Linear and Nonlinear Mendelian Randomization Analyses of the Association Between Diastolic Blood Pressure and Cardiovascular Events: The J-Curve Revisited.
Mendelian randomization analysis
blood pressure
diastole
Journal
Circulation
ISSN: 1524-4539
Titre abrégé: Circulation
Pays: United States
ID NLM: 0147763
Informations de publication
Date de publication:
02 03 2021
02 03 2021
Historique:
pubmed:
1
12
2020
medline:
4
1
2022
entrez:
30
11
2020
Statut:
ppublish
Résumé
Recent 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. We 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. Traditional 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; In 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.
Sections du résumé
BACKGROUND
Recent 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.
METHODS
We 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.
RESULTS
Traditional 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;
CONCLUSIONS
In 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.
Identifiants
pubmed: 33249881
doi: 10.1161/CIRCULATIONAHA.120.049819
pmc: PMC7920937
mid: NIHMS1664084
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
895-906Subventions
Organisme : NHGRI NIH HHS
ID : R01 HG010480
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007227
Pays : United States
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