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The Science of the Total Environment Dec 2022Perfluoroalkyl substances (PFAS) are widely used synthetic aliphatic compounds. This systematic review aims to assess PFAS associations with low-density lipoprotein... (Review)
Review
BACKGROUND
Perfluoroalkyl substances (PFAS) are widely used synthetic aliphatic compounds. This systematic review aims to assess PFAS associations with low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), total cholesterol (TC) and total triglyceride (TG) concentrations in human populations.
METHOD
We systematically searched four online databases, PubMed, Scopus, Embase, and Cochrane Library for relevant peer-reviewed English language articles published until July 2021. Additional relevant articles identified were also included in the search results. We categorised populations into adults (≥18 years old) and children. Primary findings were the associations between PFAS concentrations and LDL, HDL, TC, and TG concentrations in the serum, plasma, or whole blood; secondary findings were the associations between PFAS concentrations and the odds of lipid-related health outcomes. Quantitative synthesis was done by vote counting of the effect directions between concentrations of PFAS and lipids/health outcomes, repeated on articles with sample size >1000. Sign tests were performed to assess the statistical significance of the differences between positive and negative associations. Sensitivity analysis was performed by separating out articles with populations having high concentrations of perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS). Quality was assessed with the STROBE checklist and NHBLI Study Quality Assessment Tool.
RESULTS
A total of 58 articles were included for review. There was evidence that PFAS exposure is associated with higher concentrations of LDL, HDL, and TC, particularly for PFOA-LDL, PFOA-TC, PFOS-TC, and PFNA-LDL. Associations between PFAS and TG tended to be negative, especially for perfluoroundecanoic acid (PFUnDA). Associations between PFAS concentration and the odds of secondary outcomes generally supported a positive association between PFAS and cholesterol concentrations.
CONCLUSION
We found evidence of associations between the concentrations of some PFAS-lipid pairs in human populations. Future research should be conducted on the less well-studied PFAS to explore their effects on human health and in regions where such studies are currently lacking. (300 words).
Topics: Adolescent; Adult; Alkanesulfonic Acids; Caprylates; Child; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Environmental Pollutants; Epidemiologic Studies; Fluorocarbons; Humans; Lipids; Triglycerides
PubMed: 35973530
DOI: 10.1016/j.scitotenv.2022.158036 -
International Journal of Molecular... May 2023Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with unknown etiology. Many metabolic alterations occur during ALS progress and can be used as a... (Meta-Analysis)
Meta-Analysis Review
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with unknown etiology. Many metabolic alterations occur during ALS progress and can be used as a method of pre-diagnostic and early diagnosis. Dyslipidemia is one of the physiological changes observed in numerous ALS patients. The aim of this study is to analyze the possible relationship between the rate of disease progression (functional rating scale (ALS-FRS)) and the plasma lipid levels at the early stage of ALS. A systematic review was carried out in July 2022. The search equation was "Triglycerides AND amyotrophic lateral sclerosis" and its variants. Four meta-analyses were performed. Four studies were included in the meta-analysis. No significant differences were observed between the lipid levels (total cholesterol, triglycerides, HDL cholesterol, and LDL cholesterol) and the ALS-FRS score at the onset of the disease. Although the number of studies included in this research was low, the results of this meta-analytic study suggest that there is no clear relationship between the symptoms observed in ALS patients and the plasma lipid levels. An increase in research, as well as an expansion of the geographical area, would be of interest.
Topics: Humans; Amyotrophic Lateral Sclerosis; Neurodegenerative Diseases; Triglycerides; Cholesterol, HDL; Cholesterol, LDL
PubMed: 37240018
DOI: 10.3390/ijms24108675 -
Frontiers in Endocrinology 2022(1) To establish the prevalence of sleep disorders in women with PCOS. (2) To establish the association between sleep disturbance and cardiovascular risk factors in... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
(1) To establish the prevalence of sleep disorders in women with PCOS. (2) To establish the association between sleep disturbance and cardiovascular risk factors in women with PCOS.
METHODS
The electronic databases PubMed and EMBASE were searched for observational studies of individuals with PCOS published in English from inception to 21 October 2021. The dichotomous outcome measure was presented as odds ratio (OR) and 95% confidence interval (CI). The mean difference (MD) in continuous variables was expressed for each study.
