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Efficacy and Safety of Evinacumab for the Treatment of Hypercholesterolemia: A Meta-Analysis.
Jin, M, Meng, F, Yang, W, Liang, L, Wang, H, Fu, Z
Journal of cardiovascular pharmacology. 2021;(3):394-402
Abstract
Angiopoietin-like protein 3 is essential in lipid metabolism regulation. However, the efficacy and safety of evinacumab (angiopoietin-like protein 3 inhibition drug) for hypercholesterolemia treatment is unknown. In this study, a meta-analysis of randomized controlled trials (RCTs) was conducted to assess the efficacy and safety of evinacumab. RCTs published between January 1, 2000, and November 1, 2020, were obtained from PubMed, Embase, and Cochrane Library. All RCTs evaluating the efficacy and safety of evinacumab were included without language restrictions. Our primary end points included the percent change of low-density lipoprotein cholesterol (LDL-C) from baseline and the incidence of at least one treatment emergent adverse events including nasopharyngitis, influenza-like illness, headache, dizziness, injection-site reaction, increased aspartate aminotransferase, increased alanine aminotransferase, and any other discomfort during treatments. Percentage changes of triglycerides and high-density lipoprotein cholesterol (HDL-C) from baseline indicated secondary end points. A random-effects model was used to assess pooled data if there was moderate to high heterogeneity between studies. Four studies with 5 RCTs (568 participants) were identified. Evinacumab significantly reduced LDL-C [mean difference (MD) -33.123%, 95% confidence interval (CI), -48.639% to -17.606%, P < 0.0001], triglycerides (MD -50.959%, 95% CI, -56.555% to -45.362%, P < 0.0001), and HDL-C (MD -12.773%, 95% CI, -16.359% to -9.186%, P < 0.0001) compared with placebo. The incidence of at least 1 treatment emergent adverse events was not significantly different between evinacumab and placebo groups (relative risk 1.080, 95% CI, 0.901-1.296, P = 0.405). Evinacumab decreased triglycerides, LDL-C, and HDL-C without significant adverse effects, indicating that it can be a therapeutic strategy for hypercholesterolemia.
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Triglyceride/High-Density Lipoprotein Cholesterol Ratio: A Clue to Metabolic Syndrome, Insulin Resistance, and Severe Atherosclerosis.
Azarpazhooh, MR, Najafi, F, Darbandi, M, Kiarasi, S, Oduyemi, T, Spence, JD
Lipids. 2021;(4):405-412
Abstract
High serum levels of triglycerides (Tg) and low levels of high-density lipoprotein cholesterol (HDL-C) are characteristic of the Metabolic Syndrome (MetS). We assessed the ratio of Tg to HDL-C as a way to identify MetS and insulin resistance. We also evaluated its association with severity of carotid atherosclerosis. Data were analyzed from three cohorts totaling 13,908 participants. MetS was defined according to the International Diabetes Federation criteria. Optimal cut-off for Tg/HDL-C ratio was obtained using Youden's index in receiver-operating characteristic (ROC) curve analyses. The risk of MetS and IR in those with a Tg/HDL-C ratio above the optimum cutoff was evaluated by logistic regression analysis. A Tg/HDL-C ratio above the optimal cutoff level significantly increased the odds ratio for MetS in the three cohorts (OR 6.00, 4.04, and 3.50, least in the healthy population), identified insulin resistance defined by the homeostatic model of insulin resistance (HOMA-IR) (p < 0.0001), and was strongly associated with atherosclerosis severity (p = 0.0001). Tg/HDL-C ratio identifies persons with MetS, insulin resistance, and severe atherosclerosis. It should be used more widely to identify patients at high risk. This is clinically important because insulin resistance is treatable.
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No adverse effects of dairy products on lipid profile: A systematic review and meta-analysis of randomized controlled clinical trials.
Derakhshandeh-Rishehri, SM, Ghobadi, S, Akhlaghi, M, Faghih, S
Diabetes & metabolic syndrome. 2021;(6):102279
Abstract
BACKGROUND AND AIMS The current study aimed to review the effects of dairy foods on lipid profile in randomized controlled clinical trials (RCTs). METHODS We searched PubMed, Scopus, Embase, and Central. RCTs that assess the effects of dairy foods on lipid profile were included. RESULTS The overall effects of dairy foods on lipid profile were non-significant. Dairy foods were associated with a non-significant reduction in triacylglycerol level, and a non-significant increase in total cholesterol, low density lipoprotein cholesterol, and high-density lipoprotein cholesterol level. CONCLUSION We conclude that dairy foods doesn't have any unfavorable effects on lipids.
