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Journal of Vascular Surgery Jun 2019Chronic limb-threatening ischemia (CLTI) is associated with mortality, amputation, and impaired quality of life. These Global Vascular Guidelines (GVG) are focused on...
Chronic limb-threatening ischemia (CLTI) is associated with mortality, amputation, and impaired quality of life. These Global Vascular Guidelines (GVG) are focused on definition, evaluation, and management of CLTI with the goals of improving evidence-based care and highlighting critical research needs. The term CLTI is preferred over critical limb ischemia, as the latter implies threshold values of impaired perfusion rather than a continuum. CLTI is a clinical syndrome defined by the presence of peripheral artery disease (PAD) in combination with rest pain, gangrene, or a lower limb ulceration >2 weeks duration. Venous, traumatic, embolic, and nonatherosclerotic etiologies are excluded. All patients with suspected CLTI should be referred urgently to a vascular specialist. Accurately staging the severity of limb threat is fundamental, and the Society for Vascular Surgery Threatened Limb Classification system, based on grading of Wounds, Ischemia, and foot Infection (WIfI) is endorsed. Objective hemodynamic testing, including toe pressures as the preferred measure, is required to assess CLTI. Evidence-based revascularization (EBR) hinges on three independent axes: Patient risk, Limb severity, and ANatomic complexity (PLAN). Average-risk and high-risk patients are defined by estimated procedural and 2-year all-cause mortality. The GVG proposes a new Global Anatomic Staging System (GLASS), which involves defining a preferred target artery path (TAP) and then estimating limb-based patency (LBP), resulting in three stages of complexity for intervention. The optimal revascularization strategy is also influenced by the availability of autogenous vein for open bypass surgery. Recommendations for EBR are based on best available data, pending level 1 evidence from ongoing trials. Vein bypass may be preferred for average-risk patients with advanced limb threat and high complexity disease, while those with less complex anatomy, intermediate severity limb threat, or high patient risk may be favored for endovascular intervention. All patients with CLTI should be afforded best medical therapy including the use of antithrombotic, lipid-lowering, antihypertensive, and glycemic control agents, as well as counseling on smoking cessation, diet, exercise, and preventive foot care. Following EBR, long-term limb surveillance is advised. The effectiveness of nonrevascularization therapies (eg, spinal stimulation, pneumatic compression, prostanoids, and hyperbaric oxygen) has not been established. Regenerative medicine approaches (eg, cell, gene therapies) for CLTI should be restricted to rigorously conducted randomizsed clinical trials. The GVG promotes standardization of study designs and end points for clinical trials in CLTI. The importance of multidisciplinary teams and centers of excellence for amputation prevention is stressed as a key health system initiative.
Topics: Cardiac Imaging Techniques; Cardiology; Chronic Disease; Consensus; Evidence-Based Medicine; Heart Function Tests; Humans; Ischemia; Peripheral Arterial Disease; Predictive Value of Tests; Risk Factors; Terminology as Topic; Treatment Outcome
PubMed: 31159978
DOI: 10.1016/j.jvs.2019.02.016 -
Pharmacology & Therapeutics Apr 2019Atherosclerosis, the principal cause of cardiovascular death worldwide, is a pathological disease characterized by fibro-proliferation, chronic inflammation, lipid...
Atherosclerosis, the principal cause of cardiovascular death worldwide, is a pathological disease characterized by fibro-proliferation, chronic inflammation, lipid accumulation, and immune disorder in the vessel wall. As the atheromatous plaques develop into advanced stage, the vulnerable plaques are prone to rupture, which causes acute cardiovascular events, including ischemic stroke and myocardial infarction. Emerging evidence has suggested that atherosclerosis is also an epigenetic disease with the interplay of multiple epigenetic mechanisms. The epigenetic basis of atherosclerosis has transformed our knowledge of epigenetics from an important biological phenomenon to a burgeoning field in cardiovascular research. Here, we provide a systematic and up-to-date overview of the current knowledge of three distinct but interrelated epigenetic processes (including DNA methylation, histone methylation/acetylation, and non-coding RNAs), in atherosclerotic plaque development and instability. Mechanistic and conceptual advances in understanding the biological roles of various epigenetic modifiers in regulating gene expression and functions of endothelial cells (vascular homeostasis, leukocyte adhesion, endothelial-mesenchymal transition, angiogenesis, and mechanotransduction), smooth muscle cells (proliferation, migration, inflammation, hypertrophy, and phenotypic switch), and macrophages (differentiation, inflammation, foam cell formation, and polarization) are discussed. The inherently dynamic nature and reversibility of epigenetic regulation, enables the possibility of epigenetic therapy by targeting epigenetic "writers", "readers", and "erasers". Several Food Drug Administration-approved small-molecule epigenetic drugs show promise in pre-clinical studies for the treatment of atherosclerosis. Finally, we discuss potential therapeutic implications and challenges for future research involving cardiovascular epigenetics, with an aim to provide a translational perspective for identifying novel biomarkers of atherosclerosis, and transforming precision cardiovascular research and disease therapy in modern era of epigenetics.
