Genetically predicted blood pressure, antihypertensive drugs and risk of heart failure: a Mendelian randomization study

Lian, Jiao; Shi, Xiaoguang; Jia, Xiaocan; Fan, Jingwen; Wang, Yuping; Zhao, Yang; Yang, Yongli

doi:10.1097/hjh.0000000000003297

Cited by 4 publications

(2 citation statements)

References 38 publications

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“…8 Of note, MR is commonly considered valuable in exploring causality and predicting the effect of interventions, which may explain possible intervention targets in clinical practice including antihypertensive treatment. [9][10][11] Genome-wide association studies (GWAS), with large samples and genetic data, further permit the prediction of clinical outcomes of ischemic stroke, especially in the absence of data from RCTs. Simultaneously, the effects of drug action can be anticipated by the genetic effects in the genes of their protein targets, as has previously been applied to antihypertensive drugs.…”

Section: Introductionmentioning

confidence: 99%

Association between blood pressure and different antihypertensive drugs with outcome after ischemic stroke: A Mendelian randomization study

Liu

Zhang

Zhou

et al. 2023

International Journal of Stroke

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Background: Observational studies suggest an association between blood pressure (BP) and functional outcomes in ischemic stroke patients but whether this is causal or due to confounding is uncertain. We used Mendelian randomization (MR) to assess causality, and also explore whether particular classes of anti-hypertensives were associated with a better outcome after ischemic stroke. Methods: We selected genetic variants associated with systolic and diastolic BP and BP-lowering variants in genes encoding antihypertensive drugs from genome-wide association studies (GWAS) on 757,601 individuals. The primary outcome was 3-month dependence or death defined as a modified Rankin Scale (mRS) of 3-6. The secondary outcome was disability or death after 90 days defined as mRS 2-6. The Cochran’s Q statistic in the Inverse variance weighted (IVW) model, the weighted median, MR-Egger regression, leave-one-SNP-out analysis, MR-Pleiotropy Residual Sum and Outlier methods were adopted as sensitivity analyses. To validate our primary results, we performed independent repeat analyses and Bi-directional MR analyses. Results: Genetic predisposition to higher systolic and diastolic BP was associated with disability or death after ischemic stroke in univariable IVW MR analysis (OR=1.29, 95%CI 1.05-1.59, p=0.014; OR=1.27, 95%CI 1.07-1.51, p=0.006, respectively). Pulse pressure was associated with both dependence or death and disability or death after ischemic stroke (OR=1.05, 95%CI 1.02-1.08, p=0.002; OR=1.04, 95%CI 1.01-1.07, p=0.009, respectively). Angiotensin-converting enzyme inhibitor (ACEI) and calcium channel blocker (CCB) were significantly associated with improved functional outcomes (dependence or death, OR=0.76, 95%CI 0.62-0.94, p=0.009; OR=0.89, 95%CI 0.83-0.97, p=0.005). Proxies for β-blockers, angiotensin receptor blockers (ARB) and thiazides failed to show associations with functional outcomes (p>0.05). Conclusion: We provide evidence for an association of genetic predisposition to higher BP with a higher risk of 3-month functional dependence after ischemic stroke. Our findings support ACEI and CCB as promising antihypertensive drugs for improving functional outcomes in ischemic stroke.

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Section: Introductionmentioning

confidence: 99%

Association between blood pressure and different antihypertensive drugs with outcome after ischemic stroke: A Mendelian randomization study

Liu

Zhang

Zhou

et al. 2023

International Journal of Stroke

View full text Add to dashboard Cite

show abstract

“…(8) Of note, MR is commonly considered valuable in exploring causality and in predicting the effect of interventions, which may explain possible intervention targets in clinical practice including antihypertensive treatment. (9)(10)(11) Genome-wide association studies (GWAS), with large samples and genetic data, further permit prediction of clinical outcomes of ischemic stroke, especially in the absence of data from RCTs. Simultaneously, the effects of drug action can be anticipated by the genetic effects in the genes of their protein targets, as has previously been applied to antihypertensive drugs.…”

Section: Introductionmentioning

confidence: 99%

Genetically Determined Blood Pressure, Antihypertensive Drugs, and Genes with Clinical Outcome after Ischemic Stroke: Evidence from Mendelian Randomization

