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1.
Genome-wide meta-analysis of phytosterols reveals five novel loci and a detrimental effect on coronary atherosclerosis.
Scholz, M, Horn, K, Pott, J, Gross, A, Kleber, ME, Delgado, GE, Mishra, PP, Kirsten, H, Gieger, C, Müller-Nurasyid, M, et al
Nature communications. 2022;(1):143
Abstract
Phytosterol serum concentrations are under tight genetic control. The relationship between phytosterols and coronary artery disease (CAD) is controversially discussed. We perform a genome-wide meta-analysis of 32 phytosterol traits reflecting resorption, cholesterol synthesis and esterification in six studies with up to 9758 subjects and detect ten independent genome-wide significant SNPs at seven genomic loci. We confirm previously established associations at ABCG5/8 and ABO and demonstrate an extended locus heterogeneity at ABCG5/8 with different functional mechanisms. New loci comprise HMGCR, NPC1L1, PNLIPRP2, SCARB1 and APOE. Based on these results, we perform Mendelian Randomization analyses (MR) revealing a risk-increasing causal relationship of sitosterol serum concentrations and CAD, which is partly mediated by cholesterol. Here we report that phytosterols are polygenic traits. MR add evidence of both, direct and indirect causal effects of sitosterol on CAD.
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2.
Does letrozole treatment have favorable effects on the lipid profile? A systematic review and meta-analysis of randomized clinical trials.
Cai, T, Al-Jubairi, NN, Santos, HO, de Souza, IGO, Chen, Y
Steroids. 2021;:108875
Abstract
As an aromatase inhibitor, letrozole reduces estrogen levels, affecting lipid indices because of the positive role of estrogens in modulating lipoproteins and lipids. Thus, our aim was to meta-analyze data regarding letrozole administration and its effects on the traditional lipid profile. A systematic review and meta-analysis of randomized clinical trials (RCTs) were performed based on the PRISMA guidelines. Web of Science, Scopus, PubMed/Medline, and EMBASE databases were searched until February 11, 2021. From 341 potentially relevant publications, 8 RCTs were selected. All studies used 2.5 mg/d of letrozole. Total cholesterol changed significantly by -6.28 mg/dL (95% CI: -8.73, -3.84, P < 0.001) and HDL-C by -4.40 mg/dL (95% CI: -5.30 to -3.50, p < 0.001) in letrozole group when compared to the control group. Taking into account this comparison between groups, in contrast, LDL-C (WMD: -2.50 mg/dL, 95% CI: -9.94, 4.93, p = 0.510) and triglycerides (WMD: -0.89 mg/dL, 95% CI: -6.87 to 5.07, p = 0.768) did not alter. In conclusion, letrozole administration decreased the concentrations of HDL-C and tocal cholesterol, but not of triglycerides and LDL-C.
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3.
The effect of meal frequency on biochemical cardiometabolic factors: A systematic review and meta-analysis of randomized controlled trials.
