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Autonomic and Hemodynamic Origins of Pre-Hypertension

Objectives The purpose of this study is to better understand the origins and progression of pre-hypertension. Background Pre-hypertension is a risk factor for progression to hypertension, cardiovascular disease, and increased mortality. We used a cross-sectional twin study design to examine the role...

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Bibliographic Details
Published in:Journal of the American College of Cardiology 2012-06, Vol.59 (24), p.2206-2216
Main Authors: Davis, Jason T., MD, Rao, Fangwen, MD, Naqshbandi, Dalal, BA, Fung, Maple M., MD, Zhang, Kuixing, MD, Schork, Andrew J., BS, Nievergelt, Caroline M., PhD, Ziegler, Michael G., MD, O'Connor, Daniel T., MD
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Language:English
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Summary:Objectives The purpose of this study is to better understand the origins and progression of pre-hypertension. Background Pre-hypertension is a risk factor for progression to hypertension, cardiovascular disease, and increased mortality. We used a cross-sectional twin study design to examine the role of heredity in likely pathophysiological events (autonomic or hemodynamic) in pre-hypertension. Methods Eight hundred twelve individuals (337 normotensive, 340 pre-hypertensive, 135 hypertensive) were evaluated in a sample of twin pairs, their siblings, and other family members. They underwent noninvasive hemodynamic, autonomic, and biochemical testing, as well as estimates of trait heritability (the percentage of trait variance accounted for by heredity) and pleiotropy (the genetic covariance or shared genetic determination of traits) by variance components. Results In the hemodynamic realm, an elevation of cardiac contractility prompted increased stroke volume, in turn increasing cardiac output, which elevated blood pressure into the pre-hypertension range. Autonomic monitoring detected an elevation of norepinephrine secretion plus a decline in cardiac parasympathetic tone. Twin pair variance components documented substantial heritability as well as joint genetic determination for blood pressure and the contributory autonomic and hemodynamic traits. Genetic variation at a pathway locus also indicated pleiotropic effects on contractility and blood pressure. Conclusions Elevated blood pressure in pre-hypertension results from increased cardiac output, driven by contractility as well as heart rate, which may reflect both diminished parasympathetic and increased sympathetic tone. In the face of increased cardiac output, systemic vascular resistance fails to decline homeostatically. Such traits display substantial heritability and shared genetic determination, although by loci not yet elucidated. These findings clarify the role of heredity in the origin of pre-hypertension and its autonomic and hemodynamic pathogenesis. The results also establish pathways that suggest new therapeutic targets for pre-hypertension, or approaches to its prevention.
ISSN:0735-1097
1558-3597
DOI:10.1016/j.jacc.2012.02.040