RESULTS
A total of 18 articles were included in this meta-analysis, with a total of 16,152 participants from nine different countries. Women with PCOS had a high prevalence of sleep disturbance (OR = 6.22; 95% CI: 2.77, 13.97; < 0.001), higher PSQI scores (MD = 2.10; 95% CI: 0.29, 3.90; = 0.02), and shorter duration of sleep (MD = -15.65 min; 95% CI: -27.18, -4.13; = 0.008). We found that body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), low-density lipoprotein cholesterol (LDL-c), fasting glucose, 2-h glucose, and waist circumference (WC) levels were significantly higher and high-density lipoprotein cholesterol (HDL-c) was significantly lower in PCOS with sleep disturbance than in PCOS without sleep disturbance.
CONCLUSIONS
The current study shows a high prevalence of sleep disturbance in women with PCOS and provides evidence of an association between cardiovascular risk factors and sleep disturbance among this population. Increased attention should be paid to sleep management in clinical guidelines for PCOS.
UNLABELLED
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022298040.
Topics: Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Female; Glucose; Heart Disease Risk Factors; Humans; Polycystic Ovary Syndrome; Risk Factors; Sleep Quality; Sleep Wake Disorders
PubMed: 36176474
DOI: 10.3389/fendo.2022.971604 -
Expert Opinion on Drug Safety Feb 2024Dyslipidaemia is a crucial risk factor for cardiovascular morbidity and mortality. A short interfering RNA called inclisiran diminishes circulating levels of PCSK9 and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dyslipidaemia is a crucial risk factor for cardiovascular morbidity and mortality. A short interfering RNA called inclisiran diminishes circulating levels of PCSK9 and LDL-C by hindering PCSK9 translation in the liver.
METHODS
RCTs were electronically searched on PubMed, Cochrane Central, and Clinicaltrials.gov to assess the safety and efficacy of inclisiran. Cochrane Review Manager 5 was used to conduct the pooled analysis. Risk of bias was assessed and GRADE pro-GDT was utilized, respectively, to estimate the methodological quality and overall quality of evidence.
RESULTS
Of 218 records screened, four studies were included with 2203 participants in inclisiran and 1949 participants in the placebo group. Inclisiran was related to non-significant elevated risk of total adverse events[RR = 1.05(0.98,1.12), = 0.16; I = 53%], non-serious adverse events[RR = 1.09(0.97,1.22), = 0.15;I = 61%] and all-cause mortality[RR = 1.01(0.60,1.70), = 0.97;I = 0%] whereas a lower risk of serious adverse events[RR = 0.94(0.70,1.25), = 0.67;I = 73%], cardiac disorders [RR = 0.87(0.66,1.15), = 0.33;I = 42%] and Major adverse cardiovascular events(MACE)[RR = 0.79(0.62,1.00), = 0.05; I = 0%] as compared to placebo. Inclisiran was also linked to a substantial decline in the percentage of LDL-C, PCSK9, total cholesterol, and Apo B.
CONCLUSION
The pooled analysis of the existing evidence shows that inclisiran showed reduced risk of MACE along with excellent efficacy in managing dyslipidemia.
CLINICAL TRIAL REGISTRATION
www.clinicaltrials.gov identifiers are NCT03399370, NCT03397121, NCT03400800, and NCT02597127.