Abdollahi, S, Kazemi, A, de Souza, RJ, Clark, CCT, Soltani, S
Clinical nutrition (Edinburgh, Scotland). 2021;(5):3170-3181
Abstract
BACKGROUND Although several randomized controlled trials (RCTs) have supported the beneficial effects of higher meal frequency (MF) on cardiometabolic risk factors, the putative effects of higher MF on health remain inconclusive. This study systematically reviewed the evidence from RCTs of the effect of higher compared with lower MF on the blood lipid profile, glucose homeostasis, and adipokines. METHODS PubMed, Scopus, ISI Web of Science, and the Cochrane database were searched up to October 2020 to retrieve relevant RCTs. A DerSimonian and Laird random effects model was used to pool mean differences and 95% CI for each outcome. The quality of studies and evidence was assessed through standard methods. RESULTS Twenty-one RCTs (686 participants) were included in this meta-analysis. Overall results showed a significant improvement in total cholesterol [weighted mean difference (WMD) = -6.08 mg/dl; 95% CI: -10.68, -1.48; P = 0.01; I2 = 88%], and low-density cholesterol (LDL-C) (WMD = -6.82 mg/dl; 95% CI: -10.97, -1.60; P = 0.009; I2 = 85.7%), while LDL-C to high-density cholesterol ratio (LDL-C: HDL-C) increased (WMD = 0.22; 95% CI: 0.07, 0.36; P = 0.003; I2 = 0.0%) in higher MF vs. lower MF. No significant effects were found on measures of glycemic control, apolipoproteins-A1 and B, or leptin. In subgroup analyses, higher MF significantly reduced serum triglyceride (TG), and increased HDL-C, compared with lower MF in interventions > 12 weeks, and decreased serum TC and LDL-C in healthy participants. A significant reduction in LDL-C also was observed in studies where the same foods given both arms, simply divided into different feeding occasions, and in feeding studies, following higher MF compared to lower MF. CONCLUSION Our meta-analysis found that higher, compared with lower MF may improve total cholesterol, and LDL-C. The intervention does not affect measures of glycemic control, apolipoproteins-A1 and B, or leptin. However, the GRADE ratings of low credibility of the currently available evidence highlights the need for more high-quality studies in order to reach a firm conclusion.
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4.
Betaine Supplementation Moderately Increases Total Cholesterol Levels: A Systematic Review and Meta-Analysis.
Zawieja, EE, Zawieja, B, Chmurzynska, A
Journal of dietary supplements. 2021;(1):105-117
Abstract
Betaine is used to lower elevated plasma homocysteine levels, which are a risk factor for cardiovascular diseases (CVD). However, some studies have shown that betaine may have a negative effect on blood lipids. Betaine supplementation is becoming more and more common, but the relationship between betaine supplementation and blood lipoprotein levels are unclear. The purpose of the study described here was thus to perform a meta-analysis of randomized placebo-controlled trials on the effects of betaine supplementation at a daily dose of at least 4 g on blood lipids in adults. Six randomized controlled trials published between 2002 and 2018 were identified. All six studies used adult participants supplemented with at least 4 g/d of betaine for six to twenty-four weeks. A meta-analysis was carried out using a random-effects model, and the overall effect size was calculated for changes in plasma total cholesterol (TC), HDL cholesterol, LDL cholesterol, and triglycerides (TG). The pooled estimate of the effects of betaine supplementation compared to placebo on TC was 0.34 mmol/L (95% CI: 0.02, 0.65), p = 0.0352. No significant effect was observed for LDL, HDL, or TG. Supplementation with at least 4 g/d of betaine for a minimum of six weeks may moderately increase plasma TC, which might be important in the context of cardiovascular health.
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5.
A meta-analysis of HDL cholesterol efflux capacity and concentration in patients with rheumatoid arthritis.
