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Frontiers in Endocrinology 2023Insulin resistance (IR), a risk factor for cardiovascular diseases, has garnered significant attention in scientific research. Several studies have investigated the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Insulin resistance (IR), a risk factor for cardiovascular diseases, has garnered significant attention in scientific research. Several studies have investigated the correlation between IR and coronary artery calcification (CAC), yielding varying results. In light of this, we conducted a systematic review to investigate the association between IR as evaluated by the homeostasis model assessment (HOMA-IR) and CAC.
METHODS
A comprehensive search was conducted to identify relevant studies in PubMed, Embase, Scopus, and Web of Science databases. In addition, preprint servers such as Research Square, BioRxiv, and MedRxiv were manually searched. The collected data were analyzed using either fixed or random effects models, depending on the heterogeneity observed among the studies. The assessment of the body of evidence was performed using the GRADE approach to determine its quality.
RESULTS
The current research incorporated 15 studies with 60,649 subjects. The analysis revealed that a higher category of HOMA-IR was associated with a greater prevalence of CAC in comparison to the lowest HOMA-IR category, with an OR of 1.13 (95% CI: 1.06-1.20, I = 29%, P < 0.001). A similar result was reached when HOMA-IR was analyzed as a continuous variable (OR: 1.27, 95% CI: 1.14-1.41, I = 54%, P < 0.001). In terms of CAC progression, a pooled analysis of two cohort studies disclosed a significant association between increased HOMA-IR levels and CAC progression, with an OR of 1.44 (95% CI: 1.04-2.01, I = 21%, P < 0.05). It is important to note that the strength of the evidence was rated as low for the prevalence of CAC and very low for the progression of CAC.
CONCLUSION
There is evidence to suggest that a relatively high HOMA-IR may be linked with an increased prevalence and progression of CAC.
Topics: Humans; Insulin Resistance; Coronary Artery Disease; Risk Factors; Hyperinsulinism; Homeostasis
PubMed: 38089605
DOI: 10.3389/fendo.2023.1271857 -
PloS One 2023Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide. Atherosclerosis occurs due to accumulation of low-density lipoprotein... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide. Atherosclerosis occurs due to accumulation of low-density lipoprotein cholesterol (LDL-c) in the arterial system. Thus, lipid lowering therapy is essential for both primary and secondary prevention. Proprotein convertase subtilisn/kexin type 9 (PCSK9) inhibitors (Evolocumab, Alirocumab) and small interfering RNA (siRNA) therapy (Inclisiran) have been demonstrated to lower LDL-c and ASCVD events in conjunction with maximally tolerated statin therapy. However, the degree of LDL-c reduction and the impact on reducing major adverse cardiac events, including their impact on mortality, remains unclear.
OBJECTIVE
The purpose of this study is to examine the effects of PCSK9 inhibitors and small interfering RNA (siRNA) therapy on LDL-c reduction and major adverse cardiac events (MACE) and mortality by conducting a meta-analysis of randomized controlled trials.
METHODS
Using Pubmed, Embase, Cochrane Library and clinicaltrials.gov until April 2023, we extracted randomized controlled trials (RCTs) of PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) for lipid lowering and risk of MACE. Using random-effects models, we pooled the relative risks and 95% CIs and weighted least-squares mean difference in LDL-c levels. We estimated odds ratios with 95% CIs among MACE subtypes and all-cause mortality. Fixed-effect model was used, and heterogeneity was assessed using the I2 statistic.
RESULTS
In all, 54 studies with 87,669 participants (142,262 person-years) met criteria for inclusion. LDL-c percent change was reported in 47 studies (n = 62,634) evaluating two PCSK9 inhibitors and siRNA therapy. Of those, 21 studies (n = 41,361) included treatment with Evolocumab (140mg), 22 (n = 11,751) included Alirocumab (75mg), and 4 studies (n = 9,522) included Inclisiran (284mg and 300mg). Compared with placebo, after a median of 24 weeks (IQR 12-52), Evolocumab reduced LDL-c by -61.09% (95% CI: -64.81, -57.38, p<0.01) and Alirocumab reduced LDL-c by -46.35% (95% CI: -51.75, -41.13, p<0.01). Inclisiran 284mg reduced LDL-c by -54.83% (95% CI: -59.04, -50.62, p = 0.05) and Inclisiran 300mg reduced LDL-c by -43.11% (95% CI: -52.42, -33.80, p = 0.01). After a median of 8 months (IQR 6-15), Evolocumab reduced the risk of myocardial infarction (MI), OR 0.72 (95% CI: 0.64, 0.81, p<0.01), coronary revascularization, 0.77 (95% CI: 0.70, 0.84, p<0.01), stroke, 0.79 (95% CI: 0.66, 0.94, p = 0.01) and overall MACE 0.85 (95% CI: 0.80, 0.89, p<0.01). Alirocumab reduced MI, 0.57 (0.38, 0.86, p = 0.01), cardiovascular mortality 0.35 (95% CI: 0.16, 0.77, p = 0.01), all-cause mortality 0.60 (95% CI: 0.43, 0.84, p<0.01), and overall MACE 0.35 (0.16, 0.77, p = 0.01).
