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Nutrients Sep 2020Matrix gla protein (MGP) is an important vitamin K-dependent inhibitor of vascular calcification. High levels of uncarboxylated, dephosphorylated MGP have been...
Matrix gla protein (MGP) is an important vitamin K-dependent inhibitor of vascular calcification. High levels of uncarboxylated, dephosphorylated MGP have been associated with vascular calcification and are responsive to vitamin K treatment. In this systematic review, we summarize the available evidence examining whether vitamin K supplementation improves surrogate measures of cardiovascular disease including artery and valve calcification, atherosclerosis and artery stiffening. Data from controlled trials of adults were obtained by searching Ovid MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and the Web of Science Core Collection. We identified nine randomized controlled trials for review, including trials of vitamin K or vitamin K supplementation, that assessed a surrogate measure of cardiovascular disease including arterial calcification, atherosclerosis or arterial stiffening. For each trial, the risk of bias was assessed applying Cochrane Collaboration methodology. The findings indicate that vitamin K does not consistently prevent progression of calcification, atherosclerosis or arterial stiffness. There may be some benefit in people with calcification at study entry. Studies were heterogenous, with relatively short follow-up and outcome measures were varied. While vitamin K supplementation clearly improves the carboxylation of dephosphoylated MGP, its role in mitigating vascular calcification is uncertain, based on current evidence.
Topics: Animals; Arteries; Atherosclerosis; Calcium-Binding Proteins; Cardiovascular Diseases; Databases, Factual; Dietary Supplements; Disease Progression; Extracellular Matrix Proteins; Humans; Randomized Controlled Trials as Topic; Vascular Calcification; Vascular Stiffness; Vitamin K; Vitamin K 2; Matrix Gla Protein
PubMed: 32977548
DOI: 10.3390/nu12102909 -
Drugs Aug 2022High-quality evidence from trials directly comparing single antiplatelet therapies in symptomatic peripheral arterial disease (PAD) to dual antiplatelet therapies or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
High-quality evidence from trials directly comparing single antiplatelet therapies in symptomatic peripheral arterial disease (PAD) to dual antiplatelet therapies or acetylsalicylic acid (ASA) plus low-dose rivaroxaban is lacking. Therefore, we conducted a network meta-analysis on the effectiveness of all antithrombotic regimens studied in PAD.
METHODS
A systematic search was conducted to identify randomized controlled trials. The primary endpoints were major adverse cardiovascular events (MACE) and major bleedings. Secondary endpoints were major adverse limb events (MALE) and acute limb ischaemia (ALI). For each outcome, a frequentist network meta-analysis was used to compare relative risks (RRs) between medication and ASA. ASA was the universal comparator since a majority of studies used ASA as in the reference group.
RESULTS
Twenty-four randomized controlled trials were identified including 48,759 patients. With regard to reducing MACE, clopidogrel [RR 0.78, 95% confidence interval (CI) 0.66-0.93], ticagrelor (RR 0.79, 95% CI 0.65-0.97), ASA plus ticagrelor (RR 0.79, 95% CI 0.64-0.97), and ASA plus low-dose rivaroxaban (RR 0.84, 95% CI 0.76-0.93) were more effective than ASA, and equally effective to one another. As compared to ASA, major bleedings occurred more frequently with vitamin K antagonists, rivaroxaban, ASA plus vitamin K antagonists, and ASA plus low-dose rivaroxaban. All regimens were similar to ASA concerning MALE, while ASA plus low-dose rivaroxaban was more effective in preventing ALI (RR 0.67, 95% CI 0.55-0.80). Subgroup analysis in patients undergoing peripheral revascularization revealed that ≥ 3 months after intervention, evidence of benefit regarding clopidogrel, ticagrelor, and ASA plus ticagrelor was lacking, while ASA plus low-dose rivaroxaban was more effective in preventing MACE (RR 0.87, 95% CI 0.78-0.97) and MALE (RR 0.89, 95% CI 0.81-0.97) compared to ASA. ASA plus clopidogrel was not superior to ASA in preventing MACE ≥ 3 months after revascularization. Evidence regarding antithrombotic treatment strategies within 3 months after a peripheral intervention was lacking.
