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Cureus Jun 2023Rhinosinusitis is one of the most common inflammatory diseases. It has been recognized that intracranial vessels are involved and there might be an association with... (Review)
Review
Rhinosinusitis is one of the most common inflammatory diseases. It has been recognized that intracranial vessels are involved and there might be an association with stroke occurrence. The aim of this study was to evaluate the association between rhinosinusitis and cardiovascular diseases, especially stroke, through a literature review. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We performed on PubMed a literature search from February 2000 to February 2022, using the search terms 'rhinosinusitis' OR 'chronic rhinosinusitis' AND 'stroke' OR 'ischemic stroke'. Fourteen studies were eligible and included in the analysis. Overall, the studies encompassed a total of 1,006,338 patients included in this review. All studies concluded that there is a statistically significant correlation between clinical or radiological sinus inflammation and the risk of stroke, which is independent of traditional stroke risk factors. In conclusion, rhinosinusitis is associated with an increased incidence of stroke.
PubMed: 37496556
DOI: 10.7759/cureus.40923 -
Stroke Feb 2023Over the last decades, several individual studies on sex differences in carotid atherosclerosis have been performed covering a wide range of plaque characteristics and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Over the last decades, several individual studies on sex differences in carotid atherosclerosis have been performed covering a wide range of plaque characteristics and including different populations. This systematic review and meta-analysis aims to summarize previously reported results on sex differences in carotid atherosclerosis and present a roadmap explaining next steps needed for implementing this knowledge in clinical practice.
METHODS
We systematically searched PubMed, Embase, Web of Science, Cochrane Central, and Google Scholar for eligible studies including both male and female participants reporting prevalence of imaging characteristics of carotid atherosclerosis and meta-analyzed these studies. Studies had to report at least the following: (1) calcifications; (2) lipid-rich necrotic core; (3) intraplaque hemorrhage; (4) thin-or-ruptured fibrous cap; (5) plaque ulceration; (6) degree of stenosis; (7) plaque size; or (8) plaque inflammation. We prespecified which imaging modalities had to be used per plaque characteristic and excluded ultrasonography.
RESULTS
We included 42 articles in our meta-analyses (ranging from 2 through 23 articles per plaque characteristic). Men had more frequently a larger plaque compared to women and, moreover, had more often plaques with calcifications (odds ratio=1.57 [95% CI, 1.23-2.02]), lipid-rich necrotic core (odds ratio=1.87 [95% CI, 1.36-2.57]), and intraplaque hemorrhage (odds ratio=2.52 [95% CI, 1.74-3.66]), or an ulcerated plaque (1.81 [95% CI, 1.30-2.51]). Furthermore, we found more pronounced sex differences for lipid-rich necrotic core in symptomatic opposed to asymptomatic participants.
CONCLUSIONS
In this systematic review and meta-analysis, we demonstrate convincing evidence for sex differences in carotid atherosclerosis. All kinds of plaque features-plaque size, composition, and morphology-were more common or larger in men compared to women. Our results highlight that sex is an important variable to include in both study design and clinical-decision making. Further investigation of sex-specific stroke risks with regard to plaque composition is warranted.
Topics: Female; Male; Humans; Carotid Stenosis; Sex Characteristics; Magnetic Resonance Imaging; Carotid Artery Diseases; Plaque, Atherosclerotic; Hemorrhage; Calcinosis; Necrosis; Lipids; Carotid Arteries; Risk Factors
PubMed: 36444718
DOI: 10.1161/STROKEAHA.122.041046 -
Clinical Interventions in Aging 2017Epidemiologic and clinical data have suggested the existence of a biologic linkage between the bone system and the vascular system. Bisphosphonates (BPs) are effective... (Review)
Review
BACKGROUND
Epidemiologic and clinical data have suggested the existence of a biologic linkage between the bone system and the vascular system. Bisphosphonates (BPs) are effective inhibitors of bone resorption and are currently considered the drugs of choice for the prevention and treatment of osteoporosis and related fractures. Data from several publications have suggested that BPs may also be effective in reducing the atherosclerotic process and vascular calcification, but the results of these studies are contrasting. This review aimed to allow a better understanding of the relationships between BPs and atherosclerosis in humans.
MATERIALS AND METHODS
Electronic databases of Pubmed-Medline, Cochrane Library and SCOPUS from inception to June 30, 2016 were searched. The full texts of the articles potentially eligible were carefully assessed and reviewed. Finally, 20 studies were found to be eligible and were included in the systematic review. All included studies were published between 2000 and 2014.
