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Evaluating the safety and efficacy of a polyherbal Unani formulation in dyslipidaemia-a prospective randomized controlled trial.
Ain, Q, Nawab, M, Ahmad, T, Kazmi, MH, Naikodi, MAR
Journal of ethnopharmacology. 2022;:115036
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Unani System of Medicine offers treatment for obesity and dyslipidaemia. Jawarish Falafili (JF) is a Unani polyherbal pharmacopoeial preparation. It has been used in the treatment of obesity for a long time. Dyslipidaemia is a recognised modifiable risk factor for hypertension, ischemic heart disease and stroke. Limitations of the current conventional therapy have provided scope for research of a potential drug in this medical condition. It was hypothesised that JF may ameliorate dyslipidaemia in human participants. AIM OF THE STUDY The main objective of this study was to evaluate the safety and efficacy of the JF. MATERIALS AND METHODS This was a prospective randomized, active-controlled, open-label and parallel-group study. We randomized 74 participants of dyslipidaemia into treatment (n = 38) and control (n = 36) groups. Of them, 30 participants in each group completed the trial. The participants of any sex aged between 30 and 60 years, with serum total cholesterol (TC) ≥200 mg/dl and/or serum triglycerides (TG) ≥150 mg/dl and/or low-density lipoprotein cholesterol (LDL-C) level ≥130 mg/dl and/or high-density lipoprotein cholesterol (HDL-C) level <40 mg/dl were enrolled in this study. The participants of the treatment group were treated with JF (10 gm/day) once and atorvastatin (20 mg/day) was given to the control group for 90 days once at night daily. RESULTS We observed a significant reduction (treatment group versus control group) in mean serum TC by 22.89% versus 19.36%, TG by 29.90% versus 23.26% and LDL-C by 29.16% versus 27.92% from baseline (p < 0.05). But the change in mean serum HDL-C levels post-treatment was insignificant in both groups (p > 0.05). On intergroup comparison, the magnitude of the difference of mean TC, TG, LDL-C and HDL-C levels between the groups was not statistically significant (p > 0.00.05). CONCLUSIONS This study concluded that JF and atorvastatin were equally effective in controlling dyslipidaemia. They were tolerated well by all participants and found safe during the course of treatment.
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Reported muscle symptoms during statin treatment amongst Italian dyslipidaemic patients in the real-life setting: the PROSISA Study.
Casula, M, Gazzotti, M, Bonaiti, F, OImastroni, E, Arca, M, Averna, M, Zambon, A, Catapano, AL, ,
Journal of internal medicine. 2021;(1):116-128
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Abstract
AIM: Statin-associated muscle symptoms (SAMS) are a major determinant of poor treatment adherence and/or discontinuation, but a definitive diagnosis of SAMS is challenging. The PROSISA study was an observational retrospective study aimed to assess the prevalence of reported SAMS in a cohort of dyslipidaemic patients. METHODS Demographic/anamnestic data, biochemical values and occurrence of SAMS were collected by 23 Italian Lipid Clinics. Adjusted logistic regression was performed to estimate odds ratio (OR) and 95% confidence intervals for association between probability of reporting SAMS and several factors. RESULTS Analyses were carried out on 16 717 statin-treated patients (mean ± SD, age 60.5 ± 12.0 years; 52.1% men). During statin therapy, 9.6% (N = 1599) of patients reported SAMS. Women and physically active subjects were more likely to report SAMS (OR 1.23 [1.10-1.37] and OR 1.35 [1.14-1.60], respectively), whist age ≥ 65 (OR 0.79 [0.70-0.89]), presence of type 2 diabetes mellitus (OR 0.62 [0.51-0.74]), use of concomitant nonstatin lipid-lowering drugs (OR 0.87 [0.76-0.99]), use of high-intensity statins (OR 0.79 [0.69-0.90]) and use of potential interacting drugs (OR 0.63 [0.48-0.84]) were associated with lower probability of reporting SAMS. Amongst patients reporting SAMS, 82.2% underwent dechallenge (treatment interruption) and/or rechallenge (change or restart of statin therapy), with reappearance of muscular symptoms in 38.4% (3.01% of the whole cohort). CONCLUSIONS The reported prevalence of SAMS was 9.6% of the whole PROSISA cohort, but only a third of patients still reported SAMS after dechallenge/rechallenge. These results emphasize the need for a better management of SAMS to implement a more accurate diagnosis and treatment re-evaluation.