CONCLUSION
Clopidogrel, ticagrelor, ASA plus ticagrelor, and ASA plus low-dose rivaroxaban are superior to ASA monotherapy and equally effective to one another in preventing MACE in PAD. Of these four therapies, only ASA plus low-dose rivaroxaban provides a higher risk of major bleedings. More than 3 months after peripheral vascular intervention, ASA plus low-dose rivaroxaban is superior in preventing MACE and MALE compared to ASA but again at the cost of a higher risk of bleeding, while other treatment regimens show non-superiority. Based on the current evidence, clopidogrel may be considered the antithrombotic therapy of choice for most PAD patients, while in patients who underwent a peripheral vascular intervention, ASA plus low-dose rivaroxaban could be considered for the long-term (> 3 months) prevention of MACE and MALE.
Topics: Aspirin; Clopidogrel; Fibrinolytic Agents; Hemorrhage; Humans; Network Meta-Analysis; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Ticagrelor; Vitamin K
PubMed: 35997941
DOI: 10.1007/s40265-022-01756-6 -
Experimental Gerontology May 2022An association between osteoarthritis (OA) and atherosclerosis (AT) has been proposed, but evidence is controverted, with recent meta-analysis showing disparate results.... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
An association between osteoarthritis (OA) and atherosclerosis (AT) has been proposed, but evidence is controverted, with recent meta-analysis showing disparate results. To better refine this possible association, we performed a systematic review and meta-analysis subdividing OA by joint, i.e., hip and knee, hands, and OA in general, and stratified the results by subclinical AT, manifest cardiovascular (CV) disease, and CV death. Separation by sex, whenever this information was available, was also accounted.
METHODS
We searched PubMed, Web of Science, LILACS, and SciELO from inception until September 2021, using the MeSH search terms "osteoarthritis", "aorta", "carotid", "intima-media thickness", "coronary artery disease", "atherosclerosis", "cardiovascular disease", and "death". To appraise the quality of the studies, we applied the NewCastle-Ottawa scale. To assess for heterogeneity, I was used. A random-fixed effect model was adopted, and outliers were excluded when detected. Publication bias was ascertained by funnel plot and Egger regression test.
RESULTS
A total of 49 studies, comprising 552,857 individuals with OA and 688,820 controls, were included on the narrative synthesis, and 33 on the meta-analysis. All but five studies were deemed as of fair or good quality. Hip and knee OA increased the risk for both subclinical AT (OR 1.15, 95% CI 1.01-1.31), and CV disease (OR 1.13, 95% CI 1.05-1.22), but not for CV death (OR 1.08, 95% CI 0.99-1.19). Hands OA was associated with subclinical AT (OR 1.18, 95% CI 1.02-1.36), but not with CV disease (OR 1.49, 95% CI 0.90-2.46) or CV death (OR 1.02, 95% CI 0.73-1.44).
CONCLUSIONS
Having OA was associated with subclinical AT for all joints evaluated, but with CV disease only for weight-bearing joints. Even though there was a trend in favor of a positive association between OA and CV death, it did not reach statistical significance.
Topics: Atherosclerosis; Carotid Arteries; Hand; Humans; Knee Joint; Osteoarthritis, Hip; Osteoarthritis, Knee
PubMed: 35151784
DOI: 10.1016/j.exger.2022.111734 -
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 -
Alimentary Pharmacology & Therapeutics Aug 2023Nonalcoholic fatty liver disease (NAFLD) is a liver disorder commonly associated with metabolic syndrome and cardiovascular disease (CVD). Atherosclerosis, a leading... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nonalcoholic fatty liver disease (NAFLD) is a liver disorder commonly associated with metabolic syndrome and cardiovascular disease (CVD). Atherosclerosis, a leading cause of CVD, has been linked to liver fibrosis. However, the evidence regarding this association is conflicting.
AIM
To evaluate the link between liver fibrosis and subclinical atherosclerosis in patients with NAFLD METHODS: We conducted a comprehensive search of four databases from 1950 to February 2023 to identify eligible studies investigating the association between liver fibrosis and subclinical atherosclerosis among patients with NAFLD, utilising the PICOS framework. Two independent reviewers screened the studies; quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis was performed using the DerSimonian-Liard random-effects model, and subgroup analysis was conducted based on the severity of liver fibrosis, type of subclinical atherosclerosis diagnosis and geographic region.
RESULTS
The meta-analysis included 12 studies with a total of 4725 patients. Overall pooled odds ratio (OR) for subclinical atherosclerosis was 2.18 (95% CI: 1.62-2.93), indicating a significant association with liver fibrosis in NAFLD. Subgroup analysis revealed higher ORs in patients with more severe fibrosis: 1.64 (95% CI: 1.22-2.20) in ≥F1, 2.22 (95% CI: 1.37-3.62) in ≥F2, and 3.42 (95% CI: 1.81-6.46) in ≥F3. However, there was no significant difference between the West versus East and various measurements of subclinical atherosclerosis.
