Plasma Protein Profile of Carotid Artery Atherosclerosis and Atherosclerotic Outcomes: Meta-Analyses and Mendelian Randomization Analyses.
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ABSTRACT:
SUBMITTER: Lind L
PROVIDER: S-EPMC8062283 | biostudies-literature | 2021 May
REPOSITORIES: biostudies-literature
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Plasma Protein Profile of Carotid Artery Atherosclerosis and Atherosclerotic Outcomes: Meta-Analyses and Mendelian Randomization Analyses.
Lind Lars L Gigante Bruna B Borné Yan Y Feldreich Tobias T Leppert Jerzy J Hedberg Pär P Östgren Carl Johan CJ Nyström Fredrik H FH Sundström Johan J Ärnlöv Johan J Baldassarre Damiano D Tremoli Elena E Veglia Fabrizio F Hamsten Anders A O'Donnell Christopher J CJ Franceschini Nora N Orho-Melander Marju M Nilsson Jan J Melander Olle O Engström Gunnar G Mälarstig Anders A
Arteriosclerosis, thrombosis, and vascular biology 20210304 5
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Project description:ObjectiveTo evaluate plasma acylcarnitine profiles and their relationships with progression of carotid artery atherosclerosis among individuals with and without HIV infection.DesignProspective cohort studies of 499 HIV-positive and 206 HIV-negative individuals from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study.MethodsTwenty-four acylcarnitine species were measured in plasma samples of participants at baseline. Carotid artery plaque was assessed using repeated B-mode carotid artery ultrasound imaging in 2004-2013. We examined the associations of individual and aggregate short-chain (C2-C7), medium-chain (C8-C14) and long-chain acylcarnitines (C16-C26) with incident carotid artery plaque over 7 years.ResultsAmong 24 acylcarnitine species, C8-carnitines and C20 : 4-carnitines showed significantly lower levels comparing HIV-positive to HIV-negative individuals (false discovery rate adjusted P < 0.05); and C20-carnitines and C26-carnitines showed significantly higher levels in HIV positive using antiretroviral therapy than those without antiretroviral therapy (false discovery rate adjusted P < 0.05). In the univariate analyses, higher aggregated short-chain and long-chain acylcarnitine scores were associated with increased risk of carotid artery plaque [risk ratios (RRs) = 1.22 (95% confidence interval 1.02-1.45) and 1.20 (1.02-1.41) per SD increment, respectively]. The association for the short-chain acylcarnitine score remained significant [RR = 1.23 (1.05-1.44)] after multivariate adjustment (including traditional cardiovascular disease risk factors). This association was more evident in HIV-positive individuals without persistent viral suppression [RR = 1.37 (1.11-1.69)] compared with those with persistent viral suppression during follow-up [RR = 1.03 (0.76-1.40)] or HIV-negative individuals [RR = 1.02 (0.69-1.52)].ConclusionIn two HIV cohorts, plasma levels of most acylcarnitines were not significantly different between HIV-positive and HIV-negative individuals. However, higher levels of aggregated short-chain acylcarnitines were associated with progression of carotid artery atherosclerosis.
