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Open Heart Nov 2023Clopidogrel is a P2Y inhibitor that has become a mainstay treatment following percutaneous intervention with drug-eluting stent placement to decrease restenosis and its...
INTRODUCTION
Clopidogrel is a P2Y inhibitor that has become a mainstay treatment following percutaneous intervention with drug-eluting stent placement to decrease restenosis and its potential complications, including sudden cardiac death and ischaemic strokes in patients with significant vascular disease.
AREAS COVERED
As a prodrug, the metabolism and efficacy of clopidogrel are contingent on the presence of wild-type CYP450 (CYP2C19) alleles. Genetic polymorphisms and variants are well known to impair its ability to prevent major adverse cardiovascular events in these patients, with inadequate response rates as high as 30% in previous publications. Patterns of allelic frequencies are expected to exhibit similarities between individuals of the same ancestry, ethnic group or geographic region. Accordingly, we seek to further elucidate worldwide prevalence rates for genetic polymorphisms in the CYP2C19-dependent metabolism of clopidogrel and review the potential of personalised CYP2C19 genotyping in clinical practice to mitigate this high treatment resistance and its associated burden on patients.
EXPERTS' COMMENTARY
Our findings support the consideration of genotyping before initiation of therapy to guide adequate dosage or substitutions of other P2Y inhibitors to promote personalised, precision medicine and to prevent adverse events when these therapies may inevitably fail in patients with variants of the CYP450 (CYP2C19) system.
Topics: Humans; Clopidogrel; Platelet Aggregation Inhibitors; Cytochrome P-450 CYP2C19; Drug-Eluting Stents; Polymorphism, Genetic
PubMed: 37963685
DOI: 10.1136/openhrt-2023-002436 -
Journal of Cardiovascular Development... May 2024Atherosclerosis is a multi-factorial disease, and low-density lipoprotein cholesterol (LDL-C) is a critical risk factor in developing atherosclerotic cardiovascular... (Review)
Review
BACKGROUND
Atherosclerosis is a multi-factorial disease, and low-density lipoprotein cholesterol (LDL-C) is a critical risk factor in developing atherosclerotic cardiovascular disease (ASCVD). Cholesteryl-ester transfer-protein (CETP), synthesized by the liver, regulates LDL-C and high-density lipoprotein cholesterol (HDL-C) through the bidirectional transfer of lipids. The novelty of CETP inhibitors (CETPis) has granted new focus towards increasing HDL-C, besides lowering LDL-C strategies. To date, five CETPis that are projected to improve lipid profiles, torcetrapib, dalcetrapib, evacetrapib, anacetrapib, and obicetrapib, have reached late-stage clinical development for ASCVD risk reduction. Early trials failed to reduce atherosclerotic cardiovascular occurrences. Given the advent of some recent large-scale clinical trials (ACCELERATE, HPS3/TIMI55-REVEAL Collaborative Group), conducting a meta-analysis is essential to investigate CETPis' efficacy.
METHODS
We conducted a thorough search of randomized controlled trials (RCTs) that commenced between 2003 and 2023; CETPi versus placebo studies with a ≥6-month follow-up and defined outcomes were eligible.
PRIMARY OUTCOMES
major adverse cardiovascular events (MACEs), cardiovascular disease (CVD)-related mortality, all-cause mortality.
SECONDARY OUTCOMES
stroke, revascularization, hospitalization due to acute coronary syndrome, myocardial infarction (MI).
RESULTS
Nine RCTs revealed that the use of a CETPi significantly reduced CVD-related mortality (RR = 0.89; 95% CI: 0.81-0.98; = 0.02; I2 = 0%); the same studies also reduced the risk of MI (RR = 0.92; 95% CI: 0.86-0.98; = 0.01; I2 = 0%), which was primarily attributed to anacetrapib. The use of a CETPi did not reduce the likelihood any other outcomes.
CONCLUSIONS
Our meta-analysis shows, for the first time, that CETPis are associated with reduced CVD-related mortality and MI.
