Blood Pressure and Mortality in Mexico City: A Mendelian Randomization Study

Area of Science:

• Cardiovascular Epidemiology
• Genetic Epidemiology
• Public Health

Background:

• Observational studies may underestimate the lifelong impact of blood pressure on mortality.
• Mendelian randomization offers a robust method to assess lifelong effects, mitigating confounding and reverse causality.

Purpose of the Study:

• To estimate the lifelong effects of systolic and diastolic blood pressure on mortality using Mendelian randomization.
• To compare these lifelong estimates with those from traditional observational analyses.

Main Methods:

• Utilized Mendelian randomization with 125,895 participants from the Mexico City Prospective Study.
• Employed Cox regression, adjusted for confounders and regression dilution bias, to analyze blood pressure and mortality in 133,027 participants.

Main Results:

• Each 10 mm Hg increase in genetically predicted lifelong systolic blood pressure was associated with a 73% higher cardiovascular mortality and 42% higher kidney disease mortality.
• Lifelong rate ratios from Mendelian randomization were higher than those from observational analyses.
• Associations were consistent across sexes, diabetes status, age groups, and ancestry proportions.

Conclusions:

• Genetically informed lifelong blood pressure differences are strongly linked to cardiovascular and kidney disease mortality in a Mexican population.
• Mendelian randomization provides a more accurate assessment of the lifelong risks associated with elevated blood pressure.