scholarly journals Urate, blood pressure and cardiovascular disease: updated evidence from Mendelian randomization and meta-analysis of clinical trials

2019 ◽  
Author(s):  
Dipender Gill ◽  
Alan C. Cameron ◽  
Stephen Burgess ◽  
Xue Li ◽  
Daniel J. Doherty ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Mendelian Randomization ◽  
Meta Analysis ◽  
Serum Urate ◽  
Favorable Effect ◽  
Major Adverse Cardiovascular Events ◽  
Cvd Risk ◽  
Standard Deviation Increase ◽  
Increased Risk

AbstractAimsTo investigate the effect of serum urate on blood pressure and cardiovascular disease (CVD) risk by updating evidence from Mendelian randomization (MR) analysis and meta-analysis of randomized controlled trials (RCTs).Methods and ResultsUsing recently available data from the Million Veterans Program and UK Biobank, the main MR analyses showed that every 1-standard deviation increase in genetically predicted serum urate was associated with an increased risk of coronary heart disease (odds ratio 1.19, 95% confidence interval 1.10-1.30, P=4×10−5), peripheral artery disease (1.12, 95%CI 1.03 to 1.21, P=9×10−3), and stroke (1.11, 95%CI 1.05 to 1.18, P=2×10−4). In MR mediation analyses, SBP was estimated to mediate approximately one third the effect of urate on CVD risk. Systematic review and meta-analysis of RCTs showed a favorable effect of urate-lowering treatment on SBP (mean difference -2.55mmHg, 95%CI -4.06 to -1.05, P=1×10−3) and major adverse cardiovascular events (MACE) in those with previous CVD (OR 0.40, 95%CI 0.22 to 0.73, P=3×10−3), but no significant effect on MACE in all individuals (OR 0.73, 95%CI 0.48 to 1.09, P=0.12).ConclusionMR and clinical trial data support an effect of higher serum urate on increasing blood pressure, which may mediate a consequent effect on CVD risk. High-quality trials are necessary to provide definitive evidence on the specific clinical contexts where urate-lowering may be of cardiovascular benefit.

scholarly journals Urate, Blood Pressure, and Cardiovascular Disease

Hypertension ◽  
2020 ◽  
Author(s):  
Dipender Gill ◽  
Alan C. Cameron ◽  
Stephen Burgess ◽  
Xue Li ◽  
Daniel J. Doherty ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Odds Ratio ◽  
Mendelian Randomization ◽  
Disease Risk ◽  
Meta Analysis ◽  
Cardiovascular Disease Risk ◽  
Serum Urate ◽  
Major Adverse Cardiovascular Events ◽  
Randomized Controlled

Serum urate has been implicated in hypertension and cardiovascular disease, but it is not known whether it is exerting a causal effect. To investigate this, we performed Mendelian randomization analysis using data from UK Biobank, Million Veterans Program and genome-wide association study consortia, and meta-analysis of randomized controlled trials. The main Mendelian randomization analyses showed that every 1-SD increase in genetically predicted serum urate was associated with an increased risk of coronary heart disease (odds ratio, 1.19 [95% CI, 1.10–1.30]; P =4×10 −5 ), peripheral artery disease (1.12 [95% CI, 1.03–1.21]; P =9×10 −3 ), and stroke (1.11 [95% CI, 1.05–1.18]; P =2×10 −4 ). In Mendelian randomization mediation analyses, elevated blood pressure was estimated to mediate approximately one-third of the effect of urate on cardiovascular disease risk. Systematic review and meta-analysis of randomized controlled trials showed a favorable effect of urate-lowering treatment on systolic blood pressure (mean difference, −2.55 mm Hg [95% CI, −4.06 to −1.05]; P =1×10 −3 ) and major adverse cardiovascular events in those with previous cardiovascular disease (odds ratio, 0.40 [95% CI, 0.22–0.73]; P =3×10 −3 ) but no significant effect on major adverse cardiovascular events in all individuals (odds ratio, 0.67 [95% CI, 0.44–1.03]; P =0.07). In summary, these Mendelian randomization and clinical trial data support an effect of higher serum urate on increasing blood pressure, which may mediate a consequent effect on cardiovascular disease risk. High-quality trials are necessary to provide definitive evidence on the specific clinical contexts where urate lowering may be of cardiovascular benefit.