Topics: Animals; Atherosclerosis; Epigenesis, Genetic; Humans; Immunity; RNA, Untranslated; Risk Factors
PubMed: 30439455
DOI: 10.1016/j.pharmthera.2018.11.003 -
Lancet (London, England) May 2020Antiplatelet therapy is recommended among patients with established atherosclerosis. We compared monotherapy with a P2Y inhibitor versus aspirin for secondary prevention. (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Antiplatelet therapy is recommended among patients with established atherosclerosis. We compared monotherapy with a P2Y inhibitor versus aspirin for secondary prevention.
METHODS
In this systematic review and meta-analysis, all randomised trials comparing P2Y inhibitor with aspirin monotherapy for secondary prevention in patients with cerebrovascular, coronary, or peripheral artery disease were evaluated for inclusion. On Dec 18, 2019, we searched PubMed, Embase, BioMedCentral, Google Scholar, and the Cochrane Central Register of Controlled Trials. Additionally, we reviewed references from identified articles and searched abstracts from 2017 to 2019 presented at relevant scientific meetings. Data about year of publication, inclusion and exclusion criteria, sample size, baseline patients' features including the baseline condition determining study inclusion (ie, cerebrovascular, coronary, or peripheral artery disease), P2Y inhibitor type and dosage, aspirin dosage, endpoint definitions, effect estimates, follow-up duration, and percentage of patients lost to follow-up were collected. Odds ratios (ORs) and 95% CIs were used as metric of choice for treatment effects with random-effects models. Co-primary endpoints were myocardial infarction and stroke. Key secondary endpoints were all-cause death and vascular death. Heterogeneity was assessed with the I index. This study is registered with PROSPERO (CRD42018115037).
FINDINGS
A total of nine randomised trials were identified and included in this study, and 42 108 patients randomly allocated to a P2Y inhibitor (n=21 043) or aspirin (n=21 065) were included in our analyses. Patients who received a P2Y inhibitor had a borderline reduction for the risk of myocardial infarction compared with those who received aspirin (OR 0·81 [95% CI 0·66-0·99]; I=10·9%). Risks of stroke (OR 0·93 [0·82-1·06]; I=34·5%), all-cause death (OR 0·98 [0·89-1·08]; I=0%), and vascular death (OR 0·97 [0·86-1·09]; I=0%) did not differ between patients who received a P2Y inhibitor and those who received aspirin. Similarly, the risk of major bleeding (OR 0·90 [0·74-1·10]; I=3·9%) did not differ between patients who received a P2Y inhibitor and those who received aspirin. The number needed to treat to prevent one myocardial infarction with P2Y inhibitor monotherapy was 244 patients. Findings were consistent regardless of the type of P2Y inhibitor used.
INTERPRETATION
Compared with aspirin monotherapy, P2Y inhibitor monotherapy is associated with a risk reduction for myocardial infarction and a comparable risk of stroke in the setting of secondary prevention. The benefit of P2Y inhibitor monotherapy is of debatable clinical relevance, in view of the high number needed to treat to prevent a myocardial infarction and the absence of any effect on all-cause and vascular mortality.
FUNDING
Italian Ministry of Education.
Topics: Aged; Aspirin; Atherosclerosis; Cerebrovascular Disorders; Clopidogrel; Coronary Disease; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Risk Assessment; Secondary Prevention; Stroke; Ticagrelor; Ticlopidine
PubMed: 32386592
DOI: 10.1016/S0140-6736(20)30315-9 -
Circulation Sep 2018With advances in antiretroviral therapy, most deaths in people with HIV are now attributable to noncommunicable illnesses, especially cardiovascular disease. We... (Meta-Analysis)
Meta-Analysis
BACKGROUND
With advances in antiretroviral therapy, most deaths in people with HIV are now attributable to noncommunicable illnesses, especially cardiovascular disease. We determine the association between HIV and cardiovascular disease, and estimate the national, regional, and global burden of cardiovascular disease attributable to HIV.
METHODS
We conducted a systematic review across 5 databases from inception to August 2016 for longitudinal studies of cardiovascular disease in HIV infection. A random-effects meta-analysis across 80 studies was used to derive the pooled rate and risk of cardiovascular disease in people living with HIV. We then estimated the temporal changes in the population-attributable fraction and disability-adjusted life-years (DALYs) from HIV-associated cardiovascular disease from 1990 to 2015 at a regional and global level. National cardiovascular DALYs associated with HIV for 2015 were derived for 154 of the 193 United Nations member states. The main outcome measure was the pooled estimate of the rate and risk of cardiovascular disease in people living with HIV and the national, regional, and global estimates of DALYs from cardiovascular disease associated with HIV.
