Linear and Nonlinear Mendelian Randomization Analyses of the Association Between Diastolic Blood Pressure and...

Area of Science:

• Cardiovascular Medicine
• Genetics
• Epidemiology

Background:

• Clinical guidelines advocate for intensive blood pressure management.
• Observational studies suggest a potential J- or U-shaped relationship between diastolic blood pressure (DBP) and myocardial infarction (MI) risk.
• This implies excessive DBP lowering might increase MI risk.

Purpose of the Study:

• To investigate the relationship between diastolic blood pressure (DBP) and cardiovascular disease (CVD) risk using genetic methods.
• To evaluate the shape of the association between DBP and CVD outcomes, specifically myocardial infarction (MI).
• To determine if nonlinear relationships, such as J- or U-shaped curves, exist between DBP and CVD events.

Main Methods:

• Analysis of 47,407 participants across 5 cohorts.
• Traditional statistical methods to assess DBP-CVD association shape.
• Linear and nonlinear Mendelian randomization (MR) using polygenic risk scores for DBP and systolic blood pressure.
• Modeling of systolic blood pressure due to its correlation with DBP.

Main Results:

• Observational analyses suggested a J-shaped association between DBP and MI.
• Linear MR analyses indicated that increasing DBP is associated with higher CVD risk, including MI (HR 1.07 per 1 mmHg increase; P<0.001).
• Nonlinear MR analyses found no evidence of a J-shaped relationship; MI risk consistently decreased with lower DBP, even at low baseline levels.

Conclusions:

• Genetic analysis provides no evidence for a nonlinear J- or U-shaped relationship between DBP and adverse CVD outcomes, including MI.
• The findings support a consistent benefit of lowering DBP concerning MI risk, challenging previous observational data suggesting a lower limit.
• This genetic perspective suggests that intensive blood pressure lowering may be safe regarding MI risk.