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Scientific Reports Nov 2015Familial hypercholesterolemia (FH) is a common and serious dominant genetic disease, and its main pathogenic gene is the low-density lipoprotein receptor (LDLR) gene.... (Meta-Analysis)
Meta-Analysis Review
Familial hypercholesterolemia (FH) is a common and serious dominant genetic disease, and its main pathogenic gene is the low-density lipoprotein receptor (LDLR) gene. This study aimed to perform a systematic review of LDLR mutations in China. Using PubMed, Embase, Wanfang (Chinese), the Chinese National Knowledge Infrastructure (Chinese), and the Chinese Biological and Medical database (Chinese), public data were limited to December 2014. The Medical Subject Headings terms and the following key words were used: "familial hypercholesterolemia", "Chinese", "China", "Hong Kong", and "Taiwan". A total of 74 studies including 295 probands with 131 LDLR mutations were identified. Most of the mutations were located in exon 4 of LDLR and approximately 60% of the mutations were missense mutations. Thirty new mutations that were not recorded in the LDLR databases were found. In silico analysis revealed that most of the mutations were pathogenic. The primary LDLR mutations were C308Y, H562Y, and A606T, and all of the mutations had functional significance. Prevalence data suggest that there are nearly 3.8 million FH patients in China, although reported numbers are much smaller, suggesting that FH is widely misunderstood. This systematic review provides information that is specific to China for inclusion in the international FH database.
Topics: China; Computer Simulation; Databases, Genetic; Hong Kong; Humans; Hyperlipoproteinemia Type II; Lipids; Mutation; Mutation Rate; Phenotype; Receptors, LDL; Taiwan
PubMed: 26608663
DOI: 10.1038/srep17272 -
The Cochrane Database of Systematic... Jan 2021Statins are one of the most prescribed classes of drugs worldwide. Atorvastatin, the most prescribed statin, is currently used to treat conditions such as... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Statins are one of the most prescribed classes of drugs worldwide. Atorvastatin, the most prescribed statin, is currently used to treat conditions such as hypercholesterolaemia and dyslipidaemia. By reducing the level of cholesterol, which is the precursor of the steroidogenesis pathway, atorvastatin may cause a reduction in levels of testosterone and other androgens. Testosterone and other androgens play important roles in biological functions. A potential reduction in androgen levels, caused by atorvastatin might cause negative effects in most settings. In contrast, in the setting of polycystic ovary syndrome (PCOS), reducing excessive levels of androgens with atorvastatin could be beneficial.
OBJECTIVES
Primary objective To quantify the magnitude of the effect of atorvastatin on total testosterone in both males and females, compared to placebo or no treatment. Secondary objectives To quantify the magnitude of the effects of atorvastatin on free testosterone, sex hormone binding globin (SHBG), androstenedione, dehydroepiandrosterone sulphate (DHEAS) concentrations, free androgen index (FAI), and withdrawal due to adverse effects (WDAEs) in both males and females, compared to placebo or no treatment.
SEARCH METHODS
The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials (RCTs) up to 9 November 2020: the Cochrane Hypertension Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE; Embase; ;two international trials registries, and the websites of the US Food and Drug Administration, the European Patent Office and the Pfizer pharmaceutical corporation. These searches had no language restrictions. We also contacted authors of relevant articles regarding further published and unpublished work.
SELECTION CRITERIA
RCTs of daily atorvastatin for at least three weeks, compared with placebo or no treatment, and assessing change in testosterone levels in males or females.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the citations, extracted the data and assessed the risk of bias of the included studies. We used the mean difference (MD) with associated 95% confidence intervals (CI) to report the effect size of continuous outcomes,and the risk ratio (RR) to report effect sizes of the sole dichotomous outcome (WDAEs). We used a fixed-effect meta-analytic model to combine effect estimates across studies, and risk ratio to report effect size of the dichotomous outcomes. We used GRADE to assess the certainty of the evidence.
