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...astolic on systolic BP in individual subjects, can be determined from 24-h ambulatory BPsrecordings [2,3]. To date, several cross-sectional studies [4,5] and at least three prospectivescohort studies =-=[3,6,7]-=- demonstrated an association of AASI either with signs of target organsdamage in never-treated hypertensive patients [4] or with the incidence of cardiovascularsmortality and morbidity[3,6,7]. When ad...

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...aper by Gavish et al. [11] is a first attempt to eliminate the limitations characterizingssuch artefactual relationship by using a symmetrical regression model.sIn conclusion, the development of AASI =-=[2,10]-=- unquestionably represents a theoreticallysattractive means of easily exploring arterial stiffness without the use of dedicated, operatordependent equipment. However, given the present uncertainties r...

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...nd show a better performance than the classical risksfactors. Examples of such methods are intima media thickness (highly standardizedsmeasurement of arterial vessel wall thickness by ultrasonography)=-=[42]-=-, coronary calciumsscore (CT indexed evaluation of calcium deposits in the coronary vasculature), and indexes ofsarterial stiffness, like pulse wave velocity (measurement of blood flow velocity over t...

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...uctural aspect may explain why AASI positivelyscorrelates with pulse wave velocity and expresses arterial stiffening but not stiffness. Thespresent view is consistent with the finding of Dolan et al. =-=[7]-=- that AASI is a predictor ofscardiovascular mortality in hypertensive patients.sIn conclusion, in searching for the clinical significance and the physiological origin of theslinear relationship betwee...

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...ial stiffness, like pulse wave velocity (measurement of blood flow velocity over the largesarteries by special equipment)[43] and the newest of them all: the ambulatory arterial stiffnesssindex (AASI)=-=[44]-=-.sCardiologists in The Netherlands generally practice active cardiology, both during and in thesaftermath of a cardiovascular event. In this regard the adage ‘better to prevent than to cure’ issrelati...

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...tory blood pressure monitoringsClinic (office) blood pressure measurement has been the basis for the established relationshipsbetween elevated blood pressure and cardiovascular morbidity and mortality=-=[25]-=-. Clinic bloodspressure, however, may not necessarily represent an individual’s usual BP level andsphysicians frequently misclassify patients’ blood pressure status at the office when comparedswith am...

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...ension is hidden from the doctor and therefore not adequately treated, there issconsistent evidence that the cardiovascular risk is higher than in normotensives, and almost asshigh as in hypertensives=-=[18, 19]-=-. Both for WCH and for MH, it is not yet known how muchsthe hospital environment and the presence of the doctor contribute to the blood pressuresdifferences between home and the office.sSelf blood pre...

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...proach [19,20]. For the evaluation of reproducibility, we used the repeatability coefficient,swhich is twice the SD of the withinparticipant differences between repeat recordings (repeatsminus first) =-=[21]-=-. This measure is specifically designed to evaluate within-participantsreproducibility. To take into consideration the normal biological variation of a measure, wesexpressed the repeatability coeffici...

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...e-dependent natriuresis andsunderlying organ damage. Whether or not day and night blood pressures and their derivedsparameters can be targeted separately (chronotherapy), is a matter of ongoing debate=-=[36]-=-.sBlood pressure measurement; processsArterial stiffness and ambulatory blood pressure measurementsBecause of ageing and atherosclerosis, normal healthy compliant arteries become stiff[37].sThis proce...

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...ely reflectingssystolic and diastolic blood pressure [7]. The biological variability of blood pressure is quiteshigh, and many factors influence blood pressure itself or the blood pressuresmeasurement=-=[8]-=-.Therefore the procedure is highly standardized nowadays. Factors thatsinfluence blood pressure for example are physical activity, talking, a distended urinarysbladder, environmental noises, the prese...

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...od pressure (BP)sincrease when a physician entered the room to start a BP reading[1]. This phenomenon wasslabelled as the white coat effect (WCE). The term white coat hypertension (WCH) wassintroduced=-=[2]-=-, in case the BP was only hypertensive in the presence of physician butsnormotensive in the absence. With the entrance of automatic devices for BP measurementsoutside the clinic environment at home (H...

