-
1.
Association of m.5178C>A variant with serum lipid levels: a systematic review and meta-analysis.
Liu, F, He, J, Wang, S, Yu, F, Luo, Z
Bioscience reports. 2021;(12)
Abstract
BACKGROUND Emerging evidence shows that m.5178C>A variant is associated with a lower risk of coronary artery disease (CAD). However, the specific mechanisms remain elusive. Since dyslipidemia is one of the most critical risk factors for CAD and accounts for at least 50% of the population-attributable risk, it is tempting to speculate that the reduced CAD risk caused by the m.5178C>A variant may stem from an improved lipid profile. In order to verify this hypothesis, we conducted the present study to clarify the association of m.5178C>A variant with lipid levels. METHODS By searching ten databases for studies published before 30 June 2021. Thirteen East Asian populations (7587 individuals) were included for the analysis. RESULTS The present study showed that m.5178C>A variant was associated with higher high-density lipoprotein cholesterol (HDL-C) [standardized mean difference (SMD) = 0.12, 95% confidence interval (CI) = 0.06-0.17, P<0.001] and total cholesterol (TC) (SMD = 0.08, 95% CI = 0.02-0.14, P=0.01) levels. In subgroup analysis, the association of m.5178C>A variant with higher HDL-C levels were observed in Japanese (SMD = 0.09, 95% CI = 0.01-0.17, P=0.03) and Chinese populations (SMD = 0.13, 95% CI = 0.07-0.20, P<0.001). However, the association of m.5178C>A variant with lower low-density lipoprotein cholesterol (LDL-C) levels were only observed in Japanese populations (SMD = -0.11, 95% CI = -0.22 to 0.00, P=0.04). CONCLUSIONS The m.5178C>A variant was associated with higher HDL-C and lower LDL-C levels in Japanese populations, which may contribute to decreased CAD risk and longevity of Japanese.
-
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.
-
3.
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.
-
4.
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.
-
5.
The effects of foods on LDL cholesterol levels: A systematic review of the accumulated evidence from systematic reviews and meta-analyses of randomized controlled trials.
Schoeneck, M, Iggman, D
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2021;(5):1325-1338
Abstract
AIMS: To systematically evaluate the evidence regarding the effects of foods on LDL cholesterol levels and to compare the findings with current guidelines. DATA SYNTHESIS From inception through June 2019, we searched PubMed, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials for guidelines, systematic reviews, and RCTs (for coffee intake only) of at least 13 days duration. Additionally, we searched Trip database for guidelines from 2009 through Oct 2019. Language was restricted to English. The strength of evidence was evaluated using The Grading of Recommendations Assessment, Development, and Evaluation (GRADE). A total of 37 guidelines, 108 systematic reviews, and 20 RCTs were included. With high evidence, foods high in unsaturated and low in saturated and trans fatty acids (e.g. rapeseed/canola oil), with added plant sterols/stanols, and high in soluble fiber (e.g. oats, barley, and psyllium) caused at least moderate (i.e. 0.20-0.40 mmol/L) reductions in LDL cholesterol. Unfiltered coffee caused a moderate to large increase. Soy protein, tomatoes, flaxseeds, and almonds caused small reductions. With moderate evidence, avocados and turmeric caused moderate to large reductions. Pulses, hazelnuts, walnuts, high-fiber/wholegrain foods, and green tea caused small to moderate reductions, whereas sugar caused a small increase. Other identified foods were either neutral or had low or very low evidence regarding their effects. CONCLUSIONS Several foods distinctly modify LDL cholesterol levels. The results may aid future guidelines and dietary advice for hypercholesterolemia.
-
6.
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.
-
7.
Effect of carbohydrate-restricted dietary interventions on LDL particle size and number in adults in the context of weight loss or weight maintenance: a systematic review and meta-analysis.
Falkenhain, K, Roach, LA, McCreary, S, McArthur, E, Weiss, EJ, Francois, ME, Little, JP
The American journal of clinical nutrition. 2021;(4):1455-1466
-
-
Free full text
-
Abstract
BACKGROUND LDL particle size and number (LDL-P) are emerging lipid risk factors. Nonsystematic reviews have suggested that diets lower in carbohydrates and higher in fats may result in increased LDL particle size when compared with higher-carbohydrate diets. OBJECTIVES This study aimed to systematically review available evidence and conduct meta-analyses of studies addressing the association of carbohydrate restriction with LDL particle size and LDL-P. METHODS We searched 6 electronic databases on 4 January, 2021 for randomized trials of any length that reported on dietary carbohydrate restriction (intervention) compared with higher carbohydrate intake (control). We calculated standardized mean differences (SMDs) in LDL particle size and LDL-P between the intervention and control groups of eligible studies, and pooled effect sizes using random-effects models. We performed prespecified subgroup analyses and examined the effect of potential explanatory factors. Internal validity and publication bias were assessed using Cochrane's risk-of-bias tool and funnel plots, respectively. Studies that could not be meta-analyzed were summarized qualitatively. RESULTS This review summarizes findings from 38 randomized trials including a total of 1785 participants. Carbohydrate-restricted dietary interventions were associated with an increase in LDL peak particle size (SMD = 0.50; 95% CI: 0.15, 0.86; P < 0.01) and a reduction in LDL-P (SMD = -0.24; 95% CI: -0.43, -0.06; P = 0.02). The effect of carbohydrate-restricted dietary interventions on LDL peak particle size appeared to be partially explained by differences in weight loss between intervention groups and exploratory analysis revealed a shift from small dense to larger LDL subclasses. No statistically significant association was found between carbohydrate-restricted dietary interventions and mean LDL particle size (SMD = 0.20; 95% CI: -0.29, 0.69; P = 0.37). CONCLUSIONS The available evidence indicates that dietary interventions restricted in carbohydrates increase LDL peak particle size and decrease the numbers of total and small LDL particles.This review was registered at www.crd.york.ac.uk/prospero/ as CRD42020188745.