| S-EPMC6457128 | biostudies-literature
Project description:The Vascular Registry (VR) on carotid procedures collects long-term outcomes on carotid artery stenting (CAS) and carotid endarterectomy (CEA) patients. The purpose of this report is to describe in-hospital and 30-day CAS outcomes in patients with atherosclerotic carotid artery disease (CAD; atherosclerosis [ATH]) compared to recurrent carotid stenosis (RES) and radiation-induced stenosis (RAD).The VR collects provider-reported data on CAS using a Web-based data management system. For this report, data were analyzed at the preprocedure, procedure, predischarge, and 30-day intervals.As of November 20, 2008, there were 4017 patients with CAS with discharge data, of which 72% were due to ATH. A total of 2321 patients were available for 30-day outcomes analysis (1623 ATH, 529 restenosis, 119 radiation, 17 dissection, 3 trauma, and 30 other). Baseline demographics showed that ATH occurred in older patients (72-years-old), had the greatest history of coronary artery disease (CAD; 62%), myocardial infarction (MI; 24%), valvular heart disease (8%), arrhythmia (16%), congestive heart failure (CHF; 16%), diabetes mellitus (DM; 35%), and chronic obstructive pulmonary disease (COPD; 20%). RES had a higher degree of baseline stenosis (87.0 vs 85.8 ATH; P = .010), were less likely to be symptomatic (35.5% vs 46.3% ATH; P < .001), but had a greater history of hypertension, peripheral vascular disease (PVD), and smoking. RAD was seen in younger patients (66.6 vs 71.7 ATH; P < .001), were more likely to be male (78.2% vs 60.9% ATH; P < .001), and had less comorbidities overall, with the exception of amaurosis fugax, smoking, and cancer. The only statistically significant difference in perioperative rates was in transient ischemic attack (TIA; 2.7% ATH vs 0.9% RES; P = .02). There were no statistically significant differences in in-hospital death/stroke/MI (ATH 5.4%, RES 3.8%, RAD 4.2%) or at 30 days (ATH 7.1%, RES 5.1%, RAD 5.0%). Even after adjusting for age, gender, symptomatology, CHF, and renal failure, the only statistically significant difference at 30 days was amaurosis fugax between ATH and RAD (odds ratio [OR] 0.13; P = .01).Although patients with ATH have statistically significant comorbidities, they did not have statistically significant increased rates of death/stroke/MI during hospitalization or within 30 days after discharge when compared to RES or RAD. The CAS event rates for ATH vs RES and RAD are similar, despite prior published reports. Symptomatic ATH have statistically significant higher rates of death/stroke/MI compared to asymptomatic cohort. Finally, consistent and accurate entry of long-term data beyond initial hospitalization is essential to fully assess CAS outcomes since a significant number of adverse events occur in the interval from hospital discharge to 30 days.
| S-EPMC5557649 | biostudies-other
Project description:Calcium calcification in the wall of arteries (CAC) leads to a higher risk of atherosclerosis related outcomes, especially myocardial infarction (MI). Nevertheless, the causal role of CAC on other related outcomes is unclear. In this study, we used Mendelian randomization (MR) to systematically investigate the causal role of CAC across a broad range of atherosclerotic cardiovascular diseases including coronary heart disease, angina, MI, ischemic heart disease, stroke, and peripheral vascular disease. Publicly available data from the UK biobank and other data sources were used. Using the two-sample Mendelian randomization (MR) approach, we applied 3 MR models including the inverse variance weighted, the weighted-median, and the weighted-mode methods. Eight SNPs associated with CAC were selected as instrumental variables. We observed causal evidence of CAC on MI consistently across all MR models (PIVW = 1.0 × 10-4, PW-Median = 1.1 × 10-4, PW-Mode = 3.8 × 10-2) and this causation is shown in an acute transmural MI of inferior wall (PIVW = 1.5 × 10-4, PW-Median = 4.8 × 10-5, PW-Mode = 3.2 × 10-2) but not consistently observed in an anterior wall. As each site of acute MI was suggested to have relatively specific mechanisms, our finding suggested that the causal role of CAC on MI is in an inferior wall possibly as a consequence of large calcification from a prolonged process, whereas non-calcified artery plaque or other underlying mechanisms may predominantly play role in an anterior infarction during an advanced atherosclerotic process.
| S-EPMC9437097 | biostudies-literature
Project description:BackgroundAlterations in gut microbiota and blood metabolomic profiles have been implicated in HIV infection and cardiovascular disease. However, it remains unclear whether alterations in gut microbiota may contribute to disrupted host blood metabolomic profiles in relation to atherosclerosis, especially in the context of HIV infection.MethodsWe analyzed cross-sectional associations between gut microbiota features and carotid artery plaque in 361 women with or at high risk of HIV (67% HIV+), and further integrated plaque-associated microbial features with plasma lipidomic/metabolomic profiles. Furthermore, in 737 women and men, we examined prospective associations of baseline gut bacteria-associated lipidomic and metabolomic profiles with incident carotid artery plaque over 7-year follow-up.ResultsWe found 2 potentially pathogenic bacteria, Fusobacterium and Proteus, were associated with carotid artery plaque; while the beneficial butyrate producer Odoribacter was inversely associated with plaque. Fusobacterium and Proteus were associated with multiple lipids/metabolites which were clustered into 8 modules in network. A module comprised of 9 lysophosphatidylcholines and lysophosphatidylethanolamines and a module comprised of 9 diglycerides were associated with increased risk of carotid artery plaque (risk ratio [95% CI], 1.34 [1.09-1.64] and 1.24 [1.02-1.51] per SD increment, respectively). Functional analyses identified bacterial enzymes in lipid metabolism associated with these plasma lipids. In particular, phospholipase A1 and A2 are the key enzymes in the reactions producing lysophosphatidylcholines and lysophosphatidylethanolamines.ConclusionsAmong individuals with or at high risk of HIV infection, we identified altered gut microbiota and related functional capacities in the lipid metabolism associated with disrupted plasma lipidomic profiles and carotid artery atherosclerosis.