Xie, B, He, J, Liu, Y, Liu, T, Liu, C
Lipids in health and disease. 2021;(1):18
Abstract
BACKGROUND Poor cholesterol efflux capacity (CEC) has been proposed to be an independent risk factor for cardiovascular diseases. However, current evidence is inconsistent, especially in rheumatoid arthritis (RA) patients. This meta-analysis aims to identify whether CEC is impaired or altered by drug therapy in RA. METHODS The PubMed/MEDLINE, Embase, Cochrane Library and ClinicalTrials.gov databases were browsed to identify studies on CEC in RA patients. The searches mainly focused on studies in human subjects that were published before November 14, 2020, without any language restrictions. The effect size was pooled by the standardized mean differences and mean differences (SMD & MD) as well as the corresponding 95% confidence intervals (CIs) in a random or fixed effect model. Heterogeneity across the studies was tested using Cochran's Q test and I2 statistic. Newcastle-Ottawa Scale and the Downs and Black scale (D&B) were applied to evaluate the quality of included studies. The GRADE-system with its 4-grade evidence scale was used to assess the quality of evidence. RESULTS A total of 11 eligible articles, including 6 observational and 5 interventional studies, were retrieved. The pooled results showed that in patients with RA, CEC was not significantly different than in healthy controls (SMD: -0.34, 95% CI: - 0.83 to 0.14), whereas the plasma HDL-C levels was significantly lower (MD: -3.91, 95% CI: - 7.15 to - 0.68). Furthermore, in the before-after studies, the CEC of RA patients (SMD: 0.20, 95% CI: 0.02 to 0.37) increased, but the plasma HDL-C levels (MD: 3.63, 95% CI: - 0.13 to 7.39) remained at a comparable quantity after anti-rheumatic treatment comparing with the baseline. In addition, the funnel plot of included studies displayed a lightly asymmetry, while Egger's and Begg's test did not suggest the existence of publication bias. The quality of evidence was rated according to GRADE as moderate to very low. CONCLUSION The current meta-analysis demonstrated that HDL-mediated CEC can be improved by the early control of inflammation and anti-rheumatic treatment in RA patients, which is independent of the plasma HDL-C levels. However, the results should be interpreted with caution because of low-quality and limited quantity of evidence. Future randomized controlled trials are needed to determine whether therapeutic strategies to enhance CEC in RA patients have beneficial effects for preventing CVD.
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6.
The effect of apple cider vinegar on lipid profiles and glycemic parameters: a systematic review and meta-analysis of randomized clinical trials.
Hadi, A, Pourmasoumi, M, Najafgholizadeh, A, Clark, CCT, Esmaillzadeh, A
BMC complementary medicine and therapies. 2021;(1):179
Abstract
BACKGROUND Elevated lipid profiles and impaired glucose homeostasis are risk factors for several cardiovascular diseases (CVDs), which, subsequently, represent a leading cause of early mortality, worldwide. The aim of the current study was to conduct a systematic review and meta-analysis of the effect of apple cider vinegar (ACV) on lipid profiles and glycemic parameters in adults. METHODS A systematic search was conducted in electronic databases, including Medline, Scopus, Cochrane Library, and Web of Knowledge, from database inception to January 2020. All clinical trials which investigated the effect of ACV on lipid profiles and glycemic indicators were included. Studies were excluded if ACV was used in combination with other interventions or when the duration of intervention was < 2 weeks. To account for between-study heterogeneity, we performed meta-analysis using a random-effects model. RESULTS Overall, nine studies, including 10 study arms, were included in this meta-analysis. We found that ACV consumption significantly decreased serum total cholesterol (- 6.06 mg/dL; 95% CI: - 10.95, - 1.17; I2: 39%), fasting plasma glucose (- 7.97 mg/dL; 95% CI: - 13.74, - 2.21; I2: 75%), and HbA1C concentrations (- 0.50; 95% CI: - 0.90, - 0.09; I2: 91%). No significant effect of ACV consumption was found on serum LDL-C, HDL-C, fasting insulin concentrations, or HOMA-IR. The stratified analysis revealed a significant reduction of serum TC and TG in a subgroup of patients with type 2 diabetes, those who took ≤15 mL/day of ACV, and those who consumed ACV for > 8-weeks, respectively. Furthermore, ACV consumption significantly decreased FPG levels in a subgroup of studies that administered ACV for > 8-weeks. Further, ACV intake appeared to elicit an increase in FPG and HDL-C concentrations in apparently healthy participants. CONCLUSION We found a significant favorable effect of ACV consumption on FPG and blood lipid levels.
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7.
Evaluation of High Cholesterol and Risk of Dementia and Cognitive Decline in Older Adults Using Individual Patient Meta-Analysis.