Topics: Humans; Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol, LDL; Dyslipidemias; Hyperlipidemias; Proprotein Convertase 9; RNA, Small Interfering
PubMed: 38063346
DOI: 10.1080/14740338.2023.2293201 -
Reviews in Endocrine & Metabolic... Oct 2022Vitamin D deficiency is associated with an increase in the occurrence of cardiometabolic events, but the evidence of this relationship in adolescence is still limited.... (Meta-Analysis)
Meta-Analysis Review
Vitamin D deficiency is associated with an increase in the occurrence of cardiometabolic events, but the evidence of this relationship in adolescence is still limited. Thus, we analyzed the association between vitamin D deficiency and cardiometabolic risk factors in adolescents. Observational studies were searching in PubMed/Medline, Embase, Scopus, Web of Science, Science Direct, Lilacs, and Google Scholar database. Random effects models were used to summarize standardized mean differences for as a summary measure. The certainty of the evidence was verified using the Cochrane recommendations. A total of 7537 studies were identified, of which 32 were included in the systematic review and 24 in the meta-analysis.Vitamin D deficiency was associated with increased systolic pressure (SMD = 0.22; 95%CI = 0.10; 0.34), diastolic pressure (SMD = 0.23; 95%CI = 0.10; 0.35), glycemia (SMD = 0.13; 95%CI = 0.05; 0.12), and insulin (SMD = 0.50; 95%CI = 0.15; 0.84), an increase in the HOMA index (SMD = 0.48; 95%CI = 0.36; 0.60), high triglyceride values (SMD = 0.30; 95%CI = 0.11; 0.49), and reduced HDL concentrations (SMD= -0.25; 95%CI = -0.46; -0.04). No statistically significant association was observed for glycated hemoglobin, LDL cholesterol, and total cholesterol. Most of the studies presented low and moderate risks of bias, respectively. The certainty of the evidence was very low for all the outcomes analyzed. Vitamin D deficiency was associated with increased exposure to the factors linked to the occurrence of cardiometabolic diseases in adolescents. Systematic Review Registration: PROSPERO (record number 42,018,086,298).
Topics: Adolescent; Cardiometabolic Risk Factors; Cardiovascular Diseases; Cholesterol, LDL; Glycated Hemoglobin; Humans; Insulin; Risk Factors; Triglycerides; Vitamin D; Vitamin D Deficiency
PubMed: 35713809
DOI: 10.1007/s11154-022-09736-7 -
Virology Journal Aug 2022Lipids play a central role in the virus life cycle and are a crucial target to develop antiviral therapeutics. Importantly, among the other lipoproteins, the 'good...
BACKGROUND
Lipids play a central role in the virus life cycle and are a crucial target to develop antiviral therapeutics. Importantly, among the other lipoproteins, the 'good cholesterol' high-density lipoprotein (HDL) has been widely studied for its role in not only cardiovascular but several infectious diseases as well. Studies have suggested a role of serum lipids and lipoproteins including HDL, total cholesterol (TC), triglycerides (TG), and low-density lipoproteins (LDL) in several viral infections including COVID-19. This disease is currently a major public health problem and there is a need to explore the role of these host lipids/lipoproteins in virus pathogenesis.
METHODOLOGY
A total of 75 retrospective COVID-19 positive serum samples and 10 COVID-19 negative controls were studied for their lipid profiles including TC, HDL, LDL, and very-low-density lipoproteins (VLDL), and TG.
RESULTS
Systematic literature search on dyslipidemia status in India shows that low HDL is the most common dyslipidemia. In this cohort, 65% (49) of COVID-19 patients had severely low HDL levels whereas 35% (26) had moderately low HDL and none had normal HDL levels. On the other hand, ~ 96% of samples had normal TC (72) and LDL (72) levels. VLDL and TG levels were also variable. In the controls, 100% of samples had moderately low HDL but none severely low HDL levels.
CONCLUSION
HDL likely plays a crucial role in COVID-19 infection and outcomes. The causal relationships between HDL levels and COVID-19 need to be studied extensively for an understanding of disease pathogenesis and management.
Topics: COVID-19; Cholesterol; Dyslipidemias; Humans; Lipoproteins; Lipoproteins, HDL; Lipoproteins, VLDL; Retrospective Studies; Triglycerides
PubMed: 35999545
DOI: 10.1186/s12985-022-01865-4 -
Optometry and Vision Science : Official... Mar 2023This study aimed to use meta-analysis to estimate the association between dyslipidemia and meibomian gland dysfunction. (Meta-Analysis)
Meta-Analysis
PURPOSE
This study aimed to use meta-analysis to estimate the association between dyslipidemia and meibomian gland dysfunction.
METHODS
The following databases were searched: PubMed, Google Scholar, and Scopus. Case-control and cohort studies assessing the association between dyslipidemia and meibomian gland dysfunction were included. The association was assessed using odds ratios. Heterogeneity between studies was assessed with the χ2 statistic and degree of inconsistency. The quality of studies was assessed using the Newcastle-Ottawa Scale. The systematic review was registered on PROSPERO (ID: CRD42022347982).