MAIN RESULTS
We included six RCTs involving 265 participants who completed the study and their data was reported. Participants in two of the studies were male with normal lipid profile or mild dyslipidaemia (N = 140); the mean age of participants was 68 years. Participants in four of the studies were female with PCOS (N = 125); the mean age of participants was 32 years. We found no significant difference in testosterone levels in males between atorvastatin and placebo, MD -0.20 nmol/L (95% CI -0.77 to 0.37). In females, atorvastatin may reduce total testosterone by -0.27 nmol/L (95% CI -0.50 to -0.04), FAI by -2.59 nmol/L (95% CI -3.62 to -1.57), androstenedione by -1.37 nmol/L (95% CI -2.26 to -0.49), and DHEAS by -0.63 μmol/l (95% CI -1.12 to -0.15). Furthermore, compared to placebo, atorvastatin increased SHBG concentrations in females by 3.11 nmol/L (95% CI 0.23 to 5.99). We identified no studies in healthy females (i.e. females with normal testosterone levels) or children (under age 18). Importantly, no study reported on free testosterone levels.
AUTHORS' CONCLUSIONS
We found no significant difference between atorvastatin and placebo on the levels of total testosterone in males. In females with PCOS, atorvastatin lowered the total testosterone, FAI, androstenedione, and DHEAS. The certainty of evidence ranged from low to very low for both comparisons. More RCTs studying the effect of atorvastatin on testosterone are needed.
Topics: Aged; Androgens; Androstenedione; Atorvastatin; Bias; Dehydroepiandrosterone Sulfate; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Placebos; Polycystic Ovary Syndrome; Randomized Controlled Trials as Topic; Sex Factors; Sex Hormone-Binding Globulin; Testosterone
PubMed: 33482034
DOI: 10.1002/14651858.CD013211.pub2 -
The Cochrane Database of Systematic... Nov 2019Familial hypercholesterolemia is one of the most common inherited metabolic diseases and is an autosomal dominant disorder meaning heterozygotes, or carriers, are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Familial hypercholesterolemia is one of the most common inherited metabolic diseases and is an autosomal dominant disorder meaning heterozygotes, or carriers, are affected. Those who are homozygous have severe disease. The average worldwide prevalence of heterozygous familial hypercholesterolemia is at least 1 in 500, although recent genetic epidemiological data from Denmark and next generation sequencing data suggest the frequency may be closer to 1 in 250. Diagnosis of familial hypercholesterolemia in children is based on elevated total cholesterol and low-density lipoprotein cholesterol levels or DNA-based analysis, or both. Coronary atherosclerosis has been detected in men with heterozygous familial hypercholesterolemia as young as 17 years old and in women with heterozygous familial hypercholesterolemia at 25 years old. Since the clinical complications of atherosclerosis occur prematurely, especially in men, lifelong treatment, started in childhood, is needed to reduce the risk of cardiovascular disease. In children with the disease, diet was the cornerstone of treatment but the addition of lipid-lowering medications has resulted in a significant improvement in treatment. Anion exchange resins, such as cholestyramine and colestipol, were found to be effective, but they are poorly tolerated. Since the 1990s studies carried out on children aged 6 to 17 years with heterozygous familial hypercholesterolemia have demonstrated significant reductions in their serum total and low-density lipoprotein cholesterol levels. While statins seem to be safe and well-tolerated in children, their long-term safety in this age group is not firmly established. This is an update of a previously published version of this Cochane Review.
OBJECTIVES
To assess the effectiveness and safety of statins in children with heterozygous familial hypercholesterolemia.
SEARCH METHODS
Relevant studies were identified from the Group's Inborn Errors and Metabolism Trials Register and Medline. Date of most recent search: 04 November 2019.
SELECTION CRITERIA
Randomized and controlled clinical studies including participants up to 18 years old, comparing a statin to placebo or to diet alone.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed studies for inclusion and extracted data.
MAIN RESULTS
We found 26 potentially eligible studies, of which we included nine randomized placebo-controlled studies (1177 participants). In general, the intervention and follow-up time was short (median 24 weeks; range from six weeks to two years). Statins reduced the mean low-density lipoprotein cholesterol concentration at all time points (high-quality evidence). There may be little or no difference in liver function (serum aspartate and alanine aminotransferase, as well as creatinine kinase concentrations) between treated and placebo groups at any time point (low-quality evidence). There may be little or no difference in myopathy (as measured in change in creatinine levels) (low-quality evidence) or clinical adverse events (moderate-quality evidence) with statins compared to placebo. One study on simvastatin showed that this may slightly improve flow-mediated dilatation of the brachial artery (low-quality evidence), and on pravastatin for two years may have induced a regression in carotid intima media thickness (low-quality evidence). No studies reported rhabdomyolysis (degeneration of skeletal muscle tissue) or death due to rhabdomyolysis, quality of life or compliance to study medication.