Peters, R, Xu, Y, Antikainen, R, Beckett, N, Gussekloo, J, Jagger, C, Jukema, JW, Keinanen-Kiukaanniemi, S, Rydén, L, Skoog, I, et al
Dementia and geriatric cognitive disorders. 2021;(4):318-325
Abstract
INTRODUCTION Although increased cholesterol level has been acknowledged as a risk factor for dementia, evidence synthesis based on published data has yielded mixed results. This is especially relevant in older adults where individual studies report non-linear relationships between cholesterol and cognition and, in some cases, find higher cholesterol associated with a lower risk of subsequent cognitive decline or dementia. Prior evidence synthesis based on published results has not allowed us to focus on older adults or to standardize analyses across studies. Given our ageing population, an increased risk of dementia in older adults, and the need for proportionate treatment in this age group, an individual participant data (IPD) meta-analysis is timely. METHOD We combined data from 8 studies and over 21,000 participants aged 60 years and over in a 2-stage IPD to examine the relationship between total, high-density, and low-density lipoprotein (HDL and LDL) cholesterol and subsequent incident dementia or cognitive decline, with the latter categorized using a reliable change index method. RESULTS Meta-analyses found no relationship between total, HDL, or LDL cholesterol (per millimoles per litre increase) and risk of cognitive decline in this older adult group averaging 76 years of age. For total cholesterol and cognitive decline: odds ratio (OR) 0.93 (95% confidence interval [CI] 0.86: 1.01) and for incident dementia: OR 1.01 [95% CI 0.89: 1.13]. This was not altered by rerunning the analyses separately for statin users and non-users or by the presence of an APOE e4 allele. CONCLUSION There were no clear consistent relationships between cholesterol and cognitive decline or dementia in this older adult group, nor was there evidence of effect modification by statin use. Further work is needed in younger populations to understand the role of cholesterol across the life-course and to identify any relevant intervention points. This is especially important if modification of cholesterol is to be further evaluated for its potential influence on risk of cognitive decline or dementia.
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8.
The Effects of Different Degrees of Carbohydrate Restriction and Carbohydrate Replacement on Cardiometabolic Risk Markers in Humans-A Systematic Review and Meta-Analysis.
Fechner, E, Smeets, ETHC, Schrauwen, P, Mensink, RP
Nutrients. 2020;(4)
Abstract
Low-carbohydrate diets (LCDs) often differ in their diet composition, which may lead to conflicting results between randomized controlled trials. Therefore, we aimed to compare the effects of different degrees of carbohydrate (CHO) restriction on cardiometabolic risk markers in humans. The experimental LCDs of 37 human trials were classified as (1) moderate-low CHO diets (<45-40 E%, n = 13), (2) low CHO diets (<40-30 E%, n = 16), and (3) very-low CHO diets (<30-3 E%; n = 8). Summary estimates of weighted mean differences (WMDs) in selected risk markers were calculated using random-effect meta-analyses. Differences between the LCD groups were assessed with univariate meta-regression analyses. Overall, the LCDs resulted in significant weight loss, reduced diastolic blood pressure BP, and increased total cholesterol and high-density lipoprotein cholesterol (HDL-C), without significant differences between the three LCD groups. Higher low-density lipoprotein cholesterol (LDL-C) concentrations were found with the very-low CHO diets compared to the moderate-low CHO diets. Decreases in triacylglycerol (TAG) concentrations were more pronounced with the low and very-low CHO diets, compared to the moderate-low CHO diets. Substitution of CHO by mainly saturated fatty acids (SFAs) increased total cholesterol, LDL-C, and HDL-C concentrations. Except for LDL-C and TAGs, effects were not related to the degree of CHO restriction. Potential effects of nutrient exchanges should be considered when following LCDs.
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9.
Preoperative serum total cholesterol is a predictor of prognosis in patients with renal cell carcinoma: a meta- analysis of observational studies.