| S-EPMC9339474 | biostudies-literature
Project description:Observational studies have demonstrated an association between elevated homocysteine (Hcy) level and risk of multiple myeloma (MM). However, it remains unclear whether this relationship is causal. We conducted a Mendelian randomization (MR) study to evaluate whether genetically increased Hcy level influences the risk of MM. We used the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism as an instrumental variable, which affects the plasma Hcy levels. Estimate of its effect on plasma Hcy level was based on a recent genome-wide meta-analysis of 44,147 individuals, while estimate of its effect on MM risk was obtained through meta-analysis of case-control studies with 2,092 cases and 4,954 controls. By combining these two estimates, we found that per one standard-deviation (SD) increase in natural log-transformed plasma Hcy levels conferred a 2.67-fold increase in risk for MM (95% confidence interval (CI): 1.12-6.38; P = 2.7 × 10(-2)). Our study suggests that elevated Hcy levels are causally associated with an increased risk of developing MM. Whether Hcy-lowering therapy can prevent MM merits further investigation in long-term randomized controlled trials (RCTs).
| S-EPMC4850434 | biostudies-other
Project description:AimsWe conducted observational and Mendelian randomization (MR) analyses to explore the associations between blood proteins and risk of peripheral artery disease (PAD).Methods and resultsThe observational cohort analyses included data on 257 proteins estimated in fasting blood samples from 12 136 Swedish adults aged 55-94 years who were followed up for incident PAD via the Swedish Patient Register. Mendelian randomization analyses were undertaken using cis-genetic variants strongly associated with the proteins as instrumental variables and genetic association summary statistic data for PAD from the FinnGen study (11 924 cases and 288 638 controls) and the Million Veteran Program (31 307 cases and 211 753 controls). The observational analysis, including 86 individuals diagnosed with incident PAD during a median follow-up of 6.6-year, identified 13 proteins [trefoil factor two, matrix metalloproteinase-12 (MMP-12), growth differentiation factor 15, V-set and immunoglobulin domain-containing protein two, N-terminal prohormone brain natriuretic peptide, renin, natriuretic peptides B, phosphoprotein associated with glycosphingolipid-enriched microdomains one, C-C motif chemokine 15, P-selectin, urokinase plasminogen activator surface receptor, angiopoietin-2, and C-type lectin domain family five member A] associated with the risk of PAD after multiple testing correction. Mendelian randomization analysis found associations of T-cell surface glycoprotein CD4, MMP-12, secretoglobin family 3A member 2, and ADM with PAD risk. The observational and MR associations for T-cell surface glycoprotein CD4 and MMP-12 were in opposite directions.ConclusionThis study identified many circulating proteins in relation to the development of incident PAD. Future studies are needed to verify our findings and assess the predictive and therapeutic values of these proteins in PAD.
| S-EPMC10267302 | biostudies-literature
Project description:We conducted a Mendelian randomization analysis to differentiate associations of four glycemic indicators with a broad range of atherosclerotic and thrombotic diseases. Independent genetic variants associated with fasting glucose (FG), 2 h glucose after an oral glucose challenge (2hGlu), fasting insulin (FI), and glycated hemoglobin (HbA1c) at the genome-wide significance threshold were used as instrumental variables. Summary-level data for 12 atherosclerotic and 4 thrombotic outcomes were obtained from large genetic consortia and the FinnGen and UK Biobank studies. Higher levels of genetically predicted glycemic traits were consistently associated with increased risk of coronary atherosclerosis-related diseases and symptoms. Genetically predicted glycemic traits except HbA1c showed positive associations with peripheral artery disease risk. Genetically predicted FI levels were positively associated with risk of ischemic stroke and chronic kidney disease. Genetically predicted FG and 2hGlu were positively associated with risk of large artery stroke. Genetically predicted 2hGlu levels showed positive associations with risk of small vessel stroke. Higher levels of genetically predicted glycemic traits were not associated with increased risk of thrombotic outcomes. Most associations for genetically predicted levels of 2hGlu and FI remained after adjustment for other glycemic traits. Increase in glycemic status appears to increase risks of coronary and peripheral artery atherosclerosis but not thrombosis.