scholarly journals Effects of a Paleolithic Diet on Cardiovascular Disease Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

2019 ◽  
Vol 10 (4) ◽  
pp. 634-646 ◽  
Author(s):  
Ehsan Ghaedi ◽  
Mohammad Mohammadi ◽  
Hamed Mohammadi ◽  
Nahid Ramezani-Jolfaie ◽  
Janmohamad Malekzadeh ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Lipid Profile ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Cvd Risk Factors ◽  
Paleolithic Diet ◽  
Cvd Risk ◽  
Randomized Controlled

ABSTRACTThere is some evidence supporting the beneficial effects of a Paleolithic diet (PD) on cardiovascular disease (CVD) risk factors. This diet advises consuming lean meat, fish, vegetables, fruits, and nuts and avoiding intake of grains, dairy products, processed foods, and added sugar and salt. This study was performed to assess the effects of a PD on CVD risk factors including anthropometric indexes, lipid profile, blood pressure, and inflammatory markers using data from randomized controlled trials. A comprehensive search was performed in the PubMed, Scopus, ISI Web of Science, and Google Scholar databases up to August 2018. A meta-analysis was performed using a random-effects model to estimate the pooled effect size. Meta-analysis of 8 eligible studies revealed that a PD significantly reduced body weight [weighted mean difference (WMD) = −1.68 kg; 95% CI: −2.86, −0.49 kg], waist circumference (WMD = −2.72 cm; 95% CI: −4.04, −1.40 cm), BMI (in kg/m2) (WMD = −1.54; 95% CI: −2.22, −0.87), body fat percentage (WMD = −1.31%; 95% CI: −2.06%, −0.57%), systolic (WMD = −4.75 mm Hg; 95% CI: −7.54, −1.96 mm Hg) and diastolic (WMD = −3.23 mm Hg; 95% CI: −4.77, −1.69 mm Hg) blood pressure, and circulating concentrations of total cholesterol (WMD = −0.23 mmol/L; 95% CI: −0.42, −0.04 mmol/L), triglycerides (WMD = −0.30 mmol/L; 95% CI: −0.55, −0.06 mmol/L), LDL cholesterol (WMD = −0.13 mmol/L; 95% CI: −0.26, −0.01 mmol/L), and C-reactive protein (CRP) (WMD = −0.48 mg/L; 95% CI: −0.79, −0.16 mg/L) and also significantly increased HDL cholesterol (WMD = 0.06 mmol/L; 95% CI: 0.01, 0.11 mmol/L). However, sensitivity analysis revealed that the overall effects of a PD on lipid profile, systolic blood pressure, and circulating CRP concentrations were sensitive to removing some studies and to the correlation coefficients, hence the results must be interpreted with caution. Although the present meta-analysis revealed that a PD has favorable effects on CVD risk factors, the evidence is not conclusive and more well-designed trials are still needed.

scholarly journals Evaluating the effects of alcohol and tobacco use on cardiovascular disease using multivariable Mendelian randomization

2019 ◽  
Author(s):  
Daniel B. Rosoff ◽  
George Davey Smith ◽  
Nehal Mehta ◽  
Toni-Kim Clarke ◽  
Falk W. Lohoff
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Alcohol Use ◽  
Tobacco Use ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Density Lipoprotein ◽  
Genome Wide Association Studies ◽  
Cvd Risk ◽  
Increased Risk

