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

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Abstract
BACKGROUND: Observational studies relating blood pressure in middle age to mortality may underestimate lifelong effects. Mendelian randomization can reduce the impact of confounding and reverse causality and may better estimate lifelong effects of blood pressure on mortality. METHODS: Mendelian randomization analyses used 125 895 Mexico City Prospective Study participants aged 35 to 74 years at recruitment with valid genetic and other data. Cox regression, adjusted for confounders and regression dilution bias, related blood pressure to mortality in 133 027 participants aged 35 to 74 years without prior chronic disease (other than diabetes) at recruitment. RESULTS: In the genetic analyses (40 560 [32%] men; mean age 50 years, mean body mass index 29 kg/m 2 ) there were 13 153 deaths before age 75 years (3478 cardiovascular, 2053 kidney, and 7622 other). Each 10 mm Hg higher genetically predicted lifelong systolic blood pressure was associated with 73% higher cardiovascular mortality at ages 35 to 74 years (rate ratio, 1.73 [95% CI, 1.44–2.06]), 42% higher kidney death (1.42 [95% CI, 1.15–1.75]), but no clear increase in death from other causes. These lifelong rate ratios were higher than those estimated by observational analyses relating blood pressure in middle age to risk. Mendelian randomization analyses of lifelong diastolic blood pressure confirmed strong associations with cardiovascular but not kidney death. Mortality rate ratios were similar for men and women and in those with versus without diabetes, and broadly similar at different ages and at different proportions of Indigenous American ancestry. Sensitivity analyses gave consistent results. CONCLUSIONS: In this Mexican population, genetically informed lifelong differences in blood pressure were strongly related to death from cardiovascular and kidney disease.

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