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Umbrella Review on Non-Statin Lipid-Lowering Therapy.
Beshir, SA, Hussain, N, Elnor, AA, Said, ASA
Journal of cardiovascular pharmacology and therapeutics. 2021;(5):437-452
Abstract
OBJECTIVES The main aim of this review was to summarize current evidence on approved and emerging non-statin lipid-lowering therapies. METHODS AND MATERIALS Recent literature on U.S. FDA approved non-statin lipid-lowering therapies and evolving lipid-lowering drugs currently under development was reviewed. RESULTS AND DISCUSSION In the past 20 years, the emergence of non-statin cholesterol-lowering drugs has changed the landscape of dyslipidemia management. Food and Drug Administration approval of non-statin lipid-lowering therapies such as ezetimibe, proprotein convertase subtilisin/Kexin type 9 (PCSK9) inhibitors (evolocumab, alirocumab), bempedoic acid and combination of bempedoic acid and ezetimibe, evinacumab and other triglyceride-lowering agents (eg, icosapent ethyl) has emerged. The European Commission has also recently approved inclisiran for treatment of hypercholesterolemia and mixed hypercholesterolemia even though FDA has put the approval of this drug on hold. Recent guidelines have incorporated PCSK9 inhibitors to treat patients with primary hyperlipidemia and patients with very high-risk ASCVD, who could not achieve adequate lipid-lowering with combination therapy of maximally tolerated statin and ezetimibe. Icosapent ethyl use as an adjunct therapy to statins is also recommended to reduce the risk of ASCVD in patients with hypertriglyceridemia. CONCLUSION Despite cost limitations, the uptake of PCSK9 inhibitors is increasing. Approval of bempedoic acid alone or in combination with ezetimibe has provided additional oral lipid-lowering drug alternatives to ezetimibe. Various lipid-lowering drug targets are under investigation.
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Maternal dyslipidemia and altered cholesterol metabolism in early pregnancy as a risk factor for small for gestational age neonates.
Kim, SY, Lee, SM, Kwon, GE, Kim, BJ, Koo, JN, Oh, IH, Kim, SM, Shin, S, Kim, W, Joo, SK, et al
Scientific reports. 2021;(1):21066
Abstract
We evaluated the relationship between maternal cholesterol levels and its biologically active precursors and metabolites in the first trimester and subsequent risk for small-for-gestational-age birthweight (SGA). This is a secondary analysis of a prospective cohort study which enrolled healthy singleton pregnancies (n = 1337). Maternal fasting blood was taken in the first trimester and followed up till delivery. The lipid parameters were compared between women who delivered SGA neonates (SGA-group, birthweight < 10th percentile, n = 107) and women who did not (non-SGA-group, n = 1230). In addition, metabolic signatures of cholesterol were evaluated in a subset consisting of propensity-score matched SGA (n = 56) and control group (n = 56). Among lipid parameters, maternal high-density lipoprotein cholesterol (HDL-C) levels were significantly lower in SGA-group than in non-SGA-group (p = 0.022). The risk for SGA was negatively correlated with maternal serum HDL-C quartiles (p = 0.003), and this association remained significant after adjustment for confounding variables. In metabolic signatures of cholesterol, the cholesterol/lathosterol ratio in SGA-group was significantly higher than non-SGA-group [(2.7 (1.6-3.7) vs. 2.1 (1.5-2.9), respectively; p = 0.034)], suggesting increased endogenous cholesterol biosynthesis. We demonstrated that dyslipidemia and increased cholesterol biosynthesis led to delivery of SGA neonates even in early pregnancy.
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Nonalcoholic fatty liver disease or metabolic dysfunction-associated fatty liver disease diagnoses and cardiovascular diseases: From epidemiology to drug approaches.
