GH replacement therapy in elderly GH-deficient patients: a systematic review

ContextRecombinant human GH (rhGH) is prescribed for the treatment of adults with GH deficiency (GHD). However, conflicting data are available on the efficacy of rhGH treatment in elderly GHD patients.ObjectiveTo assess the efficacy of rhGH treatment in elderly GHD subjects.MethodsWe searched the available literature in PubMed, Cochrane Library, Web of Science and EMBASE.Study selectionStudies on GHD patients, aged >60 years, treated with rhGH were eligible for inclusion. Data extraction was performed by two reviewers independently.ResultsWe found 11 eligible studies with a total of 534 patients. Only two studies had prospective, randomized, placebo-controlled study designs of rhGH treatment with a duration of 6 (n=15) and 12 months (n=62), respectively. Treatment with rhGH decreased total and low density lipoprotein (LDL) cholesterol levels by 4–8 and 11–16%, respectively, but did not alter high density lipoprotein or triglyceride levels. RhGH did not affect body mass index, but decreased waist circumference (by ∼3 cm) and waist/hip ratio. RhGh did not consistently affect blood pressure or bone mineral density. RhGH increased lean body mass by 2–5% and decreased total fat mass by 7–10% in four studies, but did not affect body composition in two other studies. RhGH consistently improved quality of life (QoL) parameters reflected in AGHDA-scores. There were no explicit data on elderly GHD patients aged >80 years.ConclusionRhGH replacement in elderly subjects with GHD decreases LDL cholesterol levels and improves QoL, but the effects on other parameters are not unequivocal. There were no data on the efficacy and safety of rhGH treatment in octogenarians with GHD.

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Bariatric surgery and LDL cholesterol (BASALTO) trial study protocol: randomised controlled study evaluating the effect of gastric bypass versus sleeve gastrectomy on high LDL cholesterol

BMJ Open ◽

10.1136/bmjopen-2020-037712 ◽

2020 ◽

Vol 10 (9) ◽

pp. e037712

Author(s):

David Benaiges ◽

Albert Goday ◽

Juana A Flores-Le Roux ◽

Montserrat Fitó ◽

Oscar Pozo ◽

...

Keyword(s):

Bariatric Surgery ◽

Gastric Bypass ◽

Sleeve Gastrectomy ◽

Surgical Procedure ◽

Ldl Cholesterol ◽

Density Lipoprotein ◽

Controlled Study ◽

Serum Samples ◽

Cholesterol Levels ◽

Randomised Controlled

IntroductionObservational studies have shown gastric bypass to be superior to sleeve gastrectomy in terms of low-density lipoprotein (LDL) cholesterol improvement. If these results are confirmed in randomised controlled trials, presurgical LDL cholesterol status could be a relevant factor in surgical procedure election. Furthermore, it is also necessary to establish the mechanisms by which LDL cholesterol improves after surgery and whether qualitative and quantitative changes occur in the different lipoprotein subclasses. The first objective is to ascertain whether high LDL cholesterol levels before surgery can be considered an additional factor when selecting the most appropriate surgical procedure for each patient (gastric bypass or sleeve gastrectomy). Hence, the 1-year remission rates of high LDL cholesterol after gastric bypass and sleeve gastrectomy in patients with morbid obesity will be compared. Secondary objectives were (1) to compare changes in other lipoproteins and LDL composition and (2) to study the pathophysiologic mechanisms related to LDL cholesterol remission.Methods and analysisA randomised clinical trial, with intention-to-treat analysis, will be conducted to compare LDL cholesterol remission between gastric bypass and sleeve gastrectomy, with a 12-month follow-up. Inclusion criteria will be patients between 18 and 60 years of age with body mass index ≥40 kg/m2 or ≥35 kg/m2 with significant obesity-related comorbidity and high LDL cholesterol levels. Patients will be evaluated preoperatively and at 3, 6 and 12 months after bariatric surgery. Examinations will include routine blood chemistry, anthropometric measurements, food intake recall, physical activity questionnaires and serum samples for lipidomic and lipoprotein characterisation.Ethics and disseminationEthics approval has been granted by the Parc de Salut Mar Ethics Committee (2019/8471/I). The study and its conclusions regarding the primary and secondary objectives will be presented as manuscripts submitted for peer-reviewed journal publication.Trial registration numberNCT03975478.