ABSTRACTAlcohol and tobacco use, two major modifiable risk factors for cardiovascular disease (CVD), are often consumed together. Using large publicly available genome-wide association studies (results from > 940,000 participants), we conducted two-sample multivariable Mendelian randomization (MR) to simultaneously assess the independent effects of alcohol and tobacco use on CVD risk factors and events. We found genetic instruments associated with increased alcohol use, controlling for tobacco use, associated with increased high-density-lipoprotein-cholesterol (HDL-C), decreased triglycerides, but not with coronary heart disease (CHD), myocardial infarction (MI), nor stroke; and instruments for increased tobacco use, controlling for alcohol use, associated with decreased HDL-C, increased triglycerides, and increased risk of CHD and MI. Exploratory analysis found associations with HDL-C, LDL-C, and intermediate-density-lipoprotein metabolites. Consistency of results across complementary methods accommodating different MR assumptions strengthened causal inference, providing strong genetic evidence for the causal effects of modifiable lifestyle risk factors on CVD risk.

scholarly journals Risk factors mediating the effect of body-mass index and waist-to-hip ratio on cardiovascular outcomes: Mendelian randomization analysis

2020 ◽  
Author(s):  
Dipender Gill ◽  
Verena Zuber ◽  
Jesse Dawson ◽  
Jonathan Pearson-Stuttard ◽  
Alice R Carter ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Body Mass Index ◽  
Body Mass ◽  
European Ancestry ◽  
Standard Deviation Increase ◽  
Waist To Hip Ratio ◽  
Increased Risk ◽  
Artery Disease

Background: Higher body-mass index (BMI) and waist-to-hip ratio (WHR) increase the risk of cardiovascular disease, but the extent to which this is mediated by blood pressure, diabetes, lipid traits and smoking is not fully understood. Methods: Using consortia and UK Biobank genetic association summary data from 140,595 to 898,130 participants predominantly of European ancestry, MR mediation analysis was performed to investigate the degree to which genetically predicted systolic blood pressure (SBP), diabetes, lipid traits and smoking mediated an effect of genetically predicted BMI and WHR on risk of coronary artery disease (CAD), peripheral artery disease (PAD) and stroke. Results: The 49% (95% confidence interval [CI] 39%-60%) increased risk of CAD conferred per 1-standard deviation increase in genetically predicted BMI attenuated to 34% (95% CI 24%-45%) after adjusting for genetically predicted SBP, to 27% (95% CI 17%-37%) after adjusting for genetically predicted diabetes, to 47% (95% CI 36%-59%) after adjusting for genetically predicted lipids, and to 46% (95% CI 34%-58%) after adjusting for genetically predicted smoking. Adjusting for all the mediators together, the increased risk attenuated to 14% (95% CI 4%-26%). A similar pattern of attenuation was observed when considering genetically predicted WHR as the exposure, and PAD or stroke as the outcomes. Conclusions: Measures to reduce obesity will lower risk of cardiovascular disease primarily by impacting on downstream metabolic risk factors, particularly diabetes and hypertension. Reduction of obesity prevalence alongside control and management of its mediators is likely to be most effective for minimizing the burden of obesity.

scholarly journals Antidepressant Use and the Risk of Major Adverse Cardiovascular Events in Patients Without Known Cardiovascular Disease: A Retrospective Cohort Study

2020 ◽  
Vol 11 ◽  
Author(s):  
Ha Young Jang ◽  
Jae Hyun Kim ◽  
Yun-Kyoung Song ◽  
Ju-Young Shin ◽  
Hae-Young Lee ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Risk Score ◽  
Cardiovascular Events ◽  
Major Adverse Cardiovascular Events ◽  
Cvd Risk ◽  
Hazard Ratios ◽  
Increased Risk ◽  
History Of ◽  
Antidepressant Use ◽  
Cox Proportional Hazard Regression

