Statin-Induced Low Cholesterol is Not Associated With Poor Outcome in Chronic Heart Failure

Silva, Sérgio; Lourenço, Patrícia; Paulo, Cristiana; Ferreira, Ester; Lebreiro, Ana; Sousa, Alexandra; Mascaranhas, Joana; Patacho, Marta; Araújo, José Paulo; Bettencourt, Paulo

doi:10.1177/1074248411429967

Cited by 10 publications

(18 citation statements)

References 21 publications

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“…The relationship between LDL levels and HF outcomes among the elderly, which we document here, seems to be contradictory to the findings in patients with coronary artery disease [5,6,7,8,9] and in patients enrolled in other HF studies [8,9,11,18,19]. Several studies reported that patients with ischemic and nonischemic HF appear to have an opposite pattern (‘reverse epidemiology'), with low levels being associated with a worse prognosis independent of other prognostic factors [13,20].…”

Section: Discussioncontrasting

confidence: 49%

Low Levels of Low-Density Lipoprotein Cholesterol: A Negative Predictor of Survival in Elderly Patients with Advanced Heart Failure

Charach¹,

Rabinovich²,

Argov³

et al. 2013

Cardiology

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Objectives: There are conflicting reports on the role of cholesterol as an adverse prognostic predictor in patients with heart failure (HF). This study aimed to examine the impact of low levels of low-density lipoprotein cholesterol (LDL-c) on cardiac mortality in a cohort of elderly patients with moderate and severe HF. Methods: Chronic HF patients from the HF Unit at the Tel-Aviv Medical Center (n = 212, 77% males) with an average NYHA classification of 2.8, a mean age of 76.9 ± 7.3 years (range 66-91) and a mean follow-up of 3.7 years were consecutively enrolled. The cohort was divided into tertiles according to LDL-c levels: LDL <90 mg/dl (group 1), LDL 90-115 mg/dl (group 2) and LDL >115 mg/dl (group 3). Results: The Cox regression analysis revealed that group 3 patients had the best outcome (p = 0.01 vs. groups 2 and 3), with 58% of them surviving longer than 50 months compared to 34% in group 1. The same trend was seen in the group of patients suffering from ischemic cardiomyopathy and in patients who were treated by statins (p = 0.04). Conclusion: Low LDL-c levels are associated with a reduced survival in elderly patients with clinically controlled moderate and severe HF.

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Section: Discussioncontrasting

confidence: 49%

Low Levels of Low-Density Lipoprotein Cholesterol: A Negative Predictor of Survival in Elderly Patients with Advanced Heart Failure

Charach¹,

Rabinovich²,

Argov³

et al. 2013

Cardiology

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“…Statins have clinical benefits on morbidity and mortality in a wide range of diseases and particularly in diabetic patients [14,18–19]. Previous experimental studies have explained this positive effect on diabetic hearts by a normalization of RhoA signaling and an increase in NOS3 expression [24,28–29].…”

Section: Discussionmentioning

confidence: 99%

“…High dose of atorvastatin (80 vs 10 mg/day) significantly decreased hospitalization for congestive heart failure [16]. In the perioperative period, statin therapy has been reported to reduce morbidity and mortality, increasingly with high-dose of statins [17,18] whatever cholesterol blood level [13,17,19], suggesting a beneficial pleiotropic cardiovascular effect [12]. In addition, pleiotropic effects of statins decrease mortality in critically ill diabetic patients [4,20,21].…”

Section: Introductionmentioning

confidence: 99%

Atorvastatin reduces β-Adrenergic dysfunction in rats with diabetic cardiomyopathy