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Effect of ascorbate on serum lipids and urate metabolism during exhaustive training

Clinical Science ◽

10.1042/cs20030266 ◽

2004 ◽

Vol 106 (1) ◽

pp. 107-109 ◽

Cited By ~ 6

Author(s):

Hidekatsu YANAI ◽

Mie MORIMOTO

Keyword(s):

Placebo Group ◽

Serum Lipids ◽

Ldl Cholesterol ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Serum Urate ◽

Exhaustive Exercise ◽

Controlled Study ◽

Cholesterol Levels

Physical activity is associated with beneficial changes in serum lipids, but exhaustive exercise has been suggested to increase oxidative stress. To test the effect of ascorbate (vitamin C) on serum lipids and the metabolism of urate, which is the most important intrinsic antioxidant, during exhaustive exercise, we performed a randomized, blinded, placebo-controlled study on eight male well-trained athletes. subjects were randomly allocated to either a group given 1000 mg of ascorbate daily (n=4) or a placebo group (n=4). Fasting serum lipids and urate concentrations were measured before and after 3 weeks of training. Although serum low-density lipoprotein (LDL)-cholesterol levels decreased and high-density lipoprotein (HDL)-cholesterol levels increased significantly in the ascorbate group after the 3 weeks of training, serum LDL-cholesterol levels increased and HDL-cholesterol levels decreased significantly in the placebo group. Furthermore, serum urate levels were elevated significantly in the placebo group; however, these levels did not change in the ascorbate group. When compared with the placebo group, significantly higher serum HDL-cholesterol and lower serum LDL-cholesterol and urate levels were observed in the ascorbate group after training. In conclusion, our results suggested that ascorbate may contribute to the desirable changes in serum lipids during exhaustive training and suggest the significant association between ascorbate and urate under intense training.

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Abstract P307: Chitin-Glucan Fiber Effects on Oxidized Low-Density Lipoprotein: A Randomized Controlled Trial

Circulation ◽

10.1161/circ.125.suppl_10.ap307 ◽

2012 ◽

Vol 125 (suppl_10) ◽

Author(s):

Joseph L Evans ◽

Harold Bays ◽

Kevin C Maki ◽

Mal Evans ◽

Veronique Maquet ◽

...

Keyword(s):

Diabetes Complications ◽

Ldl Cholesterol ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Secondary Outcome ◽

Low Density ◽

Oxidized Low Density Lipoprotein ◽

Treatment Groups ◽

Cholesterol Levels ◽

Insoluble Fiber

Oxidized low-density lipoprotein (OxLDL) is believed to play a role in the progression of atherosclerotic coronary heart disease (CHD) and the development of diabetes complications. This randomized, double-blind, placebo-controlled study of a novel insoluble fiber derived from the mycelium Aspergillus niger , chitin-glucan (CG) (ARTINIA™), evaluated 135 patients with fasting LDL-cholesterol 130-189.9 mg/dl and fasting glucose <=125 mg/dl. Participants were randomly assigned to receive CG (4.5 g/day; n=34), CG (1.5 g/day; n=33), CG (1.5 g/day) plus olive extract (n=33), or matching placebo (n=35) for 6 weeks. The primary outcome measure was the between-group difference in OxLDL. Secondary outcome measurements included effects upon lipid, glucose, insulin, and F2-isoprostane levels. After 6 weeks, CG 4.5 g/day (CG-4.5) significantly reduced mean OxLDL 3.8 U/L compared to baseline (58.0 U/L vs 61.8 U/L, respectively; P =0.006), and reduced OxLDL 4.97 U/L compared to placebo (P=<0.05). Other treatment groups generally had no significant effect upon OxLDL. CG treatment groups reduced LDL-cholesterol levels 3.2–;6.5% compared to placebo (P<0.05). In this study population without diabetes mellitus or elevated glucose levels, CG did not significantly affect high density lipoprotein cholesterol, triglycerides, glucose, insulin, F2-isoprostanes, or the homeostasis model assessment of insulin resistance. Treatments were well tolerated and with adverse experiences comparable to placebo. These results suggest that chitin-glucan, a novel insoluble fiber, may significantly reduce OxLDL and LDL-cholesterol levels, which may have therapeutic implications for patients at risk for CHD or other diabetes complications.

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Pharmacokinetics, Distribution in Serum Lipoproteins and Tissues, and Renal Toxicities of Amphotericin B and Amphotericin B Lipid Complex in a Hypercholesterolemic Rabbit Model: Single-Dose Studies

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.42.12.3146 ◽

1998 ◽

Vol 42 (12) ◽

pp. 3146-3152 ◽

Cited By ~ 38

Author(s):

Kishor M. Wasan ◽

Allison L. Kennedy ◽

Shawn M. Cassidy ◽

Manisha Ramaswamy ◽

Lorilynne Holtorf ◽

...

