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Nutrition Reviews Jan 2021Free, or added, sugars are considered important determinants in the pandemics of obesity and associated chronic diseases, and fructose has emerged as the sugar of main... (Comparative Study)
Comparative Study Meta-Analysis
CONTEXT
Free, or added, sugars are considered important determinants in the pandemics of obesity and associated chronic diseases, and fructose has emerged as the sugar of main concern.
OBJECTIVE
The aim of this review was to assess the evidence of the effects of isoenergetic replacement of fructose or high-fructose corn syrup (HFCS) for glucose or sucrose on cardiometabolic markers in controlled dietary intervention trials.
DATA SOURCES
The electronic databases PubMed/MEDLINE, the Cochrane Library, and Embase were searched from 1980 to May 5, 2020.
STUDY SELECTION
Studies were eligible if they measured at least one of the following outcomes: total cholesterol, low- and high-density lipoprotein cholesterol, triacylglycerols, apolipoprotein A1, apolipoprotein B, systolic blood pressure, diastolic blood pressure, fasting glucose, and body weight.
DATA EXTRACTION
For each outcome, the mean values and the corresponding measure of dispersion were extracted after the intervention or control diet.
DATA ANALYSIS
Fixed-effects and random-effects models were used to pool study-specific estimates. Between-study heterogeneity was assessed by the χ2 test and the I2 statistic and publication bias by the Egger test and funnel plots.
RESULTS
Twenty-five studies involving 1744 volunteers were identified. No significant effects were found when fructose or HFCS was substituted for glucose, except for a slight decrease in diastolic blood pressure when fructose was substituted for glucose. Similarly, no effects were found when fructose or HFCS was substituted for sucrose, except for a small increase, of uncertain clinical significance, of apolipoprotein B when HFCS was substituted for sucrose.
CONCLUSIONS
Isoenergetic substitution of fructose or HFCS for glucose or sucrose has no significant effect on most of the cardiometabolic markers investigated; however, some results were affected by residual between-study heterogeneity and studies with high or unclear risk of bias.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO registration number CRD42016042930.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Apolipoprotein A-I; Apolipoproteins B; Biomarkers; Blood Pressure; Body Weight; Cardiovascular Diseases; Cholesterol; Eating; Female; Fructose; Glucose; High Fructose Corn Syrup; Humans; Male; Middle Aged; Risk Factors; Sucrose; Triglycerides; Young Adult
PubMed: 33029629
DOI: 10.1093/nutrit/nuaa077 -
PLoS Medicine Jul 2020Bempedoic acid is a first-in-class lipid-lowering drug recommended by guidelines for the treatment of hypercholesterolemia. Our objective was to estimate its average... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bempedoic acid is a first-in-class lipid-lowering drug recommended by guidelines for the treatment of hypercholesterolemia. Our objective was to estimate its average effect on plasma lipids in humans and its safety profile.
METHODS AND FINDINGS
We carried out a systematic review and meta-analysis of phase II and III randomized controlled trials on bempedoic acid (PROSPERO: CRD42019129687). PubMed (Medline), Scopus, Google Scholar, and Web of Science databases were searched, with no language restriction, from inception to 5 August 2019. We included 10 RCTs (n = 3,788) comprising 26 arms (active arm [n = 2,460]; control arm [n = 1,328]). Effect sizes for changes in lipids and high-sensitivity C-reactive protein (hsCRP) serum concentration were expressed as mean differences (MDs) and 95% confidence intervals (CIs). For safety analyses, odds ratios (ORs) and 95% CIs were calculated using the Mantel-Haenszel method. Bempedoic acid significantly reduced total cholesterol (MD -14.94%; 95% CI -17.31%, -12.57%; p < 0.001), non-high-density lipoprotein cholesterol (MD -18.17%; 95% CI -21.14%, -15.19%; p < 0.001), low-density