events by simvastatin in nondiabetic coronary heart disease patients with and without the metabolic syndrome: subgroup analyses of the Scandinavian Simvastatin Survival Study (4S).
Pyörälä, K, Ballantyne, CM, Gumbiner, B, Lee, MW, Shah, A, Davies, MJ, Mitchel, YB, Pedersen, TR, Kjekshus, J, ,
Diabetes care. 2004;(7):1735-40
Abstract
OBJECTIVE To assess the effect of simvastatin treatment on the risk of cardiovascular events in nondiabetic patients with coronary heart disease (CHD) with and without the metabolic syndrome, as defined by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP-III). RESEARCH DESIGN AND METHODS Subgroup analyses were performed on data from 3933 nondiabetic patients with clinically established CHD, serum total cholesterol level 5.5-8.0 mmol/l, and serum triglyceride level RESULTS Over the 5.4-year median follow-up period, simvastatin produced similar changes in serum lipid levels in 893 patients with the metabolic syndrome and in 3040 patients without the metabolic syndrome. The relative risks of main end points in simvastatin-treated patients compared with placebo-treated patients with the metabolic syndrome were as follows: total mortality 0.54 (95% CI 0.36-0.82), coronary mortality 0.39 (0.23-0.65), major CHD event 0.59 (0.45-0.77), and any atherosclerotic event 0.69 (0.56-0.84). The corresponding RRs in patients without the metabolic syndrome were 0.72 (0.56-0.91), 0.62 (0.45-0.84), 0.71 (0.61-0.82), and 0.76 (0.68-0.85). CONCLUSIONS Nondiabetic CHD patients with or without the metabolic syndrome realize from simvastatin treatment a similar, substantial relative reduction in the risk of cardiovascular events. The absolute benefit may be greater in patients with the metabolic syndrome because they are at a higher absolute risk.