RESULTS
In several studies, etidronate limited the progression of aortic and coronary calcification in hemodialysis patients, whereas the nitrogen-containing-BPs given orally did not significantly reduce vascular calcifications in patients with chronic kidney disease, kidney trasplant or in those with osteoporosis. Nitrogen-containing-BPs present favorable effects both on vessel wall thickness and on arterial elasticity due to both a reduction in serum lipids and the interaction of BPs with the bone tissue, with the consequent release of bone turnover markers and cytokines into the bloodstream.
CONCLUSION
To sum up, the BPs seem to have the potential of influencing atherosclerosis and calcium homeostasis at the level of vascular walls with several possible mechanisms which may differ according to the type, potency, dosage and administration route of BPs. Additional studies are needed to specifically address the mechanism by which BP use could influence cardiovascular morbidity and mortality.
Topics: Atherosclerosis; Bone Density Conservation Agents; Bone and Bones; Diphosphonates; Humans; Osteoporosis; Vascular Calcification
PubMed: 29133976
DOI: 10.2147/CIA.S138002 -
Journal of Aging Research 2022Vascular dementia (VD) is a neurocognitive disorder whose precise definition is still up for debate. VD generally refers to dementia that is primarily caused by... (Review)
Review
Vascular dementia (VD) is a neurocognitive disorder whose precise definition is still up for debate. VD generally refers to dementia that is primarily caused by cerebrovascular disease or impaired cerebral blood flow. It is a subset of vascular cognitive impairment, a class of diseases that relate any cerebrovascular injury as a causal or correlating factor for cognitive decline, most commonly seen in the elderly. Patients who present with both cognitive impairment and clinical or radiologic indications of cerebrovascular pathology should have vascular risk factors, particularly hypertension, examined and treated. While these strategies may be more effective at avoiding dementia than at ameliorating it, there is a compelling case for intensive secondary stroke prevention in these patients. Repeated stroke is related to an increased chance of cognitive decline, and poststroke dementia is connected with an increased risk of death. In general, most physicians follow recommendations for secondary stroke prevention in patients with VD, which can be accomplished by the use of antithrombotic medicines such as antiplatelets (aspirin, clopidogrel, ticlopidine, cilostazol, etc.). In individuals with a high risk of atherosclerosis and those with documented symptomatic cerebrovascular illness, antiplatelets treatment lowers the risk of stroke. While this therapy strategy of prevention and rigorous risk management has a compelling justification, there is only limited and indirect data to support it. The following systematic review examines the role of antiplatelets in the management of vascular dementia in published clinical trials and studies and comments on the current evidence available to support their use and highlights the need for further study.
PubMed: 36245899
DOI: 10.1155/2022/9780067 -
The Cochrane Database of Systematic... Dec 2021Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis. Intermittent claudication is a symptomatic form of PAD that is characterized by pain in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis. Intermittent claudication is a symptomatic form of PAD that is characterized by pain in the lower limbs caused by chronic occlusive arterial disease. This pain develops in a limb during exercise and is relieved with rest. Propionyl-L-carnitine (PLC) is a drug that may alleviate the symptoms of PAD through a metabolic pathway, thereby improving exercise performance.
OBJECTIVES
The objective of this review is to determine whether propionyl-L-carnitine is efficacious compared with placebo, other drugs, or other interventions used for treatment of intermittent claudication (e.g. exercise, endovascular intervention, surgery) in increasing pain-free and maximum walking distance for people with stable intermittent claudication, Fontaine stage II.
SEARCH METHODS
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and the ClinicalTrials.gov trials register to July 7, 2021. We undertook reference checking and contact with study authors and pharmaceutical companies to identify additional unpublished and ongoing studies.
SELECTION CRITERIA
Double-blind randomized controlled trials (RCTs) in people with intermittent claudication (Fontaine stage II) receiving PLC compared with placebo or another intervention. Outcomes included pain-free walking performance (initial claudication distance - ICD) and maximal walking performance (absolute claudication distance - ACD), analyzed by standardized treadmill exercise test, as well as ankle brachial index (ABI), quality of life, progression of disease, and adverse events.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, extracted data, and evaluated trials for risk of bias. We contacted study authors for additional information. We resolved any disagreements by consensus. We performed fixed-effect model meta-analyses with mean differences (MDs) and 95% confidence intervals (CIs). We graded the certainty of evidence according to GRADE.