CONCLUSION
PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) significantly reduced LDL-c by >40% in high-risk individuals. Additionally, both Alirocumab and Evolocumab reduced the risk of MACE, and Alirocumab reduced cardiovascular and all-cause mortality.
Topics: Humans; PCSK9 Inhibitors; Cholesterol, LDL; Myocardial Infarction; Proprotein Convertase 9; Atherosclerosis; Heart Disease Risk Factors; RNA, Small Interfering; Anticholesteremic Agents; Cardiovascular Diseases; Hydroxymethylglutaryl-CoA Reductase Inhibitors
PubMed: 38055686
DOI: 10.1371/journal.pone.0295359 -
Vascular Medicine (London, England) Apr 2024This study aimed to review the current literature exploring the utility of noninvasive ocular imaging for the diagnosis of peripheral artery disease (PAD). Our search... (Review)
Review
This study aimed to review the current literature exploring the utility of noninvasive ocular imaging for the diagnosis of peripheral artery disease (PAD). Our search was conducted in early April 2022 and included the databases Medline, Scopus, Embase, Cochrane, and others. Five articles were included in the final review. Of the five studies that used ocular imaging in PAD, two studies used retinal color fundus photography, one used optical coherence tomography (OCT), and two used optical coherence tomography angiography (OCTA) to assess the ocular changes in PAD. PAD was associated with both structural and functional changes in the retina. Structural alterations around the optic disc and temporal retinal vascular arcades were seen in color fundus photography of patients with PAD compared to healthy individuals. The presence of retinal hemorrhages, exudates, and microaneurysms in color fundus photography was associated with an increased future risk of PAD, especially the severe form of the disease. The retinal nerve fiber layer (RNFL) was significantly thinner in the nasal quadrant in patients with PAD compared to age-matched healthy individuals in OCT. Similarly, the choroidal thickness in the subfoveal region was significantly thinner in patients with PAD compared to controls. Patients with PAD also had a significant reduction in the retinal and choroidal circulation in OCTA compared to healthy controls. As PAD causes thinning and ischemic changes in retinal vessels, examination of the retinal vessels using retinal imaging techniques can provide useful information about early microvascular damage in PAD. Ocular imaging could potentially serve as a biomarker for PAD. .
Topics: Humans; Optic Disk; Tomography, Optical Coherence; Photography; Peripheral Arterial Disease; Biomarkers; Retinal Vessels
PubMed: 38054219
DOI: 10.1177/1358863X231210866 -
European Journal of Pediatrics Feb 2024To quantify the tracking of apolipoprotein B (apoB) levels from childhood and adolescence and compare the tracking of apoB with low-density lipoprotein (LDL)... (Meta-Analysis)
Meta-Analysis Review
UNLABELLED
To quantify the tracking of apolipoprotein B (apoB) levels from childhood and adolescence and compare the tracking of apoB with low-density lipoprotein (LDL) cholesterol, a systematic search of MEDLINE, Embase, Web of Science, and Google Scholar was performed in October 2023 (PROSPERO protocol: CRD42022298663). Cohort studies that measured tracking of apoB from childhood/adolescence (< 19 years) with a minimum follow-up of 1 year, using tracking estimates such as correlation coefficients or tracking coefficients, were eligible. Pooled correlations were estimated using random-effects meta-analysis. Risk of bias was assessed with a review-specific tool. Ten studies of eight unique cohorts involving 4677 participants met the inclusion criteria. Tracking of apoB was observed (pooled r = 0.63; 95% confidence interval [CI] = 0.53-0.71; I = 96%) with no significant sources of heterogeneity identified. Data from five cohorts with tracking data for both lipids showed the degree of tracking was similar for apoB (pooled r = 0.59; 95% CI = 0.55-0.63) and LDL cholesterol (pooled r = 0.58; 95% CI = 0.47-0.68). Study risk of bias was moderate, mostly due to attrition and insufficient reporting.