Dongiovanni, P, Paolini, E, Corsini, A, Sirtori, CR, Ruscica, M
European journal of clinical investigation. 2021;(7):e13519
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Abstract
BACKGROUND A consensus of experts has proposed to replace the term nonalcoholic fatty liver disease (NAFLD), whose global prevalence is 25%, with metabolic dysfunction-associated fatty liver disease (MAFLD), to describe more appropriately the liver disease related to metabolic derangements. MAFLD is closely intertwined with type 2 diabetes, obesity, dyslipidaemia, all linked to a rise in the risk of cardiovascular disease (CVDs). Since controversy still stands on whether or not NAFLD/MAFLD raises the odds of CVD, the present review aims to evaluate the impact of NAFLD/MAFLD aetiologies on CV health and the potential correction by dietary and drug approaches. RESULTS Epidemiological studies indicate that NAFLD raises risk of fatal or non-fatal CVD events. NAFLD patients have a higher prevalence of arterial plaques and stiffness, coronary calcification, and endothelial dysfunction. Although genetic and environmental factors strongly contribute to NAFLD pathogenesis, a Mendelian randomization analysis indicated that the PNPLA3 genetic variant leading to NAFLD may not be causally associated with CVD risk. Among other genetic variants related to NAFLD, TM6SF2 appears to be protective, whereas MBOAT7 may favour venous thromboembolism. CONCLUSIONS NAFLD is correlated to a higher CVD risk which may be ameliorated by dietary interventions. This is not surprising, since new criteria defining MAFLD include other metabolic risk abnormalities fuelling development of serious adverse extrahepatic outcomes, for example CVD. The present lack of a targeted pharmacological approach makes the identification of patients with liver disease at higher CVD risk (eg diabetes, hypertension, obesity or high levels of C-reactive protein) of major clinical interest.
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Role of growth hormone in hepatic and intestinal triglyceride-rich lipoprotein metabolism.
Maraninchi, M, Calabrese, A, Nogueira, JP, Castinetti, F, Mancini, J, Mourre, F, Piétri, L, Bénamo, E, Albarel, F, Morange, I, et al
Journal of clinical lipidology. 2021;(5):712-723
Abstract
BACKGROUND Elevated plasma concentrations of hepatic- and intestinally-derived triglyceride-rich lipoproteins (TRL) are implicated in the pathogenesis of atherosclerotic cardiovascular disease and all-cause mortality. Excess of TRL is the driving cause of atherogenic dyslipidemia commonly occurring in insulin-resistant individuals such as patients with obesity, type 2 diabetes and metabolic syndrome. Interestingly, growth hormone (GH)-deficient individuals display similar atherogenic dyslipidemia, suggesting an important role of GH and GH deficiency in the regulation of TRL metabolism. OBJECTIVE We aimed to examine the direct and/or indirect role of GH on TRL metabolism. METHODS We investigated the effect on fasting and postprandial hepatic-TRL and intestinal-TRL metabolism of short-term (one month) withdrawal of GH in 10 GH-deficient adults. RESULTS After GH withdrawal, we found a reduction in fasting plasma TRL concentration (significant decrease in TRL-TG, TRL-cholesterol, TRL-apoB-100, TRL-apoC-III and TRL-apoC-II) but not in postprandial TRL response. This reduction was due to fewer fasting TRL particles without a change in TG per particle and was not accompanied by a change in postprandial TRL-apoB-48 response. Individual reductions in TRL correlated strongly with increases in insulin sensitivity and decreases in TRL-apoC-III. CONCLUSION In this relatively short term 'loss of function' human experimental model, we have shown an unanticipated reduction of hepatic-TRL particles despite increase in total body fat mass and reduction in lean mass. These findings contrast with the atherogenic dyslipidemia previously described in chronic GH deficient states, providing a new perspective for the role of GH in lipoprotein metabolism.
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Emerging Pharmacotherapy to Reduce Elevated Lipoprotein(a) Plasma Levels.
Eraikhuemen, N, Lazaridis, D, Dutton, MT
American journal of cardiovascular drugs : drugs, devices, and other interventions. 2021;(3):255-265
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Abstract
Lipoprotein(a) is a unique form of low-density lipoprotein. It is associated with a high incidence of premature atherosclerotic disease such as coronary artery disease, myocardial infarction, and stroke. Plasma levels of this lipoprotein and its activities are highly variable. This is because of a wide variability in the size of the apolipoprotein A moiety, which is determined by the number of repeats of cysteine-rich domains known as "kringles." Although the exact mechanism of lipoprotein(a)-induced atherogenicity is unknown, the lipoprotein has been found in the arterial walls of atherosclerotic plaques. It has been implicated in the formation of foam cells and lipid deposition in these plaques. Pharmacologic management of elevated levels of lipoprotein(a) with statins, fibrates, or bile acid sequestrants is ineffective. The newer and emerging lipid-lowering agents, such as the second-generation antisense oligonucleotides, cholesteryl ester transfer protein inhibitors, and proprotein convertase subtilisin/kexin type 9 inhibitors offer the most effective pharmacologic therapy.
