ArticleCirculation2021
Linear and Nonlinear Mendelian Randomization Analyses of the Association Between Diastolic Blood Pressure and Cardiovascular Events: The J-Curve Revisited.
Article in Circulation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 3 of them syntheses that pooled it.
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The trial behind it
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Who cites it
62 citing papers in PubMed, 3 syntheses or guidelines pooled it, 118 citations in OpenAlex.
- Blood pressure lowering in isolated diastolic hypertension and cardiovascular risk: an individual patient data meta-analysis.European heart journal · 2026Pooled it
- European guidelines for hypertension in 2024: a comparison of key recommendations for clinical practice.Nature reviews. Cardiology · 2025Guideline
- Call to action: British and Irish hypertension society position statement on blood pressure treatment thresholds and targets.Journal of human hypertension · 2025Guideline
- Efficacy and safety of intensive antihypertensive strategy in patients with low diastolic blood pressure: a secondary analysis of a cluster randomised trial.Heart (British Cardiac Society) · 2026Trial
- Cardiovascular Risk in Patients With Treated Isolated Diastolic Hypertension and Isolated Low Diastolic Blood Pressure.Journal of the American Heart Association · 2024Trial
- NLCD: A method to discover nonlinear causal relations among genes.PLoS computational biology · 2026Article
- Widespread genetic effect heterogeneity impacts bias and power in nonlinear Mendelian randomization.medRxiv : the preprint server for health sciences · 2026Article
- Relationship between blood pressure and adverse clinical events in patients undergoing percutaneous coronary intervention (PCI): a retrospective analysis.European journal of medical research · 2025Article
- Diastolic blood pressure as a predictor of short-term mortality in infective endocarditis.International journal of cardiology. Cardiovascular risk and prevention · 2025Article
- Brazilian Guidelines of Hypertension - 2025.Arquivos brasileiros de cardiologia · 2025Article
- Association between 10-year atherosclerotic cardiovascular disease risk score and incident cardiovascular events across stages 0-3 of cardiovascular-kidney-metabolic syndrome: evidence from the China health and retirement longitudinal study (CHARLS).BMC cardiovascular disorders · 2025Article
- Blood Pressure and Cardiovascular Outcomes in Adults With Diabetes and Chronic Kidney Disease.Journal of the American Heart Association · 2025Article
- Article
- Isolated diastolic hypertension and incident cardio-renal-metabolic multimorbidity in the Tehran Lipid and Glucose Study: comparison of ACC/AHA and ESC/NICE guideline definitions.Hypertension research : official journal of the Japanese Society of Hypertension · 2025Article
- Time-varying association between blood pressure and malignant brain edema after large hemispheric infarction: a prospective cohort study.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025Article
- Distinct pathway-based effects of blood pressure and body mass index on cardiovascular traits: comparison of novel Mendelian randomization approaches.Genome medicine · 2025Article
- Visit-to-visit blood pressure variability and clinical outcomes in peritoneal dialysis - based on machine learning algorithms.Hypertension research : official journal of the Japanese Society of Hypertension · 2025Article
- Baseline Diastolic BP and BP-Lowering Effects on Cardiovascular Outcomes and All-Cause Mortality: A Meta-Analysis.Journal of the American Society of Nephrology : JASN · 2025Article
- Interaction and combined effect of triglyceride-glucose index and hypertension on type 2 diabetes individuals' peripheral arterial disease risk.Acta diabetologica · 2025Article
- Epigenomics and transcriptomics association study of blood pressure and incident diagnosis of hypertension in twins.Hypertension research : official journal of the Japanese Society of Hypertension · 2025Article
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundRecent clinical guidelines support intensive blood pressure treatment targets. However, observational data suggest that excessive diastolic blood pressure (DBP) lowering might increase the risk of myocardial infarction (MI), reflecting a J- or U-shaped relationship.
methodsWe analyzed 47 407 participants from 5 cohorts (median age, 60 years). First, to corroborate previous observational analyses, we used traditional statistical methods to test the shape of association between DBP and cardiovascular disease (CVD). Second, we created polygenic risk scores of DBP and systolic blood pressure and generated linear Mendelian randomization (MR) estimates for the effect of DBP on CVD. Third, using novel nonlinear MR approaches, we evaluated for nonlinearity in the genetic relationship between DBP and CVD events. Comprehensive MR interrogation of DBP required us to also model systolic blood pressure, given that the 2 are strongly correlated.
resultsTraditional observational analysis of our cohorts suggested a J-shaped association between DBP and MI. By contrast, linear MR analyses demonstrated an adverse effect of increasing DBP increments on CVD outcomes, including MI (MI hazard ratio, 1.07 per unit mm Hg increase in DBP;
conclusionsIn this analysis of the genetic effect of DBP, we found no evidence for a nonlinear J- or U-shaped relationship between DBP and adverse CVD outcomes; including MI.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.