Genetic influences on blood pressure response to the cold pressor test: results from the Heredity and Phenotype Intervention Heart Study

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Abstract
Objectives Blood pressure (BP) response to the cold pressor test (CPT) has been found to predict the development of hypertension and cardiovascular disease in prospective studies. The determinants of BP response to the CPT, including the role of genetic factors, however, are largely unknown. Additionally, to our knowledge, no study has examined the genetics of BP recovery from the CPT, including whether shared genetic factors influence both reactivity and recovery. Methods As part of the Heredity and Phenotype Intervention Heart Study, we administered a 2.5 min hand CPT to 835 participants from 18 extended Amish families. We estimated the heritability of BP reactivity and recovery (measured by the incremental area under the curve) and the genetic correlations between baseline, reactivity, and recovery BP phenotypes. Results After adjusting for relevant covariates, including baseline BP, the heritability estimates for both systolic BP (SBP) and diastolic BP (DBP) reactivity and recovery differed significantly from zero (P < 0.01), with 12–25% of the total variation in BP response attributable to additive genetic effects. The genetic correlations between baseline DBP and response phenotypes were not significantly different from zero, whereas the genetic correlation between DBP reactivity and recovery (0.74) was significantly different from zero and 1 (P < 0.005). The genetic correlation between SBP reactivity and recovery was similar (0.81; P < 0.05). Conclusion We conclude that, independent of baseline BP, BP response to CPT is heritable, and that both shared and unshared genetic factors influence BP reactivity and recovery, thus stressing the importance of identifying genetic variants that influence both traits.