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Crosstalk of Magnesium and Serum Lipids in Dyslipidemia and Associated Disorders: A Systematic Review.
Găman, MA, Dobrică, EC, Cozma, MA, Antonie, NI, Stănescu, AMA, Găman, AM, Diaconu, CC
Nutrients. 2021;(5)
Abstract
Dyslipidemia is a significant threat to public health worldwide and the identification of its pathogenic mechanisms, as well as novel lipid-lowering agents, are warranted. Magnesium (Mg) is a key element to human health and its deficiency has been linked to the development of lipid abnormalities and related disorders, such as the metabolic syndrome, type 2 diabetes mellitus, or cardiovascular disease. In this review, we explored the associations of Mg (dietary intake, Mg concentrations in the body) and the lipid profile, as well as the impact of Mg supplementation on serum lipids. A systematic search was computed in PubMed/MEDLINE and the Cochrane Library and 3649 potentially relevant papers were detected and screened (n = 3364 following the removal of duplicates). After the removal of irrelevant manuscripts based on the screening of their titles and abstracts (n = 3037), we examined the full-texts of 327 original papers. Finally, after we applied the exclusion and inclusion criteria, a number of 124 original articles were included in this review. Overall, the data analyzed in this review point out an association of Mg concentrations in the body with serum lipids in dyslipidemia and related disorders. However, further research is warranted to clarify whether a higher intake of Mg from the diet or via supplements can influence the lipid profile and exert lipid-lowering actions.
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THERAPY OF ENDOCRINE DISEASE: Endocrine-metabolic effects of treatment with multikinase inhibitors.
Fallahi, P, Ferrari, SM, Elia, G, Ragusa, F, Paparo, SR, Camastra, S, Mazzi, V, Miccoli, M, Benvenga, S, Antonelli, A
European journal of endocrinology. 2021;(1):R29-R40
Abstract
Tyrosine kinase inhibitors (TKIs) are emerging as potentially effective options in the treatment of cancer, acting on the pathways involved in growth, avoidance of apoptosis, invasiveness, angiogenesis, and local and distant spread. TKIs induce significant adverse effects, that can negatively affect patients' quality of life. The most common adverse events (AEs) include fatigue, hand-foot skin reaction, decreased appetite, nausea, diarrhea, hypertension, vomiting, weight loss, endocrinopaties and metabolic disorders. Patients in therapy with TKIs can develop endocrine-metabolic disorders, including dyslipidemia (~50%), diabetes (~15-40%), and dysthyroidism (~20%). In some cases, patients show an improved glycemia or hypoglycemia. The effects of TKIs on adrenal or gonadal function are still not completely known. It was shown a higher prevalence of subclinical hypocortisolism in patients treated with imatinib, while an increase of cortisol was reported in patients receiving vandetanib. Long-term treatment with imatinib could impact significantly the ovarian reserve and embryo developmental capacity. It is important to evaluate patients, measure glucose levels, and manage hyperglycemia. Mild treatment-related hyperglycemia can be controlled modifying the diet and with exercise, while grade 3 and 4 hyperglycemia can lead to dose reductions and/or oral antihyperglycemic therapy. Regarding thyroid dysfunctions, it is recommendable to measure the thyroid-stimulating hormone (TSH)/free thyroxine (FT4) levels before starting the therapy, and every 3-4 weeks during the first 6 months as changes in FT4 levels precede the changes in TSH by 3-6 weeks. Additional studies are necessary to definitely clarify the mechanism of TKIs-induced endocrine-metabolic effects.
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Biotechnology Approaches for the Treatment of Dyslipidemia.
Parolini, C
Cardiovascular drugs and therapy. 2021;(1):167-183
Abstract
BACKGROUND Despite advances in the development of lipid-lowering therapies, clinical trials have shown that a significant residual risk of cardiovascular disease persists. Specifically, new drugs are needed for non-responding or statin-intolerant subjects or patients considered at very high risk for cardiovascular events even though are already on treatment with the best standard of care. RESULTS AND CONCLUSIONS Besides, genetic and epidemiological studies and Mendelian randomization analyses have strengthened the linear correlation between the concentration of low-density lipoprotein cholesterol (LDL-C) and the incidence of cardiovascular events and highlighted various novel therapeutic targets. This review describes the novel strategies to reduce the levels of LDL-C, non-HDL-C, triglyceride, apolipoprotein B, and Lp(a), focusing on those developed using biotechnology-based strategies.