Aims: Conflicting data exist on whether an association exists between antidepressants and the risk of major adverse cardiovascular events (MACEs) in patients with depression. This may be due to the use of various study designs and residual or unmeasured confounding. We aimed to assess the association between antidepressant use and the risk of MACEs while considering various covariates, including severity of depression and the cardiovascular disease (CVD) risk score.Methods: Patients newly diagnosed with depression with no history of ischemic heart disease and stroke were followed-up from 2009 to 2015. We conducted Cox proportional hazard regression analysis to estimate hazard ratios (HRs) for each antidepressant for MACE risk.Result: We followed-up (median, 4.4 years) 31,830 matched patients with depression (15,915 antidepressant users and 15,915 non-users). In most patients (98.7%), low-dose tricyclic antidepressants (TCAs) were related with a significantly increased risk of MACEs [adjusted HR = 1.20, 95% confidence interval (CI) = 1.03–1.40]. Duration response relationship showed a gradually increasing HR from 1.15 (95% CI = 0.98–1.33; <30 days of use) to 1.84 (95% CI = 1.35–2.51; ≥365 days of use) (p for trend <0.01). High Korean atherosclerotic CVD risk score (≥7.5%) or unfavorable lifestyle factors (smoking, alcohol intake, and exercise) were significantly associated with MACEs.Conclusion: Even at low doses, TCA use was associated with MACEs during primary prevention. Longer duration of TCA use correlated with higher HR. Careful monitoring is needed with TCA use in patients with no known CVD history.

scholarly journals Harms and Benefits of Using Aspirin for Primary Prevention of Cardiovascular Disease: A Narrative Overview

2018 ◽  
Vol 45 (02) ◽  
pp. 157-163 ◽  
Author(s):  
Elisa Danese ◽  
Emmanuel Favaloro ◽  
Giuseppe Lippi
Keyword(s):  
Cardiovascular Disease ◽  
Primary Prevention ◽  
The Elderly ◽  
Favorable Effect ◽  
Major Adverse Cardiovascular Events ◽  
Increased Risk ◽  
Group Randomized Trial ◽  
Meta Analyses ◽  
Group Trial ◽  
Prevention Of Cardiovascular Disease

AbstractAspirin is one of the most often used drugs for prevention and treatment of a variety of thrombotic disorders. This narrative review aims to provide an overview of evidence highlighting potential benefits and relative harms of aspirin in primary prevention of cardiovascular disease. The authors summarize key findings of the ASPirin in Reducing Events in the Elderly (ASPREE) Investigator Group randomized trial and also provide a comparative overview of recent meta-analyses. Overall, all-cause mortality was largely heterogeneous, with some meta-analyses showing a modestly decreased risk in patients taking aspirin, with others reporting no effects, but the ASPREE Investigator Group trial evidencing 14% higher risk. Regarding cardiovascular disease, the most favorable impact could be noted for major adverse cardiovascular events, with most meta-analyses reporting a decreased risk in people receiving aspirin. Conversely, the ASPREE Investigator Group trial demonstrated no significant impact of aspirin on risk of cardiovascular mortality or ischemic stroke. A modest favorable effect of aspirin in decreasing the risk of myocardial infarction was noted in two meta-analyses, but not in other reports or in the ASPREE Investigator Group trial. Furthermore, one meta-analysis reported a lower risk of future cancer, others failed to report a significant effect, and the ASPREE Investigator Group trial reported a 31% increased risk. Unlike these conflicting outcomes, the bleeding risk of patients receiving aspirin was found to be consistently enhanced in all reports reviewed. These recent findings would lead us to conclude that the harms of aspirin in primary prevention of cardiovascular disease may be larger than the benefits, especially in the elderly general population.

scholarly journals Risk factors mediating the effect of body mass index and waist-to-hip ratio on cardiovascular outcomes: Mendelian randomization analysis

2021 ◽  
Author(s):  
Dipender Gill ◽  
Verena Zuber ◽  
Jesse Dawson ◽  
Jonathan Pearson-Stuttard ◽  
Alice R. Carter ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Body Mass Index ◽  
Body Mass ◽  
Mendelian Randomization ◽  
European Ancestry ◽  
Standard Deviation Increase ◽  
Waist To Hip Ratio ◽  
Artery Disease

