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Background: Guidelines on the required number of ambulatory blood pressure (ABP) readings focus on individual patients. Clinical researchers often face the dilemma of applying recommendations and discarding potentially valuable information or accepting fewer readings., Methods: Starting from ABP recordings with ≥30/≥10 awake/asleep readings in 4277 participants enrolled in eight population studies in the International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcomes (IDACO), we randomly selected a certain number of readings (from 30 to 1 awake and 10 to 1 asleep readings) at a time over 1000 bootstraps at each step. We evaluated: (i) concordance of the ABP level; (ii) consistency of the cross-classification based on office blood pressure and ABP; and (iii) accuracy in predicting cardiovascular complications. For each criterion, we fitted a regression line joining data points relating outcome to the number of readings covering the ranges of 30-20/10-7 for awake/asleep readings., Results: Reducing readings widened the SD of the systolic/diastolic differences between full (reference) and selected recordings from 1.7/1.2 (30 readings) to 14.3/10.3 mm Hg (single reading) during wakefulness, and from 1.9/1.4 to 10.3/7.7 mm Hg during sleep; lowered the κ statistic from 0.94 to 0.63, and decreased the hazard ratio associated with 10/5 mm Hg increments in systolic/diastolic ABP from 1.21/1.14 to 1.06/1.04 during wakefulness and from 1.26/1.17 to 1.14/1.08 during sleep. The first data points falling off these regression lines during wakefulness/sleep corresponded to 8/3 and 8/4 readings for criteria (i) and (iii) and to 5 awake readings for criterion (ii)., Conclusions: 24-h ambulatory recordings with ≥8/≥4 awake/asleep readings yielded ABP levels similar to recordings including the guideline-recommended ≥20/≥7 readings. These criteria save valuable data in a research setting, but are not applicable to clinical practice.

Hypertension is a major global health problem, but prevalence rates vary widely among regions. To determine prevalence, treatment, and control rates of hypertension, we measured conventional blood pressure (BP) and 24-hour ambulatory BP in 6546 subjects, aged 40 to 79 years, recruited from 10 community-dwelling cohorts on 3 continents. We determined how between-cohort differences in risk factors and socioeconomic factors influence hypertension rates. The overall prevalence was 49.3% (range between cohorts, 40.0%-86.8%) for conventional hypertension (conventional BP ≥140/90 mm Hg) and 48.7% (35.2%-66.5%) for ambulatory hypertension (ambulatory BP ≥130/80 mm Hg). Treatment and control rates for conventional hypertension were 48.0% (33.5%-74.1%) and 38.6% (10.1%-55.3%) respectively. The corresponding rates for ambulatory hypertension were 48.6% (30.5%-71.9%) and 45.6% (18.6%-64.2%). Among 1677 untreated subjects with conventional hypertension, 35.7% had white coat hypertension (23.5%-56.2%). Masked hypertension (conventional BP <140/90 mm Hg and ambulatory BP ≥130/80 mm Hg) occurred in 16.9% (8.8%-30.5%) of 3320 untreated subjects who were normotensive on conventional measurement. Exclusion of participants with diabetes mellitus, obesity, hypercholesterolemia, or history of cardiovascular complications resulted in a <9% reduction in the conventional and 24-hour ambulatory hypertension rates. Higher social and economic development, measured by the Human Development Index, was associated with lower rates of conventional and ambulatory hypertension. In conclusion, high rates of hypertension in all cohorts examined demonstrate the need for improvements in prevention, treatment, and control. Strategies for the management of hypertension should continue to not only focus on preventable and modifiable risk factors but also consider societal issues., (© 2017 American Heart Association, Inc.)