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A systematic review and meta-analysis of the association between clozapine and norclozapine serum levels and peripheral adverse drug reactions.
Tan, MSA, Honarparvar, F, Falconer, JR, Parekh, HS, Pandey, P, Siskind, DJ
Psychopharmacology. 2021;(3):615-637
Abstract
RATIONALE Clozapine is the most effective antipsychotic for treatment-refractory schizophrenia for reducing positive psychotic symptoms. It is associated with a reduction in hospitalisation and overall mortality. In spite of this, clozapine remains underutilised due to its complex adverse drug reaction (ADR) profile. OBJECTIVE This systematic review aims to investigate the association of clozapine and norclozapine serum levels, and peripheral ADRs. METHODS Studies were searched from four electronic databases (PubMed, EMBASE, PsycINFO and CINAHL) from inception to 12 June 2020. Studies were included if they had adult patients, provided data on steady-state trough clozapine or norclozapine levels and reported on clozapine-associated ADRs. Pregnant women, case reports and series were excluded. RESULTS A statistically significant correlation was found for clozapine serum levels and triglycerides (n = 70; r = 0.303, 95% CI 0.0119-0.546, p = 0.042), heart rate (n = 137; r = 0.269, 95% CI 0.0918-0.486, p = 0.035), and overall combined ADRs (n = 160; r = 0.264, 95% CI 0.110-0.405, p = 0.001), but not for absolute neutrophil count (n = 223; r = - 0.164, 95% CI - 0.529-0.253, p = 0.444) or total white cell count (n = 18; r = 0.0176, 95% CI - 0.203-0.237, p = 0.878). Interestingly, norclozapine serum levels were found to be statistically correlated to triglycerides (n = 120; r = 0.211, 95% CI 0.0305-0.378, p = 0.022), total cholesterol (n = 120; r = 0.272, 95% CI 0.0948-0.432, p = 0.003) and weight gain (n = 118; r = 0.208, 95% CI 0.0261-0.377, p = 0.025). CONCLUSIONS Heart rate, triglycerides and combined ADRs are significantly correlated with clozapine levels, and triglycerides, total cholesterol and weight gain with norclozapine levels. Future prospective, randomised controlled studies are needed to identify the cause-effect relationship between clozapine levels and peripheral ADRs.
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Serum lipid abnormalities in migraine: A meta-analysis of observational studies.
Liampas, I, Mylonas, KS, Brotis, A, Dervenis, P, Siokas, V, Mentis, AA, Dastamani, M, Aloizou, AM, Tsouris, Z, Aslanidou, P, et al
Headache. 2021;(1):44-59
Abstract
BACKGROUND The association of migraine with vascular comorbidities is long-established. The contribution of the "traditional" cardiovascular risk factors to this connection remains unclear. OBJECTIVE To determine-quantify the differences in the serum lipid concentrations between lipid-lowering agents-naïve individuals with migraine and healthy controls (HC). METHODS The study protocol was not preregistered with an online systematic review-protocol registry. A literature search involving MEDLINE, EMBASE, CENTRAL, Google Scholar, and the OpenGrey database was performed. Case-control, cross-sectional, or cohort studies involving HC and participants with migraine (with and without aura regardless of the use of prophylactic treatment) that quantitatively assessed serum low-density lipoprotein cholesterol (LDL-C) (primary index) and/or total cholesterol (TC) and/or high-density lipoprotein cholesterol (HDL-C) and/or triglycerides (TG) (secondary indices) were retrieved. Articles including participants with known dyslipidemia (or under lipid-lowering medications) or with secondary causes of dyslipidemia (aside from the subjectively assessed lifestyle parameters) were excluded. Studies with abstracts and full texts not published in English and articles reporting the implementation of other study designs (reviews, meta-analyses, commentaries, case reports, etc.) were excluded as well. Conference abstracts and English abstracts from studies with full texts not published in English were evaluated as part of the gray literature. Each step of the review process was performed by two investigators independently, and relevant data were abstracted based on standardized extraction forms. Any discrepancies were resolved by a third investigator. RESULTS Seventeen studies (16 case-control and 1 cross-sectional) fulfilled the eligibility criteria. Retrieved articles involved adult participants, principally during the fourth decade of life. Results were compatible with higher LDL-C levels in migraine individuals (1370) than in HC (1215) [12 studies, mean difference (MD) = 10.4 mg/dl, 95% confidence interval (CI) = (1.6, 19.2)]. Similarly, higher TC levels were determined in migraine patients [14 