Response to Essential Hypertension, Hypertension in Pregnancy, and Subsequent Blood Pressure: Another Old Dilemma Revisited
Cockcroft et al present data from the ENIGMA study to highlight the methodological relation that exists between carotid-femoral pulse wave velocity and mean arterial blood pressure independent of any true causal association between blood pressure and arterial stiffness.3 As they point out, in common with many other investigators, we do not adjust pulse wave velocity for mean arterial blood pressure. We accept that, based on the presented data, we should remain circumspect about our hypothesis that increased arterial stiffness accounts for the difference in blood pressure between our controls and those born preterm after normotensive pregnancies. Our ongoing studies in this group, including use of blood pressure-independent measures of arterial stiffness, will generate more detailed mechanistic insights to support or refute the hypothesis. However, this is not a distraction from the key message of the article, which was that the offspring vascular phenotype depends on the blood pressure of the mother during pregnancy. Offspring born preterm to mothers with either hypertensive or normotensive pregnancies had similar mean arterial pressure (88.07±6.9 vs 87.93±7.61 mm Hg; P=0.94). Therefore, differences in blood pressure do not explain the difference in pulse wave velocity between these groups. Offspring born to normotensive pregnancies had significantly greater arterial stiffness than those born to hypertensive pregnancies, who, in contrast, had a selective 30% reduction in endothelial response.
Cockcroft et al also raise the issue of whether pre-pregnancy maternal blood pressure may be relevant to our observation of higher blood pressure in preterm offspring and that familial predisposition might explain the variation in offspring blood pressure. We agree these 2 possibilities warrant further investigation, but we point out that they may not necessarily be intrinsically linked. We have been purposefully reticent to propose either as the explanation for our findings for the following reasons. First, our data show offspring born preterm to mothers with normal blood pressure throughout pregnancy still had higher blood pressure in early adulthood, which goes against the hypothesis that an elevated maternal blood pressure is necessary for elevated blood pressure in the offspring. Second, the magnitude of the difference in blood pressure we have identified (5–10 mm Hg) is substantially greater than the 1-mm Hg variance in blood pressure accounted for in variation identified in recent genome-wide association studies,4 and the results of many large multigeneration studies designed to identify genetic variation to account for hypertensive predisposition in pregnancy so far have been disappointing.5 Finally, the purpose of our investigation was to characterize the vascular pathophysiology that may underlie elevated blood pressure rather than to determine whether genetics, pre-pregnancy maternal blood pressure, or some other factor was responsible. We believe understanding the underlying biology may provide insight into potential targeted approaches to intervention and prevention.
Sources of Funding
The work was supported by grants from the British Heart Foundation (FS/06/024), the National Institute for Health Research Oxford Biomedical Research Centre, and the Oxford Health Services Research Committee.
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