Mean daytime ambulatory blood pressure (BP) values are considered to be lower than conventional BP values, but data on this relation among younger individuals <50 years are scarce. Conventional and 24-hour ambulatory BP were measured in 9550 individuals not taking antihypertensive treatment from 13 population-based cohorts. We compared individual differences between daytime ambulatory and conventional BP according to 10-year age categories. Age-specific prevalences of white coat and masked hypertension were calculated. Among individuals aged 18 to 30, 30 to 40, and 40 to 50 years, mean daytime BP was significantly higher than the corresponding conventional BP (6.0, 5.2, and 4.7 mm Hg for systolic; 2.5, 2.7, and 1.7 mm Hg for diastolic BP; all P<0.0001). In individuals aged 60 to 70 and ≥70 years, conventional BP was significantly higher than daytime ambulatory BP (5.0 and 13.0 mm Hg for systolic; 2.0 and 4.2 mm Hg for diastolic BP; all P<0.0001).The prevalence of white coat hypertension exponentially increased from 2.2% to 19.5% from those aged 18 to 30 years to those aged ≥70 years, with little variation between men and women (8.0% versus 6.1%; P=0.0003). Masked hypertension was more prevalent among men (21.1% versus 11.4%; P<0.0001). The age-specific prevalences of masked hypertension were 18.2%, 27.3%, 27.8%, 20.1%, 13.6%, and 10.2% among men and 9.0%, 9.9%, 12.2%, 11.9%, 14.7%, and 12.1% among women. In conclusion, this large collaborative analysis showed that the relation between daytime ambulatory and conventional BP strongly varies by age. These findings may have implications for diagnosing hypertension and its subtypes in clinical practice., (© 2014 American Heart Association, Inc.)

Outcome-driven recommendations about time intervals during which ambulatory blood pressure should be measured to diagnose white-coat or masked hypertension are lacking. We cross-classified 8237 untreated participants (mean age, 50.7 years; 48.4% women) enrolled in 12 population studies, using ≥140/≥90, ≥130/≥80, ≥135/≥85, and ≥120/≥70 mm Hg as hypertension thresholds for conventional, 24-hour, daytime, and nighttime blood pressure. White-coat hypertension was hypertension on conventional measurement with ambulatory normotension, the opposite condition being masked hypertension. Intervals used for classification of participants were daytime, nighttime, and 24 hours, first considered separately, and next combined as 24 hours plus daytime or plus nighttime, or plus both. Depending on time intervals chosen, white-coat and masked hypertension frequencies ranged from 6.3% to 12.5% and from 9.7% to 19.6%, respectively. During 91 046 person-years, 729 participants experienced a cardiovascular event. In multivariable analyses with normotension during all intervals of the day as reference, hazard ratios associated with white-coat hypertension progressively weakened considering daytime only (1.38; P=0.033), nighttime only (1.43; P=0.0074), 24 hours only (1.21; P=0.20), 24 hours plus daytime (1.24; P=0.18), 24 hours plus nighttime (1.15; P=0.39), and 24 hours plus daytime and nighttime (1.16; P=0.41). The hazard ratios comparing masked hypertension with normotension were all significant (P<0.0001), ranging from 1.76 to 2.03. In conclusion, identification of truly low-risk white-coat hypertension requires setting thresholds simultaneously to 24 hours, daytime, and nighttime blood pressure. Although any time interval suffices to diagnose masked hypertension, as proposed in current guidelines, full 24-hour recordings remain standard in clinical practice., (© 2014 American Heart Association, Inc.)

Overweight clusters with high blood pressure (BP), but the independent contribution of both risk factors remains insufficiently documented. In a prospective population study involving 8467 participants (mean age 54.6 years; 47.0% women) randomly recruited from 10 populations, we studied the contribution of body mass index (BMI) to risk over and beyond BP, taking advantage of the superiority of ambulatory over conventional BP. Over 10.6 years (median), 1271 participants (15.0%) died and 1092 (12.9%), 637 (7.5%) and 443 (5.2%) experienced a fatal or nonfatal cardiovascular, cardiac or cerebrovascular event. Adjusted for sex and age, low BMI (<20.7 kg m(-2)) predicted death (hazard ratio (HR) vs average risk, 1.52; P<0.0001) and high BMI (> or = 30.9 kg m(-2)) predicted the cardiovascular end point (HR, 1.27; P=0.006). With adjustments including 24-h systolic BP, these HRs were 1.50 (P<0.001) and 0.98 (P=0.91), respectively. Across quartiles of the BMI distribution, 24-h and nighttime systolic BP predicted every end point (1.13 < or = standardized HR < or = 1.67; 0.046 < or = P<0.0001). The interaction between systolic BP and BMI was nonsignificant (P > or = .22). Excluding smokers removed the contribution of BMI categories to the prediction of mortality. In conclusion, BMI only adds to BP in risk stratification for mortality but not for cardiovascular outcomes. Smoking probably explains the association between increased mortality and low BMI.