Liu

Zhang

Zhou

et al. 2023

Preprint

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Background: Observational studies suggest a robust association between blood pressure (BP) and functional outcomes in ischemic stroke patients. We sought to identify novel associations of the genetic basis of 3-month functional outcome after ischemic stroke based on a Mendelian randomization (MR) framework.<break><break>Methods: We selected genetic variants associated with systolic and diastolic BP and BP-lowering variants in genes encoding antihypertensive drugs from genome-wide association studies (GWAS) on 757,601 individuals. The primary outcome was 3-month favorable functional outcome defined as modified Rankin Scale (mRS) of 0-2. The secondary outcome was excellent 90-day outcome defined as mRS 0-1. The Cochrans Q statistic in Inverse variance weighted (IVW) model, the weighted median, MR-Egger regression, leave-one-SNP-out analysis, MR-Pleiotropy Residual Sum and Outlier methods were adopted as sensitivity analyses. To validate our primary results, we performed independent repeat analyses and Bi-directional MR analyses.<break><break>Results: Genetic predisposition to higher systolic and diastolic BP was associated with a lower probability of 3-month excellent functional outcome after ischemic stroke in univariable IVW MR analysis (OR=1.29, 95%CI 1.05-1.59, p=0.014; OR=1.27, 95%CI 1.07-1.51, p=0.006, respectively). Pulse pressure was associated with both excellent and favorable functional outcome (OR=1.05, 95%CI 1.02-1.08, p=0.002; OR=1.04, 95%CI 1.01-1.07, p=0.009, respectively). Angiotensin-converting enzyme inhibitor (ACEI) and calcium channel blocker (CCB), were significantly associated with improved favorable functional outcome (OR=0.76, 95%CI 0.62-0.94, p=0.009; OR=0.89, 95%CI 0.83-0.97, p=0.005). Proxies for -blockers, angiotensin receptor blocker (ARB) and thiazides failed to show associations with functional outcome (p>0.05). <break><break>Conclusion: We provide evidence for a potential association of genetic predisposition to higher BP with higher risk of 3-month functional dependence after ischemic stroke. Our findings support ACEI and CCB as promising antihypertensive drugs for improving functional outcome in ischemic stroke.

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Birth Weight, Cardiometabolic Factors, and Coronary Heart Disease: A Mendelian Randomization Study

Fan

Yang

et al. 2023

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context Observational studies have shown associations of birth weight (BW) with coronary heart disease (CHD), but results are inconsistent and do not distinguish the fetal or maternal effect of BW. Objective This study aims to explore the causal association between BW and CHD, analyze the fetal and maternal contribution, and quantify mediating effects of cardiometabolic factors. Method Genetic variants form GWAS summary-level data of own BW (N = 298,142), offspring BW (N = 210,267 mothers) and 16 cardiometabolic factors (anthropometric, glycemic, lipidemic and blood pressure factors) were extracted as instrumental variables. We used two-sample Mendelian randomization study (MR) to estimate the causal effect of BW on CHD (60,801 cases and 123,504 controls from mixed ancestry), and explore the fetal and maternal contributions. Then, mediation analyses were conducted to analyze the potential mediating effects of 16 cardiometabolic factors using two-step MR. Result Inverse variance weighted method exhibited lower BW raised the CHD risk (β: -0.30; 95%CI: -0.40, -0.20) and consistent results were observed in fetal/maternal-specific BW. We identified 5 mediators in the causal pathway from BW to CHD, including hip circumference adjust body mass index, triglycerides, diastolic blood pressure, systolic blood pressure (SBP), with mediated proportion ranging from 7.44% for triglycerides to 27.75% for SBP. Causality between fetal/maternal-specific BW and CHD was mediated by glycemic factors and SBP, respectively. Conclusion Our findings supported that lower BW increased CHD risk and revealed the fetal/maternal specific BW may both contribute to this effect. The causality between BW and CHD was mediated by several cardiometabolic factors.

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Genetically predicted blood pressure, antihypertensive drugs and risk of heart failure: a Mendelian randomization study

Cited by 4 publications

References 38 publications

Association between blood pressure and different antihypertensive drugs with outcome after ischemic stroke: A Mendelian randomization study

Association between blood pressure and different antihypertensive drugs with outcome after ischemic stroke: A Mendelian randomization study

Genetically Determined Blood Pressure, Antihypertensive Drugs, and Genes with Clinical Outcome after Ischemic Stroke: Evidence from Mendelian Randomization

Birth Weight, Cardiometabolic Factors, and Coronary Heart Disease: A Mendelian Randomization Study

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