Abstract Background Higher body mass index (BMI) and waist-to-hip ratio (WHR) increase the risk of cardiovascular disease, but the extent to which this is mediated by blood pressure, diabetes, lipid traits, and smoking is not fully understood. Methods Using consortia and UK Biobank genetic association summary data from 140,595 to 898,130 participants predominantly of European ancestry, Mendelian randomization mediation analysis was performed to investigate the degree to which systolic blood pressure (SBP), diabetes, lipid traits, and smoking mediated an effect of BMI and WHR on the risk of coronary artery disease (CAD), peripheral artery disease (PAD) and stroke. Results The odds ratio of CAD per 1-standard deviation increase in genetically predicted BMI was 1.49 (95% CI 1.39 to 1.60). This attenuated to 1.34 (95% CI 1.24 to 1.45) after adjusting for genetically predicted SBP (proportion mediated 27%, 95% CI 3% to 50%), to 1.27 (95% CI 1.17 to 1.37) after adjusting for genetically predicted diabetes (41% mediated, 95% CI 18% to 63%), to 1.47 (95% CI 1.36 to 1.59) after adjusting for genetically predicted lipids (3% mediated, 95% −23% to 29%), and to 1.46 (95% CI 1.34 to 1.58) after adjusting for genetically predicted smoking (6% mediated, 95% CI −20% to 32%). Adjusting for all the mediators together, the estimate attenuated to 1.14 (95% CI 1.04 to 1.26; 66% mediated, 95% CI 42% to 91%). A similar pattern was observed when considering genetically predicted WHR as the exposure, and PAD or stroke as the outcome. Conclusions Measures to reduce obesity will lower the risk of cardiovascular disease primarily by impacting downstream metabolic risk factors, particularly diabetes and hypertension. Reduction of obesity prevalence alongside control and management of its mediators is likely to be most effective for minimizing the burden of obesity.

scholarly journals Longitudinal association between cardiovascular risk factors and depression in young people: a systematic review and meta-analysis of cohort studies

2021 ◽  
pp. 1-11
Author(s):  
Anna B. Chaplin ◽  
Natasha F. Daniels ◽  
Diana Ples ◽  
Rebecca Z. Anderson ◽  
Amy Gregory-Jones ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Young People ◽  
Cohort Studies ◽  
Meta Analysis ◽  
Random Effect ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Increased Risk ◽  
Longitudinal Association

Abstract Background Depression is a common and serious mental illness that begins early in life. An association between cardiovascular disease (CVD) and subsequent depression is clear in adults. We examined associations between individual CVD risk factors and depression in young people. Methods We searched MEDLINE, EMBASE, and PsycINFO databases from inception to 1 January 2020. We extracted data from cohort studies assessing the longitudinal association between CVD risk factors [body mass index (BMI), smoking, systolic blood pressure (SBP), total cholesterol, high-density lipoprotein] and depression, measured using a validated tool in individuals with mean age of 24 years or younger. Random effect meta-analysis was used to combine effect estimates from individual studies, including odds ratio (OR) for depression and standardised mean difference for depressive symptoms. Results Based on meta-analysis of seven studies, comprising 15 753 participants, high BMI was associated with subsequent depression [pooled OR 1.61; 95% confidence interval (CI) 1.21–2.14; I2 = 31%]. Based on meta-analysis of eight studies, comprising 30 539 participants, smoking was associated with subsequent depression (pooled OR 1.73; 95% CI 1.36–2.20; I2 = 74%). Low, but not high, SBP was associated with an increased risk of depression (pooled OR 3.32; 95% CI 1.68–6.55; I2 = 0%), although this was based on a small pooled high-risk sample of 893 participants. Generalisability may be limited as most studies were based in North America or Europe. Conclusions Targeting childhood/adolescent smoking and obesity may be important for the prevention of both CVD and depression across the lifespan. Further research on other CVD risk factors including blood pressure and cholesterol in young people is required.

scholarly journals Aspirin for primary prevention: yes or no?