CONCLUSION
ApoB levels track strongly from childhood, but do not surpass LDL cholesterol in this regard. While there is strong evidence that apoB is more effective at predicting ASCVD risk than LDL cholesterol in adults, there is currently insufficient evidence to support its increased utility in pediatric settings. This also applies to tracking data, where more comprehensive data are required.
WHAT IS KNOWN
• Apolipoprotein B is a known cause of atherosclerotic cardiovascular disease. • Apolipoprotein B levels are not typically measured in pediatric settings, where low-density lipoprotein cholesterol remains the primary lipid screening measure.
WHAT IS NEW
• This meta-analysis of 10 studies showed apolipoprotein B levels tracked strongly from childhood but did not exceed low-density lipoprotein cholesterol in this regard. • More comprehensive tracking data are needed to provide sufficient evidence for increased utility of apolipoprotein B in pediatric settings.
Topics: Adult; Humans; Adolescent; Child; Cholesterol, LDL; Apolipoproteins B; Cholesterol; Atherosclerosis; Cohort Studies; Cholesterol, HDL
PubMed: 38051379
DOI: 10.1007/s00431-023-05350-0 -
Frontiers in Cardiovascular Medicine 2023Carotid atherosclerotic plaque is an important independent risk factor for stroke. Apolipoprotein E (APOE) influences cholesterol levels and certain isoforms are...
INTRODUCTION
Carotid atherosclerotic plaque is an important independent risk factor for stroke. Apolipoprotein E (APOE) influences cholesterol levels and certain isoforms are associated with increased carotid atherosclerosis, though the exact association between APOE and carotid plaque is uncertain. The study aimed to evaluate the association between APOE and carotid plaque.
METHODS
A systematic review was performed to retrieve all studies which examined the association between carotid plaque and APOE. This study was conducted in accordance with the PRISMA guidelines. Independent readers extracted the relevant data from each study including the type of imaging assessment, plaque definition, frequency of APOE E4 carrier status and type of genotyping. Meta-analyses with an assessment of study heterogeneity and publication bias were performed. Results were presented in a forest plot and summarized using a random-effects model.
RESULTS
After screening 838 studies, 17 studies were included for systematic review. A meta-analysis of 5 published studies showed a significant association between 4 homozygosity and carotid plaque [odds ratio (OR), 1.53; 95% CI, 1.16, 2.02; = .003]. Additionally, there was a significant association between patients possessing at least one 4 allele, heterozygotes or homozygotes, and carotid plaque (OR, 1.25; 95% CI, 1.03, 1.52; = .03). Lastly, there was no association between 4 heterozygosity and carotid plaque (OR, 1.08; 95% CI, 0.93, 1.26; = .30).
CONCLUSION
APOE 4 allele is significantly associated with extracranial carotid atherosclerotic plaque, especially for homozygous individuals.
PubMed: 38034385
DOI: 10.3389/fcvm.2023.1155916 -
Cardiovascular Therapeutics 2023Cardiovascular diseases (CDs), notably coronary artery disease (CAD) due to atherosclerosis, impose substantial global health and economic burdens. Fatty acid-binding... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cardiovascular diseases (CDs), notably coronary artery disease (CAD) due to atherosclerosis, impose substantial global health and economic burdens. Fatty acid-binding proteins (FABPs), including FABP-4, have been recently linked to CDs. This study conducted a systematic review and meta-analysis to examine FABP-4 levels in CAD and atherosclerosis patients, exploring their potential links to these conditions.
METHODS
A systematic review and meta-analysis were done based on the PRISMA guideline. The international databases including Medline, Embase, Cochrane Library, Scopus, Web of Science, and UpToDate were searched to find all related studies on the effect of FABP-4 on patients with CAD or atherosclerosis which were published till June 2022 without language restriction. The Cochran's -test and statistic were applied to assess heterogeneity, a random effect model was used to estimate the pooled standardized mean difference (SMD), a metaregression method was utilized to investigate the factors affecting heterogeneity between studies, and Egger's test was used to assess the publication bias.
RESULTS
Of 1051 studies, 9 studies with a sample size of 2327 were included in the systematic review and meta-analysis. The level of circulating FABP-4 in the patient groups was significantly higher than in the control groups (SMD = 0.60 (95% CI: 0.30 to 0.91, : 91.47%)). The SMD in female and male patients were 0.26 (95% CI: 0.01 to 0.52, : 0%) and 0.22 (95% CI: 0.08 to 0.35, : 44.7%), respectively. There was considerable heterogeneity between the studies. The countries had a positive relationship with heterogeneity (coefficient = 0.29, < 0.001); but BMI, lipid indices, gender, study design, and type of kit had no effect on the heterogeneity. No publication bias was observed (: 0.137).
