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Analysis of blood pressure waveform: a new method for the classification of hypertensive pregnancy disorders

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Analysis of blood pressure waveform: a new method for the classification of hypertensive pregnancy disorders
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  RESEARCH LETTER Analysis of blood pressure waveform:a new method for the classification ofhypertensive pregnancy disorders  Journal of Human Hypertension  (2004)  18,  135–137.doi:10.1038/sj.jhh.1001652 Dear Sir, In pregnancies with hypertensive disorders, the blood pressure and vascular resistance are in-creased, blood volume is smaller, and blood pres-sure and heart rate responses to variousprovocations are changed compared to those of normotensive pregnant women. 1,2 In the pathogen-esis of hypertensive disorders in pregnancies,especially in pre-eclampsia, the shallow endovas-cular cytotrophoblast invasion in the spiral arteries 3 and the following systemic endothelial cell dysfunc-tion of pregnant women are two key features. 4,5 Theprecise classification of distinct hypertensive preg-nancy disorders is very often difficult in clinicalpractice due to methodological limitations. Heartrate variability (HRV) and blood pressure variability(BPV) are useful tools to differentiate betweendifferent cardiovascular disorders and predict mor-tality of those patients. 6,7 To evaluate HRV and BPVas potential diagnostic tools for different hyperten-sive pregnancy disorders, we initiated a pilot studyto determine whether these variability parameterscan distinguish between pregnancy-induced hyper-tension (PIH) and pre-eclampsia (PE).In this cross-sectional study, 23 healthy pregnantwomen (age: 28 7 5 years, gestational week: 33 7 4),14 women with PIH (age: 28 7 6 years, gestationalweek: 34 7 5), and 15 women with-PE (age: 28 7 5years, gestational week: 30 7 3) were recruited fromthe Department of Obstetrics and Gynecology,University of Leipzig. Approval of the study wasobtained from the medical scientific and ethicalcommittee of the University of Leipzig. All diag-noses at admission were re-examined and confirmed6 weeks after delivery. The classification of thehypertensive disorders is according to the ‘NationalHigh Blood Pressure Education Program WorkingGroup on High Blood Pressure in Pregnancy’. 5 To analyse blood pressure waveform in additionto HRV, BPV, and baroreflex sensitivity (BRS),synchronously high-resolution ECG (1600Hz) andnoninvasive continuous blood pressure were re-corded via finger cuff (200Hz, PORTAPRES deviceModel 2, BMI-TNO, Amsterdam, The Netherlands).All measurements were performed over 30minunder standardized resting conditions between8am and 12am as described previously by Voss et al  . 8 The parameters of BPV evaluated by our groupdiffer between normotensive pregnant women andthose with hypertensive pregnancy diseases. 9 Forinstance, patients with PIH were characterized bysignificant increases of various time and frequencyparameters in low- and high-frequency domainscompared to normotensive pregnancies, but noadditional parameter of BPV is changed in PE.However, no parameter of BPV has been found yetthat was able to achieve a 100% discrimination between PIH and PE. 9 Moreover, the preliminaryanalysis of the pilot study showed that also theintroduction of HRV and BRS parameters did notallow a precise and clinically feasible classificationof the hypertensive pregnancy disorders. Since PE isthought to be a general endothelial disease, it should be distinguishable from PIH as a ‘normal’ hyperten-sive disorder. 5 We therefore analysed various parameters of the blood pressure waveform (Figure 1, panel a), sincethe shape of this curve is modulated by peripheralvessel resistance and reflects mainly endothelialfunction. A number of waveform parameters showedsignificant differences between the two hyperten-sive disorders in pregnancy (data not shown).Further analysis revealed the surprising fact thatone parameter, Amp1, is significantly increased inthe pre-eclamptic patients and that only the use of Amp1 enabled the correct classification of PE(Figure 1, panel b) compared to normal pregnanciesas well as PIH ( P  ¼ 0.0000066). This parameterAmp1 is the pressure amplitude of one heart action,that is, the difference between maximal systolic andminimal diastolic blood pressure. Interestingly, onlyone patient who was diagnosed as having PE atadmission due to hypertension plus mild proteinur-ia did not show an increased Amp1. Exactly thiswoman had to be reclassified as a chronic hyperten-sion by a follow-up examination 12 weeks afterdelivery. The increased Amp1 in PE reflects anincreased difference between diastolic and systolic blood pressure, and is caused by a reduced vascularreactivity resulting from generalized endothelialdysfunction. At present, there is overwhelming  Journal of Human Hypertension (2004) 18,  135–137 &  2004 Nature Publishing Group All rights reserved 0950-9240/04  $ 25.00 www.nature.com/jhh  evidence for endothelial damage in PE. Thisdysfunction includes morphological changes likerenal endotheliosis and structural changes in theuteroplacental vessels as well as functional pro- blems of the endothelium. Increased concentrationsof the Von Willebrand factor and endothelin and analtered balance between PGI 2  and TxA 2  influencevascular tone and peripheral resistance. 