studies, migraine = 1325, HC = 1213, MD = 10.6 mg/dl, 95% CI = (1.8, 19.3)], as were TG levels [15 studies, migraine = 1526, HC = 1262, MD = 11.8 mg/dl, 95% CI = (3.6, 20.0)]. HDL-C concentrations were not different between the two groups [14 studies, migraine = 1488, HC = 1328, MD = -0.4 mg/dl, 95% CI = (-2.2, 1.5)]. Prespecified sensitivity analysis following the exclusion of studies not presenting comparable body mass index values between the groups nullified the significant difference regarding LDL-C levels [MD = 5.3 mg/dl, 95% CI = (-0.1, 10.8)]. Subgroup analyses as well as the direct comparison of migraine with aura and migraine without aura individuals were compatible with no difference regarding lipid concentrations, but only a small fraction of the retrieved studies presented relevant figures. CONCLUSIONS Although our results are of limited generalizability, since most retrieved studies were performed in Turkey (nine studies), TC abnormalities may provide part of the explanation for the unfavorable cardiovascular profile of migraine patients. Lifestyle may be partly or entirely accountable for the determined increased serum TC. Additional studies that will completely address the effect that lifestyle parameters exert on lipid concentrations are required to better capture existing abnormalities.
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Effect of vitamin D supplementation on markers of cardiometabolic risk in children and adolescents: A meta-analysis of randomized clinical trials.
Cai, B, Luo, X, Zhang, P, Luan, Y, Cai, X, He, X
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2021;(10):2800-2814
Abstract
BACKGROUND AND AIMS An increasing attention to the effect of vitamin D supplementation on cardiometabolic risk markers in children and adolescents has been gained recently. However, the results are inconsistent. Therefore, we conducted a meta-analysis to examine the effect of vitamin D supplementation on cardiometabolic risk markers in children and adolescents. METHODS AND RESULTS Eligible randomized controlled trials (RCTs) were identified by searching PubMed, EMBASE and Web of Science. The results of this study are synthetized and reported in accordance with the PRISMA statement. GRADE system was used to assess the certainty of evidence. A total of 9 RCTs were identified and included in the meta-analysis. We found that vitamin D supplementation did not affect the changes of cardiometabolic risk markers including high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), body mass index (BMI), waist circumferences, systolic blood pressure (SDP) and diastolic blood pressure (DBP). However, vitamin D supplementation showed a beneficial effect on fasting glucose (MD, -1.54 mg/dl, 95% CI -2.98 to -0.10) and TG (MD, -24.76 mg/dl, 95% CI -37.66 to -11.86) in the sub-group analysis of total vitamin D supplementation ≥ 200,000 IU. CONCLUSIONS Vitamin D supplementation appeared to have a beneficial effect on reducing fasting glucose and TG level when total vitamin D supplementation ≥200,000 IU but not HDL-C, LDL-C TC, blood pressure and waist circumferences levels in children and adolescents. Further studies are needed to address this issue.
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Lipid profile and risk of ovarian tumours: a meta-analysis.
Onwuka, JU, Okekunle, AP, Olutola, OM, Akpa, OM, Feng, R
BMC cancer. 2020;(1):200
Abstract
BACKGROUND Existing data from several reports on the association between lipid profile and ovarian tumour (OT) suggests divergent conclusions. Our aim was to examine whether circulating lipid profile: total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) differed between cases and non-cases of OT. METHODS Electronic repositories; PUBMED, EMBASE and Cochrane library were explored through December 2019 to retrieve published articles for inclusion in the meta-analysis after quality assessment. Heterogeneity was assessed using I2 statistics, the effect of individual studies on the overall effect size was tested using sensitivity analysis and funnel plot was used to evaluate publication bias. RESULTS Twelve studies, involving 1767 OT cases and 229,167 non-cases of OT were included in this meta-analysis and I2 statistics ranged between 97 and 99%. Mean circulating TC (- 16.60 [- 32.43, - 0.77]mg/dL; P = 0.04) and HDL (- 0.25[- 0.43, - 0.08]mmol/L; P = 0.005) were significantly lower among OT cases compared to non-OT cases. CONCLUSION Decreased TC and HDL profiles were observed among subjects with OT in this collection of reports. The implications of TC and HDL in tumour manifestations and growth need to be validated in a large multi-ethnic longitudinal cohort adjusting for relevant confounders.