Li, B, Huang, D, Zheng, H, Cai, Q, Guo, Z, Wang, S
International braz j urol : official journal of the Brazilian Society of Urology. 2020;(2):158-168
Abstract
PURPOSE Several studies have demonstrated the strong correlation between the levels of preoperative serum total cholesterol (TC) and the survival of patients with surgically treated renal cell carcinoma (RCC). However, this association remains controversial. We performed a meta-analysis of published reports to evaluate the prognostic signifi cance of the preoperative serum TC levels for patients with surgically treated RCC. MATERIAL AND METHODS The databases from MEDLINE (via PubMed), Embase, Web of Science and Cochrane Library were systematically searched to identify the eligible studies published before August 2019. Multivariate adjusted hazard ratios (HRs) with 95% confi dence intervals (CIs) were calculated through inverse variance by using random effects models. RESULTS Nine cohort studies comprising 15.609 patients were identifi ed. Low preopera- tive serum TC levels were associated with poor cancer-specifi c survival (CSS; HR=0.98, 95% CI: 0.97-0.99; P=0.005; I2=74.2%) and progression-free survival (PFS; HR=0.69, 95% CI: 0.49-0.98; P=0.036; I2=80%) in patients with surgically treated RCC. However, no signifi cant association was observed between low preoperative serum TC levels and shorter overall survival (HR=0.93, 95% CI: 0.87-1.00; P=0.057; I2=86.2%). Sensitivity analyses validated the reliability and rationality of the results. CONCLUSIONS Preoperative serum TC level is an independent poor prognostic factor for patients with surgically treated RCC, with lower levels associated with worse CSS and PFS. Hence, this parameter may provide additional guidance in the selection of therapeutic strategies to improve prognosis, considering that cholesterol is a broadly applied routine marker in clinical practice.
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10.
A systematic review and meta-analysis of serum cholesterol and triglyceride levels in patients with Parkinson's disease.
Fu, X, Wang, Y, He, X, Li, H, Liu, H, Zhang, X
Lipids in health and disease. 2020;(1):97
Abstract
OBJECTIVES Numerous studies have reported that lipid metabolic abnormalities may play an important role in the development of Parkinson's disease (PD), with mixed results. This meta-analysis aims to systematically assess the relationship between serum cholesterol or triglyceride and the PD risk and to further determine the role of dyslipidemia in potential predictive value. METHODS This research systematically consulted and screened observational studies to evaluate the association of serum lipids with the risk of PD as of April 01, 2020 based on the inclusion and exclusion criteria. Two researchers screened and extracted the data independently. Then this article summarized the characteristics of all clinical studies and collected the corresponding data to perform pooled and sensitivity analyses. The meta-analysis was performed by using the RevMan 5.3 software after data extraction, quality assessment and analysis of publication bias. RESULTS Twenty-one related studies (13 case-control and 8 cohort studies) were selected with a total of 980,180 subjects, including 11,188 PD patients. Meta-analysis showed that higher levels of serum triglyceride (S-TG) [standard mean different (SMD) = - 0.26 (95% confidence interval (CI): - 0.39 to - 0.13, p<0.00001), relative risk (RR) = 0.67 (95% CI: 0.60 to 0.75, p<0.00001)] could be considered as protective factors for the pathogenesis of PD. However, there was no significant association between serum high density lipoprotein cholesterol (S-HDL) and the risk of PD. Meanwhile, serum low density lipoprotein cholesterol (S-LDL) [SMD = -0.26 (95% CI: - 0.43 to - 0.07, p = 0.006), RR = 0.76 (95% CI: 0.59 to 0.97, p = 0.03)] and serum total cholesterol (S-TC) levels [SMD = -0.21 (95% CI: - 0.33 to - 0.10, p = 0.0002), RR = 0.86 (95% CI: 0.77 to 0.97, p = 0.01)] were negatively associated with PD risk. CONCLUSIONS This systematic review suggests that elevated serum levels of TG, LDL and TC may be protective factors for the pathogenesis of PD. Further longitudinal and well-designed prospective studies with a large sample size are needed to confirm the findings in this meta-analysis.