-
8.
Effect of pharmacist interventions on reducing low-density lipoprotein cholesterol (LDL-C) levels: A systematic review and meta-analysis.
Dixon, DL, Khaddage, S, Bhagat, S, Koenig, RA, Salgado, TM, Baker, WL
Journal of clinical lipidology. 2020;(3):282-292.e4
Abstract
BACKGROUND Clinical practice guidelines recommend team-based care as one strategy to improve dyslipidemia outcomes. Randomized controlled trials (RCTs) have demonstrated that pharmacist interventions reduce low-density lipoprotein cholesterol (LDL-C) levels. OBJECTIVE The objective of the study was to conduct a meta-analysis to determine the effectiveness of pharmacist interventions on reducing LDL-C levels. METHODS A literature search of RCTs published after January 1, 2000 was performed using MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. Included RCTs evaluated a pharmacist intervention compared with usual care, reported baseline and follow-up LDL-C levels, and enrolled at least 100 patients. Mean differences in LDL-C and other lipid parameters were calculated using a random effects model. RESULTS Twenty-six RCTs (n = 22,095 patients) were included in the meta-analysis. Compared with usual care, pharmacist interventions significantly reduced LDL-C levels by -7.9 mg/dL (95% confidence interval (CI) -11.43 to -4.35; I2 = 94%). A subgroup analysis revealed a greater reduction in LDL-C (-13.73 mg/dL; 95% CI -24.07 to -3.40; I2 = 96%) when LDL-C was the sole primary outcome. Significant improvements in total cholesterol (-12.73 mg/dL, 95% CI -19.18 to -6.27), triglycerides (-13.25 mg/dL, 95% CI -26.10 to -0.41), and high-density lipoprotein cholesterol (1.75 mg/dL, 95% CI 0.03 to 3.46) were also found. CONCLUSION Pharmacist interventions significantly reduced LDL-C levels compared with usual care. Further research is warranted to determine the optimal pharmacist intervention for reducing LDL-C levels and to evaluate the comprehensive role of pharmacists in lipid management.
-
9.
PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease.
Schmidt, AF, Carter, JL, Pearce, LS, Wilkins, JT, Overington, JP, Hingorani, AD, Casas, JP
The Cochrane database of systematic reviews. 2020;(10):CD011748
-
-
Free full text
-
Abstract
BACKGROUND Despite the availability of effective drug therapies that reduce low-density lipoprotein (LDL)-cholesterol (LDL-C), cardiovascular disease (CVD) remains an important cause of mortality and morbidity. Therefore, additional LDL-C reduction may be warranted, especially for people who are unresponsive to, or unable to take, existing LDL-C-reducing therapies. By inhibiting the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme, monoclonal antibodies (PCSK9 inhibitors) reduce LDL-C and CVD risk. OBJECTIVES Primary To quantify the effects of PCSK9 inhibitors on CVD, all-cause mortality, myocardial infarction, and stroke, compared to placebo or active treatment(s) for primary and secondary prevention. Secondary To quantify the safety of PCSK9 inhibitors, with specific focus on the incidence of influenza, hypertension, type 2 diabetes, and cancer, compared to placebo or active treatment(s) for primary and secondary prevention. SEARCH METHODS We identified studies by systematically searching CENTRAL, MEDLINE, Embase, and Web of Science in December 2019. We also searched ClinicalTrials.gov and the International Clinical Trials Registry Platform in August 2020 and screened the reference lists of included studies. This is an update of the review first published in 2017. SELECTION CRITERIA All parallel-group and factorial randomised controlled trials (RCTs) with a follow-up of at least 24 weeks were eligible. DATA COLLECTION AND ANALYSIS Two review authors independently reviewed and extracted data. Where data were available, we calculated pooled effect estimates. We used GRADE to assess certainty of evidence and in 'Summary of findings' tables. MAIN RESULTS We included 24 studies with data on 60,997 participants. Eighteen trials randomised participants to alirocumab and six to evolocumab. All participants received background lipid-lowering treatment or lifestyle counselling. Six alirocumab studies used an active treatment comparison group (the remaining used placebo), compared to three evolocumab active comparison trials. Alirocumab compared with placebo decreased the risk of CVD events, with an absolute risk difference (RD) of -2% (odds ratio (OR) 0.87, 95% confidence interval (CI) 0.80 to 0.94; 10 studies, 23,868 