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The Cochrane Database of Systematic... Aug 2023Carotid artery stenosis is narrowing of the carotid arteries. Asymptomatic carotid stenosis is when this narrowing occurs in people without a history or symptoms of this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Carotid artery stenosis is narrowing of the carotid arteries. Asymptomatic carotid stenosis is when this narrowing occurs in people without a history or symptoms of this disease. It is caused by atherosclerosis; that is, the build-up of fats, cholesterol, and other substances in and on the artery walls. Atherosclerosis is more likely to occur in people with several risk factors, such as diabetes, hypertension, hyperlipidaemia, and smoking. As this damage can develop without symptoms, the first symptom can be a fatal or disabling stroke, known as ischaemic stroke. Carotid stenosis leading to ischaemic stroke is most common in men older than 70 years. Ischaemic stroke is a worldwide public health problem.
OBJECTIVES
To assess the effects of pharmacological interventions for the treatment of asymptomatic carotid stenosis in preventing neurological impairment, ipsilateral major or disabling stroke, death, major bleeding, and other outcomes.
SEARCH METHODS
We searched the Cochrane Stroke Group trials register, CENTRAL, MEDLINE, Embase, two other databases, and three trials registers from their inception to 9 August 2022. We also checked the reference lists of any relevant systematic reviews identified and contacted specialists in the field for additional references to trials.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs), irrespective of publication status and language, comparing a pharmacological intervention to placebo, no treatment, or another pharmacological intervention for asymptomatic carotid stenosis.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures. Two review authors independently extracted the data and assessed the risk of bias of the trials. A third author resolved disagreements when necessary. We assessed the evidence certainty for key outcomes using GRADE.
MAIN RESULTS
We included 34 RCTs with 11,571 participants. Data for meta-analysis were available from only 22 studies with 6887 participants. The mean follow-up period was 2.5 years. None of the 34 included studies assessed neurological impairment and quality of life. Antiplatelet agent (acetylsalicylic acid) versus placebo Acetylsalicylic acid (1 study, 372 participants) may result in little to no difference in ipsilateral major or disabling stroke (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.47 to 2.47), stroke-related mortality (RR 1.40, 95% CI 0.54 to 3.59), progression of carotid stenosis (RR 1.16, 95% CI 0.79 to 1.71), and adverse events (RR 0.81, 95% CI 0.41 to 1.59), compared to placebo (all low-certainty evidence). The effect of acetylsalicylic acid on major bleeding is very uncertain (RR 0.98, 95% CI 0.06 to 15.53; very low-certainty evidence). The study did not measure neurological impairment or quality of life. Antihypertensive agents (metoprolol and chlorthalidone) versus placebo The antihypertensive agent, metoprolol, may result in no difference in ipsilateral major or disabling stroke (RR 0.14, 95% CI 0.02 to1.16; 1 study, 793 participants) and stroke-related mortality (RR 0.57, 95% CI 0.17 to 1.94; 1 study, 793 participants) compared to placebo (both low-certainty evidence). However, chlorthalidone may slow the progression of carotid stenosis (RR 0.45, 95% CI 0.23 to 0.91; 1 study, 129 participants; low-certainty evidence) compared to placebo. Neither study measured neurological impairment, major bleeding, adverse events, or quality of life. Anticoagulant agent (warfarin) versus placebo The evidence is very uncertain about the effects of warfarin (1 study, 919 participants) on major bleeding (RR 1.19, 95% CI 0.97 to 1.46; very low-certainty evidence), but it may reduce adverse events (RR 0.89, 95% CI 0.81 to 0.99; low-certainty evidence) compared to placebo. The study did not measure neurological impairment, ipsilateral major or disabling stroke, stroke-related mortality, progression of carotid stenosis, or quality of life. Lipid-lowering agents (atorvastatin, fluvastatin, lovastatin, pravastatin, probucol, and rosuvastatin) versus placebo or no treatment Lipid-lowering agents may result in little to no difference in ipsilateral major or disabling stroke (atorvastatin, lovastatin, pravastatin, and rosuvastatin; RR 0.36, 95% CI 0.09 to 1.53; 5 studies, 2235 participants) stroke-related mortality (lovastatin and pravastatin; RR 0.25, 95% CI 0.03 to 2.29; 2 studies, 1366 participants), and adverse events (fluvastatin, lovastatin, pravastatin, probucol, and rosuvastatin; RR 0.76, 95% CI 0.53 to1.10; 7 studies, 3726 participants) compared to placebo or no treatment (all low-certainty evidence). The studies did not measure neurological impairment, major bleeding, progression of carotid stenosis, or quality of life.