PubMed: 38786974
DOI: 10.3390/jcdd11050152 -
Nigerian Journal of Clinical Practice Oct 2023Over the years, the literature dealt with venous thromboembolism (VTE) and atherosclerosis as two distinct pathologic processes but recently this theory has been... (Meta-Analysis)
Meta-Analysis Review
Over the years, the literature dealt with venous thromboembolism (VTE) and atherosclerosis as two distinct pathologic processes but recently this theory has been challenged. This research aims to determine the relationship between cardiovascular risk factors and VTE. This meta-analysis and systemic review included case-control and non-case-control studies. We searched Google Scholar, Web of Science, MEDLINE, and EMBASE for studies conducted in Saudi Arabia, addressing the relationship between VTE and cardiovascular risk factors, and published during the period from January 2001 to December 2021. Quality assessment was done for included studies and pooled odds and prevalence ratios were reported. Evidence of bias was assessed using funnel plots and the Egger regression test. A total of 3291 patients with VTE and 3393 controls from 24 studies were enrolled. The pooled odds ratios were 1.33 (95% confidence interval (95% CI) = 1.01-1.77), 1.2 (95% CI = 0.88-1.64), 0.881 (95% CI = 0.55-1.41), 0.676 (95% CI = 0.04-11.25), 1.15 (95% CI = 0.75-1.75), 0.925 (95% CI = 0.55-1.56), 1.45 (95% CI = 0.89-2.35), and 1.49 (95% CI = 0.24-5.23) for age >60 years, female gender, hypertension, dyslipidemia, diabetes, cardiovascular disease, obesity, and smoking, respectively. The pooled prevalence ratios were 42.6%, 55.7%, 51.6%, 48%, 44%, 32.8%, 30.9%, and 46.6%, respectively, for the same factors. Few studies reported dyslipidemia and smoking. In conclusion, old Old age, female gender, diabetes, obesity, and smoking are associated with increased risk of VTE with the highest risks seen with obesity and smoking. Additionally, female gender was the most prevalent risk factor among VTE patients.
Topics: Humans; Female; Middle Aged; Venous Thromboembolism; Risk Factors; Cardiovascular Diseases; Saudi Arabia; Diabetes Mellitus; Heart Disease Risk Factors; Obesity; Dyslipidemias
PubMed: 37929514
DOI: 10.4103/njcp.njcp_229_23 -
Clinical Nutrition (Edinburgh, Scotland) Apr 2024Continuous glucose monitoring (CGM) provides data on short-term glycemic variability (GV). GV is associated with adverse outcomes in individuals with diabetes. Whether... (Meta-Analysis)
Meta-Analysis
Glycemic variability assessed using continuous glucose monitoring in individuals without diabetes and associations with cardiometabolic risk markers: A systematic review and meta-analysis.
BACKGROUND & AIMS
Continuous glucose monitoring (CGM) provides data on short-term glycemic variability (GV). GV is associated with adverse outcomes in individuals with diabetes. Whether GV is associated with cardiometabolic risk in individuals without diabetes is unclear. We systematically reviewed the literature to assess whether GV is associated with cardiometabolic risk markers or outcomes in individuals without diabetes.
METHODS
Searches were performed in PubMed/Medline, Embase and Cochrane from inception through April 2022. Two researchers were involved in study selection, data extraction and quality assessment. Studies evaluating GV using CGM for ≥24 h were included. Studies in populations with acute and/or critical illness were excluded. Both narrative synthesis and meta-analyzes were performed, depending on outcome.
RESULTS
Seventy-one studies were included; the majority were cross-sectional. Multiple measures of GV are higher in individuals with compared to without prediabetes and GV appears to be inversely associated with beta cell function. In contrast, GV is not clearly associated with insulin sensitivity, fatty liver disease, adiposity, blood lipids, blood pressure or oxidative stress. However, GV may be positively associated with the degree of atherosclerosis and cardiovascular events in individuals with coronary disease.
CONCLUSION
GV is elevated in prediabetes, potentially related to beta cell dysfunction, but less clearly associated with obesity or traditional risk factors. GV is associated with coronary atherosclerosis development and may predict cardiovascular events and type 2 diabetes. Prospective studies are warranted, investigating the predictive power of GV in relation to incident disease. GV may be an important risk measure also in individuals without diabetes.