lipoprotein cholesterol (MD -22.94%; 95% CI -26.63%, -19.25%; p < 0.001), low-density lipoprotein particle number (MD -20.67%; 95% CI -23.84%, -17.48%; p < 0.001), apolipoprotein B (MD -15.18%; 95% CI -17.41%, -12.95%; p < 0.001), high-density lipoprotein cholesterol (MD -5.83%; 95% CI -6.14%, -5.52%; p < 0.001), high-density lipoprotein particle number (MD -3.21%; 95% CI -6.40%, -0.02%; p = 0.049), and hsCRP (MD -27.03%; 95% CI -31.42%, -22.64%; p < 0.001). Bempedoic acid did not significantly modify triglyceride level (MD -1.51%; 95% CI -3.75%, 0.74%; p = 0.189), very-low-density lipoprotein particle number (MD 3.79%; 95% CI -9.81%, 17.39%; p = 0.585), and apolipoprotein A-1 (MD -1.83%; 95% CI -5.23%, 1.56%; p = 0.290). Treatment with bempedoic acid was positively associated with an increased risk of discontinuation of treatment (OR 1.37; 95% CI 1.06, 1.76; p = 0.015), elevated serum uric acid (OR 3.55; 95% CI 1.03, 12.27; p = 0.045), elevated liver enzymes (OR 4.28; 95% CI 1.34, 13.71; p = 0.014), and elevated creatine kinase (OR 3.79; 95% CI 1.06, 13.51; p = 0.04), though it was strongly associated with a decreased risk of new onset or worsening diabetes (OR 0.59; 95% CI 0.39, 0.90; p = 0.01). The main limitation of this meta-analysis is related to the relatively small number of individuals involved in the studies, which were often short or middle term in length.
CONCLUSIONS
Our results show that bempedoic acid has favorable effects on lipid profile and hsCRP levels and an acceptable safety profile. Further well-designed studies are needed to explore its longer-term safety.
Topics: Anticholesteremic Agents; Apolipoproteins B; Cholesterol; Cholesterol, LDL; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Dicarboxylic Acids; Fatty Acids; Humans; Hypercholesterolemia; Peptide Fragments; Randomized Controlled Trials as Topic
PubMed: 32673317
DOI: 10.1371/journal.pmed.1003121 -
Atherosclerosis Jul 2020Genetic identification is a public health care concern for management of familial hypercholesterolemia (FH) associated cardiovascular morbidity and mortality. This study...
BACKGROUND AND AIMS
Genetic identification is a public health care concern for management of familial hypercholesterolemia (FH) associated cardiovascular morbidity and mortality. This study presents the spectrum and distribution of LDLR, APOB, PCSK9 gene mutations in Asia.
METHODS
Databases were searched for English papers from 1950 to 2019. The spectrum of the variants was investigated in 8994 FH families in 48 Asian countries. We determined the frequency of variants, zygosity, and clinical features.
RESULTS
Twenty countries have studied LDLR variants. A total of 629 mutations were reported and twenty variants were accounted as common variants in different populations. China, Japan, India and Taiwan constituted 68% of published articles. The most frequent mutation was reported in Japan but was not common in other countries. Other missense variants accounted for 50% of the mutations, frameshifts 19%, and nonsense 11%. The pooled frequency of variation was estimated in 1867 individuals. Approximately 67% of Iranian families were homozygous.,The common variant was p.Ser130Ter. p.Arg3527Trp in APOB was common among 184 heterozygous patients; the common variant of PCSK9 was p.Glu32Lys.
CONCLUSIONS
This is the first systematic review of LDLR, APOB, PCSK9 mutations in FH patients in Asia. These findings underscore the need to fill in the gap of studies on different populations in Asia. It also underlies the importance of early detection and management to decrease atherosclerosis and cardiovascular risk in different ethnicities.
Topics: Apolipoprotein B-100; Asia; China; DNA Mutational Analysis; Humans; India; Iran; Japan; Mutation; Phenotype; Proprotein Convertase 9; Receptors, LDL; Taiwan
PubMed: 32629184
DOI: 10.1016/j.atherosclerosis.2020.05.004 -
Cardiovascular Drugs and Therapy Feb 2021Despite advances in the development of lipid-lowering therapies, clinical trials have shown that a significant residual risk of cardiovascular disease persists....
