scholarly journals Genetic determinants of lipids and cardiovascular disease outcomes: a wide-angled Mendelian randomization investigation

2019 ◽  
Author(s):  
Elias Allara ◽  
Gabriele Morani ◽  
Paul Carter ◽  
Apostolos Gkatzionis ◽  
Verena Zuber ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Valve ◽  
Aortic Aneurysm ◽  
Aortic Stenosis ◽  
Aortic Valve Stenosis ◽  
Ldl Cholesterol ◽  
Mendelian Randomization ◽  
Cardiovascular Outcomes ◽  
Lipid Lowering ◽  
Abdominal Aortic

ABSTRACTAimsTo systematically investigate causal relationships between circulating lipids and cardiovascular outcomes, using a Mendelian randomization approach.Methods and ResultsIn the primary analysis, we performed two-sample multivariable Mendelian randomization using data from participants of European ancestry. We also conducted univariable analyses using inverse-variance weighted and robust methods, and gene-specific analyses using variants that can be considered as proxies for specific lipid-lowering medications. We obtained associations with lipid fractions from the Global Lipids Genetics Consortium, a meta-analysis of 188,577 participants, and genetic associations with cardiovascular outcomes from 367,703 participants in UK Biobank.For LDL-cholesterol, in addition to the expected positive associations with coronary artery disease (CAD) risk (odds ratio per 1 standard deviation increase [OR], 1.45; 95% confidence interval [95%CI] 1.35-1.57) and other atheromatous outcomes (ischemic cerebrovascular disease and peripheral vascular disease), we found independent associations of genetically-predicted LDL-cholesterol with abdominal aortic aneurysm (OR 1.75; 95%CI 1.40-2.17), and aortic valve stenosis (OR 1.46; 95%CI 1.25-1.70). Genetically-predicted triglyceride levels were positively associated with CAD (OR 1.25; 95%CI 1.12-1.40), aortic valve stenosis (OR 1.29; 95%CI 1.04-1.61), and hypertension (OR 1.17; 95%CI 1.07-1.27), but inversely associated with venous thromboembolism (OR 0.79; 95%CI 0.67-0.93). The positive associations of genetically-predicted LDL-cholesterol and triglycerides with heart failure and aortic stenosis appeared to be mediated by CAD.ConclusionLowering LDL-cholesterol is likely to prevent abdominal aortic aneurysm and aortic stenosis, in addition to CAD and other atheromatous cardiovascular outcomes. Lowering triglycerides is likely to prevent CAD and aortic valve stenosis, but may increase risk of thromboembolism.

scholarly journals Genetic Determinants of Lipids and Cardiovascular Disease Outcomes

2019 ◽  
Vol 12 (12) ◽  
Author(s):  
Elias Allara ◽  
Gabriele Morani ◽  
Paul Carter ◽  
Apostolos Gkatzionis ◽  
Verena Zuber ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Valve ◽  
Aortic Aneurysm ◽  
Aortic Valve Stenosis ◽  
Ldl Cholesterol ◽  
Mendelian Randomization ◽  
Cardiovascular Outcomes ◽  
Lipid Lowering ◽  
Abdominal Aortic ◽  
Cad Risk