2010 ◽  
Vol 2 (2) ◽  
pp. 92 ◽  
Author(s):  
Vanessa Selak ◽  
C Raina Elley ◽  
Sue Wells ◽  
Anthony Rodgers ◽  
Norman Sharpe
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Disease ◽  
Primary Prevention ◽  
Meta Analysis ◽  
Risk Category ◽  
Age Group ◽  
Blood Pressure Lowering ◽  
Net Benefit ◽  
Cvd Risk ◽  
Pressure Lowering

AIM: To assess benefit versus harm of aspirin for cardiovascular disease (CVD) primary prevention by age group, gender and risk category and to interpret these results in light of current New Zealand CVD risk assessment and management guidelines. METHODS: Rates of benefit (avoided vascular events) and harm (additional major extracranial bleeds) for each gender and age group were calculated from data from the six randomised controlled trials included in the Anti-Thrombotic Trialists’ (ATT) Collaboration meta-analysis. These rates were applied to CVD risk categories to calculate the net benefit or net harm likely to occur from the use of aspirin in primary prevention of CVD as monotherapy and when added to lipid and blood pressure–lowering therapies. RESULTS: Benefits of aspirin monotherapy outweigh the harms for both men and women aged up to 80 years with calculated five-year CVD risk >15% in primary prevention. Harm may outweigh benefit for primary prevention for those over 80 years. For men 70–79 years the benefit of aspirin in primary prevention is marginal when added to lipid and blood pressure–lowering therapies. DISCUSSION: The recent ATT Collaboration meta-analysis has raised doubts about the relative safety of aspirin in primary prevention of CVD. However, modelling by risk category and age group suggests that current guidelines are justified in recommending aspirin for primary prevention of CVD in those with five-year CVD risk ≥15% up to the age of 80 years. For men 70–79, consider lipid and blood pressure - lowering therapies first then reassess whether aspirin adds additional net benefit. KEYWORDS: Aspirin; primary prevention; cardiovascular disease; cardiovascular risk

Efficacy and safety of aspirin for cardiovascular risk prevention in younger and older age: an updated systematic review and meta-analysis

2021 ◽  
Author(s):  
Dario Calderone ◽  
Antonio Greco ◽  
Salvatore Ingala ◽  
Federica Agnello ◽  
Antonio Gabriele Franchina ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Major Bleeding ◽  
Cardiovascular Events ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Major Adverse Cardiovascular Events ◽  
Older Individuals ◽  
Efficacy And Safety ◽  
Safety Outcome ◽  
Increased Risk

Aims - The efficacy and safety of aspirin for primary cardiovascular disease (CVD) prevention is controversial. The aim of this study was to investigate the merits of aspirin in subjects with no overt CVD, with a focus on age as a treatment modifier. Methods and results - Randomized trials comparing aspirin use versus no aspirin use or placebo were included. The primary efficacy outcome was all-cause death. The primary safety outcome was major bleeding. Subgroups analyses were conducted to investigate the consistency of the effect sizes in studies including younger and older individuals, using a cut-off of 65 years. A total of 21 randomized trials including 173,810 individuals at a mean follow-up of 5.3 years were included. Compared with control, aspirin did not reduce significantly the risk of all-cause death (risk ratio 0.96, 95% CI 0.92-1.00, p=0.057). Major adverse cardiovascular events were significantly reduced by 11%, paralleled by significant reductions in myocardial infarction and transient ischemic attack. Major bleeding, intracranial hemorrhage, and gastrointestinal bleeding were significantly increased by aspirin. There was a significant age interaction for death (p for interaction=0.007), with aspirin showing a statistically significant 7% relative benefit on all-cause death in studies including younger patients. Conclusions - The use of aspirin in subjects with no overt cardiovascular disease was associated with a neutral effect on all-cause death and a modest lower risk of major cardiovascular events at the price of an increased risk in major bleeding. The benefit of aspirin might be more pronounced in younger individuals.

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