Topics: Humans; Blood Glucose; Blood Glucose Self-Monitoring; Cardiovascular Diseases; Continuous Glucose Monitoring; Diabetes Mellitus, Type 2; Prediabetic State
PubMed: 38401227
DOI: 10.1016/j.clnu.2024.02.014 -
Cureus Oct 2023Cardiovascular disease (CVD) is the primary cause of death all over the world, especially due to myocardial ischemia caused by atherosclerosis that blocks cardiac... (Review)
Review
Cardiovascular disease (CVD) is the primary cause of death all over the world, especially due to myocardial ischemia caused by atherosclerosis that blocks cardiac arteries and leads to arrhythmia and other cardiac diseases. Meanwhile, diabetes mellitus (DM) and elevated cholesterol level are the risk factors for cardiovascular (CV) disease. This noncommunicable disease has become a main concern for us as cardiovascular disease develops in a slow manner without any symptoms in the early stage. Early prevention and intervention have a major impact on improving the outcome of cardiovascular health in diabetic patients. Controlling cholesterol level by administering statin has shown some beneficial impacts in reducing the risk of cardiovascular disease in patients with DM. This study used a systematic literature review (SLR) approach to give an overview of the current literature and to analyze the effects of statin therapy on cardiovascular outcomes in patients with DM. The literature search was conducted in PubMed and Google Scholar databases. The total number of articles included in the present review is six, obtained from reputable journals published between 2013 and 2023, and we only focused on reviewing six articles for in-depth analysis. The evidence we collected showed a positive outcome in terms of cardiovascular health in persons with DM after statin therapy. However, there are several risk factors that interfere with the effectiveness of statin in diabetic patients.
PubMed: 38021726
DOI: 10.7759/cureus.47294 -
PloS One 2023Elevated lipoprotein(a) [Lp(a)] level is an independent genetic risk factor that increases the risk of atherosclerotic cardiovascular disease (ASCVD) by 2-4 fold. We...
Burden of elevated lipoprotein(a) among patients with atherosclerotic cardiovascular disease: Evidence from a systematic literature review and feasibility assessment of meta-analysis.
BACKGROUND
Elevated lipoprotein(a) [Lp(a)] level is an independent genetic risk factor that increases the risk of atherosclerotic cardiovascular disease (ASCVD) by 2-4 fold. We aimed to report the burden of clinically relevant elevated Lp(a) in secondary prevention ASCVD population as the evaluation of such evidence is lacking.
METHODS
A systematic literature review (SLR) was conducted using Embase®, MEDLINE®, and MEDLINE® In-Process databases to identify studies reporting burden of elevated Lp(a) levels from January 1, 2010, to March 28, 2022. Full-text, English-language studies including ≥500 participants with ≥1 Lp(a) assessment were included.
RESULTS
Sixty-one studies reported clinical burden of elevated Lp(a). Of these, 25 observational studies and one clinical trial reported clinical burden of clinically relevant elevated Lp(a) levels. Major clinical outcomes included major adverse cardiovascular event (MACE; n = 20), myocardial infarction (MI; n = 11), revascularization (n = 10), stroke (n = 10), cardiovascular (CV) mortality (n = 9), and all-cause mortality (n = 10). Elevated Lp(a) levels significantly increased the risk of MACE (n = 15) and revascularization (n = 8), while they demonstrated a trend for positive association with remaining CV outcomes. Meta-analysis was not feasible for included studies due to heterogeneity in Lp(a) thresholds, outcome definitions, and patient characteristics. Three studies reported humanistic burden. Patients with elevated Lp(a) levels had higher odds of manifesting cognitive impairment (odds ratio [OR] [95% confidence interval; CI]: 1.62 [1.11-2.37]) and disability related to stroke (OR [95% CI]:1.46 [1.23-1.72)]) (n = 2). Elevated Lp(a) levels negatively correlated with health-related quality of life (R = -0.166, p = 0.014) (n = 1). A single study reported no association between elevated Lp(a) levels and economic burden.