AUTHORS' CONCLUSIONS
Although there is no high-certainty evidence to support pharmacological intervention, this does not mean that pharmacological treatments are ineffective in preventing ischaemic cerebral events, morbidity, and mortality. High-quality RCTs are needed to better inform the best medical treatment that may reduce the burden of carotid stenosis. In the interim, clinicians will have to use other sources of information.
Topics: Humans; Warfarin; Carotid Stenosis; Metoprolol; Atorvastatin; Chlorthalidone; Fluvastatin; Pravastatin; Probucol; Rosuvastatin Calcium; Stroke; Hemorrhage; Aspirin; Ischemic Stroke; Atherosclerosis
PubMed: 37565307
DOI: 10.1002/14651858.CD013573.pub2 -
In Vivo (Athens, Greece) 2020Thyroid dysfunction, both hypo- and hyperthyroidism, has been associated with cardiovascular disease. The aim of this study was to evaluate the association between...
BACKGROUND/AIM
Thyroid dysfunction, both hypo- and hyperthyroidism, has been associated with cardiovascular disease. The aim of this study was to evaluate the association between thyroid dysfunction and atherosclerosis measured mostly by carotid intima-media thickness, as well as discuss whether L-T4 replacement is able to reverse or slow down the progression of atherosclerosis.
MATERIALS AND METHODS
The review was conducted according the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We performed on PubMed a literature search from May 2004 to January 2020, using the search terms 'subclinical hypothyroidism' or 'thyroid disorders' and 'carotid artery', 'carotid intima-media thickness (IMT)', 'levothyroxine', and 'atherosclerosis'.
RESULTS
Twenty-six studies were eligible and included in the analysis. Overall, the studies encompassed a total of 36.434 patients included in this review. Most studies indicated a proportional correlation between IMT and thyroid dysfunction. Levothyroxine (L-T4) replacement led to significant decrease of IMT after 1 year in most studies.
CONCLUSION
Most studies have concluded that thyroid dysfunction is associated with arterial wall remodeling and, thus, with increased cardiovascular risk. However, the exact mechanistic background of pathological structural changes in the arterial wall is still unsettled. Large randomized controlled studies are required to definitively address the extent to which T4 replacement therapy might benefit patients with subclinical thyroid disorders.
Topics: Atherosclerosis; Carotid Intima-Media Thickness; Humans; Hypothyroidism; Risk Factors; Thyroxine
PubMed: 33144416
DOI: 10.21873/invivo.12147 -
Advances in Clinical and Experimental... May 2024Atherosclerosis is a complex process involving endothelial dysfunction, vascular inflammation, vascular smooth muscle cell (VSMC) proliferation, angiogenesis, and... (Review)
Review
Atherosclerosis is a complex process involving endothelial dysfunction, vascular inflammation, vascular smooth muscle cell (VSMC) proliferation, angiogenesis, and calcification. One of the pathomechanisms of atherosclerosis is the upregulation of Wnt signaling. This study aimed to summarize the current knowledge regarding the role of Wnt signaling and sclerostin in atherosclerosis, vascular calcification, aneurysms, and mortality based on the PubMed database. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendation and identified 160 papers that were included in this systematic review. The published data highlight that the upregulation of Wnt components facilitates the initiation and progression of atherosclerosis, arterial remodeling, VSMCs proliferation and phenotypic transition to the osteoblastic lineage in the arterial wall. This results in protein secretion, cell migration, calcification, fibrosis and aneurysm formation. The transformation of VSMCs into osteoblast-like cells that is observed in atherosclerosis results in sclerostin expression inhibiting the Wnt pathway. Furthermore, it was shown that sclerostin, expressed in atherosclerotic plaques, inhibits aneurysm formation in a mouse model. However, in humans, while the antisclerostin antibody romosozumab inhibits bone resorption, biochemical parameters of endothelial activation and inflammation are not affected, and the incidence of aneurysms is not increased. It was suggested that detecting sclerostin in the calcified aortic atherosclerotic plaques reflects a defense mechanism against Wnt activation and inhibition of atherosclerosis, although this has only been shown in animal models. Moreover, an increased number of vascular cells converted to osteogenic phenotypes results in increased plasma sclerostin concentrations. Therefore, plasma sclerostin derived from bone limits its importance as a global marker of vascular calcification.