RESULTS
The systematic review included three case-control and two cohort studies. The odds of hypercholesterolemia and hypertriglyceridemia in meibomian gland dysfunction were 5.45 (95% confidence interval [CI], 1.65 to 17.95) and 3.28 (95% CI, 1.25 to 8.62), respectively. The odds of elevated serum low-density lipoprotein and reduced high-density lipoprotein in meibomian gland dysfunction were 2.72 (95% CI, 1.24 to 5.98) and 1.15 (95% CI, 0.74 to 1.79), respectively. The current study's limitation is that the effects of sex, age, and meibomian gland dysfunction severity on the association between dyslipidemia and meibomian gland dysfunction were not assessed.
CONCLUSIONS
The current study suggests a significant association between dyslipidemia and meibomian gland dysfunction. This finding suggests that meibomian gland dysfunction diagnosis may call for dyslipidemia screening.
Topics: Humans; Meibomian Gland Dysfunction; Meibomian Glands; Eyelid Diseases; Dyslipidemias; Cohort Studies; Tears
PubMed: 36722777
DOI: 10.1097/OPX.0000000000001994 -
European Journal of Clinical... Nov 2022Patients with severe hypertriglyceridaemia (sHTG) are often refractory to lipid-lowering therapy. Apolipoprotein (Apo) CIII inhibition could be promising to treat... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients with severe hypertriglyceridaemia (sHTG) are often refractory to lipid-lowering therapy. Apolipoprotein (Apo) CIII inhibition could be promising to treat subjects with sHTG. The antisense oligonucleotide against APOC3 mRNA volanesorsen was recently introduced to treat sHTG. We performed a systematic review and meta-analysis of RCTs on the efficacy and safety of volanesorsen as compared to placebo treatment in patients with severe HTG.
METHODS
Studies were systematically searched in the PubMed, Web of Science and Scopus databases according to PRISMA guidelines. The last search was performed on 7 February 2022.
RESULTS
Four studies showed significant reduction in TG after 3 months of treatment with volanesorsen as compared with placebo (MD: -73.9%; 95%CI: -93.5%, -54.2; p < .001 I = 89.05%; p < .001); VLDL-C level (MD: -71.0%; 95%CI: -76.6%, -65.4%; p < .001 I = 94.1%; p < .001); Apo-B48 level (MD: -69.03%; 95%CI: -98.59.4%, -39.47%; p < .001, I = 93.51%; p < .001) and Apo-CIII level (MD: -80.0%; 95%CI: -97.5%, -62.5; p < .001 I = 94.1%; p < .001) with an increase in HDL-C level (MD: +45.92%, 95%CI: +37.24%, +54.60%; p < .001 I = 94.34%; p < .001) and in LDL-C level (MD: +68.6%, 95%CI: +7.0%, +130.1%; p < .001 I = 96.18%; p < .001) without a significant elevation of Apo-B100 level (MD: +4.58%, 95%CI: -5.64%, +14.79%; p = .380 I = 95.09%; p < .001) in 139 volanesorsen patients as compared to 100 placebo-treated controls. Most of adverse events were mild and related to local injection site reactions.
CONCLUSIONS
In patients with severe HTG, volanesorsen is associated with a significant reduction in TG, VLDL-C, Apo-B48 and non-HDL-C and increment of HDL-C as compared to placebo. Documented efficacy is accompanied by an acceptable safety profile.
Topics: Apolipoprotein B-48; Apolipoprotein C-III; Cholesterol, LDL; Humans; Hyperlipidemias; Hypertriglyceridemia; Oligonucleotides; Oligonucleotides, Antisense; RNA, Messenger; Randomized Controlled Trials as Topic; Triglycerides
PubMed: 35851450
DOI: 10.1111/eci.13841 -
Clinics and Research in Hepatology and... Dec 2023Obeticholic acid (OCA) is the second-line therapy for primary biliary cholangitis (PBC), as well as an attractive candidate as a treatment for metabolic... (Meta-Analysis)
Meta-Analysis Review
Effect on lipid profile and clinical outcomes of obeticholic acid for the treatment of primary biliary cholangitis and metabolic dysfunction-associated steatohepatitis: A systematic review and meta-analysis.