AUTHORS' CONCLUSIONS
Statin treatment is an effective lipid-lowering therapy in children with familial hypercholesterolemia. Few or no safety issues were identified. Statin treatment seems to be safe in the short term, but long-term safety remains unknown. Children treated with statins should be carefully monitored and followed up by their pediatricians and their care transferred to an adult lipidologist once they reach 18 years of age. Large long-term randomized controlled trials are needed to establish the long-term safety issues of statins.
Topics: Adolescent; Adult; Child; Cholesterol, LDL; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipoproteinemia Type II; Male; Randomized Controlled Trials as Topic; Young Adult
PubMed: 31696945
DOI: 10.1002/14651858.CD006401.pub5 -
Journal of Comparative Effectiveness... Apr 2023There is a need to understand the management status of hypertension, dyslipidemia/hypercholesterolemia, and diabetes mellitus in the Asia-Pacific region (APAC). We... (Meta-Analysis)
Meta-Analysis
There is a need to understand the management status of hypertension, dyslipidemia/hypercholesterolemia, and diabetes mellitus in the Asia-Pacific region (APAC). We conducted a systematic literature review and meta-analysis to summarize the awareness, treatment, and/or control rates of these risk factors in adults across 11 APAC countries/regions. We included 138 studies. Individuals with dyslipidemia had the lowest pooled rates compared with those with other risk factors. Levels of awareness with diabetes mellitus, hypertension, and hypercholesterolemia were comparable. Individuals with hypercholesterolemia had a statistically lower pooled treatment rate but a higher pooled control rate than those with hypertension. The management of hypertension, dyslipidemia, and diabetes mellitus was suboptimal in these 11 countries/regions.
Topics: Adult; Humans; Asia; Cardiovascular Diseases; Diabetes Mellitus; Dyslipidemias; Health Knowledge, Attitudes, Practice; Heart Disease Risk Factors; Hypercholesterolemia; Hypertension; Prevalence; Risk Factors
PubMed: 36861459
DOI: 10.57264/cer-2022-0085 -
The Cochrane Database of Systematic... May 2016Withdrawal: The editors of Cochrane Heart consider this title as low priority for the current portfolio of the Heart Group and therefore this title is not open to a new... (Meta-Analysis)
Meta-Analysis Review
Withdrawal: The editors of Cochrane Heart consider this title as low priority for the current portfolio of the Heart Group and therefore this title is not open to a new author team. The editorial group responsible for this previously published document have withdrawn it from publication.
Topics: Cholesterol; Cynara scolymus; Humans; Hypercholesterolemia; Phytotherapy; Plant Extracts; Plant Leaves; Randomized Controlled Trials as Topic
PubMed: 27195440
DOI: 10.1002/14651858.CD003335.pub4 -
Journal of Lipid Research Oct 2010Genetic variation at the ABCG5/G8 locus has been associated with markers of cholesterol homeostasis. As data originate from small-scale studies, we performed a... (Meta-Analysis)
Meta-Analysis Review
Genetic variation at the ABCG5/G8 locus has been associated with markers of cholesterol homeostasis. As data originate from small-scale studies, we performed a meta-analysis to study these associations in a large dataset. We first investigated associations between five common ABCG5/G8 polymorphisms (p.Q604E, p.D19H, p.Y54C, p.T400K, and p.A632V) and plasma sterol levels in 245 hypercholesterolaemic individuals. No significant associations were found. Subsequently, our data were pooled into a meta-analysis that comprised 3,364 subjects from 16 studies (weighted mean age, 46.7 ± 10.5 years; BMI, 23.9 ± 3.5 kg/m(2)). Presence of the minor 632V allele correlated with reduced LDL-C concentrations (n = 367) compared with homozygosity for the 632A variant [n = 614; -0.11 mmol/l (95% CI, range: -0.20 to -0.02 mmol/l); P = 0.01]. The remaining polymorphisms were not associated with plasma lipid levels. Carriers of the 19H allele exhibited lower campesterol/TC (n = 83; P < 0.001), sitosterol/TC (P < 0.00001), and cholestanol/TC (P < 0.00001), and increased lathosterol/TC ratios (P = 0.001) compared with homozygous 19D allele carriers (n = 591). The ABCG8 632V variant was associated with a clinically irrelevant LDL-C reduction, whereas the 19H allele correlated with decreased cholesterol absorption and increased synthesis without affecting the lipid profile. Hence, associations between frequently studied missense ABCG5/G8 polymorphisms and markers of cholesterol homeostasis are modest at best.