CONCLUSIONS
Any degree of fibrosis is significantly associated with subclinical atherosclerosis, with fibrosis severity amplifying the association.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Atherosclerosis; Liver Cirrhosis; Metabolic Syndrome; Cardiovascular Diseases
PubMed: 37345533
DOI: 10.1111/apt.17617 -
Progress in Cardiovascular Diseases 2023With expanding commercial space programs, uncertainty remains about the cardiovascular effects of space environmental exposures including microgravity, confinement,... (Review)
Review
BACKGROUND
With expanding commercial space programs, uncertainty remains about the cardiovascular effects of space environmental exposures including microgravity, confinement, isolation, space radiation, and altered bacterial virulence. Current limited data suggests additional health threats compared to Earth.
METHODS
We systematically reviewed PubMed, CENTRAL, Web of Science, EMBASE and Cochrane databases for prospective studies on spaceflight and cardiovascular outcomes. Search terms combined cardiovascular disease topics with spaceflight concepts. No date or language restrictions were imposed.
RESULTS
35 studies representing 2696 space travelers met inclusion criteria. Studies were grouped into spaceflight associations with: atherosclerosis, mortality, cardiac function, orthostatic intolerance, and arrhythmias. Atherosclerosis evidence was limited, with animal studies linking space radiation to endothelial damage, oxidative stress, and inflammation. However, human data showed no significantly increased atherosclerotic disease in astronauts. Mortality studies demonstrated lower cardiovascular mortality in astronauts compared to the general population however there was conflicting data. Cardiac function studies revealed physiologic ventricular atrophy, increased arterial stiffness, and altered blood flow distribution attributed to microgravity exposure. Effects appeared transient and reversible post-flight. Orthostatic intolerance studies found astronauts experienced altered heart rate variability, baroreflex response, and blood pressure changes post-flight. Arrhythmia studies showed increased ventricular ectopy during spaceflight, but limited data on long term flights.
CONCLUSIONS
Environmental space hazards impact the cardiovascular system through multiple mechanisms. Microgravity causes cardiac atrophy and orthostatic intolerance while space radiation may potentially accelerate atherosclerosis. Further research is needed, especially regarding long-term spaceflights.
Topics: Humans; Cardiovascular Diseases; Orthostatic Intolerance; Prospective Studies; Space Flight; Hemodynamics; Arrhythmias, Cardiac; Atherosclerosis; Atrophy
PubMed: 37531984
DOI: 10.1016/j.pcad.2023.07.009 -
Endocrine Mar 2023Statin intolerance is a key barrier to the effective prevention of atherosclerotic cardiovascular disease (ASCVD). Experts do not agree on what it is and how to respond... (Review)
Review
BACKGROUND
Statin intolerance is a key barrier to the effective prevention of atherosclerotic cardiovascular disease (ASCVD). Experts do not agree on what it is and how to respond to this problem clinically.
OBJECTIVE
To characterize the range of expert recommendations about the care of patients with statin intolerance.
METHODS
Systematic review registered in PROSPERO that searched on April 1 2022 in PubMed, EMBASE, Scopus, Cochrane, online textbooks, and specialty textbooks for expert reviews (e.g., review articles and book chapters), systematic reviews, or clinical practice guidelines published in the past 5 years without language restriction. Authors working in duplicate extracted definitions, management recommendations, and supportive evidence cited.
RESULTS
We identified 26 eligible articles, none of which described a systematic method to summarize the evidence or to develop and grade recommendations. Of these, 14 (54%) offered a definition of statin intolerance. A sequenced approach to management of statin intolerance was suggested in 24 (92%) articles describing 12 different approaches without supporting evidence of efficacy. Investigating for other causes was the most common first step. All authors suggested rechallenging after a washout period with either the same or other statin. Few considered nonlipid approaches to reducing ASCVD risk and none recommended involving patients in shared decision making.
CONCLUSION
We found substantial variability in the definition and management of statin intolerance among experts. Few focused on ASCVD risk reduction and none promoted the participation of patients in shared decision making about how to address the threat of ASCVD with or without statins.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cardiovascular Diseases; Atherosclerosis
PubMed: 36459335
DOI: 10.1007/s12020-022-03263-w -
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 -
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