Background: Evidence from randomized trials has shown that therapies that lower LDL (low-density lipoprotein)-cholesterol and triglycerides reduce coronary artery disease (CAD) risk. However, there is still uncertainty about their effects on other cardiovascular outcomes. We therefore performed a systematic investigation of causal relationships between circulating lipids and cardiovascular outcomes using a Mendelian randomization approach. Methods: In the primary analysis, we performed 2-sample multivariable Mendelian randomization using data from participants of European ancestry. We also conducted univariable analyses using inverse-variance weighted and robust methods, and gene-specific analyses using variants that can be considered as proxies for specific lipid-lowering medications. We obtained associations with lipid fractions from the Global Lipids Genetics Consortium, a meta-analysis of 188 577 participants, and genetic associations with cardiovascular outcomes from 367 703 participants in UK Biobank. Results: For LDL-cholesterol, in addition to the expected positive associations with CAD risk (odds ratio [OR] per 1 SD increase, 1.45 [95% CI, 1.35–1.57]) and other atheromatous outcomes (ischemic cerebrovascular disease and peripheral vascular disease), we found independent associations of genetically predicted LDL-cholesterol with abdominal aortic aneurysm (OR, 1.75 [95% CI, 1.40–2.17]) and aortic valve stenosis (OR, 1.46 [95% CI, 1.25–1.70]). Genetically predicted triglyceride levels were positively associated with CAD (OR, 1.25 [95% CI, 1.12–1.40]), aortic valve stenosis (OR, 1.29 [95% CI, 1.04–1.61]), and hypertension (OR, 1.17 [95% CI, 1.07–1.27]), but inversely associated with venous thromboembolism (OR, 0.79 [95% CI, 0.67–0.93]) and hemorrhagic stroke (OR, 0.78 [95% CI, 0.62–0.98]). We also found positive associations of genetically predicted LDL-cholesterol and triglycerides with heart failure that appeared to be mediated by CAD. Conclusions: Lowering LDL-cholesterol is likely to prevent abdominal aortic aneurysm and aortic stenosis, in addition to CAD and other atheromatous cardiovascular outcomes. Lowering triglycerides is likely to prevent CAD and aortic valve stenosis but may increase thromboembolic risk.

Simultaneous Transcatheter Aortic Valve Implantation and Infrarenal Aortic Aneurysm Repair for Severe Aortic Stenosis and Abdominal Aortic Aneurysm: Report of 2 Cases and Literature Review

2020 ◽  
Vol 54 (6) ◽  
pp. 544-548
Author(s):  
Stylianos Koutsias ◽  
Georgios I. Karaolanis ◽  
Michail I. Papafaklis ◽  
Michail Peroulis ◽  
Petros Tzimas ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Valve ◽  
Aortic Aneurysm ◽  
Aortic Stenosis ◽  
Transcatheter Aortic Valve Implantation ◽  
Severe Aortic Stenosis ◽  
Transcatheter Aortic Valve ◽  
Abdominal Aortic ◽  
Aortic Valve Implantation ◽  
Valve Implantation

The prevalence of concomitant abdominal aortic aneurysm (AAA) and severe aortic stenosis (AS) has been increasing in the elderly population. Both conditions have adverse outcomes, if not adequately managed. No clear recommendations are available in the literature until today, in regards of the management sequence making thus the decision-making challenging. We report 2 cases of AAA and significant AS treated with endovascular aortic repair (EVAR) and transcatheter aortic valve implantation (TAVI) during the same procedure and a review of the literature on this topic. Based on our experience, the combined procedure with TAVI followed by EVAR seems to be feasible, safe, and effective while detailed preoperative planning and a carefully tailored management strategy by a multidisciplinary team are essential.

scholarly journals Plasma lipids and risk of aortic valve stenosis: a Mendelian randomization study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Nazarzadeh ◽  
A.-C Pinho-Gomes ◽  
Z Bidel ◽  
A Dehghan ◽  
D Canoy ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Mitral Regurgitation ◽  
Aortic Stenosis ◽  
Aortic Valve Stenosis ◽  
Ldl Cholesterol ◽  
Mendelian Randomization ◽  
Density Lipoprotein ◽  
Funding Source ◽  
Causal Association ◽  
Lipid Levels

Abstract Background Aortic valve stenosis is commonly considered a degenerative disorder with no recommended preventive intervention, with only valve replacement surgery or catheter intervention as treatment options. Purpose We sought to assess the causal association between exposure to lipid levels and risk of aortic stenosis. Methods Causality of association was assessed using two-sample Mendelian Randomization (MR) framework through different statistical methods. MR approach uses instrumental variable analysis to mimic the randomization process that underpins causal inference in clinical trials. It takes advantage of the naturally-occurring random allocation of alleles inherited by offspring from their parents during the formation of the zygote. We retrieved summary estimations of 157 genetic variants that have been shown to be associated with plasma lipid levels in the Global Lipids Genetics Consortium that included 188,577 participants, mostly European ancestry, and genetic association with aortic stenosis as the main outcome from a total of 432,173 participants in the UK Biobank. Secondary negative control outcomes included aortic regurgitation and mitral regurgitation. Results The odds ratio (OR) for developing aortic stenosis per unit increase in lipid parameter was 1.52 (95% confidence interval [CI], 1.22 to 1.90; per 0.98 mmol/L) for low-density lipoprotein (LDL) cholesterol, 1.03 (95% CI, 0.80 to 1.31; per 0.41 mmol/L) for high-density lipoprotein (HDL) cholesterol, and 1.38 (95% CI 0.92 to 2.07; per 1 mmol/L) for triglycerides. There was no evidence of a causal association between any of the lipid parameters and aortic or mitral regurgitation. Conclusion Lifelong exposure to high LDL-cholesterol increases the risk of symptomatic aortic stenosis, suggesting that LDL-lowering treatment may be effective in its prevention. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation

scholarly journals Plasma lipids and risk of aortic valve stenosis: a Mendelian randomization study

2020 ◽  
Vol 41 (40) ◽  
pp. 3913-3920 ◽  
Author(s):  
Milad Nazarzadeh ◽  
Ana-Catarina Pinho-Gomes ◽  
Zeinab Bidel ◽  
Abbas Dehghan ◽  
Dexter Canoy ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Mitral Regurgitation ◽  
Aortic Stenosis ◽  
Aortic Valve Stenosis ◽  
Ldl Cholesterol ◽  
Mendelian Randomization ◽  
Density Lipoprotein ◽  
European Ancestry ◽  
Causal Association ◽  
Lipid Levels

Abstract Aims  Aortic valve stenosis is commonly considered a degenerative disorder with no recommended preventive intervention, with only valve replacement surgery or catheter intervention as treatment options. We sought to assess the causal association between exposure to lipid levels and risk of aortic stenosis. Methods and results  Causality of association was assessed using two-sample Mendelian randomization framework through different statistical methods. We retrieved summary estimations of 157 genetic variants that have been shown to be associated with plasma lipid levels in the Global Lipids Genetics Consortium that included 188 577 participants, mostly European ancestry, and genetic association with aortic stenosis as the main outcome from a total of 432 173 participants in the UK Biobank. Secondary negative control outcomes included aortic regurgitation and mitral regurgitation. The odds ratio for developing aortic stenosis per unit increase in lipid parameter was 1.52 [95% confidence interval (CI) 1.22–1.90; per 0.98 mmol/L] for low density lipoprotein (LDL)-cholesterol, 1.03 (95% CI 0.80–1.31; per 0.41 mmol/L) for high density lipoprotein (HDL)-cholesterol, and 1.38 (95% CI 0.92–2.07; per 1 mmol/L) for triglycerides. There was no evidence of a causal association between any of the lipid parameters and aortic or mitral regurgitation. Conclusion  Lifelong exposure to high LDL-cholesterol increases the risk of symptomatic aortic stenosis, suggesting that LDL-lowering treatment may be effective in its prevention.

The Role of Smoking in Abdominal Aortic Aneurysm Development

Angiology ◽  
2008 ◽  
Vol 60 (1) ◽  
pp. 115-119 ◽  
Author(s):  
Stephen A. Badger ◽  
Mark E. O'Donnell ◽  
Muhammed A. Sharif ◽  
Cyril McMaster ◽  
Ian S. Young ◽  
...  
Keyword(s):  
Risk Factors ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Cardiac Disease ◽  
Significant Risk ◽  
Lipid Lowering ◽  
Smoking History ◽  
Lipid Lowering Therapy ◽  
Abdominal Aortic ◽  
Aneurysm Development

Abdominal aortic aneurysm is common. The aim of this study was to assess the effect of smoking on prevalence and management. Patients attending the vascular unit and appropriate controls were prospectively recruited. A smoking history revealed tobacco exposure in pack years. Serum cotinine was assessed biochemically. Independent risk factors were statistically determined. In all, 202 (186 men) patients were recruited, with 202 (197 men) controls. A total of 69 patients tested positive for cotinine, whereas 39 controls were positive ( P = .001). Smoking and ischemic heart disease were significant predictors for aneurysm prevalence. Cardiac disease emerged as a more important predictor than smoking in symptomatic patients. In noncardiac patients, smoking and hypercholesterolemia were significant risk factors. Smoking is a significant predictor for aneurysm development. In high-risk patients, the cardiac disease process is the most important factor, with control of this imperative. However, in noncardiac patients, smoking cessation and lipid-lowering therapy are crucial.

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