Keyword(s):

Amphotericin B ◽

Ldl Cholesterol ◽

Renal Toxicity ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Total Serum ◽

Lipid Complex ◽

Blood Samples ◽

Regular Diet ◽

Cholesterol Levels

ABSTRACT The purpose of this study was to determine if a relationship exists among total serum and lipoprotein cholesterol concentration, the severity of amphotericin B (AmpB)-induced renal toxicity, and the serum pharmacokinetics of AmpB in hypercholesterolemic rabbits administered AmpB and AmpB lipid complex (ABLC). After 10 days of cholesterol-enriched diet (0.50% [wt/vol]) or regular rabbit diet (control), each rabbit was administered a single intravenous bolus of AmpB or ABLC (1.0 mg/kg of body weight). Blood samples were obtained before administration and serially thereafter for the assessment of serum pharmacokinetics, kidney toxicity, and serum lipoprotein distribution. Rabbits were humanely sacrificed after all blood samples were obtained, and tissues were harvested for drug analysis. Before drug treatment, cholesterol-fed rabbits demonstrated marked increases in total serum cholesterol and low-density lipoprotein (LDL) cholesterol levels compared with levels in rabbits on a regular diet. No significant differences in triglyceride levels were observed. A significant increase in serum creatinine levels was observed in cholesterol-fed and regular diet-fed rabbits administered AmpB. However, the magnitude of this increase was 2.5-fold greater in cholesterol-fed rabbits than in regular diet-fed rabbits. No significant differences in triglyceride levels were observed. A significant increase in serum creatinine levels was observed in cholesterol-fed and regular diet-fed rabbits administered ABLC. Whereas AmpB pharmacokinetics were significantly altered in cholesterol-fed rabbits administered free AmpB, similar AmpB pharmacokinetics were observed in both rabbit groups administered ABLC. Renal AmpB levels were significantly increased in cholesterol-fed rabbits administered AmpB compared with those in all other groups. Hepatic and lung AmpB levels were elevated in cholesterol-fed rabbits administered free AmpB compared to controls. In addition, hepatic, lung, and spleen AmpB levels were significantly decreased in cholesterol-fed rabbits administered ABLC compared to controls. An increased percentage of AmpB was recovered in LDL–very-low-density lipoprotein fraction when free AmpB was administered to cholesterol-fed rabbits compared with those in all other groups. These findings suggest that increases in cholesterol, specifically, LDL cholesterol levels, modify the disposition and renal toxicity of free AmpB. However, the pharmacokinetics and renal toxicity of ABLC were independent of elevations in total and LDL cholesterol levels.

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Dyslipidaemia

The ESC Handbook on Cardiovascular Pharmacotherapy ◽

10.1093/med/9780198759935.003.0002 ◽

2019 ◽

pp. 33-48

Author(s):

Heinz Drexel

Keyword(s):

Cardiovascular Disease ◽

Randomized Clinical Trials ◽

Ldl Cholesterol ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Epidemiological Studies ◽

Residual Risk ◽

Atherosclerotic Cardiovascular Disease ◽

Cholesterol Levels

Lipid metabolism has gained cardiological interest only after statins were demonstrated to reduce cardiovascular disease in secondary and primary prevention. Therefore, this chapter first introduces the physiological and atherogenic properties of lipoproteins, before focusing on interventions. Both the efficacy and safety of statins have been proven in numerous randomized clinical trials. Because there is a considerable residual risk in statin-treated patients, additional approaches have been investigated. The focus is now on further reductions in low-density lipoprotein (LDL) cholesterol levels. First, high-intensity statin regimens were shown to reduce residual risk. Subsequently, ezetimibe was demonstrated, for the first time, to have a beneficial effect as a non-statin lipid intervention. More recently, inhibitors of the enzyme PCSK9 have demonstrated a very high efficacy in reducing LDL cholesterol levels. Although the causality of LDL for atherosclerotic cardiovascular disease has been proven in epidemiological studies, including Mendelian randomization studies, as well as interventional trials, adherence to statins and other therapies is far from optimal. In contrast, interventions to increase high-density lipoprotein (HDL) cholesterol levels could not proven to have further benefits when combined with statins.

