Clinical Implications

Abstract

HomeHypertensionVol. 66, No. 6Clinical Implications Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUBClinical Implications Originally published1 Dec 2015https://doi.org/10.1161/HYPERTENSIONAHA.115.06698Hypertension. 2015;66:1089Systolic Blood Pressure Trajectories (p 1108)Download figureDownload PowerPointIdentifying people in early life who are at the greatest risk of developing adult hypertension might permit effective risk reduction via age-appropriate prevention and intervention strategies, thereby reducing the burden of blood pressure-related disease in later life. There are conflicting recommendations on routine screening for primary hypertension in children, and better information is needed for medical decision-making around risk assessment. In this issue of Hypertension, results from the Dunedin Multidisciplinary Health and Development Study, a longitudinal representative birth cohort study (n=975), show that subgroups within the population who are on trajectories toward developing prehypertension or hypertension by early midlife can be identified as early as 7 years of age. Early life risk factors for high blood pressure trajectory group membership were identified, including male sex, having a family history of hypertension, being the first born, and lower birth weight. Having a higher body mass index and cigarette smoking over time resulted in increasing blood pressure levels, especially among individuals in the higher blood pressure groups. Many early midlife cardiovascular correlates, including a composite index of metabolic abnormalities, were associated with prehypertensive and hypertensive blood pressure trajectory group membership, demonstrating the broader clinical utility of these trajectories. These data suggest that estimating risk for future hypertension (and cardiovascular disease more generally) can begin in childhood before blood pressure reaches prehypertensive or hypertensive levels in adulthood.Cerebrospinal Fluid NaCl Increases Sympathetic Nerve Activity via Rostral Ventrolateral Medulla (p 1184)Download figureDownload PowerPointEvidence from both salt-sensitive humans and animal models indicates that the ingestion of excess dietary salt produces discrete increases in cerebrospinal fluid NaCl concentrations by ≈2 to 5 mmol/L. This central hypernatremia subsequently activates the sympathetic nervous system to raise arterial blood pressure. Although changes in cerebrospinal fluid NaCl concentrations are sensed by specialized neurons in the hypothalamus, it is not clear how these changes translate into activation of the sympathetic nervous system and hypertension. In this issue of Hypertension, Stocker et al identified several novel mechanisms, including a distinct population of hindbrain neurons that mediate the sympathoexcitatory actions of NaCl. The authors demonstrated for the first time that intracerebroventricular infusion of hypertonic NaCl increases sympathetic outflow to the hindlimb vasculature and adrenal gland but decreases renal or does not alter splanchnic sympathetic nerve activity. This pattern results in a sympathetically mediated increase in blood pressure. Additional neurophysiological recordings suggest that these complex responses to central hypernatremia are mediated by a glutamatergic activation of bulbospinal, and likely C1 (or catecholaminergic), neurons of the rostral ventrolateral medulla (Figure). These findings have several important implications: (1) the brain selectively regulates sympathetic outflow to various end organs, (2) a discrete population of hindbrain neurons via glutamatergic input mediates the sympathoexcitatory response to central hypernatremia, and (3) both findings may represent future clinical targets for the treatment of salt-sensitive hypertension.Soluble fms-Like Tyrosine Kinase-1 e15a: Serum Levels and Bioactivity (p 1251)Download figureDownload PowerPointIn preeclampsia, there is excess secretion of the antiangiogenic factor soluble fms-like tyrosine kinase (sFLT-1) into the maternal circulation, leading to endothelial dysfunction, hypertension, and multiorgan injury. sFLT-1 e15 is by far the dominant placental sFLT-1 variant, and given preeclampsia is undoubtedly a placental disease (because delivery resolves the condition), sFLT-1 e15a may be the main sFLT-1 variant causing preeclampsia. Surprisingly, sFLT-1 e15a protein has been poorly characterized. In this issue of Hypertension, Palmer et al characterized sFLT-1 e15a protein bioactivity and reported circulating levels in pregnant women. It is conceivable that an sFLT-1 e15a ELISA may be better at predicting preeclampsia than the existing sFLT-1 ELISA (which indiscriminately detects all sFLT-1 variants). The team raised antibodies and developed a sFLT-1 e15a ELISA. Using this, they reported that circulating sFLT-1 e15a concentrations increased across gestation and were 10-fold higher in women with preterm preeclampsia compared with controls (Figure). They also showed that sFLT-1 e15a is bioactive. sFLT-1 e15a blocked vascular endothelial growth factor activation of its own receptor, decreased endothelial cell migration and invasion, and decreased endothelial tube formation. Furthermore, sFLT-1 e15a blocked vascular endothelial growth factor–induced sprouting from mouse aortic rings. The development of therapeutics should take sFLT-1 e15a into account. Identifying medications that decrease placental sFLT-1 e15a secretion or neutralize its biological activity may be a therapeutic strategy. Furthermore, it is possible that an sFLT-1 e15a ELISA has potential as a biomarker test to predict preeclampsia. Previous Back to top Next FiguresReferencesRelatedDetails December 2015Vol 66, Issue 6 Advertisement Article InformationMetrics © 2015 American Heart Association, Inc.https://doi.org/10.1161/HYPERTENSIONAHA.115.06698 Originally publishedDecember 1, 2015 PDF download Advertisement