Background: Data on risk associated with 24-hour ambulatory diastolic (DBP24) versus systolic (SBP24) blood pressure are scarce., Methods and Results: We recorded 24-hour blood pressure and health outcomes in 8341 untreated people (mean age, 50.8 years; 46.6% women) randomly recruited from 12 populations. We computed hazard ratios (HRs) using multivariable-adjusted Cox regression. Over 11.2 years (median), 927 (11.1%) participants died, 356 (4.3%) from cardiovascular causes, and 744 (8.9%) experienced a fatal or nonfatal cardiovascular event. Isolated diastolic hypertension (DBP24≥80 mm Hg) did not increase the risk of total mortality, cardiovascular mortality, or stroke (HRs≤1.54; P≥0.18), but was associated with a higher risk of fatal combined with nonfatal cardiovascular, cardiac, or coronary events (HRs≥1.75; P≤0.0054). Isolated systolic hypertension (SBP24≥130 mm Hg) and mixed diastolic plus systolic hypertension were associated with increased risks of all aforementioned end points (P≤0.0012). Below age 50, DBP24 was the main driver of risk, reaching significance for total (HR for 1-SD increase, 2.05; P=0.0039) and cardiovascular mortality (HR, 4.07; P=0.0032) and for all cardiovascular end points combined (HR, 1.74; P=0.039) with a nonsignificant contribution of SBP24 (HR≤0.92; P≥0.068); above age 50, SBP24 predicted all end points (HR≥1.19; P≤0.0002) with a nonsignificant contribution of DBP24 (0.96≤HR≤1.14; P≥0.10). The interactions of age with SBP24 and DBP24 were significant for all cardiovascular and coronary events (P≤0.043)., Conclusions: The risks conferred by DBP24 and SBP24 are age dependent. DBP24 and isolated diastolic hypertension drive coronary complications below age 50, whereas above age 50 SBP24 and isolated systolic and mixed hypertension are the predominant risk factors., (© 2014 American Heart Association, Inc.)

Background: Guidelines propose classification of conventional blood pressure (CBP) into normotension (<120/<80 mm Hg), prehypertension (120-139/80-89 mm Hg), and hypertension (≥140/≥90 mm Hg)., Methods: To assess the potential differential contribution of ambulatory blood pressure (ABP) in predicting risk across CBP strata, we analyzed outcomes in 7,826 untreated people recruited from 11 populations., Results: During an 11.3-year period, 809 participants died (276 cardiovascular deaths) and 639, 383, and 225 experienced a cardiovascular, cardiac, or cerebrovascular event. Compared with normotension (n = 2,639), prehypertension (n = 3,076) carried higher risk (P ≤ 0.015) of cardiovascular (+41%) and cerebrovascular (+92%) endpoints; compared with hypertension (n = 2,111) prehypertension entailed lower risk (P ≤ 0.005) of total mortality (-14%) and cardiovascular mortality (-29%) and of cardiovascular (-34%), cardiac (-33%), or cerebrovascular (-47%) events. Multivariable-adjusted hazard ratios (HRs) for stroke associated with 24-hour and daytime diastolic ABP (+5 mm Hg) were higher (P ≤ 0.045) in normotension than in prehypertension and hypertension (1.98 vs.1.19 vs.1.28 and 1.73 vs.1.09 vs. 1.24, respectively) with similar trends (0.03 ≤ P ≤ 0.11) for systolic ABP (+10 mm Hg). However, HRs for fatal endpoints and cardiac events associated with ABP did not differ significantly (P ≥ 0.13) across CBP categories. Of normotensive and prehypertensive participants, 7.5% and 29.3% had masked hypertension (daytime ABP ≥135/≥85 mm Hg). Compared with true normotension (P ≤ 0.01), HRs for stroke were 3.02 in normotension and 2.97 in prehypertension associated with masked hypertension with no difference between the latter two conditions (P = 0.93)., Conclusion: ABP refines risk stratification in normotension and prehypertension mainly by enabling the diagnosis of masked hypertension., (© American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Experts proposed blood pressure (BP) load derived from 24-hour ambulatory BP recordings as a more accurate predictor of outcome than level, in particular in normotensive people. We analyzed 8711 subjects (mean age, 54.8 years; 47.0% women) randomly recruited from 10 populations. We expressed BP load as percentage (%) of systolic/diastolic readings ≥135/≥85 mm Hg and ≥120/≥70 mm Hg during day and night, respectively, or as the area under the BP curve (mm Hg×h) using the same ceiling values. During a period of 10.7 years (median), 1284 participants died and 1109 experienced a fatal or nonfatal cardiovascular end point. In multivariable-adjusted models, the risk of cardiovascular complications gradually increased across deciles of BP level and load (P<0.001), but BP load did not substantially refine risk prediction based on 24-hour systolic or diastolic BP level (generalized R(2) statistic ≤0.294%; net reclassification improvement ≤0.28%; integrated discrimination improvement ≤0.001%). Systolic/diastolic BP load of 40.0/42.3% or 91.8/73.6 mm Hg×h conferred a 10-year risk of a composite cardiovascular end point similar to a 24-hour systolic/diastolic BP of 130/80 mm Hg. In analyses dichotomized according to these thresholds, increased BP load did not refine risk prediction in the whole study population (R(2)≤0.051) or in untreated participants with 24-hour ambulatory normotension (R(2)≤0.034). In conclusion, BP load does not improve risk stratification based on 24-hour BP level. This also applies to subjects with normal 24-hour BP for whom BP load was proposed to be particularly useful in risk stratification.

