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PloS One 2023Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide. Atherosclerosis occurs due to accumulation of low-density lipoprotein... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality worldwide. Atherosclerosis occurs due to accumulation of low-density lipoprotein cholesterol (LDL-c) in the arterial system. Thus, lipid lowering therapy is essential for both primary and secondary prevention. Proprotein convertase subtilisn/kexin type 9 (PCSK9) inhibitors (Evolocumab, Alirocumab) and small interfering RNA (siRNA) therapy (Inclisiran) have been demonstrated to lower LDL-c and ASCVD events in conjunction with maximally tolerated statin therapy. However, the degree of LDL-c reduction and the impact on reducing major adverse cardiac events, including their impact on mortality, remains unclear.
OBJECTIVE
The purpose of this study is to examine the effects of PCSK9 inhibitors and small interfering RNA (siRNA) therapy on LDL-c reduction and major adverse cardiac events (MACE) and mortality by conducting a meta-analysis of randomized controlled trials.
METHODS
Using Pubmed, Embase, Cochrane Library and clinicaltrials.gov until April 2023, we extracted randomized controlled trials (RCTs) of PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) for lipid lowering and risk of MACE. Using random-effects models, we pooled the relative risks and 95% CIs and weighted least-squares mean difference in LDL-c levels. We estimated odds ratios with 95% CIs among MACE subtypes and all-cause mortality. Fixed-effect model was used, and heterogeneity was assessed using the I2 statistic.
RESULTS
In all, 54 studies with 87,669 participants (142,262 person-years) met criteria for inclusion. LDL-c percent change was reported in 47 studies (n = 62,634) evaluating two PCSK9 inhibitors and siRNA therapy. Of those, 21 studies (n = 41,361) included treatment with Evolocumab (140mg), 22 (n = 11,751) included Alirocumab (75mg), and 4 studies (n = 9,522) included Inclisiran (284mg and 300mg). Compared with placebo, after a median of 24 weeks (IQR 12-52), Evolocumab reduced LDL-c by -61.09% (95% CI: -64.81, -57.38, p<0.01) and Alirocumab reduced LDL-c by -46.35% (95% CI: -51.75, -41.13, p<0.01). Inclisiran 284mg reduced LDL-c by -54.83% (95% CI: -59.04, -50.62, p = 0.05) and Inclisiran 300mg reduced LDL-c by -43.11% (95% CI: -52.42, -33.80, p = 0.01). After a median of 8 months (IQR 6-15), Evolocumab reduced the risk of myocardial infarction (MI), OR 0.72 (95% CI: 0.64, 0.81, p<0.01), coronary revascularization, 0.77 (95% CI: 0.70, 0.84, p<0.01), stroke, 0.79 (95% CI: 0.66, 0.94, p = 0.01) and overall MACE 0.85 (95% CI: 0.80, 0.89, p<0.01). Alirocumab reduced MI, 0.57 (0.38, 0.86, p = 0.01), cardiovascular mortality 0.35 (95% CI: 0.16, 0.77, p = 0.01), all-cause mortality 0.60 (95% CI: 0.43, 0.84, p<0.01), and overall MACE 0.35 (0.16, 0.77, p = 0.01).
CONCLUSION
PCSK9 inhibitors (Evolocumab, Alirocumab) and siRNA therapy (Inclisiran) significantly reduced LDL-c by >40% in high-risk individuals. Additionally, both Alirocumab and Evolocumab reduced the risk of MACE, and Alirocumab reduced cardiovascular and all-cause mortality.
Topics: Humans; PCSK9 Inhibitors; Cholesterol, LDL; Myocardial Infarction; Proprotein Convertase 9; Atherosclerosis; Heart Disease Risk Factors; RNA, Small Interfering; Anticholesteremic Agents; Cardiovascular Diseases; Hydroxymethylglutaryl-CoA Reductase Inhibitors
PubMed: 38055686
DOI: 10.1371/journal.pone.0295359 -
Journal of Foot and Ankle Research 2019The ankle brachial index (ABI) is widely used in clinical practice as a non-invasive method to detect the presence and severity of peripheral arterial disease (PAD)....
BACKGROUND
The ankle brachial index (ABI) is widely used in clinical practice as a non-invasive method to detect the presence and severity of peripheral arterial disease (PAD). Current guidelines suggest that it should be used to monitor potential progression of PAD in affected individuals. As such, it is important that the test is reliable when used for repeated measurements, by the same or different health practitioners. This systematic review aims to examine the literature to evaluate the inter- and intra-rater reliability of the ABI.
METHODS
A systematic search of MEDLINE, EMBASE and CINAHL Complete was conducted to 20 January 2019. Two authors independently reviewed and selected relevant studies and extracted the data. Methodological quality was determined using the Quality Appraisal of Reliability (QAREL) Checklist.
RESULTS
Fifteen studies of ABI reliability in a range of patient populations were identified as suitable for inclusion in the review: seven considered inter-rater reliability, four intra-rater reliability, and four studies evaluated both inter- and intra-rater reliability. Inter-rater reliability was found to be highly variable, with intraclass correlation coefficients (ICC's) ranging from poor to excellent (ICC 0.42-1.00), while intra-rater also demonstrated considerable variation, with ICCs from 0.42-0.98. Meta-analysis was not possible due to the lack of statistical information reported.