BACKGROUND
Despite advances in the development of lipid-lowering therapies, clinical trials have shown that a significant residual risk of cardiovascular disease persists. Specifically, new drugs are needed for non-responding or statin-intolerant subjects or patients considered at very high risk for cardiovascular events even though are already on treatment with the best standard of care.
RESULTS AND CONCLUSIONS
Besides, genetic and epidemiological studies and Mendelian randomization analyses have strengthened the linear correlation between the concentration of low-density lipoprotein cholesterol (LDL-C) and the incidence of cardiovascular events and highlighted various novel therapeutic targets. This review describes the novel strategies to reduce the levels of LDL-C, non-HDL-C, triglyceride, apolipoprotein B, and Lp(a), focusing on those developed using biotechnology-based strategies.
Topics: Antibodies, Monoclonal, Humanized; Apolipoproteins B; Cholesterol, LDL; Clinical Trials as Topic; Dyslipidemias; Genetic Therapy; Humans; Hypolipidemic Agents; Lysophospholipids; Oligonucleotides, Antisense; RNA, Small Interfering; Triglycerides
PubMed: 32519066
DOI: 10.1007/s10557-020-07017-6 -
Circulation. Genomic and Precision... Nov 2019The prevalence of familial hypercholesterolemia is 1 in 250, but <10% of patients are diagnosed. Cascade testing enables early detection of cases through systematic...
BACKGROUND
The prevalence of familial hypercholesterolemia is 1 in 250, but <10% of patients are diagnosed. Cascade testing enables early detection of cases through systematic family tracing. Establishment of familial hypercholesterolemia cascade testing programs in the US could be informed by approaches used elsewhere.
METHODS
We conducted a systematic review of published studies in the English language of cascade testing for familial hypercholesterolemia, which reported the number of index cases and number of relatives tested and specified methods of contacting relatives and testing modalities methods utilized. For each study, we calculated yield (proportion of relatives who test positive) and new cases per index case, to facilitate comparison.
RESULTS
We identified 10 studies from the literature that met inclusion criteria; the mean number of probands and relatives per study was 242 and 826, respectively. The average yield was 44.76% with a range of 30% to 60.5%, and the mean new cases per index case was 1.65 with a range of 0.22 to 8.0. New cases per index case tended to be greater in studies that used direct contact versus indirect contact (2.06 versus 0.86), tested beyond first-degree relatives versus only first-degree relatives (3.65 versus 0.80), used active sample collection versus collection at clinic (4.11 versus 1.06), and utilized genetic testing versus biochemical testing (2.47 versus 0.42).
CONCLUSIONS
New case detection in familial hypercholesterolemia cascade testing programs tended to be higher with direct contact of relatives, testing beyond first-degree relatives, in-home-based sample collection, and genetic testing. These findings should be helpful for establishing cascade testing programs in the United States.
Topics: Apolipoproteins B; Genetic Testing; Humans; Hyperlipoproteinemia Type II; Mutation; Pedigree; Proprotein Convertase 9; Receptors, LDL
PubMed: 31638829
DOI: 10.1161/CIRCGEN.119.002723 -
European Journal of Preventive... Aug 2020The effect of therapeutic lowering of apolipoprotein B (apoB) on mortality and major adverse cardiovascular events is uncertain. It is also unclear whether these... (Meta-Analysis)
Meta-Analysis
AIMS
The effect of therapeutic lowering of apolipoprotein B (apoB) on mortality and major adverse cardiovascular events is uncertain. It is also unclear whether these potential effects vary by different lipid-lowering strategies.
METHODS
A total of 29 randomized controlled trials were selected using PubMed, Cochrane Library and EMBASE through 2018. We selected trials of therapies which ultimately clear apolipoprotein B particles by upregulating low-density lipoprotein receptor (LDL-R) expression (statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, bile acid sequestrants) or therapies which reduce apolipoprotein B independent of LDL-R (cholesteryl ester transfer protein inhibitor, fibrates, niacin, omega-3 fatty acids) with sample size of ≥1000 patients and follow-up of ≥1 year. The meta-regression and meta-analyses were constructed using a random effects model.