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Effects of Interrupting Prolonged Sitting with Physical Activity Breaks on Blood Glucose, Insulin and Triacylglycerol Measures: A Systematic Review and Meta-analysis.
Loh, R, Stamatakis, E, Folkerts, D, Allgrove, JE, Moir, HJ
Sports medicine (Auckland, N.Z.). 2020;(2):295-330
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Abstract
BACKGROUND Physical activity (PA) breaks in sitting time might attenuate metabolic markers relevant to the prevention of type 2 diabetes. OBJECTIVES The primary aim of this paper was to systematically review and meta-analyse trials that compared the effects of breaking up prolonged sitting with bouts of PA throughout the day (INT) versus continuous sitting (SIT) on glucose, insulin and triacylglycerol (TAG) measures. A second aim was to compare the effects of INT versus continuous exercise (EX) on glucose, insulin and TAG measures. METHODS The review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recommendations. Eligibility criteria consisted of trials comparing INT vs. SIT or INT vs. one bout of EX before or after sitting, in participants aged 18 or above, who were classified as either metabolically healthy or impaired, but not with other major health conditions such as chronic obstructive pulmonary disease or peripheral arterial disease. RESULTS A total of 42 studies were included in the overall review, whereas a total of 37 studies were included in the meta-analysis. There was a standardised mean difference (SMD) of - 0.54 (95% CI - 0.70, - 0.37, p = 0.00001) in favour of INT compared to SIT for glucose. With respect to insulin, there was an SMD of - 0.56 (95% CI - 0.74, - 0.38, p = 0.00001) in favour of INT. For TAG, there was an SMD of - 0.26 (95% CI - 0.44, - 0.09, p = 0.002) in favour of INT. Body mass index (BMI) was associated with glucose responses (β = - 0.05, 95% CI - 0.09, - 0.01, p = 0.01), and insulin (β = - 0.05, 95% CI - 0.10, - 0.006, p = 0.03), but not TAG (β = 0.02, 95% CI - 0.02, 0.06, p = 0.37). When energy expenditure was matched, there was an SMD of - 0.26 (95% CI - 0.50, - 0.02, p = 0.03) in favour of INT for glucose, but no statistically significant SMDs for insulin, i.e. 0.35 (95% CI - 0.37, 1.07, p = 0.35), or TAG i.e. 0.08 (95% CI - 0.22, 0.37, p = 0.62). It is worth noting that there was possible publication bias for TAG outcomes when PA breaks were compared with sitting. CONCLUSION The use of PA breaks during sitting moderately attenuated post-prandial glucose, insulin, and TAG, with greater glycaemic attenuation in people with higher BMI. There was a statistically significant small advantage for PA breaks over continuous exercise for attenuating glucose measures when exercise protocols were energy matched, but no statistically significant differences for insulin and TAG. PROSPERO Registration: CRD42017080982. PROSPERO REGISTRATION CRD42017080982.
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Effect of Omega-3 Polyunsaturated Fatty Acids Treatment on Lipid Pattern of HIV Patients: A Meta-Analysis of Randomized Clinical Trials.
Fogacci, F, Strocchi, E, Veronesi, M, Borghi, C, Cicero, AFG
Marine drugs. 2020;(6)
Abstract
Even though omega-3 polyunsaturated fatty acids (PUFAs) seem to be effective in the treatment of human immunodeficiency virus (HIV)-associated dyslipidemia, their impact is still debated. For this reason, our aim was to perform a meta-analysis of the clinical evidence available to date. A systematic literature search was conducted in order to identify published clinical trials assessing the effect of PUFAs treatment on serum lipoproteins, and its safety profile. The effect sizes for lipid changes were expressed as mean difference (MD) and 95% confidence interval (CI). For safety analysis, odd ratios and the 95% CI were calculated with the Mantel-Haenszel method. Data were pooled from nine clinical studies comprising overall 578 HIV-affected subjects. Meta-analysis of the data suggested that omega-3 PUFAs significantly reduced triglycerides (TG) (MD = -1.04, 95% CI: -1.5, -0.58 mmol/L, p < 0.001), while increasing high-density lipoprotein cholesterol (MD = 0.36, 95% CI: 0.12, 0.61 mmol/L, p = 0.004), without affecting serum levels of total cholesterol, very-low- and low-density lipoprotein cholesterol, and apolipoprotein B and A1. Change in TG was significantly associated with eicosapentaenoic acid administered via daily dose. PUFA treatment did not lead to an increased risk of adverse events. In conclusion, PUFAs are safe and exert a significant plasma lipid improving effect in HIV-positive patients.