CONCLUSIONS
This SLR demonstrated a significant association of elevated Lp(a) levels with major CV outcomes and increased humanistic burden in secondary prevention ASCVD population. These results reinforce the need to quantify and manage Lp(a) for CV risk reduction and to perform further studies to characterize the economic burden.
Topics: Humans; Atherosclerosis; Cardiovascular Diseases; Feasibility Studies; Lipoprotein(a); Quality of Life; Stroke; Meta-Analysis as Topic
PubMed: 37983217
DOI: 10.1371/journal.pone.0294250 -
European Journal of Vascular and... Jun 2024This scoping review summarises health literacy and disease knowledge in patients with abdominal aortic aneurysm (AAA) or peripheral arterial disease (PAD) and the... (Review)
Review
OBJECTIVE
This scoping review summarises health literacy and disease knowledge in patients with abdominal aortic aneurysm (AAA) or peripheral arterial disease (PAD) and the influencing factors.
DATA SOURCES
A systematic search was conducted in PubMed, Embase, PsychINFO, and CINAHL covering the period January 2012 to October 2022.
REVIEW METHODS
This scoping review was undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Inclusion criteria encompassed studies addressing health literacy, knowledge, perception, or awareness in patients with AAA or PAD. Two authors independently reviewed abstracts and full texts, resolving any discrepancies through discussion or by consulting a third author for consensus. All article types were included except letters, editorials, study protocols, reviews, and guidelines. No language restrictions were applied. Primary outcomes were health literacy and disease knowledge. Secondary outcomes were factors that could influence this. Quality assessment was done using the Mixed Methods Appraisal Tool (MMAT).
RESULTS
The review included 32 articles involving a total of 5 268 patients. Four articles reported health literacy and the rest disease knowledge. Ten studies (31%) met all quality criteria. Twenty studies were quantitative, eight were qualitative, and four were mixed methods studies. The review revealed inadequate health literacy in the majority of patients, and disease knowledge was relatively low among patients with AAA and PAD, with disparities in measures and assessment tools across studies. Factors influencing health literacy and disease knowledge included socioeconomic status, education, income, and employment.
CONCLUSION
This scoping review revealed low health literacy and low disease knowledge in patients with AAA and PAD. Standardised health literacy assessment may contribute to improve communication strategies and decision aids to enhance patients' understanding and engagement in healthcare decisions, however further research is needed to prove its merits.
Topics: Humans; Health Literacy; Aortic Aneurysm, Abdominal; Peripheral Arterial Disease; Health Knowledge, Attitudes, Practice; Patient Education as Topic
PubMed: 38552837
DOI: 10.1016/j.ejvs.2024.03.040 -
IScience Nov 2023Atherosclerosis is the main cause of cardiovascular diseases that seriously endanger human health. The existing treatment drugs are effective, but they have some side...
Atherosclerosis is the main cause of cardiovascular diseases that seriously endanger human health. The existing treatment drugs are effective, but they have some side effects. Accumulating evidence suggests that flavonoids have attracted wide attention due to their multiple cardioprotective effects and fewer side effects. PubMed, Web of Science database, Embase, and Cochrane Library were searched for studies evaluating the effects of flavonoids against atherosclerosis. 119 studies published from August 1954 to April 2023 were included. Random-effects models were performed for synthesis. Compared with the control group, flavonoids significantly reduced longitudinal and cross-sectional plaque area. The findings indicated that flavonoids significantly reduced the concentrations of serum TC, TG, and LDL-C and increased serum HDL-C concentrations. Besides, flavonoids reduced the levels of circulating pro-inflammatory factors, including TNF-α, IL-1β, and IL-6, and increased the serum IL-10 level. This study provides evidence for the potential cardiovascular benefits of flavonoids.