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Effects of recombinant human macrophage colony-stimulating factor on plasma cholesterol levels

Blood ◽

10.1182/blood.v77.4.750.750 ◽

1991 ◽

Vol 77 (4) ◽

pp. 750-755 ◽

Cited By ~ 32

Author(s):

JB Stoudemire ◽

MB Garnick

Keyword(s):

Nonhuman Primates ◽

Ldl Cholesterol ◽

Plasma Cholesterol ◽

Density Lipoprotein ◽

Cholesterol Homeostasis ◽

Human Macrophage ◽

Cholesterol Levels ◽

Macrophage Colony Stimulating Factor ◽

Macrophage Colony ◽

Stimulating Factor

Abstract Recombinant human macrophage colony-stimulating factor (rhM-CSF) is a hematopoietic growth factor that stimulates the growth, differentiation, proliferation, and activation of cells of the monocyte/macrophage lineage. rhM-CSF was administered to rabbits and nonhuman primates to evaluate effects on cholesterol homeostasis. Decreases in plasma cholesterol concentrations were observed during rhM- CSF administration. The observed mean (+/- SD) decreases over a range of doses in nonhuman primates receiving rhM-CSF by continuous intravenous infusion (CIVI) or intravenous bolus (IVB) injection were approximately 16% +/- 8% and 43% +/- 10%, respectively. Low-density lipoprotein (LDL) cholesterol levels decreased 55% +/- 9% from pretreatment baseline values in the animals receiving rhM-CSF by IVB. Normocholesterolemic New Zealand white rabbits receiving rhM-CSF over a range of doses by CIVI showed a decrease from baseline in total cholesterol of approximately 28% +/- 17%, with LDL cholesterol levels decreasing by approximately 72% +/- 33%, while high-density lipoprotein levels showed variable changes, including increased values. A decrease of 36% +/- 26% in total plasma cholesterol was observed in Watanabe Heritable Hyperlipidemic rabbits receiving rhM-CSF by CIVI for 7 days. This decrease was attributable almost entirely to decreases in LDL cholesterol, which fell approximately 34% +/- 24% from baseline. Although the mechanism of this cholesterol-lowering effect is unknown, these results strongly suggest that rhM-CSF may provide a novel treatment for hypercholesterolemia and may be useful in investigations into the mechanisms of cholesterol homeostasis and atherogenesis.

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Exercise therapy improves eGFR, and reduces blood pressure and BMI in non-dialysis CKD patients: evidence from a meta-analysis

BMC Nephrology ◽

10.1186/s12882-019-1586-5 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 9

Author(s):

Lijun Zhang ◽

Yangyang Wang ◽

Lianlian Xiong ◽

Yanfang Luo ◽

Zhijun Huang ◽

...

Keyword(s):

Systematic Review ◽

Blood Pressure ◽

Exercise Therapy ◽

Cardiovascular Health ◽

Data Extraction ◽

Meta Analysis ◽

Density Lipoprotein ◽

Cochrane Library ◽

Healthy Population ◽

Short Term

Abstract Background Patients with chronic kidney disease (CKD) have a high prevalence of cardiovascular diseases, which often lead to physical inactivity that correlates with CKD exacerbation. The benefits of regular exercise to cardiovascular health have been well established in healthy population and highly suggestive in patients with CKD. To further strengthen the evidence base for the management of CKD, this meta-analysis was performed to systematically evaluate the effects of exercise therapy on renal function, blood pressure, blood lipid and body mass index (BMI) in non-dialysis CKD patients. Methods This meta-analysis was conducted following a previous protocol. Randomized controlled trials (RCTs) examining the effects of exercise therapy in non-dialysis CKD patients were searched in Pubmed, Embase, Cochrane Library, and three major Chinese biomedical databases (CNKI, WANGFANG and VIP) from their start date to October 30th, 2018. The Cochrane systematic review methods were applied for quality assessment and data extraction, and Revman version 5.3 was used for systematic review and meta-analysis. Results 13 RCTs, representing 421 patients with non-dialysis CKD, were included in this meta-analysis. Compared to the controls, exercise therapy brought an increase in eGFR (MD = 2.62, 95% CI:0.42 to 4.82, P = 0.02, I2 = 22%), and decreases in systolic blood pressure (SBP) (MD = -5.61, 95% CI:-8.99 to − 2.23, P = 0.001, I2 = 44%), diastolic blood pressure (DBP) (MD = -2.87, 95% CI:-3.65 to − 2.08, P < 0.00001, I2 = 16%) and BMI (MD = -1.32, 95% CI:-2.39 to − 0.25, P = 0.02, I2 = 0%) in non-dialysis CKD patients. Exercise therapy of short-term (< 3 months) decreased triglyceride (TG) level (P = 0.0006). However, exercise therapy did not significantly affect serum creatinine (SCr), total cholesterol (TC), high density lipoprotein (HDL) or low density lipoprotein (LDL) in non-dialysis CKD patients. Conclusion Exercise therapy could benefit non-dialysis CKD patients by increasing eGFR while reducing SBP, DBP and BMI. Additionally, short-term intervention of exercise could decrease TG.