RESULTS
In 332,912 patients, meta-regression analyses showed relative risks of 0.95 for all-cause mortality (95% confidence interval 0.92-0.99) and 0.93 (0.88-0.98) for cardiovascular mortality for every 10 mg/dL decrease in apolipoprotein B by all interventions combined. Reduction in all-cause mortality was limited to statins (0.92 (0.86-0.98)). For MACE, the relative risk per 10 mg/dL reduction in apolipoprotein B was 0.93 (0.90-0.97) for all therapies combined, with both statin (0.88 (0.83-0.93)) and non-statin therapies (0.96 (0.94-0.99)). which clear apolipoprotein B by upregulating LDL-R showing significant reductions; whereas interventions which lower apolipoprotein B independent of LDL-R did not demonstrate this effect (1.02 (0.81-1.30)).
CONCLUSION
While both statin and established non-statin therapies (PCSK9 inhibitor and ezetimibe) reduced cardiovascular risk per decrease in apolipoprotein B, interventions which reduce apolipoprotein B independently of LDL-R were not associated with cardiovascular benefit.
Topics: Apolipoproteins B; Biomarkers; Cardiovascular Diseases; Humans; Hypolipidemic Agents; Prognosis; Risk Factors
PubMed: 31475865
DOI: 10.1177/2047487319871733 -
Advances in Nutrition (Bethesda, Md.) Nov 2019Evidence suggests that eating nuts may reduce the risk of cardiovascular disease (CVD). We conducted a systematic review and meta-analysis of randomized controlled... (Meta-Analysis)
Meta-Analysis
Evidence suggests that eating nuts may reduce the risk of cardiovascular disease (CVD). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating almond consumption and risk factors for CVD. MEDLINE, Cochrane Central, Commonwealth Agricultural Bureau, and previous systematic reviews were searched from 1990 through June 2017 for RCTs of ≥3 wk duration that evaluated almond compared with no almond consumption in adults who were either healthy or at risk for CVD. The most appropriate stratum was selected with an almond dose closer to 42.5 g, with a control most closely matched for macronutrient composition, energy intake, and similar intervention duration. The outcomes included risk factors for CVD. Random-effects model meta-analyses and subgroup meta-analyses were performed. Fifteen eligible trials analyzed a total of 534 subjects. Almond intervention significantly decreased total cholesterol (summary net change: -10.69 mg/dL; 95% CI: -16.75, -4.63 mg/dL), LDL cholesterol (summary net change: -5.83 mg/dL; 95% CI: -9.91, -1.75 mg/dL); body weight (summary net change: -1.39 kg; 95% CI: -2.49, -0.30 kg), HDL cholesterol (summary net change: -1.26 mg/dL; 95% CI: -2.47, -0.05 mg/dL), and apolipoprotein B (apoB) (summary net change: -6.67 mg/dL; 95% CI: -12.63, -0.72 mg/dL). Triglycerides, systolic blood pressure, apolipoprotein A1, high-sensitivity C-reactive protein, and lipoprotein (a) showed no difference between almond and control in the main and subgroup analyses. Fasting blood glucose, diastolic blood pressure, and body mass index significantly decreased with almond consumption of >42.5 g compared with ≤42.5 g. Almond consumption may reduce the risk of CVD by improving blood lipids and by decreasing body weight and apoB. Substantial heterogeneity in eligible studies regarding almond interventions and dosages precludes firmer conclusions.
Topics: Adult; Apolipoproteins B; Biomarkers; Body Weight; Cardiovascular Diseases; Diet; Female; Humans; Lipids; MEDLINE; Male; Nuts; Prunus dulcis; Randomized Controlled Trials as Topic
PubMed: 31243439
DOI: 10.1093/advances/nmz043 -
The Breast Journal Jul 2019
Topics: Apolipoprotein B-100; Breast Neoplasms; Case-Control Studies; Cohort Studies; Female; Heterozygote; Humans; Hypobetalipoproteinemia, Familial, Apolipoprotein B; Hypobetalipoproteinemias; Lipoproteins, LDL; Risk Factors
PubMed: 31111608
DOI: 10.1111/tbj.13341 -
Atherosclerosis. Supplements Mar 2019To investigate the status of familial hypercholesterolemia (FH) research and the characteristics of patients with FH in China.