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...a 20% rise in the risk of cardiovascular mortality. Subjects with less than 10% BP decrease atsnight, or even an increase in BP during the night were those who exhibit a worsescardiovascular prognosis=-=[27, 31, 32]-=-. It has been claimed however that categorization of patientssinto dippers and nondippers is poorly reproducible[33]. Historically not only an attenuatedsnocturnal BP decline, but also a high nocturna...

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...ce versus at home, and because of different techniquessused (oscillometric in self blood pressure measurement versus auscultatory in conventional),sdifferences in cut-off values for hypertension exist=-=[22]-=-. At present, results of 30 years ofsresearch regarding cut-off limits for hypertension and normotension of the self-measuredsblood pressure are available. Still, different guidelines report different...

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...ve of severeshypertension or proteinuria. However, there is only indirect evidence to support operationalsthresholds for the self-measured blood pressure in antenatal care.sRoss-McGill and colleagues =-=[38]-=- randomized 80 women at 24–28 weeks of their pregnancy tosa standard nine-visit schedule (30, 32, 34, 36–41 weeks) or to a reduced schedule (34, 38, 41sweeks). Women with multiple pregnancies, establi...

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... training.sIn prospective and cross-sectional studies, AASI proved to predict totalscardiovascular mortality, fatal and non-fatal stroke and target organ damage, over and beyondsclassical risk factors=-=[5, 22, 23, 27, 40, 41, 56]-=-.sAASI proved to be significantly related tosother measures of arterial stiffness, and complementary to the other measures in providingscardiovascular risk[5, 27]. Further standardization and refineme...

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...AASI remained significant for the normotensive cohort (mean±SD; nondipper,s0.35±0.15; dipper, 0.29±0.11; P=0.04). Therefore, our data are in line with the work ofsseveral groups including the authors =-=[3]-=-.sSchillaci et al. [4] pointed out hemodynamic factors potentially influencing AASI. Similarly,sour discussion focused on the potential role of autonomic nerve function as a cause of dippings[5] and t...

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...urate prognostic information of cardiovascular outcomes than officesreadings[14]. This has been clearly demonstrated in population-based surveys and both instreated and untreated hypertensive subjects=-=[29]-=-. In addition to the mean 24-hour BP level,svariation in the day-night difference in BP (the dipping status) has also been claimed as ansimportant predictor of both target-organ damage and cardiovascu...

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...the elderly : meta-analysis ofsoutcome trials. Lancet 2000; 355:865-872.s6.sMancia G, Grassi G. Treating very elderly hypertensive patients is rewarding: thesHYVET results. Curr Hypertens Rep 2008; 10=-=(4)-=-:301-302.s7.sO'Brien E, Asmar R, Beilin L, Imai Y, Mancia G, Mengden T, et al. Practicesguidelines of the European Society of Hypertension for clinic, ambulatory and selfsblood pressure measurement. J...

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...sIn a second prospective study AASI was evaluated in terms of fatal and non-fatalscardiovascular complications in a cohort with 1829 randomly selected participants from thesCopenhagen County (Denmark)=-=[23]-=-. Median follow-up was 9.4 years and included 60scardiovascular deaths, 128 coronary events, and 24 strokes. While after full adjustment, AASIsremained independently and significantly predictive for f...

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...thm (24-hour period andsnight-day patterns) and has become an efficacious instrument helping to make therapeuticsdecisions in hypertensive patients and other subjects at risk of cardiovascular disease=-=[27, 28]-=-.sMoreover, ABPM is more strongly correlated with target-organ damage than office BP andsoffers more accurate prognostic information of cardiovascular outcomes than officesreadings[14]. This has been ...

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...e rigid than in an elastic artery. AIx rests on thesprinciple that in stiffer arteries reflected waves travel faster and augment SBP. Both measuressof arterial stiffness predict cardiovascular disease=-=[9, 10]-=-. These techniques however requiresthe use of expensive devices and the involvement of highly trained observers, which renderssthem unsuitable for use in routine clinical practice. Moreover they shoul...