Topics: Humans; Vascular Calcification; Atherosclerosis; Animals; Wnt Signaling Pathway; Adaptor Proteins, Signal Transducing; Genetic Markers
PubMed: 37676098
DOI: 10.17219/acem/169567 -
European Review For Medical and... Sep 2023Hyperhomocysteinemia is a well-known marker that is associated with an increased risk of atherosclerosis due to its toxic effect on endothelial cells. This, in turn,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Hyperhomocysteinemia is a well-known marker that is associated with an increased risk of atherosclerosis due to its toxic effect on endothelial cells. This, in turn, leads to cardiovascular injury and increases morbidity. Different studies have shown alterations in the levels of homocysteine with respect to multiple disease states. Whether this non-traditional marker is associated with cardiovascular injury or not is subject to conflicting results. The purpose of this systematic review is to evaluate the role of homocysteine in the formation of atherosclerotic cardiovascular disease in young adults and children.
MATERIALS AND METHODS
This systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA). A search was done using specific keywords, including "homocysteine", "coronary artery disease", and "atherosclerosis", amongst several others, from the databases of PubMed, COCHRANE, and EBSCO. The data items included the diseased sample population along with the intervention used, or investigations carried out and the findings of the studies. Finally, 35 eligible studies were included.
RESULTS
Young patients with atherosclerotic cardiovascular disease were more likely to have elevated levels of homocysteine compared to elderly patients. Elevated levels of homocysteine have been observed with several genetic, nutritional deficiencies, and autoimmune states such as rheumatoid arthritis. On the other hand, decreased levels of homocysteine have been observed after certain intervention treatments, such as oral contraceptive pills, L-thyroxine, and even the adoption of certain diets. In the majority of studies, whenever homocysteine levels were higher than normal, this was reflected by an increased carotid intima-media thickness.
CONCLUSIONS
Homocysteine has a high correlation with atherosclerotic cardiovascular disease in young and overweight patients. In addition, the relationship of homocysteine with smoking, genetic polymorphism, specific hormonal and renal disorders, nutritional deficiencies (vitamin B12 and folic acid), and the use of specific medicines are among the other recurring findings. Given that many of these studies focus only on women, the relationship between homocysteine and atherosclerotic cardiovascular diseases in males is still unclear. Whether males are more prone to hyperhomocysteinemia needs to be assessed. Still, precise processes underlying variations in homocysteine in relation to all influencing factors are unclear and need further studies.
Topics: Male; Child; Humans; Female; Aged; Cardiovascular Diseases; Carotid Intima-Media Thickness; Prognosis; Hyperhomocysteinemia; Homocysteine; Endothelial Cells; Atherosclerosis; Folic Acid; Vitamin B 12; Risk Factors
PubMed: 37782175
DOI: 10.26355/eurrev_202309_33784 -
Cardiovascular & Hematological... 2017Atherosclerosis is a chronic inflammatory condition causing very high morbidity and mortality. It is characterized by accumulation of plaques within arteries.... (Review)
Review
BACKGROUND
Atherosclerosis is a chronic inflammatory condition causing very high morbidity and mortality. It is characterized by accumulation of plaques within arteries. Nanomedicine is an emerging field of medicine utilizing nanotechnology for advanced imaging and therapy. Nanomedicine has led to significant developments in the field of cardiovascular diseases, including atherosclerosis. Many nanoformulations have been developed with anti-atherosclerotic effects. Nanomedicine tools have been used in the imaging of atherosclerosis. Various nanocarriers have been employed for successful localization in atherosclerotic lesions. The biggest challenge for such delivery vehicles has been localization to atherosclerosis lesions. Several strategies have been employed to overcome these defects. Strategies have also been developed for stabilization of atherosclerotic lesions.
