Abstract

Introduction: We assessed the hypothesis that a novel healthy blood pressure phenotype is familial and sought to identify factors associated with this phenotype in the Long Life Family Study (LLFS). Methods: The LLFS is a unique multi-center, international study that recruited families demonstrating clustering for longevity. Families were recruited from four centers; three in the U.S.: Boston, New York, and Pittsburgh and one in Denmark. The pedigrees included two generations: 1) probands and their siblings and 2) offspring of participants in the proband generation. Offspring (n=2211, ages 32-88, mean age=60.5; 43% male) were classified as having healthy blood pressure if their age- and sex-adjusted systolic blood pressure z-score was between -1.5 and -0.5 (i.e., a systolic blood pressure lower than expected for their age and sex, but not “too low”). Offspring on anti-hypertensive medications were classified as not having healthy blood pressure. Families (n=419) were defined as having healthy blood pressure if ≥2 and ≥50% of their offspring met the healthy blood pressure phenotype. Results: There were 476 (22%) offspring who met the healthy blood pressure phenotype. These offspring tended to have a better health profile than remaining offspring. When examining families, only 44 (11%) families met the criteria for healthy blood pressure. Both offspring and probands from families with healthy blood pressure performed better on neuropsychological tests that place demands on complex attention and executive function than offspring and probands from remaining families. Among families with healthy blood pressure, a higher proportion of offspring met the American Heart Association ideal cardiovascular health definition compared to remaining families (11% versus 4%, respectively, p<0.0001; not including the diet component). There was also a larger proportion of probands (n=1164, ages 71-110, mean age=90.5; 45% male) who met the American Heart Association ideal cardiovascular health definition when compared to the U.S. prevalence for ≥6 components among those ages ≥60 (1% versus 0.1%, respectively). Conclusion: In this cohort of familial longevity, few families had a novel healthy blood pressure phenotype in multiple members. Families and individuals with healthy blood pressure performed better on neuropsychological tests that represent aspects of executive function and had a higher proportion with ideal cardiovascular health than the U.S. population. In summary, a novel healthy blood pressure phenotype was rarely familial in this cohort; however, when it was, it was associated with cognitive and cardiovascular health benefits. Blood pressure may be a key pathway for family longevity.

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