RESULTS
In 793 635 people living with HIV and a total follow-up of 3.5 million person-years, the crude rate of cardiovascular disease was 61.8 (95% CI, 45.8-83.4) per 10 000 person-years. In comparison with individuals without HIV, the risk ratio for cardiovascular disease was 2.16 (95% CI, 1.68-2.77). Over the past 26 years, the global population-attributable fraction from cardiovascular disease attributable to HIV increased from 0.36% (95% CI, 0.21%-0.56%) to 0.92% (95% CI, 0.55%-1.41%), and DALYs increased from 0.74 (95% CI, 0.44-1.16) to 2.57 (95% CI, 1.53-3.92) million. There was marked regional variation with most DALYs lost in sub-Saharan Africa (0.87 million, 95% CI, 0.43-1.70) and the Asia Pacific (0.39 million, 95% CI, 0.23-0.62) regions. The highest population-attributable fraction and burden were observed in Swaziland, Botswana, and Lesotho.
CONCLUSIONS
People living with HIV are twice as likely to develop cardiovascular disease. The global burden of HIV-associated cardiovascular disease has tripled over the past 2 decades and is now responsible for 2.6 million DALYs per annum with the greatest impact in sub-Saharan Africa and the Asia Pacific regions.
CLINICAL TRIAL REGISTRATION
URL: https://www.crd.york.ac.uk/prospero . Unique identifier: CRD42016048257.
Topics: Adult; Atherosclerosis; Cost of Illness; Female; Global Health; HIV Infections; HIV Long-Term Survivors; Humans; Incidence; Male; Middle Aged; Prevalence; Prognosis; Risk Assessment; Risk Factors; Time Factors
PubMed: 29967196
DOI: 10.1161/CIRCULATIONAHA.117.033369 -
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 -
International Angiology : a Journal of... Apr 2011The aim of this paper was to examine the interaction between depression and atherosclerosis through a systematic review. A Medline search was performed from 1966 through... (Review)
Review
The aim of this paper was to examine the interaction between depression and atherosclerosis through a systematic review. A Medline search was performed from 1966 through 2009 using relevant terms such as depression, epidemiology and atherosclerosis. This was supplemented by a thorough manual search using bibliographies of reviews and full articles. The papers were divided and analyzed separately for each vascular bed. Depression is diagnosed usually before atherosclerosis becomes obvious. The contribution of depression in the development of atherosclerosis emerges from various mechanisms, including lack of physical activity, that exist in this illness. Controversies about the etiology and pathogenesis exist. These interactions of all elements and the importance of each one have not been investigated adequately. Repeated objective measurements for atherosclerosis are lacking. There is an association between depression and atherosclerosis, but the strength of this relationship has to be determined. Prospective studies are needed to determine the early and long term effects of their interaction.
Topics: Adolescent; Adult; Aged; Atherosclerosis; Comorbidity; Depression; Female; Humans; Male; Middle Aged; Prognosis; Risk Assessment; Risk Factors; Young Adult
PubMed: 21427645
DOI: No ID Found -
The Lancet. Global Health Aug 2019Peripheral artery disease is a major cardiovascular disease that affected 202 million people worldwide in 2010. In the past decade, new epidemiological data on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Peripheral artery disease is a major cardiovascular disease that affected 202 million people worldwide in 2010. In the past decade, new epidemiological data on peripheral artery disease have emerged, enabling us to provide updated estimates of the prevalence and risk factors for peripheral artery disease globally and regionally and, for the first time, nationally.
METHODS
For this systematic review and analysis, we did a comprehensive literature search for studies reporting on the prevalence of peripheral artery disease in the general population that were published between Jan 1, 2011, and April 30, 2019, in PubMed, MEDLINE, Embase, the Global Health database, CINAHL, the Global Health Library, the Allied and Complementary Medicine Database, and ProQuest Dissertations and Theses Global. We also included the Global Peripheral Artery Disease Study of 2013 and the China Peripheral Artery Disease Study as sources. Peripheral artery disease had to be defined as an ankle-brachial index lower than or equal to 0·90. With a purpose-built data collection form, data on study characteristics, sample characteristics, prevalence, and risk factors were abstracted from all the included studies identified from the sources. Age-specific and sex-specific prevalence of peripheral artery disease was estimated in both high-income countries (HICs) and low-income and middle-income countries (LMICs). We also did random-effects meta-analyses to pool the odds ratios of 30 risk factors for peripheral artery disease in HICs and LMICs. UN population data were used to generate the number of people affected by the disease in 2015. Finally, we derived the regional and national numbers of people with peripheral artery disease on the basis of a risk factor-based model.
