Statins and Exercise Training Response in Heart Failure Patients

Kelly, Jacob P.; Dunning, Allison; Schulte, Phillip J.; Fiuzat, Mona; Leifer, Eric; Fleg, Jerome L.; Cooper, Lawton S.; Keteyian, Steven J.; Kitzman, Dalane W.; Piña, Ileana L.; Kraus, William E.; Whellan, David J.; O’Connor, Christopher M.; Mentz, Robert J.

doi:10.1016/j.jchf.2016.05.006

Cited by 10 publications

(5 citation statements)

References 34 publications

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“…In addition, IVST and LVDD decreased and LVEF increased with the former, showing superior results over those obtained with simvastatin treatment alone. This suggests that simvastatin combined with resistance training improves the therapeutic effect on patients with CHF as well as improves ventricular remodeling and cardiac function, which is consistent with the findings of an earlier study [ 12 ].…”

Section: Discussionsupporting

confidence: 91%

Simvastatin Combined with Resistance Training Improves Outcomes in Patients with Chronic Heart Failure by Modulating Mitochondrial Membrane Potential and the Janus Kinase/Signal Transducer and Activator of Transcription 3 Signaling Pathways

Wang

Yan

Wen

et al. 2022

Cardiovascular Therapeutics

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Background. Chronic heart failure (CHF) is the end stage of cardiac disease with a 5-year mortality rate reaching 50%. Simvastatin is an antioxidant with lipid-lowering effects, which is commonly used to treat CHF. Resistance training is a nondrug treatment for CHF and exerts a positive effect on both the myocardial structure and function. Objective. This study is aimed at exploring the effects and outcomes of simvastatin combined with resistance training on the mitochondrial membrane potential (MMP) of peripheral blood lymphocytes and the Janus kinase/signal transducer and activator of the transcription 3 (JAK/STAT3) signaling pathway in patients with CHF. Methods. One hundred and eleven patients with CHF were allocated to the control group (CNG) ( n = 55 ) and intervention group (IG) ( n = 56 ) using the random number table method. The CNG received simvastatin treatment only, whereas the IG received simvastatin treatment plus resistance training. Treatment efficacy, diastolic interventricular septal thickness (IVST), left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVDD), MMP fluorescence intensity, JAK mRNA and STAT3 mRNA relative expression levels, serum C-reactive protein (CRP), galectin-3, interleukin-6 (IL-6), N-terminal–probrain natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and heart-type fatty acid-binding protein (H-FABP) levels were compared in both groups. Results. After 6 months of treatment, diastolic IVST, LVDD, and serum levels of CRP, galectin-3, IL-6, NT-proBNP, hs-cTnT, and H-FABP decreased in both groups and were lower in the IG than in the CNG ( P < 0.05 ), whereas LVEF, JAK and STAT3 mRNA relative expression levels, and MMP fluorescence intensity of peripheral blood lymphocytes were higher in the IG than in the CNG ( P < 0.05 ). Conclusion. Simvastatin combined with resistance training improves heart function and reduces myocardial damage as well as the occurrence of adverse cardiac events compared with simvastatin alone. The mechanism may be related to the increase of expression of MMP, JAK, and STAT3, the regulation of MMP and JAK/STAT3 signaling pathways in peripheral lymphocytes, the alleviation of mitochondrial damage, and the inhibition of inflammatory response.

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Section: Discussionsupporting

confidence: 91%

Simvastatin Combined with Resistance Training Improves Outcomes in Patients with Chronic Heart Failure by Modulating Mitochondrial Membrane Potential and the Janus Kinase/Signal Transducer and Activator of Transcription 3 Signaling Pathways

Wang

Yan

Wen

et al. 2022

Cardiovascular Therapeutics

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“…Change in peak V̇ o 2 after 3 months did not differ significantly between patients taking and not taking β-blockers or statins. The latter confirms the results of a secondary analysis of the HF-ACTION study in patients with heart failure with reduced ejection fraction . However, it must be highlighted that these results should be interpreted as exploratory because the OptimEx-Clin trial was not adequately powered for these analyses, and the confidence intervals have not been adjusted for multiplicity.…”

supporting

confidence: 72%

“…We agree that based on expert opinion and some observational trials, changes in peak V̇ o 2 less than our a priori definition of 2.5 mL/kg/min may be of clinical relevance. However, it is currently unresolved whether modest improvements in peak V̇ o 2 , as shown for patients with heart failure with reduced ejection fraction, are also associated with lower clinical event rates in HFpEF. Therefore, we agree with Buckley and colleagues that prospective studies examining the effects of exercise training on clinical outcomes in patients with HFpEF are needed.…”

mentioning

confidence: 99%

Effect of Training on Peak Oxygen Consumption in Patients With Heart Failure With Preserved Ejection Fraction—Reply