CONCLUSIONS
Results of included studies suggest the inter- and intra-tester reliability of the ABI is acceptable. However, inconsistencies in obtaining systolic pressure measurements, calculating ABI values, and incomplete reporting of methodologies and statistical analysis make it difficult to determine the validity of the results of included studies. Further research, with more consistent reliability methodology, statistical analysis and reporting conducted in populations at risk of PAD is needed to conclusively determine the ABI reliability.
Topics: Adult; Aged; Ankle Brachial Index; Female; Humans; Male; Middle Aged; Peripheral Arterial Disease; Reproducibility of Results
PubMed: 31388357
DOI: 10.1186/s13047-019-0350-1 -
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 -
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 -
Circulation Research Feb 2019Loss-of-function variants in PCSK9 (proprotein convertase subtilisin-kexin type 9) are associated with lower lifetime risk of atherosclerotic cardiovascular disease)...
Loss-of-function variants in PCSK9 (proprotein convertase subtilisin-kexin type 9) are associated with lower lifetime risk of atherosclerotic cardiovascular disease) events. Confirmation of these genetic observations in large, prospective clinical trials in participants with atherosclerotic cardiovascular disease has provided guidance on risk stratification and enhanced our knowledge on hitherto unresolved and contentious issues concerning the efficacy and safety of markedly lowering LDL-C (low-density lipoprotein cholesterol). PCSK9 has a broad repertoire of molecular effects. Furthermore, clinical trials with PCSK9 inhibitors demonstrate that reductions in atherosclerotic cardiovascular disease events are more effective in patients with recent myocardial infarction, multiple myocardial infarctions, multivessel coronary artery disease, and lower extremity arterial disease. The potent LDL-C lowering efficacy of PCSK9 inhibitors provides the opportunity for more aggressive LDL-lowering strategies in high-risk patients with atherosclerotic cardiovascular disease and supports the notion that there is no lower limit for LDL-C. Aggressive LDL-C lowering with fully human PCSK9 monoclonal antibodies has been associated by a safety profile superior to that of other classes of LDL-lowering agents. These clinical trials provide evidence that LDL lowering with PCSK9 inhibitors is an effective therapy for lowering cardiovascular events in high-risk patients with LDL-C levels ≥70 mg/dL on maximally tolerated oral therapies, including statins and ezetimibe.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Anticholesteremic Agents; Atherosclerosis; Cardiovascular Diseases; Cholesterol, LDL; Clinical Trials as Topic; Diabetes Mellitus, Type 2; HIV Infections; Humans; Hyperlipoproteinemia Type II; Lipoproteins; Mutation; PCSK9 Inhibitors; Proprotein Convertase 9; Renal Insufficiency, Chronic
PubMed: 30702994
DOI: 10.1161/CIRCRESAHA.118.313238 -
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 -
Cardiovascular Research Aug 2017An increased risk of cardiovascular disease (CVD) has long been recognized amongst people with autoimmune disease. It has been unclear whether this is due mainly to the... (Meta-Analysis)
Meta-Analysis Review
An increased risk of cardiovascular disease (CVD) has long been recognized amongst people with autoimmune disease. It has been unclear whether this is due mainly to the ensuing treatment, particularly steroids, or whether some of this risk is due to the autoimmune process itself with subsequent inflammation. Indeed, a large body of evidence supports a role for chronic inflammation in atherogenesis, and autoantibodies have been identified as mediators in this complex inflammatory environment. Our aim is to carry out a systematic review of existing literature in order to formally establish the strength of the association between autoantibodies and atherosclerosis, amongst individuals without clinical autoimmune disease. An electronic search of five databases to June 2016 was performed by two independent reviewers. Inclusion criteria were analytical studies of adults, with at least two studies per autoantibody. Quality analysis was carried out using the Newcastle-Ottawa scale and the Cochrane Risk of Bias Quality Assessment Tool where appropriate. Where possible, studies were pooled using random effects models. Raised levels of anti-cardiolipin (odds ratio [OR] = 1.30; 95% CI: 1.15-1.49) and anti-oxidized low-density lipoprotein Immunoglobulin (Ig) G (OR = 1.25; 95% CI: 1.11-1.41), unspecified anti-cyclic citrullinated protein (OR = 3.09; 95% CI: 1.49-6.41) and anti-human heat shock protein 60 IgA (OR = 1.57; 95% CI: 1.15-2.16) were observed to increase the risk of cardiovascular outcomes. Alternatively, Anti-phosphorylcholine IgM (OR = 1.31; 95% CI: 1.14-1.50) conferred protection against CVD. Our results support an important role for autoantibodies in mediating cardiovascular events, independent of therapeutic treatments. Future research may focus on the presence of autoantibodies as markers of immune dysregulation and CVD risk.
Topics: Atherosclerosis; Autoantibodies; Autoimmune Diseases; Autoimmunity; Biomarkers; Humans; Odds Ratio; Protective Factors; Risk Assessment; Risk Factors
PubMed: 28899001
DOI: 10.1093/cvr/cvx112 -
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 -
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