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... thatsdifferences can be present between office and home blood pressure. Home blood pressure cansbe significantly lower than in the office and conversely can be significantly higher than in thesoffice=-=[10, 11]-=-. The clinical significance of isolated office or “white coat” hypertensions(WCH), a condition in which blood pressure is elevated in the clinic environment but normalsin daily life, is still controve...

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...stotalled 297, that is 152 patients from Nijmegen and 145 Syst-Eur trial patients.sThe validated monitors used in Nijmegen were the auscultatory Oxford Medilog (OxfordsMedical Systems Ltd, Oxford, UK =-=[12]-=-) in 54 patients (35.5%), the oscillometric Mobil OsGraph (I.E.M., Stolberg, Germany [13]) in 43 patients (28.3%), and the oscillometricsSpaceLabs 90207 (SpaceLabs Inc., Redmond, Washington, USA [14])...

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...o handle measures aresneeded for diagnostic and therapeutic decision making. All above mentioned new indexesshave proven to predict cardiovascular disease above and beyond the traditional risksfactors=-=[39, 41, 45, 46]-=-, however only AASI does not require special equipment and highlystrained technicians, since it can be derived from simple 24-hour ABPM.sIn 1914, MacWilliam and Melvin wrote that loss of elasticity in...

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...pertensivespatients referred to the Nijmegen clinic for ambulatory BP monitoring [29]. Severalsinvestigators demonstrated poor reproducibility of dipping status in hypertensive pati Hernandez-del Rey =-=[30]-=- performed repeat ambulatory monitoring on 2 consecutive days an noticed that of 611 patients 147 (24.1%) participants switched from a nighttime dipper tosnondipper or vice versa. Other studies [31] r...

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...nt of an unfavourable prognosis[34]. In longitudinal studies and in meta-analyses,snocturnal BP seems to correlate better with signs of target organ damage and cardiovascularsmorbidity than daytime BP=-=[34, 35]-=-. Nondipping and high nighttime BP seem to share commonsdeterminants such as sympathetic overactivity, sleep apnoea, pressure-dependent natriuresis andsunderlying organ damage. Whether or not day and ...

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... and simultaneously inflated.sThe measurement of cAIX was done by multielement applanation tonometry. The Japanese investigators used the correlation between paired measurements as index of agreement =-=[26]-=-.sThe correlation coefficients were 0.89 for abPWV and 0.87 for cAIX. In our study, thescorrelation coefficients for AASI ranged from 0.52 to 0.61. In the absence of statisticss129 specifically design...

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...h nighttime BPsare a consequence of hypertensive target organ damage and tend to occur when target organsdamage is present. Therefore it is hypothesized that these phenomena indicate reversescausality=-=[37]-=-. For diagnostic uses therefore, these parameters are useful, however forstreatment purposes, it is debatable if these parameters themselves should be targeteds(chronotherapy)[40]. It may be more logi...

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...it can besdetermined automatically and non-invasively.sIn march 2006, a consortium of researchers introduced a new indirect marker of arterialsstiffness, the Ambulatory Arterial Stiffness Index (AASI)=-=[5]-=-.sThis method is based onsphysiological insights, already reviewed in 1914[6]. In elastic arteries any increase in systolicsblood pressure (SBP) will be accompanied by a similar rise in diastolic bloo...

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...iterature depicts important differences in meansAASI, which can not be entirely attributed to determinants like age, sex, cardiovascularshistory, hypertensive and diabetic status and arterial pressure=-=[55]-=-. Other factors, like studysset-up and methods for determining AASI, could possibly account for these differences.sTherefore, AASI determination should be standardized. After doing so, cut-off values ...

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...m (137/85mmHg [20]). Roundingsthese thresholds [20,21] to 135mmHg systolic and 85mmHg produced diagnostic limitsssimilar to those in the meta-analysis of aggregate data [19] and in several guideliness=-=[49,50,57,62]-=-.sThe Japanese investigators subsequently published a subgroup analysis of Ohasama residentsswith and without cardiovascular risk factors, including diabetes mellitus,shypercholesterolaemia, habitual ...