Evidence-based thresholds for risk stratification based on pulse pressure (PP) are currently unavailable. To derive outcome-driven thresholds for the 24-hour ambulatory PP, we analyzed 9938 participants randomly recruited from 11 populations (47.3% women). After age stratification (<60 versus ≥60 years) and using average risk as reference, we computed multivariable-adjusted hazard ratios (HRs) to assess risk by tenths of the PP distribution or risk associated with stepwise increasing (+1 mm Hg) PP levels. All adjustments included mean arterial pressure. Among 6028 younger participants (68 853 person-years), the risk of cardiovascular (HR, 1.58; P=0.011) or cardiac (HR, 1.52; P=0.056) events increased only in the top PP tenth (mean, 60.6 mm Hg). Using stepwise increasing PP levels, the lower boundary of the 95% confidence interval of the successive thresholds did not cross unity. Among 3910 older participants (39 923 person-years), risk increased (P≤0.028) in the top PP tenth (mean, 76.1 mm Hg). HRs were 1.30 and 1.62 for total and cardiovascular mortality, and 1.52, 1.69, and 1.40 for all cardiovascular, cardiac, and cerebrovascular events. The lower boundary of the 95% confidence interval of the HRs associated with stepwise increasing PP levels crossed unity at 64 mm Hg. While accounting for all covariables, the top tenth of PP contributed less than 0.3% (generalized R(2) statistic) to the overall risk among the elderly. Thus, in randomly recruited people, ambulatory PP does not add to risk stratification below age 60; in the elderly, PP is a weak risk factor with levels below 64 mm Hg probably being innocuous.

Background: Average real variability (ARV) is a recently proposed index for short-term blood pressure (BP) variability. We aimed to determine the minimum number of BP readings required to compute ARV without loss of prognostic information., Methods: ARV was calculated from a discovery dataset that included 24-hour ambulatory BP measurements for 1,254 residents (mean age = 56.6 years; 43.5% women) of Copenhagen, Denmark. Concordance between ARV from full (≥80 BP readings) and randomly reduced 24-hour BP recordings was examined, as was prognostic accuracy. A test dataset that included 5,353 subjects (mean age = 54.0 years; 45.6% women) with at least 48 BP measurements from 11 randomly recruited population cohorts was used to validate the results., Results: In the discovery dataset, a minimum of 48 BP readings allowed an accurate assessment of the association between cardiovascular risk and ARV. In the test dataset, over 10.2 years (median), 806 participants died (335 cardiovascular deaths, 206 cardiac deaths) and 696 experienced a major fatal or nonfatal cardiovascular event. Standardized multivariable-adjusted hazard ratios (HRs) were computed for associations between outcome and BP variability. Higher diastolic ARV in 24-hour ambulatory BP recordings predicted (P < 0.01) total (HR = 1.12), cardiovascular (HR = 1.19), and cardiac (HR = 1.19) mortality and fatal combined with nonfatal cerebrovascular events (HR = 1.16). Higher systolic ARV in 24-hour ambulatory BP recordings predicted (P < 0.01) total (HR = 1.12), cardiovascular (HR = 1.17), and cardiac (HR = 1.24) mortality., Conclusions: Forty-eight BP readings over 24 hours were observed to be adequate to compute ARV without meaningful loss of prognostic information.