participants; high-certainty evidence), decreased the risk of mortality (RD -1%; OR 0.83, 95% CI 0.72 to 0.96; 12 studies, 24,797 participants; high-certainty evidence), and MI (RD -2%; OR 0.86, 95% CI 0.79 to 0.94; 9 studies, 23,352 participants; high-certainty evidence) and for any stroke (RD 0%; OR 0.73, 95% CI 0.58 to 0.91; 8 studies, 22,835 participants; high-certainty evidence). Compared to active treatment the alirocumab effects, for CVD, the RD was 1% (OR 1.37, 95% CI 0.65 to 2.87; 3 studies, 1379 participants; low-certainty evidence); for mortality, RD was -1% (OR 0.51, 95% CI 0.18 to 1.40; 5 studies, 1333 participants; low-certainty evidence); for MI, RD was 1% (OR 1.45, 95% CI 0.64 to 3.28, 5 studies, 1734 participants; low-certainty evidence); and for any stroke, RD was less than 1% (OR 0.85, 95% CI 0.13 to 5.61; 5 studies, 1734 participants; low-certainty evidence). Compared to placebo the evolocumab, for CVD, the RD was -2% (OR 0.84, 95% CI 0.78 to 0.91; 3 studies, 29,432 participants; high-certainty evidence); for mortality, RD was less than 1% (OR 1.04, 95% CI 0.91 to 1.19; 3 studies, 29,432 participants; high-certainty evidence); for MI, RD was -1% (OR 0.72, 95% CI 0.64 to 0.82; 3 studies, 29,432 participants; high-certainty evidence); and for any stroke RD was less than -1% (OR 0.79, 95% CI 0.65 to 0.94; 2 studies, 28,531 participants; high-certainty evidence). Compared to active treatment, the evolocumab effects, for any CVD event RD was less than -1% (OR 0.66, 95% CI 0.14 to 3.04; 1 study, 218 participants; very low-certainty evidence); for all-cause mortality, the RD was less than 1% (OR 0.43, 95% CI 0.14 to 1.30; 3 studies, 5223 participants; very low-certainty evidence); and for MI, RD was less than 1% (OR 0.66, 95% CI 0.23 to 1.85; 3 studies, 5003 participants; very low-certainty evidence). There were insufficient data on any stroke. AUTHORS' CONCLUSIONS The evidence for the clinical endpoint effects of evolocumab and alirocumab were graded as high. There is a strong evidence base to prescribe PCSK9 monoclonal antibodies to people who might not be eligible for other lipid-lowering drugs, or to people who cannot meet their lipid goals on more traditional therapies, which was the main patient population of the available trials. The evidence base of PCSK9 inhibitors compared with active treatment is much weaker (low very- to low-certainty evidence) and it is unclear whether evolocumab or alirocumab might be effectively used as replacement therapies. Related, most of the available studies preferentially enrolled people with either established CVD or at a high risk already, and evidence in low- to medium-risk settings is minimal. Finally, there is very limited evidence on any potential safety issues of both evolocumab and alirocumab. While the current evidence synthesis does not reveal any adverse signals, neither does it provide evidence against such signals. This suggests careful consideration of alternative lipid lowering treatments before prescribing PCSK9 inhibitors.
-
10.
Effect of bempedoic acid on new onset or worsening diabetes: A meta-analysis.
Masson, W, Lobo, M, Lavalle-Cobo, A, Masson, G, Molinero, G
Diabetes research and clinical practice. 2020;:108369
Abstract
INTRODUCTION Bempedoic acid is a new agent that reduces low-density lipoprotein cholesterol. Since inhibits cholesterol synthesis through a different mechanism than statins, the adverse effects related to it may also be different. Therefore, the objective of the present meta-analysis was to evaluate the effect of bempedoic acid on new onset or worsening diabetes. METHODS We performed a meta-analysis including randomized trials of bempedoic acid therapy, reporting new onset or worsening diabetes with a minimum of 4 weeks of follow-up. The fixed-effects model was performed. This meta-analysis was performed according to PRISMA guidelines. RESULTS Five eligible trials of bempedoic acid, including 3629 patients, were identified and considered eligible for the analyses. A total of 2419 subjects were allocated to receive bempedoic acid while 1210 subjects were allocated to the respective control arms. Bempedoic acid therapy is associated with a significant reduction in new onset or worsening diabetes [Odds Ratio: 0.66, 95% confidence interval: 0.48-0.90; I2: 0%]. CONCLUSION This data suggests that the use of bempedoic acid significantly reduces the new onset or worsening diabetes risk. This finding should be confirmed with future studies.