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...er meansarterial pressure and to diminish with higher 24-hour pulse rate and body height[15].sIn thesInternational Database of Ambulatory blood pressure in relation to Cardiovascular Outcomess(n=7604)=-=[28]-=-, it was confirmed in multivariate analyses, that AASI associated positively withsage and 24-h mean arterial pressure and negatively with height and 24-h heart rate, insdifferent sex and ethnicities.s...

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...distinguish between low risk and high risk patients, beyond BP and pulse pressure (see figures2). There are already very promising results in terms of prediction of cardiovascular eventssand mortality=-=[40, 41, 46, 48]-=-. Before implementing this new risk-stratifying tool at largesscale, the new technique should be validated. One way to do this is to comprehensivelysreview the literature. Furthermore the determinants...

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... 24-hour PP.sOthers evaluated the relationship between AASI and glomerular filtration rate (GFR), in 143suntreated hypertensive patients without CV complications and without severe renalsinsufficiency=-=[45]-=-.sMean (± SD) GFR (assessed by a radioisotopic technique) was 110.5 ±s33.4 ml/min/1.73 m. A significant inverse correlation between AASI and GFR was found (rs= −0.30; P<0.001). This association was a...

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...o handle measures aresneeded for diagnostic and therapeutic decision making. All above mentioned new indexesshave proven to predict cardiovascular disease above and beyond the traditional risksfactors=-=[39, 41, 45, 46]-=-, however only AASI does not require special equipment and highlystrained technicians, since it can be derived from simple 24-hour ABPM.sIn 1914, MacWilliam and Melvin wrote that loss of elasticity in...

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...n the clinic environment but normalsin daily life, is still controversial. Some studies have shown the prevalence and degree ofsorgan damage in subjects with WCH to be similar to that of normotensives=-=[12, 13]-=-, whereassothers have shown them to be greater than those of normotensives or even similar to that ofshypertensive individuals[14, 15]. Furthermore longitudinal studies have not found thisscondition t...

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...itoringsAmbulatory blood pressure monitoring (ABPM) helps to make therapeutic decisions in patientsswho exhibit discordance between clinic and ambulatory BP values (WCH, resistant hypertensionsand MH)=-=[34]-=-. It has also augmented our understanding of BP circadian rhythm (24-hoursperiod and night-day patterns) and has become an efficacious instrument aiding therapeuticsdecisions in hypertensive patients ...

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.... After asstandardized treatment schedule, investigators had to reach the target blood pressure levels ofs120–139 mmHg systolic and 80–89mmHg diastolic. This goal was similar in both treatmentsgroups =-=[47]-=-. A blinded physician at the coordinating centre took the treatment decisions. Thesstated hypothesis [88] was that at the end of the 1-year follow-up period, patients in bothsgroups would have the sam...

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...m (137/85mmHg [20]). Roundingsthese thresholds [20,21] to 135mmHg systolic and 85mmHg produced diagnostic limitsssimilar to those in the meta-analysis of aggregate data [19] and in several guideliness=-=[49,50,57,62]-=-.sThe Japanese investigators subsequently published a subgroup analysis of Ohasama residentsswith and without cardiovascular risk factors, including diabetes mellitus,shypercholesterolaemia, habitual ...

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...n 24-h BP monitoring[13].sFrom multiple linear regression of QKD according to SBP and heart rate, the theoretical valuesof the QKD for a SBP of 100 mm Hg and a heart rate of 60 beats/min is determined=-=[14]-=-.sLi and colleagues assessed the correlation of AASI with carotid-femoral PWV in a group ofs166 healthy Chinese volunteers[15]. A close relation was present between PWV and AASIs(r=0.51, P<0.0001). An...