CONCLUSION
Nanotechnology is also an important tool for the development of novel biomarkers. At the same time there are also potential limitations. Toxicity, lack of translation from preclinical phase to clinical development, and the inability to address the chronic phase of atherosclerosis are the most important among them. Future toxicity studies shall enlighten us further on this exciting research area.
Topics: Animals; Atherosclerosis; Biomarkers; Drug Delivery Systems; Humans; Magnetic Resonance Imaging; Nanomedicine; Nanoparticles; Tomography, Emission-Computed
PubMed: 28925905
DOI: 10.2174/1871529X17666170918142653 -
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 -
Seminars in Arthritis and Rheumatism Feb 2016To evaluate subclinical atherosclerosis in Behcet disease (BD), we performed a systematic review and meta-analysis of studies where atherosclerosis was determined by... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate subclinical atherosclerosis in Behcet disease (BD), we performed a systematic review and meta-analysis of studies where atherosclerosis was determined by flow-mediated dilatation (FMD) and endothelial-mediated dilatation (EMD) and by measurement of intima media thickness (IMT) of carotid arteries.
METHODS
Systematic search of EMBASE and PubMed databases from January 2000 to January 2014 according to PRISMA guidelines.
RESULTS
Nine studies met the inclusion criteria on FMD/EMD, 11 on IMT and 4 on both. BD had lower FMD than controls (SMD = -0.89, 95% CI: -0.660 to -1.11, p < 0.001), which was confirmed by subgroup analyses on active and inactive patients (SMD = -1.17, 95% CI: -1.45 to -0.89 and SMD = -0.72, 95% CI: -0.97 to -0.46, p = 0.0001 for both). EMD was lower in BD but with a large estimate (SMD = 0.38, 95% CI: -0.79 to -0.03, p = 0.06, I(2) = 82.2%). IMT was greater in BD and the large estimate (SMD = 0.95, 95% CI: 0.63-1.28, p < 0.0001, I(2) = 87.6%) persisted after subgroup analysis on active and inactive patients (I(2) = 88.4% and 86.7%, respectively). Pooling IMT studies by a Newcastle Ottawa Scale of 5 and 6/7 yielded lower estimates (SMD = 0.54, 95% CI: 0.32-0.75, p < 0.0001, I(2) = 58.7% and SMD = 1.72, 95% CI: 1.35-2.09 p < 0.05, I(2) = 48.6%).
CONCLUSIONS
FMD is impaired in BD even in inactive state and IMT is greater despite a degree of statistical heterogeneity that reflects the clinical heterogeneity of BD. Future prospective studies should account for risk stratification of atherosclerosis in BD.
Topics: Atherosclerosis; Behcet Syndrome; Carotid Arteries; Carotid Intima-Media Thickness; Endothelium, Vascular; Humans; Severity of Illness Index
PubMed: 26239908
DOI: 10.1016/j.semarthrit.2015.06.018 -
International Journal of Molecular... May 2023Atherosclerosis is a complex pathological condition marked by the accumulation of lipids in the arterial wall, leading to the development of plaques that can eventually... (Review)
Review
Atherosclerosis is a complex pathological condition marked by the accumulation of lipids in the arterial wall, leading to the development of plaques that can eventually rupture and cause thrombotic events. In recent years, hydrogen sulfide (HS) has emerged as a key mediator of cardiovascular homeostasis, with potential therapeutic applications in atherosclerosis. This systematic review highlights the importance of understanding the complex interplay between HS, oxygen homeostasis, and atherosclerosis and suggests that targeting HS signaling pathways may offer new avenues for treating and preventing this condition. Oxygen homeostasis is a critical aspect of cardiovascular health, and disruption of this balance can contribute to the development and progression of atherosclerosis. Recent studies have demonstrated that HS plays an important role in maintaining oxygen homeostasis by regulating the function of oxygen-sensing enzymes and transcription factors in vascular cells. HS has been shown to modulate endothelial nitric oxide synthase (eNOS) activity, which plays a key role in regulating vascular tone and oxygen delivery to tissues. The comprehensive analysis of the current understanding of HS in atherosclerosis can pave the way for future research and the development of new therapeutic strategies for this debilitating condition. PROSPERO ID: 417150.
