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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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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.
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The interplay between metabolic dysregulations and non-alcoholic fatty liver disease in women after menopause.
Robeva, R, Mladenović, D, Vesković, M, Hrnčić, D, Bjekić-Macut, J, Stanojlović, O, Livadas, S, Yildiz, BO, Macut, D
Maturitas. 2021;:22-30
Abstract
The hypoestrogenic period after menopause and associated metabolic imbalance might facilitate the onset of non-alcoholic fatty liver disease (NAFLD) and its progression. The prevalence of NAFLD increases in patients experiencing premature ovarian insufficiency, as well as surgical or natural menopause. The postmenopausal period is characterized by dyslipidemia and insulin resistance associated with an increased influx of free fatty acids to the liver with consequent steatosis and further progression of NAFLD. More than half of postmenopausal women with diabetes mellitus type 2 suffer from NAFLD. It is suggested that estrogens slow the progression of chronic liver diseases by suppression of inflammation, improvement of mitochondrial function, alleviation of oxidative stress, insulin resistance, and fibrogenesis. The hyperandrogenic state of polycystic ovary syndrome (PCOS) is associated with the development of NAFLD in women of reproductive age, but it is difficult to extend these findings to menopause due to inappropriate diagnosis of PCOS after menopause. Lifestyle intervention, including physical activity and dietary regimens, remains the first-line preventive and therapeutic option for NAFLD. There are contradictory reports on the use of menopausal hormonal therapy (MHT) and NAFLD. It is necessary to investigate the potential effects of estradiol dose, progesterone type, selective estrogen receptor modulators and tissue-selective estrogen complex compounds on NAFLD development and progression in postmenopausal women. The present review aims to explore the pathophysiological and clinical aspects of liver metabolic disturbances in women after menopause, focusing on the possible preventive and therapeutic strategies in NAFLD, including the potential role of MHT.
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Prevalence and correlates of dyslipidemia in HIV positive and negative adults in Western Kenya: A cross-sectional study.
Tilahun, H, Masyuko, SJ, Mogaka, JN, Temu, T, Kinuthia, J, Osoti, AO, Nakanjako, D, Farquhar, C, Page, ST
Medicine. 2021;(10):e24800
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Abstract
There is increasing morbidity and mortality from cardiovascular diseases (CVD) in sub-Saharan Africa (SSA). Dyslipidemia is a well-known CVD risk factor which has been associated with human immunodeficiency virus (HIV) infection and its treatment in high-income countries. Studies in SSA that have examined the relationship between HIV and dyslipidemia have reported mixed results. In this study, we sought to determine the prevalence of dyslipidemia in HIV positive and negative adults (>=30 years old) and evaluate for association in Western Kenya with a higher prevalence expected among HIV positive individuals.HIV positive adults receiving antiretroviral therapy (ART) and HIV negative individuals seeking HIV testing and counseling services were recruited into a cross-sectional study. Demographic and behavioral data and fasting blood samples were collected. Dyslipidemia was defined according to the National Cholesterol Education Program Adult Treatment Panel III. Associations between baseline demographic and clinical variables and dyslipidemia were analyzed using logistic regression.A total of 598 participants, 300 HIV positive and 298 HIV negative adults were enrolled. Dyslipidemia data was available for 564 (94%) participants. In total, 267 (47%) had dyslipidemia. This was not significantly different between HIV positive and HIV negative individuals (46% vs 49%, P = .4). In a multivariate analysis including both HIV positive and negative individuals, adults 50 to 59 years of age had a 2-fold increased risk of dyslipidemia (Odds ratio [OR] 2.1, 95% confidence interval (1.2-3.5) when compared to 30 to 39-years-old participants. Abdominal obesity (OR 2.5), being overweight (OR 1.9), and low fruit and vegetable intake (OR 2.2) were significantly associated with dyslipidemia. Among HIV positive participants, time since HIV diagnosis, ART duration, use of (PI) protease inhibitor-based ART, viral load suppression, current cluster of differentiation (CD4) count and nadir CD4 did not have significant associations with dyslipidemia.The prevalence of dyslipidemia is high in Western Kenya, with nearly half of all participants with lipid abnormalities. Dyslipidemia was not significantly associated with HIV status, or with HIV-specific factors. Older age, being overweight, abdominal obesity, and low fruit and vegetable intake were associated with dyslipidemia and may be targets for public health interventions to lower the prevalence of dyslipidemia and CVD risk in sub-Saharan Africa.
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Low-level environmental lead and cadmium exposures and dyslipidemia in adults: Findings from the NHANES 2005-2016.
Xu, H, Mao, Y, Xu, B, Hu, Y
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS). 2021;:126651
Abstract
BACKGROUND Previous experimental and occupational health studies have shown the toxic effects of relatively high-level cadmium and lead on lipid metabolism. However, limited studies investigated the relationships between serum lipid levels and exposure to low-level lead and cadmium in adults. OBJECTIVE To investigate the associations between lead and cadmium levels in blood and dyslipidemia in adults. METHODS A retrospective cross-sectional study of 7,457 adults aged 20-79 years who were recruited in the National Health and Nutrition Examination Survey (NHANES, 2005-2016) was conducted. Multivariate linear and logistic regressions were used to examine the associations of blood lead and cadmium levels with serum lipid profiles and risk of dyslipidemia, respectively. RESULTS The weighted geometric means [95% confidence intervals (CIs)] of lead and cadmium in blood were 1.23 (1.21, 1.25) μg/dL and 0.36 (0.35, 0.37) μg/L, respectively. Blood lead was significantly associated with serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B (Apo B) levels after adjusting for covariates. Compared with the adults in the lowest blood lead quartile (≤0.76 μg/dL), those in the highest lead quartile (>1.90 μg/dL) had higher risks of elevated TC (OR = 1.88, 95% CI: 1.59-2.22), non-HDL-C (OR = 1.59, 95% CI: 1.33-1.91), LDL-C (OR = 1.68, 95% CI: 1.41-1.99) and Apo B (OR = 2.00, 95% CI: 1.46-2.73). However, the single effect of cadmium exposure and the joint effect of lead and cadmium exposures on dyslipidemia were not observed. CONCLUSION Blood lead well below the current recommended level was positively associated with the risk of dyslipidemia in adults, while the low-level cadmium exposure currently observed in adults did not show any significant associations with lipid levels.
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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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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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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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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.