CONCLUSION
In summary, this meta-analysis revealed elevated circulating FABP-4 levels in CDs, suggesting its potential as a biomarker for these conditions. Further research is warranted to explore its clinical relevance.
Topics: Female; Humans; Male; Atherosclerosis; Biomarkers; Coronary Artery Disease; Global Health
PubMed: 38024104
DOI: 10.1155/2023/1092263 -
PloS One 2023Cardiovascular diseases are some of the leading causes of death worldwide, with coronary artery disease leading as one of the primary causes of mortality in both the...
BACKGROUND
Cardiovascular diseases are some of the leading causes of death worldwide, with coronary artery disease leading as one of the primary causes of mortality in both the developing and developed worlds. Despite its prevalence, there is a disproportionately small number of studies conducted in populations of non-European ancestry, with the limited sample sizes of such studies further restricting the power and generalizability of respective findings. This research aimed at understanding the differences in the genetic architecture of coronary artery disease (CAD) in populations of diverse ancestries in order to contribute towards the understanding of the pathophysiology of coronary artery disease.
METHODS
We performed a systematic review on the 6th of October, 2022 summarizing genome-wide association studies on coronary artery disease, while employing the GWAS Catalog as an independent database to support the search. We developed a framework to assess the methodological quality of each study. We extracted and grouped associated single nucleotide polymorphisms and genes according to ancestry groups of participants.
RESULTS
We identified 3100 studies, of which, 36 relevant studies were included in this research. Three of the studies that were included were not listed in the GWAS Catalog, highlighting the value of conducting an independent search alongside established databases in order to ensure the full research landscape has been captured. 743,919 CAD case participants from 25 different countries were analysed, with 61% of the studies identified in this research conducted in populations of European ancestry. No studies investigated populations of Africans living in continental Africa or admixed American ancestry groups besides African-Americans, while limited sample sizes were included of population groups besides Europeans and East Asians. This observed disproportionate population representation highlights the gaps in the literature, which limits our ability to understand coronary artery disease as a global disease. 71 genetic loci were identified to be associated with coronary artery disease in more than one article, with ancestry-specific genetic loci identified in each respective population group which were not detected in studies of other ancestries.
CONCLUSIONS
Although the replication and validation of these variants are still warranted, these finding are indicative of the value of including diverse ancestry populations in GWAS reference panels, as a more comprehensive understanding of the genetic architecture and pathophysiology of CAD can be achieved.
Topics: Humans; Africa; Coronary Artery Disease; Genetic Predisposition to Disease; Genome-Wide Association Study; Polymorphism, Single Nucleotide; Population Groups; Racial Groups
PubMed: 38019802
DOI: 10.1371/journal.pone.0294341 -
Ageing Research Reviews Dec 2023Alterations in nitric oxide (NO) synthesis have been reported in Alzheimer's disease and vascular dementia. However, as the measurement of NO in biological samples is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Alterations in nitric oxide (NO) synthesis have been reported in Alzheimer's disease and vascular dementia. However, as the measurement of NO in biological samples is analytically challenging, alternative, stable circulatory biomarkers of NO synthesis may be useful to unravel new pathophysiological mechanisms and treatment targets in dementia.
METHODS
We conducted a systematic review and meta-analysis of the circulating concentrations of arginine metabolites linked to NO synthesis, arginine, citrulline, asymmetric (ADMA) and symmetric (SDMA) dimethylarginine, and ornithine, in Alzheimer's disease and vascular dementia. We searched for relevant studies in PubMed, Scopus, and Web of Science from inception to the 31st of May 2023. The JBI checklist and GRADE were used to assess the risk of bias and the certainty of evidence, respectively.
RESULTS
In 14 selected studies, there were no significant between-group differences in arginine and ornithine concentrations. By contrast, compared to controls, patients with dementia had significantly higher ADMA (standard mean difference, SMD=0.62, 95% CI 0.06-1.19, p = 0.029), SDMA (SMD=0.70, 95% CI 0.34-1.35, p<0.001), and citrulline concentrations (SMD=0.50, 95% CI 0.08-0.91, p = 0.018). In subgroup analysis, the effect size was significantly associated with treatment with cholinesterase inhibitors and/or antipsychotics for ADMA, and underlying disorder (Alzheimer's disease), study continent, and analytical method for citrulline.
CONCLUSION
Alterations in ADMA, SDMA, and citrulline, biomarkers of NO synthesis, may be useful to investigate the pathophysiology of different forms of dementia and identify novel therapeutic strategies. (PROSPERO registration number: CRD42023439528).