Topics: Humans; Hydrogen Sulfide; Atherosclerosis; Molecular Biology; Arteries; Homeostasis; Oxygen; Nitric Oxide
PubMed: 37176083
DOI: 10.3390/ijms24098376 -
Brain and Behavior Apr 2020To evaluate the relationship between atherosclerosis and Alzheimer's disease (AD), we conducted a systematic review and meta-analysis to study the difference of carotid... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To evaluate the relationship between atherosclerosis and Alzheimer's disease (AD), we conducted a systematic review and meta-analysis to study the difference of carotid intima-media thickness (CIMT) and the prevalence of atherosclerosis between AD patients and non-AD controls.
METHODS
The studies on the association between atherosclerosis and AD were manually searched in PubMed, Embase, Cochrane Library, and CNKI (China National Knowledge Infrastructure) spanned to September 2018 according to PRISMA (the Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines.
RESULTS
Thirteen studies were included in the final analysis, seven studies with data on the mean CIMT (610 cases and 417 controls) and ten studies reporting on the prevalence of atherosclerosis (1,698 cases and 6,452 controls). Compared with controls, AD group showed a significantly higher CIMT (overall standard mean difference = 0.94; 95% CI, 0.48-1.40; p < .0001) and an increased prevalence of atherosclerosis (OR = 1.46; 95% CI, 1.26-1.68; p < .0001).
CONCLUSIONS
Atherosclerosis is significantly associated with AD. CIMT might be a useful marker to predict the risk of AD and assess the vascular burden. The finding is also important for possible prevention and treatment of AD in the future.
Topics: Alzheimer Disease; Atherosclerosis; Biomarkers; Carotid Intima-Media Thickness; China; Comorbidity; Humans; Prevalence; Risk Factors
PubMed: 32162494
DOI: 10.1002/brb3.1601 -
Cardiovascular Diabetology Dec 2022Apolipoprotein C1 (apoC1) is a small size apolipoprotein whose exact role is not totally clarified but which seems to modulate significantly the metabolism of... (Review)
Review
Apolipoprotein C1 (apoC1) is a small size apolipoprotein whose exact role is not totally clarified but which seems to modulate significantly the metabolism of lipoproteins. ApoC1 is involved in the metabolism of triglyceride-rich lipoproteins by inhibiting the binding of very low density lipoproteins (VLDL) to VLDL-receptor (VLDL-R), to low density lipoprotein receptor (LDL-R) and to LDL receptor related protein (LRP), by reducing the activity of lipoprotein lipase (LPL) and by stimulating VLDL production, all these effects leading to increase plasma triglycerides. ApoC1 takes also part in the metabolism of high density lipoproteins (HDL) by inhibiting Cholesterol Ester Transfer Protein (CETP). The functionality of apoC1 on CETP activity is impaired in diabetes that might account, at least in part, for the increased plasma CETP activity observed in patients with diabetes. Its different effects on lipoprotein metabolism with a possible role in the modulation of inflammation makes the net impact of apoC1 on cardiometabolic risk difficult to figure out and apoC1 might be considered as pro-atherogenic or anti-atherogenic depending on the overall metabolic context. Making the link between total plasma apoC1 levels and the risk of cardio-metabolic diseases is difficult due to the high exchangeability of this small protein whose biological effects might depend essentially on its association with VLDL or HDL. The role of apoC1 in humans is not entirely elucidated and further studies are needed to determine its precise role in lipid metabolism and its possible pleiotropic effects on inflammation and vascular wall biology. In this review, we will present data on apoC1 structure and distribution among lipoproteins, on the effects of apoC1 on VLDL metabolism and HDL metabolism and we will discuss the possible links between apoC1, atherosclerosis and diabetes.
Topics: Humans; Apolipoprotein C-I; Atherosclerosis; Cholesterol Ester Transfer Proteins; Diabetes Mellitus; Inflammation; Lipoproteins, HDL; Lipoproteins, VLDL; Triglycerides
PubMed: 36471375
DOI: 10.1186/s12933-022-01703-5