FINDINGS
We included 118 articles for systematic review and analysis. The prevalence of peripheral artery disease increased consistently with age. At younger ages, prevalence was slightly higher in LMICs than HICs (4·32%, 95% CI 3·01-6·29, vs 3·54%, 1·17-10·24, at 40-44 years), but the increase with age was greater in HICs than LMICs, leading to a higher prevalence in HICs than LMICs at older ages (21·24%, 15·22-28·90, vs 12·04%, 8·67-16·60, at 80-84 years). In HICs, prevalence was slightly higher in women than in men up to age 75 years (eg, 7·81%, 3·97-14·77, vs 6·60%, 3·74-11·38, at 55-59 years), whereas in LMICs little difference was found between women and men (eg, 6·40%, 5·06-8·05, vs 6·37%, 4·74-8·49, at 55-59 years). Overall, the global prevalence of peripheral artery disease in people aged 25 years and older was 5·56%, 3·79-8·55, and the prevalence estimate was higher in HICs than that in LMICs (7·37%, 4·35-13·66, vs 5·09%, 3·64-7·24). Smoking, diabetes, hypertension, and hypercholesterolaemia were major risk factors for peripheral artery disease. Globally, a total of 236·62 million people aged 25 years and older were living with peripheral artery disease in 2015, among whom 72·91% were in LMICs. The Western Pacific Region had the most peripheral artery disease cases (74·08 million), whereas the Eastern Mediterranean Region had the least (14·67 million). More than two thirds of the global peripheral artery disease cases were concentrated in 15 individual countries in 2015.
INTERPRETATION
Peripheral artery disease continues to become an increasingly serious public health problem, especially in LMICs. With the demographic trend towards ageing and projected rise in important risk factors, a larger burden of peripheral artery disease is to be expected in the foreseeable future.
FUNDING
None.
Topics: Adult; Aged; Aged, 80 and over; Female; Global Health; Humans; Male; Middle Aged; Peripheral Arterial Disease; Prevalence; Risk Factors
PubMed: 31303293
DOI: 10.1016/S2214-109X(19)30255-4 -
Circulation Jun 2020Contemporary studies suggest that familial hypercholesterolemia (FH) is more frequent than previously reported and increasingly recognized as affecting individuals of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Contemporary studies suggest that familial hypercholesterolemia (FH) is more frequent than previously reported and increasingly recognized as affecting individuals of all ethnicities and across many regions of the world. Precise estimation of its global prevalence and prevalence across World Health Organization regions is needed to inform policies aiming at early detection and atherosclerotic cardiovascular disease (ASCVD) prevention. The present study aims to provide a comprehensive assessment and more reliable estimation of the prevalence of FH than hitherto possible in the general population (GP) and among patients with ASCVD.
METHODS
We performed a systematic review and meta-analysis including studies reporting on the prevalence of heterozygous FH in the GP or among those with ASCVD. Studies reporting gene founder effects and focused on homozygous FH were excluded. The search was conducted through Medline, Embase, Cochrane, and Global Health, without time or language restrictions. A random-effects model was applied to estimate the overall pooled prevalence of FH in the general and ASCVD populations separately and by World Health Organization regions.
RESULTS
From 3225 articles, 42 studies from the GP and 20 from populations with ASCVD were eligible, reporting on 7 297 363 individuals/24 636 cases of FH and 48 158 patients/2827 cases of FH, respectively. More than 60% of the studies were from Europe. Use of the Dutch Lipid Clinic Network criteria was the commonest diagnostic method. Within the GP, the overall pooled prevalence of FH was 1:311 (95% CI, 1:250-1:397; similar between children [1:364] and adults [1:303], =0.60; across World Health Organization regions where data were available, =0.29; and between population-based and electronic health records-based studies, =0.82). Studies with ≤10 000 participants reported a higher prevalence (1:200-289) compared with larger cohorts (1:365-407; <0.001). The pooled prevalence among those with ASCVD was 18-fold higher than in the GP (1:17 [95% CI, 1:12-1:24]), driven mainly by coronary artery disease (1:16; [95% CI, 1:12-1:23]). Between-study heterogeneity was large (>95%). Tests assessing bias were nonsignificant (>0.3).
CONCLUSIONS
With an overall prevalence of 1:311, FH is among the commonest genetic disorders in the GP, similarly present across different regions of the world, and is more frequent among those with ASCVD. The present results support the advocacy for the institution of public health policies, including screening programs, to identify FH early and to prevent its global burden.
Topics: Adult; Atherosclerosis; Child; Comorbidity; Global Health; Health Priorities; Humans; Hyperlipoproteinemia Type II; Prevalence; Public Health
PubMed: 32468833
DOI: 10.1161/CIRCULATIONAHA.119.044795 -
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 -
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