Carillion

Feldman

et al. 2017

PLoS ONE

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BackgroundIn the diabetic heart the β-adrenergic response is altered partly by down-regulation of the β1-adrenoceptor, reducing its positive inotropic effect and up-regulation of the β3-adrenoceptor, increasing its negative inotropic effect. Statins have clinical benefits on morbidity and mortality in diabetic patients which are attributed to their “pleiotropic” effects. The objective of our study was to investigate the role of statin treatment on β-adrenergic dysfunction in diabetic rat cardiomyocytes.Methodsβ-adrenergic responses were investigated in vivo (echocardiography) and ex vivo (left ventricular papillary muscles) in healthy and streptozotocin-induced diabetic rats, who were pre-treated or not by oral atorvastatin over 15 days (50 mg.kg-1.day-1). Micro-array analysis and immunoblotting were performed in left ventricular homogenates. Data are presented as mean percentage of baseline ± SD.ResultsAtorvastatin restored the impaired positive inotropic effect of β-adrenergic stimulation in diabetic hearts compared with healthy hearts both in vivo and ex vivo but did not suppress the diastolic dysfunction of diabetes. Atorvastatin changed the RNA expression of 9 genes in the β-adrenergic pathway and corrected the protein expression of β1-adrenoceptor and β1/β3-adrenoceptor ratio, and multidrug resistance protein 4 (MRP4). Nitric oxide synthase (NOS) inhibition abolished the beneficial effects of atorvastatin on the β-adrenoceptor response.ConclusionsAtorvastatin restored the positive inotropic effect of the β-adrenoceptor stimulation in diabetic cardiomyopathy. This effect is mediated by multiple modifications in expression of proteins in the β-adrenergic signaling pathway, particularly through the NOS pathway.

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“…Для объяснения неэффективности статинов при ХСН со сниженной ФВ ЛЖ предложены гипотезы коэнзима Q (убихинона), липопротеина эндотоксина и селенопротеи-на [22]. Хотя низкий уровень холестерина ассоциируется с ухудшением исходов у больных с ХСН, он безопасен, если обусловлен приемом статинов [23].…”

Section: Discussionunclassified

Treatment of Chronic Heart Failure With Preserved Left Ventricular Ejection Fraction in Patients With Hypertension Disease: Potential Therapeutic Role of Statines

Канорский¹,

Середа²

2017

Med. sov.

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КАРДИОЛОГИЯХ роническая сердечная недостаточность (ХСН) с сохраненной фракцией выброса левого желудочка (ФВ ЛЖ) является наиболее рас-пространенным осложнением артериальной гипертен-зии [1]. Поскольку способы фармакотерапии, улучшав-шие прогноз больных с ХСН и сниженной ФВ ЛЖ, не влияли на исходы у пациентов с ХСН и сохраненной ФВ ЛЖ [2], в последнем случае главным образом реко-мендуется целенаправленно лечить основную патоло-гию [3,4]. Антагонисты кальция не только являются эффективными средствами лечения артериальной гипертензии, но и способны повышать толерантность больных с ХСН и сохраненной ФВ ЛЖ к физической нагрузке [5,6]. Влияние антагонистов кальция на про-гноз пациентов с ХСН и сохраненной ФВ ЛЖ, согласно данным крупного регистра OPTIMIZE-HF, оценивается как нейтральное [7].Статины снижали смертность больных с ХСН и сохра-ненной ФВ ЛЖ по данным метаанализа 4 проспективных наблюдательных исследований (n = 5 536) (относитель-ный риск -ОР 0,69 при 95%-ном доверительном интер-вале -ДИ от 0,493 до 0,965; р = 0,030) [8]. Однако круп-ных рандомизированных контролируемых исследований статинов у пациентов с ХСН и сохраненной ФВ ЛЖ не проводилось, поэтому статины остаются препаратами с потенциалом улучшения исходов у таких больных.Цель исследования -сравнение эффективности лече-ния ХСН с сохраненной ФВ ЛЖ у пациентов с гипертони-ческой болезнью различными антагонистами кальция с добавлением и без добавления аторвастатина.

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Statin-Induced Low Cholesterol is Not Associated With Poor Outcome in Chronic Heart Failure

Abstract: Patients with HF with instrisically low cholesterol levels have a double risk of death up to 5 years compared to patients with pharmacologically induced low cholesterol. Clinicians should not limit the use of statins by fear of lowering the cholesterol levels.

Cited by 10 publications

References 21 publications

Low Levels of Low-Density Lipoprotein Cholesterol: A Negative Predictor of Survival in Elderly Patients with Advanced Heart Failure

Low Levels of Low-Density Lipoprotein Cholesterol: A Negative Predictor of Survival in Elderly Patients with Advanced Heart Failure

Atorvastatin reduces β-Adrenergic dysfunction in rats with diabetic cardiomyopathy

Treatment of Chronic Heart Failure With Preserved Left Ventricular Ejection Fraction in Patients With Hypertension Disease: Potential Therapeutic Role of Statines

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