PubMed: 38026172
DOI: 10.1016/j.isci.2023.108337 -
International Wound Journal Aug 2023Pressure injuries (PIs) are one of the major and costliest medical problems with severe implications for patients. Cardiovascular surgery patients are at the higher risk... (Meta-Analysis)
Meta-Analysis Review
Pressure injuries (PIs) are one of the major and costliest medical problems with severe implications for patients. Cardiovascular surgery patients are at the higher risk of developing surgery-related PIs. So this study was conducted with the aim of investigating the prevalence and factors associated with PIs in patients undergoing open heart surgery. We identified articles through electronic databases such as Web of Science, Scopus, PubMed, ProQuest; and Persian Databases: SID, Magiran and Irandoc without restriction on language or publication period (from inception through June 2022). Finally, 17 studies that fulfilled eligibility criteria were included in final systematic review and meta-analysis. Data analyses were conducted using STATA version 14. The pooled prevalence of PI in patients undergoing open heart surgery was 24.06% (95% CI: 17.85-30.27). High heterogeneity was observed across the included studies (I = 96.0, P < 0.000). The prevalence by gender was reported as 25.19% (95% CI: 13.45-36.93) in men and 33.36% (95 CI%: 19.99-46.74) in women. The result showed there was statistically significant association between PI and Female sex (Pooled Est: 1.551, 95% CI: 1.199-2.006, z = 3.345, P = 0.001), diabetes (Pooled Est: 1.985, 95% CI: 1.383-2.849, z = 3.719, P = 0.000), advanced age (SMD: 0.33 years; 95% CI: 0.09-0.57), Duration of surgery (SMD: 0.47; 95% CI: 0.19-0.75) and preoperative serum albumin level (SMD: 0.56; 95% CI: 0.14-0.98). The relatively high PIs incidence among patients undergoing open heart surgery suggests that typical PI prevention methods are insufficient for this population. Targeted prevention measures must be developed and implemented.
Topics: Male; Humans; Female; Infant; Pressure Ulcer; Prevalence; Cardiac Surgical Procedures; Incidence
PubMed: 36447333
DOI: 10.1111/iwj.14040 -
Journal of Cardiology Jul 2024Atherosclerosis is a chronic, progressive cardiovascular disease characterized by cholesterol deposition within blood vessel walls. Recent literature has suggested that... (Meta-Analysis)
Meta-Analysis Review
Atherosclerosis is a chronic, progressive cardiovascular disease characterized by cholesterol deposition within blood vessel walls. Recent literature has suggested that the NLRP3 [NOD (nucleotide oligomerization domain)-, LRR (leucine-rich repeat)-, and PYD (pyrin domain)-containing protein 3] inflammasome is a key mediator in the development, progression, and destabilization of atherosclerotic plaques. This review aims to evaluate the current literature on the role of NLRP3 in human atherosclerosis. This systematic review was registered on the PROSPERO database (ID = CRD42022340039) and involved the search of a total of 8 databases. Records were screened in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A total of 20 studies were included and quality assessed using the NIH: NHLBI tool. Six were eligible for meta-analysis using RevMan 5.4.1. We identified 20 relevant articles representing 3388 participants. NLRP3 mRNA levels and downstream cytokines, interleukin (IL)-1β and IL-18 were found to be associated with atherosclerotic disease. Fold changes in NLRP3 mRNA levels were most strongly associated with high risk atherosclerotic disease, compared to controls [0.84 (95 % CI: 0.41-1.28)]. IL-1β mRNA fold change was more robustly associated with high-risk atherosclerotic disease [0.61 (95 % CI: 0.10-1.13)] than IL-18 [0.47 (95 % CI: 0.02-0.91)]. NLRP3, IL-1β, and IL-18 are associated with high-risk atherosclerotic disease. However, given the scope of this review, the role of this inflammasome and its cytokine counterparts in acting as prognosticators of coronary artery disease severity is unclear. Several upstream activators such as cholesterol crystals are involved in the canonical or non-canonical activation of the NLRP3 inflammasome and its downstream cytokines. These findings highlight the necessity for further research to delineate the exact mechanisms of NLRP3 inflammasome activation and potential drug targets.
Topics: NLR Family, Pyrin Domain-Containing 3 Protein; Humans; Atherosclerosis; Inflammasomes; Interleukin-18; Interleukin-1beta
PubMed: 38521117
DOI: 10.1016/j.jjcc.2024.03.003