| S-EPMC7613853 | biostudies-literature
Project description:Background Systemic iron status has been implicated in atherosclerosis and thrombosis. The aim of this study was to investigate the effect of genetically determined iron status on carotid intima-media thickness, carotid plaque, and venous thromboembolism using Mendelian randomization. Methods and Results Genetic instrumental variables for iron status were selected from a genome-wide meta-analysis of 48 972 subjects. Genetic association estimates for carotid intima-media thickness and carotid plaque were obtained using data from 71 128 and 48 434 participants, respectively, and estimates for venous thromboembolism were obtained using data from a study incorporating 7507 cases and 52 632 controls. Conventional 2-sample summary data Mendelian randomization was performed for the main analysis. Higher genetically determined iron status was associated with increased risk of venous thromboembolism. Odds ratios per SD increase in biomarker levels were 1.37 (95% CI 1.14-1.66) for serum iron, 1.25 (1.09-1.43) for transferrin saturation, 1.92 (1.28-2.88) for ferritin, and 0.76 (0.63-0.92) for serum transferrin (with higher transferrin levels representing lower iron status). In contrast, higher iron status was associated with lower risk of carotid plaque. Corresponding odds ratios were 0.85 (0.73-0.99) for serum iron and 0.89 (0.80-1.00) for transferrin saturation, with concordant trends for serum transferrin and ferritin that did not reach statistical significance. There was no Mendelian randomization evidence of an effect of iron status on carotid intima-media thickness. Conclusions These findings support previous work to suggest that higher genetically determined iron status is protective against some forms of atherosclerotic disease but increases the risk of thrombosis related to stasis of blood.
| S-EPMC6761644 | biostudies-literature
Project description:AimsBetatrophin is a recently identified circulating adipokine that may affect lipid and glucose metabolism. However, the association between plasma betatrophin levels and carotid atherosclerosis has not been elucidated.MethodsWe investigated plasma betatrophin levels in 153 subjects undergoing carotid ultrasonography. The severity of plaque was evaluated as plaque score.ResultsOf the 153 subjects, plaque was found in 63 (41%). Plasma betatrophin levels were higher in 63 subjects with plaque than in 90 without plaque (median 906 vs. 729 pg/mL, P < 0.025). A stepwise increase in betatrophin levels was found depending on the plaque score: 729 pg/mL in score = 0 (n = 90), 802 pg/mL in score = 1 (n = 31), and 978 pg/mL in score ≥ 2 (n = 32) (P < 0.01). In particular, betatrophin levels in subjects with score ≥ 2 were higher than in those with score = 0 (P < 0.05). Moreover, betatrophin levels correlated with plaque score (r = 0.23, P < 0.01), but no significant correlation was found between betatrophin levels and triglyceride or HbA1c levels. The percentage of subjects with betatrophin > 800 pg/mL was higher in subjects with plaque than in those without plaque (65% vs. 44%) and was highest in score ≥ 2 (78%) (P < 0.005). In the multivariate analysis, betatrophin level was not a significant factor for the presence of plaque but was a significant factor for plaque score ≥ 2, independent of atherosclerotic risk factors. The odds ratio for score ≥ 2 was 4.9 (95% CI = 1.9-12.8) for betatrophin > 800 pg/mL.ConclusionsPlasma betatrophin levels were found to be high in subjects with carotid plaque and to be associated with the severity of plaque. Betatrophin may play a role in the progression of carotid atherosclerosis.
| S-EPMC6854246 | biostudies-literature
Project description:Intracranial atherosclerotic disease is a significant cause of stroke in the United States. Much like coronary atherosclerosis, this disease leads to arterial stenosis secondary to the buildup of lipid-based plaques in intracranial vessels. Ischemic stroke may occur following thromboembolic events near the site of stenosis or from watershed ischemia secondary to cerebral hypoperfusion. While this disease has been treated with intracranial angioplasty and stenting and cerebrovascular bypass surgery, the current literature supports aggressive medical management with dual antiplatelet therapy, treatment of comorbidities such as hypertension, diabetes, and hyperlipidemia, and lifestyle modification. Intracranial angioplasty and stenting is reserved for cases of medical failure.
| S-EPMC4300064 | biostudies-other