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Cardiometabolic health in offspring of women with PCOS compared to healthy controls: a systematic review and individual participant data meta-analysis.
Gunning, MN, Sir Petermann, T, Crisosto, N, van Rijn, BB, de Wilde, MA, Christ, JP, Uiterwaal, CSPM, de Jager, W, Eijkemans, MJC, Kunselman, AR, et al
Human reproduction update. 2020;(1):103-117
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Abstract
BACKGROUND Women diagnosed with polycystic ovary syndrome (PCOS) suffer from an unfavorable cardiometabolic risk profile, which is already established by child-bearing age. OBJECTIVE AND RATIONALE The aim of this systematic review along with an individual participant data meta-analysis is to evaluate whether cardiometabolic features in the offspring (females and males aged 1-18 years) of women with PCOS (OPCOS) are less favorable compared to the offspring of healthy controls. SEARCH METHODS PubMed, Embase and gray literature databases were searched by three authors independently (M.N.G., M.A.W and J.C.) (last updated on 1 February 2018). Relevant key terms such as 'offspring' and 'PCOS' were combined. Outcomes were age-specific standardized scores of various cardiometabolic parameters: BMI, blood pressure, glucose, insulin, lipid profile and the sum scores of various cardiometabolic features (metabolic sum score). Linear mixed models were used for analyses with standardized beta (β) as outcome. OUTCOMES Nine relevant observational studies could be identified, which jointly included 1367 children: OPCOS and controls, originating from the Netherlands, Chile and the USA. After excluding neonates, duplicate records and follow-up screenings, a total of 885 subjects remained. In adjusted analyses, we observed that OPCOS (n = 298) exhibited increased plasma levels of fasting insulin (β = 0.21(95%CI: 0.01-0.41), P = 0.05), insulin-resistance (β = 0.21(95%CI: 0.01-0.42), P = 0.04), triglycerides (β = 0.19(95%CI: 0.02-0.36), P = 0.03) and high-density lipoprotein (HDL)-cholesterol concentrations (β = 0.31(95%CI: 0.08-0.54), P < 0.01), but a reduced birthweight (β = -116(95%CI: -195 to 38), P < 0.01) compared to controls (n = 587). After correction for multiple testing, however, differences in insulin and triglycerides lost their statistical significance. Interaction tests for sex revealed differences between males and females when comparing OPCOS versus controls. A higher 2-hour fasting insulin was observed among female OPCOS versus female controls (estimated difference for females (βf) = 0.45(95%CI: 0.07 to 0.83)) compared to the estimated difference between males ((βm) = -0.20(95%CI: -0.58 to 0.19)), with interaction-test: P = 0.03. Low-density lipoprotein-cholesterol differences in OPCOS versus controls were lower among females (βf = -0.39(95%CI: -0.62 to 0.16)), but comparable between male OPCOS and male controls (βm = 0.27(95%CI: -0.03 to 0.57)), with interaction-test: P < 0.01. Total cholesterol differences in OPCOS versus controls were also lower in females compared to the difference in male OPCOS and male controls (βf = -0.31(95%CI: -0.57 to 0.06), βm = 0.28(95%CI: -0.01 to 0.56), interaction-test: P = 0.01). The difference in HDL-cholesterol among female OPCOS versus controls (βf = 0.53(95%CI: 0.18-0.88)) was larger compared to the estimated mean difference among OPCOS males and the male controls (βm = 0.13(95%CI: -0.05-0.31), interaction-test: P < 0.01). Interaction test in metabolic sum score revealed a significant difference between females (OPCOS versus controls) and males (OPCOS versus controls); however, sub analyses performed in both sexes separately did not reveal a difference among females (OPCOS versus controls: βf = -0.14(95%CI: -1.05 to 0.77)) or males (OPCOS versus controls: βm = 0.85(95%CI: -0.10 to 1.79)), with P-value < 0.01. WIDER IMPLICATIONS We observed subtle signs of altered cardiometabolic health in OPCOS. Therefore, the unfavorable cardiovascular profile of women with PCOS at childbearing age may-next to a genetic predisposition-influence the health of their offspring. Sensitivity analyses revealed that these differences were predominantly observed among female offspring aged between 1 and 18 years. Moreover, studies with minimal risk of bias should elucidate the influence of a PCOS diagnosis in mothers on both sexes during fetal development and subsequently during childhood.