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...er the signs of target organ damage in never-treated hypertensive patients [11] or thesincidence of cardiovascular mortality and morbidity [2,13,14]. When adjusted for pulsespressure [2,13,14] or PWV =-=[15]-=-, AASI remained predictive, in particular of stroke.sReferencess1 Li Y, Wang JG, Dolan E, Gao PJ, Guo HF, Nawrot T, et al. Ambulatory arterial stiffnesssindex derived from 24-h ambulatory blood pressu...

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...with an adverse cardiovascular prognosis. These studies sometimesshad the limitation of a small number of cardiovascular events or a relatively short duration ofsthe follow-up after WCH identification=-=[16, 17]-=-. Surprisingly, “masked” hypertension (MH), ascondition in which BP is normal in the clinic environment but elevated in daily life, seems toshave a similar prevalence in the population (10-20%)[11]. F...

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...ited. For thessensitivity analysis involving dipping status, we defined daytime and nighttime in bothscohorts as the intervals ranging from 10:00 to 20:00 h and from midnight to 06:00 h,srespectively =-=[17,18]-=-. We weighted the individual means of the ambulatory BP by the intervalsbetween readings.sFrom individual 24-h recordings, we computed the regression slope of diastolic on systolicsBP. We defined the ...

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....sEvidence from two meta-analysessIn an attempt to define diagnostic thresholds for the selfmeasured blood pressure, wesperformed in collaboration with a large number of researchers two meta-analyses =-=[19,20]-=-,swhich were respectively based on aggregate data extracted from published articles [19] and onsindividual patient data, made available to the International Database of Self-Recorded BloodsPressures [...

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... ambulatory blood pressure [91,92]. The firstsreference values for the self-measured blood pressure started from its distributionalscharacteristics in participants with a normal office blood pressure =-=[19,20]-=-. Subsequent crosssectional studies demonstrated stronger association of target-organ damage with the selfmeasured than with the office blood pressure. It, however, took over 20 years to collect thesn...

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... this relation does not affect intra-individual repeatability of AASI to a large extent in stratified analyses.sIn impact on the repeatability of AASI. Similar to recent observations by Gavish et al. =-=[32]-=-, wesdemonstrated in 7604 participants enrolled in the International Database on Ambulatory BPsmonitoring in relation to Cardiovascular Outcomes (IDACO [33]) that the association ofsAASI with four mai...

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... BP during the night were those who exhibit a worsescardiovascular prognosis[27, 31, 32]. It has been claimed however that categorization of patientssinto dippers and nondippers is poorly reproducible=-=[33]-=-. Historically not only an attenuatedsnocturnal BP decline, but also a high nocturnal blood pressure itself was considered to be asdeterminant of an unfavourable prognosis[34]. In longitudinal studies...

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...distinguish between low risk and high risk patients, beyond BP and pulse pressure (see figures2). There are already very promising results in terms of prediction of cardiovascular eventssand mortality=-=[40, 41, 46, 48]-=-. Before implementing this new risk-stratifying tool at largesscale, the new technique should be validated. One way to do this is to comprehensivelysreview the literature. Furthermore the determinants...

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... for cardiovascular disease and nosstatistical test was provided to compare the QKD to the AASI.sViewpoints and future of AASIsO’Brien stressed in an editorial that AASI extends the usefulness of ABPM=-=[49]-=-. Besidessproviding prognostic information through circadian blood pressure variation, assessment ofswhite coat and masked hypertension, additionally arterial stiffness could be determined insassessin...

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...sthe office and home blood pressures after stratification for cardiovascular risk based on thescriteria jointly proposed by the European Society of Hypertension and the European Societysof Cardiology =-=[53]-=-. The key points emerging from these analyses (Fig. 3) were that even inspatients with low added risk both the office and self-measured blood pressures predictedsstroke, and that across the strata of ...

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...n the selfmeasured blood pressure [49] or later [50–52,54,56–62]. Selfmonitoring refers to the blood pressure measured at home in all guidelines [49–52,54,56–62],swhereas the American recommendations =-=[56,61]-=- leave the possibility open for self-monitoringsat the work place. The results of our review of guidelines are summarized in Table 4.s72sProposal for diagnostic and therapeutic thresholdssThe associat...