Haller

Halle

2021

JAMA

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To the Editor We were surprised by the OptimEx-Clin trial 1 conclusion that the study findings did not support either highintensity interval training or moderate continuous training compared with guideline-based physical activity for patients with heart failure with preserved ejection fraction (HFpEF). This conclusion was based on the a priori decision to use 2.5 mL/kg/min as the minimum clinically important difference for the primary end point of peak oxygen uptake (V ˙O2 ). However, as the accompanying Editorial highlighted, 2 a 1.0-mL/kg/min value has long been considered a clinically meaningful difference for this outcome measure in a variety of other patient populations, regardless of baseline peak V ˙O2 . For older patients with HFpEF whose baseline peak V ˙O2 is often very low (typically 13-19 mL/kg/min), a 1.0-mL/kg/min difference from usual care following an exercise intervention may represent a larger percentage improvement than is often observed for healthier populations.As previously highlighted, 3 when baseline peak V ˙O2 approaches the threshold of 16 mL/kg/min, a patient's ability to perform routine activities of daily living diminishes, with a concomitant adverse effect on quality of life. Thus, improving exercise capacity and possibly returning baseline peak V ˙O2 to a level above 16 mL/kg/min can decrease heart failure symptoms and improve overall quality of life. Furthermore, a secondary analysis of data from the HF-ACTION trial showed that for patients with heart failure with reduced ejection fraction and a baseline peak V ˙O2 of 15 mL/kg/min, a 6% increase in peak V ˙O2 was associated with a significant reduction in clinical events. 4 Therefore, we believe that the 2.2-mL/kg/min difference in peak V ˙O2 in OptimEx-Clin (moderate continuous training, 1.6 mL/kg/min, vs guideline control, −0.6 mL/kg/min) at 3-month follow-up makes a strong case that moderate continuous training is beneficial for patients with HFpEF. Indeed, this conclusion is supported by prior reports. 5

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“…Statins increase the expression of LDL receptors at the cell surface, which results in the absorption of LDL into cells. These medications, by increasing the synthesis of HMG-CoA reductase, lead to the preservation and regeneration of cellular VLDL for a short time and temporarily, thereby reducing plasma LDL levels and eventually maintaining the normal state of intracellular cholesterol [ 24 , 25 ]. Statins can also have a decreasing effect on VLDL by the effect on the secretion of apolipoprotein B [ 26 , 27 ].…”

Section: Statinsmentioning

confidence: 99%

A Review of the Role of Statins in Heart Failure Treatment

Niazi

Galehdar

Jamshidi

et al. 2020

CCP

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Background: Heart failure is a common medical problem in the world, which has a high prevalence in both developed and developing countries. Today, among the medications used for the heart failure treatment, there are many medications with a positive cardiac contraction effect (positive inotropic such as digital glycosides, adrenergic receptor stimulants, and phosphodiesterase inhibitors), a large number of cardiac diluents (such as Angiotensin-Converting Enzyme (ACE) inhibitor group), and a few other types of drugs whose final effects are still under review. Statins are valuable drugs that are broadly prescribed in hyperlipidemia and cardiovascular patients due to their multiple properties, such as cholesterol reduction, endothelial function improvement, antioxidative, anti-inflammatory, neovascularization, and immunomodulatory activities. Methods: There is evidence that the therapeutic role of statins in HF, due to myocardial hypertrophy, show reduction in cardiomyocyte loss in the apoptosis process, oxidative stress, inflammation, and also the return of neurohormonal imbalance. However, the fact that these drugs have no sideeffects has not been confirmed in all studies, as statins prevent the production of particular beneficial and protective factors, such as coenzyme Q10 (CoQ10), while inhibiting the production of specific proteins involved in pathologic mechanisms. Results: Recently, it has been hypothesized that, despite the positive effects reported, high doses of statins in patients with long-term heart failure lead to progress in heart failure by inhibiting CoQ10 synthesis and intensifying hypertrophy. Conclusion: Thus, it can be stated that the advantage of using statins depends on factors, such as stroke fraction, and the existence of other standard indications such as atherosclerotic diseases or high Low-Density Lipoprotein-C (LDL-C).

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Statins and Exercise Training Response in Heart Failure Patients

Cited by 10 publications

References 34 publications

Simvastatin Combined with Resistance Training Improves Outcomes in Patients with Chronic Heart Failure by Modulating Mitochondrial Membrane Potential and the Janus Kinase/Signal Transducer and Activator of Transcription 3 Signaling Pathways

Simvastatin Combined with Resistance Training Improves Outcomes in Patients with Chronic Heart Failure by Modulating Mitochondrial Membrane Potential and the Janus Kinase/Signal Transducer and Activator of Transcription 3 Signaling Pathways

Effect of Training on Peak Oxygen Consumption in Patients With Heart Failure With Preserved Ejection Fraction—Reply

A Review of the Role of Statins in Heart Failure Treatment

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