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A dose-response meta-analysis to evaluate the relationship between high-density lipoprotein cholesterol and all-cause and cardiovascular disease mortality.
Liu, L, Han, M, Qie, R, Li, Q, Zhang, X, Zhang, J, Zhan, S, Zhang, L, Xu, Z, Zhang, C, et al
Journal of endocrinological investigation. 2022;(3):551-562
Abstract
PURPOSE Previous studies have not fully described the relationship between high-density lipoprotein cholesterol (HDL-C) and death risks from all cause and cardiovascular disease (CVD). This study quantitatively evaluates HDL-C-mortality associations. METHODS Embase and PubMed databases were searched for relevant articles published up to 1 June 2019. Random-effects models were used to pool relative risks (RRs) and 95% confidence intervals (CIs). We used restricted cubic splines to model the dose-response association. RESULTS We identified 32 prospective cohort studies including 369,904 participants and 33,473 total deaths (9426 CVD deaths). Compared to the lowest HDL-C levels, all cause and CVD mortality risks were reduced by 18% (RR 0.82; 95% CI, 0.73-0.93) and 36% (0.64, 0.46-0.89), respectively, for the highest HDL-C levels. All cause and CVD mortality risks were reduced by 15% (0.85, 0.79-0.92) and 23% (0.77, 0.69-0.87), respectively, with each 1 mmol/L increment of HDL-C. We found evidence of nonlinear and negative dose-response associations of HDL-C with all cause and CVD mortality (Pnonlinearity < 0.001), and the lowest death risks from all cause and CVD were observed at approximately 1.34 and 1.55 mmol/L, respectively. CONCLUSION HDL-C is inversely associated with all cause and CVD mortality risks under approximately 2.05 and 2.33 mmol/L, respectively. Optimal doses require investigation via clinical practice or high-quality research.
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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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Dose-Response Association Between High-Density Lipoprotein Cholesterol and Stroke: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.
Qie, R, Liu, L, Zhang, D, Han, M, Wang, B, Zhao, Y, Liu, D, Guo, C, Li, Q, Zhou, Q, et al
Preventing chronic disease. 2021;:E45
Abstract
INTRODUCTION Studies investigating the effect of high-density lipoprotein cholesterol (HDL-C) on stroke and stroke subtypes have reached inconsistent conclusions. The purpose of our study was to clarify the dose-response association between HDL-C level and risk of total stroke and stroke subtypes by a systematic review and meta-analysis. METHODS We performed a systematic search of PubMed, Embase, and Web of Science databases through July 30, 2020, for prospective cohort studies that reported the HDL-C-stroke association and extracted the estimate that was adjusted for the greatest number of confounding factors. Restricted cubic splines were used to evaluate the linear and nonlinear dose-response associations. RESULTS We included 29 articles, which reported on 62 prospective cohort studies including 900,501 study participants and 25,678 with stroke. The summary relative risk per 1-mmol/L increase in HDL-C level for total stroke was 0.82 (95% CI, 0.76-0.89; I2 = 42.9%; n = 18); ischemic stroke (IS), 0.75 (95% CI, 0.69-0.82; I2 = 50.1%; n = 22); intracerebral hemorrhage (ICH), 1.21 (95% CI, 1.04-1.42; I2 = 33.4%; n = 10); and subarachnoid hemorrhage (SAH), 0.98 (95% CI, 0.96-1.00; I2 = 0%; n = 7). We found a linear inverse association between HDL-C level and risk of total stroke and SAH, a nonlinear inverse association for IS risk, but a linear positive association for ICH risk. The strength and the direction of the effect size estimate for total stroke, IS, ICH, and SAH remained stable for most subgroups. We found no publication bias with Begg's test and Egger's test for the association of HDL-C level with risk of total stroke, IS, and ICH. CONCLUSION A high HDL-C level is associated with reduced risk of total stroke and IS and an increased risk of ICH.
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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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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.
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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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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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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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Association between HDL-C levels and menopause: a meta-analysis.
Li, H, Sun, R, Chen, Q, Guo, Q, Wang, J, Lu, L, Zhang, Y
Hormones (Athens, Greece). 2021;(1):49-59
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Abstract
PURPOSE Menopause modifies women's lipid profiles. However, the fact that it is still unclear whether high-density lipoprotein-cholesterol (HDL-C) levels decrease in postmenopausal women necessitated a systematic review and meta-analysis. METHODS The PubMed, EMBASE, Cochrane Library, and Web of Science databases were searched and 498 articles published between 1987 and 2020 were retrieved. Studies reporting HDL-C, low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC), and triglyceride (TG) levels in both postmenopausal and premenopausal populations were included. The quality of the included studies was assessed using the Cross-Sectional/Prevalence Study Quality tool. The standard mean difference (SMD) and 95% confidence interval (CI) were estimated using random effects models. A meta-regression analysis and subgroup analysis were performed to identify potential modifiers. Egger's test and funnel plots were constructed to evaluate publication biases. RESULTS Lipid profiles from 18 cross-sectional studies and two cohort studies including 5652 postmenopausal women and 7825 premenopausal women were meta-analyzed. HDL-C levels were not significantly different between the postmenopausal and premenopausal women (SMD = - 0.053, 95% CI - 0.171 to 0.066, p = 0.383) and were not affected by country, publication year, study quality in the meta-regression analysis, or significant publication bias. Higher LDL-C, TC, and TG levels were detected in postmenopausal women than in premenopausal controls. CONCLUSION Unlike increased LDL-C, TC, and TG levels, HDL-C levels in pre- and postmenopausal women were not different in this first meta-analysis of lipid profiles in premenopausal and postmenopausal women. Prospective studies with large populations examining HDL-C levels and functions in women with different menopausal statuses are essential in the future. TRIAL REGISTRATION NUMBER None.
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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.