AIMS
To investigate the status of familial hypercholesterolemia (FH) research and the characteristics of patients with FH in China.
METHODS
Published papers in Chinese or English language from PubMed, SinoMed and CNKI databases from 1971 to March 2018 were searched using 'Familial hypercholesterolemia', 'Chinese' and 'Han' as keywords. A systematic review of studies on familial hypercholesterolemia was then conducted.
RESULTS
A total of 391 articles were found, in which 22% were in English and 78% were in Chinese; approximately 43% are case reports and 34% are genetic reports according to the study type; 52% discussed the status of the disease and 11% investigated the subclinical status according to the study content. Furthermore, 96% of the articles were published by tertiary hospitals and 46% were conducted by cardiologists. The first expert consensus was issued in February 2018. Of the 163 case reports published before 2018, 48.7% used the Chinese FH clinical diagnostic criteria and 34.4% did not clearly indicate the diagnostic criteria. The incidence rates of low-density lipoprotein receptor (LDLR) and apolipoprotein B (APOB) mutations were 82% and 9%, and proprotein convertase subtilisin/kexin type 9 (PCSK9) mutations were rare in Chinese patients with FH. However, the data on lipid-lowering treatment rates, compliance rates and cardiovascular events in FH remain insufficient.
CONCLUSIONS
Large-scale epidemiological investigation of FH has not been demonstrated, the recognition of FH remains rudimentary, and the guidelines are incomplete in China. The diagnosis and management of Chinese FH needs to be improved.
Topics: Anticholesteremic Agents; Apolipoprotein B-100; Asian People; Cardiovascular Diseases; China; Female; Genetic Predisposition to Disease; Humans; Hyperlipoproteinemia Type II; Male; Middle Aged; Mutation; Mutation Rate; Phenotype; Proprotein Convertase 9; Receptors, LDL; Risk Factors; Treatment Outcome
PubMed: 30876527
DOI: 10.1016/j.atherosclerosissup.2019.01.003 -
Atherosclerosis Dec 2018Familial hypercholesterolemia (FH) is an inherited genetic disorder of lipid metabolism characterized by a high serum LDL-cholesterol profile and xanthoma formation, and...
BACKGROUND AND AIMS
Familial hypercholesterolemia (FH) is an inherited genetic disorder of lipid metabolism characterized by a high serum LDL-cholesterol profile and xanthoma formation, and FH increases the risk of premature atherosclerosis and cardiovascular disease (CVD). Mutations in the low-density lipoprotein (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin 9 (PCSK9), and LDLRAP1 genes have been associated with FH. Although FH is a major risk for CVD, the disease prevalence and its underlying molecular basis in the 22 Arab countries are still understudied. This study aimed to analyze all peer-reviewed studies related to the prevalence of FH and its causative mutations in the 22 Arab countries.
METHODS
We searched five literature databases (Scopus, Science Direct, Web of Science, PubMed, and Google Scholar) from inception until June 2018, using all possible search terms to capture all of the genetic and prevalence data related to Arab patients with FH.
RESULTS
A total of 5,484 titles and abstracts were identified; 51 studies met our inclusion criteria for the final systematic review. Fifty-one mutations in Arab patients with FH were identified in only eight Arab countries; 47 were identified in the LDLR gene, two in the PCSK9 gene, and two in LDLRAP1 gene. Twenty mutations in the LDLR gene were distinctive to Arab patients. A few studies reported prevalence estimates, ranging from 0.4% to 6.8%.
CONCLUSIONS
This is the first systematic review to dissect the up-to-date status of the genetic epidemiology of Arab patients with FH. It seems that FH is underdiagnosed and that its prevalence is understudied due to the dearth of published information about Arab patients with FH. Therefore, there is a need for well-controlled genetic epidemiological studies on Arab patients with FH.
Topics: Adaptor Proteins, Signal Transducing; Apolipoprotein B-100; Arabs; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Hyperlipoproteinemia Type II; Middle East; Mutation; Phenotype; Prevalence; Proprotein Convertase 9; Receptors, LDL; Risk Factors
PubMed: 30415195
DOI: 10.1016/j.atherosclerosis.2018.10.022