Topics: ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; ATP-Binding Cassette Transporters; Adult; Cholesterol; Genotype; Humans; Hypercholesterolemia; Lipoproteins; Middle Aged; Polymorphism, Genetic
PubMed: 20581104
DOI: 10.1194/jlr.M008128 -
Diabetes & Metabolic Syndrome 2021Identify the prevalence, risk factors and outcomes of lower extremity ischemic complications.
AIMS
Identify the prevalence, risk factors and outcomes of lower extremity ischemic complications.
METHODS
A systematic review was conducted by searching PubMed and SCOPUS databases for SARS-CoV-2, COVID-19 and peripheral arterial complications.
RESULTS
Overall 476 articles were retrieved and 31 articles describing 133 patients were included. The mean age was 65.4 years. Pain and gangrene were the most common presentation. Hypertension (51.3%), diabetes (31.9%) and hypercholesterolemia (17.6%) were associated co-morbidities. Overall, 30.1% of patients died and amputation was required in 11.8% patients.
CONCLUSIONS
COVID-19 patients with diabetes or hypertension are susceptible for lower limb complications and require therapeutic anti-coagulation.
Topics: Aged; Amputation, Surgical; COVID-19; Comorbidity; Diabetes Mellitus; Diabetic Angiopathies; Female; Gangrene; Humans; Hypertension; Lower Extremity; Male; Middle Aged; Peripheral Arterial Disease; Prevalence; Prognosis; Risk Factors; SARS-CoV-2
PubMed: 34303918
DOI: 10.1016/j.dsx.2021.102204 -
Obesity Facts 2013The aim of this study was to systematically describe the gender and ethnic differences regarding the prevalence of general/central obesity and cardiovascular disease... (Meta-Analysis)
Meta-Analysis Review
AIM
The aim of this study was to systematically describe the gender and ethnic differences regarding the prevalence of general/central obesity and cardiovascular disease (CVD) risk factors such as diabetes mellitus type 2, hypertension, and hypercholesterolemia among the indigenous and immigrant Pakistani communities.
METHODS
The search engine used was PubMed, supplemented with regional data from the Medical Institutes of Pakistan. The focus was on the adult Pakistani population (18 years and older).
RESULTS
We found only 7 studies among the immigrant Pakistani community and 24 studies among the indigenous Pakistani community. The studies had limitations such as low participation rates and use of self-reported data. There is a higher prevalence of central obesity among women (42.2%) than among men (14.7%) (National Health Survey of Pakistan). Certain ethnicities such as Muhajir and Baluchis showed a higher prevalence of cardiovascular risk factors when compared to other ethnicities in the indigenous Pakistani population. The results also indicate that the prevalence of obesity is 10-20% higher among the immigrant Pakistanis than in the indigenous Pakistanis.
CONCLUSION
The relatively high prevalence of obesity and associated CVD risk factors (especially in women) among both indigenous and immigrant Pakistani populations require the attention of the healthcare professionals and policy makers, both inside and outside Pakistan.
Topics: Asian People; Cardiovascular Diseases; Emigrants and Immigrants; Emigration and Immigration; Ethnicity; Humans; Norway; Obesity, Abdominal; Pakistan; Risk Factors; Sex Factors; United Kingdom
PubMed: 24296750
DOI: 10.1159/000357176 -
European Journal of Vascular and... Apr 2018Screening for abdominal aortic aneurysm (AAA) during transthoracic echocardiography (TTE) may be an effective targeted screening strategy. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Screening for abdominal aortic aneurysm (AAA) during transthoracic echocardiography (TTE) may be an effective targeted screening strategy.
OBJECTIVE
The aim was to assess the feasibility of AAA screening during TTE and to estimate the prevalence of AAA in patients undergoing TTE.
METHODS
Electronic bibliographic sources were interrogated using a combination of free text and controlled vocabulary searches to identify studies reporting on AAA screening during TTE. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement standards. Fixed effect or random effects models were used to calculate pooled prevalence estimates.