Topics: Humans; Alzheimer Disease; Dementia, Vascular; Citrulline; Arginine; Biomarkers; Ornithine
PubMed: 38007048
DOI: 10.1016/j.arr.2023.102139 -
Biomolecules Nov 2023Peripheral artery disease (PAD) involves atherosclerosis of the lower extremity arteries and is a major contributor to limb loss and death worldwide. Several studies... (Review)
Review
Peripheral artery disease (PAD) involves atherosclerosis of the lower extremity arteries and is a major contributor to limb loss and death worldwide. Several studies have demonstrated that interleukins (ILs) play an important role in the development and progression of PAD; however, a comprehensive literature review has not been performed. A systematic review was conducted and reported according to PRISMA guidelines. MEDLINE was searched from inception to 5 December 2022, and all studies assessing the association between ILs and PAD were included. We included 17 studies from a pool of 771 unique articles. Five pro-inflammatory ILs (IL-1β, IL-2, IL-5, IL-6, and IL-8) and one pro-atherogenic IL (IL-12) were positively correlated with PAD diagnosis and progression. In contrast, two anti-inflammatory ILs (IL-4 and IL-10) were protective against PAD diagnosis and adverse limb events. Specifically, IL-6 and IL-8 were the most strongly associated with PAD and can act as potential disease biomarkers to support the identification and treatment of PAD. Ongoing work to identify and validate diagnostic/prognostic inflammatory biomarkers for PAD has the potential to assist clinicians in identifying high-risk patients for further evaluation and management which could reduce the risk of adverse cardiovascular and limb events.
Topics: Humans; Interleukin-6; Prognosis; Interleukin-8; Peripheral Arterial Disease; Atherosclerosis; Biomarkers; Risk Factors
PubMed: 38002322
DOI: 10.3390/biom13111640 -
PloS One 2023Elevated lipoprotein(a) [Lp(a)] level is an independent genetic risk factor that increases the risk of atherosclerotic cardiovascular disease (ASCVD) by 2-4 fold. We...
Burden of elevated lipoprotein(a) among patients with atherosclerotic cardiovascular disease: Evidence from a systematic literature review and feasibility assessment of meta-analysis.
BACKGROUND
Elevated lipoprotein(a) [Lp(a)] level is an independent genetic risk factor that increases the risk of atherosclerotic cardiovascular disease (ASCVD) by 2-4 fold. We aimed to report the burden of clinically relevant elevated Lp(a) in secondary prevention ASCVD population as the evaluation of such evidence is lacking.
METHODS
A systematic literature review (SLR) was conducted using Embase®, MEDLINE®, and MEDLINE® In-Process databases to identify studies reporting burden of elevated Lp(a) levels from January 1, 2010, to March 28, 2022. Full-text, English-language studies including ≥500 participants with ≥1 Lp(a) assessment were included.
RESULTS
Sixty-one studies reported clinical burden of elevated Lp(a). Of these, 25 observational studies and one clinical trial reported clinical burden of clinically relevant elevated Lp(a) levels. Major clinical outcomes included major adverse cardiovascular event (MACE; n = 20), myocardial infarction (MI; n = 11), revascularization (n = 10), stroke (n = 10), cardiovascular (CV) mortality (n = 9), and all-cause mortality (n = 10). Elevated Lp(a) levels significantly increased the risk of MACE (n = 15) and revascularization (n = 8), while they demonstrated a trend for positive association with remaining CV outcomes. Meta-analysis was not feasible for included studies due to heterogeneity in Lp(a) thresholds, outcome definitions, and patient characteristics. Three studies reported humanistic burden. Patients with elevated Lp(a) levels had higher odds of manifesting cognitive impairment (odds ratio [OR] [95% confidence interval; CI]: 1.62 [1.11-2.37]) and disability related to stroke (OR [95% CI]:1.46 [1.23-1.72)]) (n = 2). Elevated Lp(a) levels negatively correlated with health-related quality of life (R = -0.166, p = 0.014) (n = 1). A single study reported no association between elevated Lp(a) levels and economic burden.
CONCLUSIONS
This SLR demonstrated a significant association of elevated Lp(a) levels with major CV outcomes and increased humanistic burden in secondary prevention ASCVD population. These results reinforce the need to quantify and manage Lp(a) for CV risk reduction and to perform further studies to characterize the economic burden.
Topics: Humans; Atherosclerosis; Cardiovascular Diseases; Feasibility Studies; Lipoprotein(a); Quality of Life; Stroke; Meta-Analysis as Topic
PubMed: 37983217
DOI: 10.1371/journal.pone.0294250