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Secondary prevention care and effect: Total and low-density lipoprotein cholesterol levels and lipid-lowering drug use in women and men after incident myocardial infarction – The Tromsø Study 1994–2016

European Journal of Cardiovascular Nursing ◽

10.1177/1474515118762541 ◽

2018 ◽

Vol 17 (6) ◽

pp. 563-570 ◽

Cited By ~ 1

Author(s):

Laila A Hopstock ◽

Anne Elise Eggen ◽

Maja-Lisa Løchen ◽

Ellisiv B Mathiesen ◽

Inger Njølstad ◽

...

Keyword(s):

Ldl Cholesterol ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipid Lowering ◽

Low Density ◽

Lipid Levels ◽

Treatment Target ◽

Cholesterol Levels ◽

Lipid Lowering Drug ◽

Lowering Drug

Background: Secondary prevention guidelines after myocardial infarction (MI) are gender neutral, but underutilisation of treatment in women has been reported. Design: We investigated the change in total and low-density lipoprotein (LDL) cholesterol levels and lipid-lowering drug (LLD) use after first-ever MI in a population-based study. Methods: We followed 10,005 participants (54% women) attending the Tromsø Study 1994–1995 and 8483 participants (55% women) attending the Tromsø Study 2007–2008 for first-ever MI up to their participation in 2007–2008 and 2015–2016, respectively. We used linear and logistic regression models to investigate sex differences in change in lipid levels. Results: A total of 395 (MI cohort I) and 132 participants (MI cohort II) had a first-ever MI during 1994–2008 and 2007–2013, respectively. Mean change in total cholesterol was −2.34 mmol/L (SD 1.15) in MI cohort I, and in LDL cholesterol was −1.63 mmol/L (SD 1.12) in MI cohort II. Men had a larger decrease in lipid levels compared to women: the linear regression coefficient for change was −0.33 (95% confidence interval [CI] −0.51 to −0.14) for total cholesterol and −0.21 (95% CI −0.37 to −0.04) for LDL cholesterol, adjusted for baseline lipid value, age and cohort. Men had 73% higher odds (95% CI 1.15−2.61) of treatment target achievement compared to women, adjusted for baseline lipid value, age and cohort. LLD use was reported in 85% of women and 92% of men in MI cohort I, and 80% in women and 89% in men in MI cohort II. Conclusions: Compared to men, women had significantly less decrease in lipid levels after MI, and a smaller proportion of women achieved the treatment target.

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Proprotein Convertase Subtilisin/Kexin Type 9: From the Discovery to the Development of New Therapies for Cardiovascular Diseases

Scientifica ◽

10.6064/2012/927352 ◽

2012 ◽

Vol 2012 ◽

pp. 1-21 ◽

Cited By ~ 4

Author(s):

Nicola Ferri

Keyword(s):

Cardiovascular Diseases ◽

Ldl Cholesterol ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Cholesterol Homeostasis ◽

Low Density ◽

Regulatory Effect ◽

Proprotein Convertase ◽

Pharmacological Modulation ◽

Cholesterol Levels

The identification of the HMG-CoA reductase inhibitors, statins, has represented a dramatic innovation of the pharmacological modulation of hypercholesterolemia and associated cardiovascular diseases. However, not all patients receiving statins achieve guideline-recommended low density lipoprotein (LDL) cholesterol goals, particularly those at high risk. There remains, therefore, an unmet medical need to develop additional well-tolerated and effective agents to lower LDL cholesterol levels. The discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9), a secretory protein that posttranscriptionally regulates levels of low density lipoprotein receptor (LDLR) by inducing its degradation, has opened a new era of pharmacological modulation of cholesterol homeostasis. This paper summarizes the current knowledge of the basic molecular mechanism underlying the regulatory effect of LDLR expression by PCSK9 obtained fromin vitrocell-cultured studies and the analysis of the crystal structure of PCSK9. It also describes the epidemiological and experimental evidences of the regulatory effect of PCSK9 on LDL cholesterol levels and cardiovascular diseases and summarizes the different pharmacological approaches under development for inhibiting PCSK9 expression, processing, and the interaction with LDLR.

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