MAIN RESULTS
We included 12 studies in this review with a total number of 1423 randomized participants. A majority of the included studies assessed PLC versus placebo (11 studies, 1395 participants), and one study assessed PLC versus L-carnitine (1 study, 26 participants). We identified no RCTs that assessed PLC versus any other medication, exercise, endovascular intervention, or surgery. Participants received PLC 1 grams to 2 grams orally (9 studies) or intravenously (3 studies) per day or placebo. For the comparison PLC versus placebo, there was a high level of both clinical and statistical heterogeneity due to study size, participants coming from different countries and centres, the combination of participants with and without diabetes, and use of different treadmill protocols. We found a high proportion of drug company-backed studies. The overall certainty of the evidence was moderate. For PLC compared with placebo, improvement in maximal walking performance (ACD) was greater for PLC than for placebo, with a mean difference in absolute improvement of 50.86 meters (95% CI 50.34 to 51.38; 9 studies, 1121 participants), or a 26% relative improvement (95% CI 23% to 28%). Improvement in pain-free walking distance (ICD) was also greater for PLC than for placebo, with a mean difference in absolute improvement of 32.98 meters (95% CI 32.60 to 33.37; 9 studies, 1151 participants), or a 31% relative improvement (95% CI 28% to 34%). Improvement in ABI was greater for PLC than for placebo, with a mean difference in improvement of 0.09 (95% CI 0.08 to 0.09; 4 studies, 369 participants). Quality of life improvement was greater with PLC (MD 0.06, 95% CI 0.05 to 0.07; 1 study, 126 participants). Progression of disease and adverse events including nausea, gastric intolerance, and flu-like symptoms did not differ greatly between PLC and placebo. For the comparison of PLC with L-carnitine, the certainty of evidence was low because this included a single, very small, cross-over study. Mean improvement in ACD was slightly greater for PLC compared to L-carnitine, with a mean difference in absolute improvement of 20.00 meters (95% CI 0.47 to 39.53; 1 study, 14 participants) or a 16% relative improvement (95% CI 0.4% to 31.6%). We found no evidence of a clear difference in the ICD (absolute improvement 4.00 meters, 95% CI -9.86 to 17.86; 1 study, 14 participants); or a 3% relative improvement (95% CI -7.4% to 13.4%). None of the other outcomes of this review were reported in this study.
AUTHORS' CONCLUSIONS
When PLC was compared with placebo, improvement in walking distance was mild to moderate and safety profiles were similar, with moderate overall certainty of evidence. Although In clinical practice, PLC might be considered as an alternative or an adjuvant to standard treatment when such therapies are found to be contraindicated or ineffective, we found no RCT evidence comparing PLC with standard treatment to directly support such use.
Topics: Ankle Brachial Index; Carnitine; Humans; Intermittent Claudication; Peripheral Arterial Disease; Randomized Controlled Trials as Topic; Walking
PubMed: 34954832
DOI: 10.1002/14651858.CD010117.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 -
Diagnostics (Basel, Switzerland) Dec 2022Uveitis is not only an intraocular inflammatory disease, but also an indicator of systemic inflammation. It is unclear whether uveitis can increase the risk of... (Review)
Review
BACKGROUND
Uveitis is not only an intraocular inflammatory disease, but also an indicator of systemic inflammation. It is unclear whether uveitis can increase the risk of cardiovascular disease (CVD) through the atherosclerotic pathway.
METHODS
PubMed and Embase databases were searched until 5 September, 2022. Original studies investigating uveitis and cardiovascular events were selected. The random-effects model was used to calculate the difference of groups in pooled estimates.
RESULTS
A total of six observational studies that included mainly ankylosing spondylitis (AS) patients were included. Of these, three studies reported data on carotid plaques and carotid intima-media thickness (cIMT) and the other three studies provided data on atherosclerosis-related CVD. No significant difference was found in cIMT between uveitis and controls (MD = 0.01, 95% CI = -0.03-0.04, = 0.66), consistent with the findings of carotid plaque incidence (OR = 1.30, 95% CI = 0.71-2.41, = 0.39). However, uveitis was associated with a 1.49-fold increase in atherosclerosis-related CVD (HR = 1.49, 95% CI = 1.20-1.84, = 0.0002).
CONCLUSIONS
Uveitis is a predictor of atherosclerosis-related CVD in AS patients. For autoimmune disease patients with uveitis, earlier screening of cardiovascular risk factors and the implementation of corresponding prevention strategies may be associated with a better prognosis.
PubMed: 36553185
DOI: 10.3390/diagnostics12123178 -
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 -
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