Obeticholic acid (OCA) is the second-line therapy for primary biliary cholangitis (PBC), as well as an attractive candidate as a treatment for metabolic dysfunction-associated steatohepatitis (MASH). This meta-analysis aims to assess the impact of OCA on lipid profiles and clinical outcomes in patients with PBC and MASH. A comprehensive systematic review and meta-analysis of randomized controlled trials (RCTs) from five major databases were conducted. Changes in lipid profiles from baseline were compared between groups receiving placebo and OCA. Efficacy outcomes were evaluated separately for PBC and MASH trials, while safety outcomes included pruritus, gastrointestinal disturbances, and headache. OCA treatment exhibited a significant increase in low-density lipoprotein cholesterol (LDL-C) (standardized mean difference [SMD] = 0.39; 95 % confidence interval [CI] = 0.15 to 0.63) and a decrease in high-density lipoprotein cholesterol (HDL-C) (SMD = -0.80; 95 % CI = -1.13 to -0.47) in both PBC and MASH patients compared to placebo. OCA demonstrated superior efficacy to placebo in treating PBC and MASH, evident in both primary and secondary outcomes. The incidence of pruritus was significantly higher with OCA compared to placebo (risk ratio = 1.78, 95 % CI = 1.42 to 2.25). OCA is more efficacious than a placebo in the treatment of PBC and MASH. However, caution is needed given the association of OCA use with a significant increase in LDL-C levels and a decrease in HDL-C levels among patients with these conditions.
Topics: Humans; Liver Cirrhosis, Biliary; Cholesterol, LDL; Fatty Liver; Pruritus
PubMed: 37884091
DOI: 10.1016/j.clinre.2023.102227 -
Journal of Stroke and Cerebrovascular... Apr 2024Investigate the efficacy and safety of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) on stroke prevention. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Investigate the efficacy and safety of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) on stroke prevention.
BACKGROUND
PCSK9i reduce low-density lipoprotein cholesterol (LDL-C) and lipoprotein a (LpA) levels. Their efficacy in reducing the risk of major cardiovascular events has been shown in multiple randomized clinical trials (RCT). However, clinical equipoise remains on the magnitude and mechanisms by which PCSK9i decrease the risk of stroke.
METHODS
We performed a systematic search of biomedical databases from inception to January 15, 2024, to identify RCTs that investigated the efficacy of PCSK9i versus placebo for major cardiovascular event prevention. The primary outcome was total stroke. The safety outcome was the risk of adverse neurological events, as defined by each trial. Effect size was represented by risk ratio (RR), and analysis was done using random-effects meta-analysis. Heterogeneity was assessed by I and Cochrane Q statistics. Meta-regression analyses were performed to assess the association between LDL-C and LpA reduction and stroke risk.
RESULTS
Overall, 20 studies with 93,093 patients were included. The quality of the evidence was moderate and heterogeneity for all comparisons was low (I < 25 %). The mean age was 60.1 years for the PCSK9i group and 59.6 years for the placebo group, with a mean follow-up time of 60.1 weeks. PCSK9i reduced the LDL-C levels by 11 % and LpA levels by 8 %. PCSK9i were associated with a significant reduction in stroke risk (RR 0.75, 95 % CI 0.66-0.86, I = 0 %), without an increase in mortality (RR 0.97, 95 % CI 0.87-1.08, I = 0 %). The risk of adverse neurological events was similar between groups (RR 0.99, 95 % CI 0.84-1.18, I = 11 %). In meta-regression analyses, the stroke risk was not associated with the magnitude of the effect of PCSK9i on LDL-C (LDL C β = -0.01, 95 % CI = -0.03-0.02) and LpA (β = -0.01, 95 % CI = -0.06-0.04) levels.
CONCLUSIONS
PCSK9i significantly reduced the stroke risk, without increasing mortality or the risk of adverse neurological events. Our findings also suggest that the beneficial effect of PCSK9i on stroke risk is mediated by LDL-C- and LpA-independent mechanisms.
Topics: Humans; Middle Aged; PCSK9 Inhibitors; Cholesterol, LDL; Antibodies, Monoclonal, Humanized; Stroke; Anticholesteremic Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cardiovascular Diseases; Proprotein Convertase 9
PubMed: 38336118
DOI: 10.1016/j.jstrokecerebrovasdis.2024.107633