10 Previousinvestigations such as the measurement of the flow-mediated dilation of the brachial artery showed thatthis impaired endothelial function and reducedvasorelaxation can be measured in pregnant womenwith PE. 11 Thus, our results clearly indicate adifferent pathophysiology for the two hypertensivedisorders, PIH and PE, characterize PE as anendothelial disease, and demonstrate that the com-plex alterations in endothelial function and vascularregulation have impact on the blood pressure wave-form.Previous studies aimed to give a complex descrip-tion of blood pressure patterns in normal andhypertensive pregnancies using the circadian bloodpressure variability or the 24-h blood pressureamplitude. 12 However, for clinical practice and anearly prediction of PE a simple and reliable test isneeded. To our knowledge, there are no reportsabout the blood pressure amplitude and its analysisas performed in our study. Moreover, we are the firstto describe a single as well as simple blood pressureparameter that discriminates between PIH and PEand may enable obstetricians to classify borderlinepatients. Since it can be estimated that a number of hypertensive pregnancy diseases are not correctlyclassified and particularly a number of pre-eclamp-tic women have an undetected chronic hyperten-sion, the described method might become clinicallyrelevant. A more accurate diagnosis of a hyperten-sive pregnancy disease using blood pressure curveanalysis should improve identification of high-riskpatients as well as their management and treatment.Considering this fact, it seems amazing that such asimple parameter like the blood pressure amplitudehas not been investigated yet. One has to state that aprecise blood pressure waveform analysis includingamplitude (Amp1) requires an advanced methodlike the PORTAPRES technique described by ourgroup and cannot be achieved with a conventional blood pressure cuff.Further studies are needed to determinewhether this increase of Amp1, specific for PE, isdetectable prior to the clinical manifestation of the disease and if this parameter has a predictivevalue, possibly in combination with the assessmentof uterine artery doppler waveforms. Furthermore,we want to evaluate its possible use as anambulatory test and its ability to differentiate between all types of hypertensive disorders of pregnancy.R Faber 1 , H Stepan 1 , M Baumert 2 ,A Voss 2 and T Walther 31 Department of Obstetrics and Gynecology,University of Leipzig, Germany; 2 Faculty of Medical Engineering, University of Applied Sciences, Jena, Germany; 3 Department of Cardiology, UKBF, Free University Berlin, Germany Correspondence: R Faber,Universita¨ tsfrauenklinik,Philipp-Rosenthalstr. 55,04103 Leipzig, Germany  E-mail: fabr@medizin.uni-leipzig.de Figure 1  Panel a: Parameters for waveform analysis of continuous blood pressure (Amp1–Amp3 ¼ amplitudes; A1–A4 ¼ areas underthe curve; T1–T4 ¼ time intervals). Panel b: Box blots of theparameter Amp1 (systolic minus preceding diastolic bloodpressure amplitudes in mmHg) for normal pregnancies (CON),PIH, and PE. Research Letter 136 Journal of Human Hypertension  References 1 EkholmEMK,Erkkola RU. Autonomiccardiovascularcontrolinpregnancy.  Eur J Obstet Gynecol Reprod Med   1996;  64 : 29–36.2 Ekholm EMK  et al  . Autonomic hemodynamic control inpregnancy-induced hypertension.  Hypertens Pregnancy   194; 13 : 253–264.3 Caniggia I, Winter J, Lye SJ, Post M. Oxygen and placentaldevelopment during the first trimester: implications for thepathophysiology of preeclampsia.  Placenta  2000;  21 : 25–30.4 Dekker GA, Sibai BM. Etiology and pathogenesis of preeclamp-sia:currentconcepts. AmJObstetGynecol  1998; 179 :1359–1375.5 National High Blood Pressure Education Program WorkingGroup on High Blood Pressure in Pregnancy: Report of theNational High Blood Pressure Education Program WorkingGroup on High Blood Pressure in Pregnancy.  Am J Obstet Gynecol   2000;  183 : S1–S22.6 Algra A  et al  . Heart rate variability from 24-our electrocardio-graphy and the 2-year risk for sudden death.  Circulation  1993; 88 : 180–184.7 Zuanetti G  et al  . Prognostic significance of heart ratevariability in post-myocardial infarction patients in thefibrinolytic era.  Circulation  1996;  94 : 432–436.8 Voss A  et al  . Baroreflex sensitivity, heart rate and bloodpressure variability in normal pregnancy.  Am J Hypertens 2000;  13 : 1218–1225.9 Faber R  et al  . Baroreflex sensitivity, heart rate and bloodpressure variability in hypertensive disorders pregnancy. Hypertens Pregnancy   2002;  21 (Suppl 1) S29.10 Van Wijk MJ, Kublickiene K, Boer K, Van Bavel E.Vascular function in preeclampsia.  Cardiovasc Res  2000;  47 :38–48.11 Savvidou MD  et al  . Endothelial dysfunction and raisedplasma concentrations of asymmetric dimethylarginine inpregnant women who subsequently develop pre-eclampsia. Lancet   2003;  361 : 1511–1517.12 Hermides RC  et al  . Differences in circardian blood pressurevariability during gestation between healthy and complicatedpregnancies.  Am J Hypertens  2003;  16 : 200–208. Research Letter 137 Journal of Human Hypertension
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