RESULTS
Twenty observational cohort studies were identified reporting a total of 43,341 participants (23,291 men and 20,050 women). Hypertension was reported in 41% (95% CI 38-43), hypercholesterolemia in 31% (95% CI 29-32), diabetes mellitus in 20% (95% CI 19-22), and tobacco use in 37% (95% CI 35-38). The aorta was visualised in 86% (95% CI 84-88) of the screened population. The pooled prevalence of AAA in the entire screened population was 0.033 (95% CI 0.024-0.044). The pooled prevalence of AAA in men was 0.046 (95% CI 0.032-0.065) and in women it was 0.014 (95% CI 0.008-0.022). The mean age of participants in whom an AAA was detected ranged across the studies from 66 to 85 years. The mean diameter of the aneurysm identified ranged across the studies from 35 mm to 45 mm. Clinical outcomes in participants with a detected AAA were poorly reported.
CONCLUSIONS
Screening for AAA during TTE may identify a population group with a high risk of AAA in whom targeted screening may be beneficial. Further research is required to investigate the cost-effectiveness and clinical benefits of AAA screening in this setting.
Topics: Aortic Aneurysm, Abdominal; Diabetes Mellitus; Echocardiography; Humans; Hypercholesterolemia; Hypertension; Mass Screening; Risk Factors; Smoking
PubMed: 29433798
DOI: 10.1016/j.ejvs.2018.01.003 -
The Cochrane Database of Systematic... Oct 2021Familial hypercholesterolaemia is a common inherited condition that is associated with premature cardiovascular disease. The increased cardiovascular morbidity and... (Review)
Review
BACKGROUND
Familial hypercholesterolaemia is a common inherited condition that is associated with premature cardiovascular disease. The increased cardiovascular morbidity and mortality, resulting from high levels of cholesterol since birth, can be prevented by starting lipid-lowering therapy. However, the majority of patients in the UK and worldwide remain undiagnosed. Established diagnostic criteria in current clinical practice are the Simon-Broome and Dutch Lipid Clinical network criteria and patients are classified as having probable, possible or definite familial hypercholesterolaemia.
OBJECTIVES
To assess the effectiveness of healthcare interventions strategies to systematically improve identification of familial hypercholesterolaemia in primary care and other community settings compared to usual care (incidental approaches to identify familial hypercholesterolaemia in primary care and other community settings).
SEARCH METHODS
We searched the Cochrane Inborn Errors of Metabolism Trials Register. Date of last search: 13 September 2021. We also searched databases (Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, PubMed, Embase, CINAHL, Web of Science, and SCOPUS) as well as handsearching relevant conference proceedings, reference lists of included articles, and the grey literature. Date of last searches: 05 March 2020. SELECTION CRITERIA: As per the Effective Practice and Organisation of Care (EPOC) Group guidelines, we planned to include randomised controlled trials (RCTs), cluster-RCTs and non-randomised studies of interventions (NRSI). Eligible NRSI were non-randomised controlled trials, prospective cohort studies, controlled before-and-after studies, and interrupted-time-series studies. We planned to selected studies with healthcare interventions strategies that aimed to systematically identify people with possible or definite clinical familial hypercholesterolaemia, in primary care and other community settings. These strategies would be compared with usual care or no intervention. We considered participants of any age from the general population who access primary care and other community settings.
DATA COLLECTION AND ANALYSIS
Two authors planned to independently select studies according to the inclusion criteria, to extract data and assess for risk of bias and the certainty of the evidence (according to the GRADE criteria). We contacted corresponding study authors in order to obtain further information for all the studies considered in the review.
MAIN RESULTS
No eligible RCTs or NRSIs were identified for inclusion, however, we excluded 28 studies.
AUTHORS' CONCLUSIONS
Currently, there are no RCTs or controlled NRSI evidence to determine the most appropriate healthcare strategy to systematically identify possible or definite clinical familial hypercholesterolaemia in primary care or other community settings. Uncontrolled before-and-after studies were identified, but were not eligible for inclusion. Further studies assessing healthcare strategies of systematic identification of familial hypercholesterolaemia need to be conducted with diagnosis confirmed by genetic testing or validated through clinical phenotype (or both).
Topics: Bias; Humans; Hyperlipoproteinemia Type II; Interrupted Time Series Analysis; Primary Health Care
PubMed: 34617591
DOI: 10.1002/14651858.CD012985.pub2