To analyze sex-specific relative and absolute risks associated with blood pressure (BP), we performed conventional and 24-hour ambulatory BP measurements in 9357 subjects (mean age, 52.8 years; 47% women) recruited from 11 populations. We computed standardized multivariable-adjusted hazard ratios for associations between outcome and systolic BP. During a course of 11.2 years (median), 1245 participants died, 472 of cardiovascular causes. The number of fatal combined with nonfatal events was 1080, 525, and 458 for cardiovascular and cardiac events and for stroke, respectively. In women and men alike, systolic BP predicted outcome, irrespective of the type of BP measurement. Women compared with men were at lower risk (hazard ratios for death and all cardiovascular events=0.66 and 0.62, respectively; P<0.001). However, the relation of all cardiovascular events with 24-hour BP (P=0.020) and the relations of total mortality (P=0.023) and all cardiovascular (P=0.0013), cerebrovascular (P=0.045), and cardiac (P=0.034) events with nighttime BP were steeper in women than in men. Consequently, per a 1-SD decrease, the proportion of potentially preventable events was higher in women than in men for all cardiovascular events (35.9% vs 24.2%) in relation to 24-hour systolic BP (1-SD, 13.4 mm Hg) and for all-cause mortality (23.1% vs 12.3%) and cardiovascular (35.1% vs 19.4%), cerebrovascular (38.3% vs 25.9%), and cardiac (31.0% vs 16.0%) events in relation to systolic nighttime BP (1-SD, 14.1 mm Hg). In conclusion, although absolute risks associated with systolic BP were lower in women than men, our results reveal a vast and largely unused potential for cardiovascular prevention by BP-lowering treatment in women.

Background: We and other investigators previously reported that isolated nocturnal hypertension on ambulatory measurement (INH) clustered with cardiovascular risk factors and was associated with intermediate target organ damage. We investigated whether INH might also predict hard cardiovascular endpoints., Methods and Results: We monitored blood pressure (BP) throughout the day and followed health outcomes in 8711 individuals randomly recruited from 10 populations (mean age 54.8 years, 47.0% women). Of these, 577 untreated individuals had INH (daytime BP <135/85 mmHg and night-time BP ≥120/70 mmHg) and 994 untreated individuals had isolated daytime hypertension on ambulatory measurement (IDH; daytime BP ≥135/85 mmHg and night-time BP <120/70 mmHg). During follow-up (median 10.7 years), 1284 deaths (501 cardiovascular) occurred and 1109 participants experienced a fatal or nonfatal cardiovascular event. In multivariable-adjusted analyses, compared with normotension (n = 3837), INH was associated with a higher risk of total mortality (hazard ratio 1.29, P = 0.045) and all cardiovascular events (hazard ratio 1.38, P = 0.037). IDH was associated with increases in all cardiovascular events (hazard ratio 1.46, P = 0.0019) and cardiac endpoints (hazard ratio 1.53, P = 0.0061). Of 577 patients with INH, 457 were normotensive (<140/90 mmHg) on office BP measurement. Hazard ratios associated with INH with additional adjustment for office BP were 1.31 (P = 0.039) and 1.38 (P = 0.044) for total mortality and all cardiovascular events, respectively. After exclusion of patients with office hypertension, these hazard ratios were 1.17 (P = 0.31) and 1.48 (P = 0.034)., Conclusion: INH predicts cardiovascular outcome in patients who are normotensive on office or on ambulatory daytime BP measurement.

Objectives: The International Database on Ambulatory Blood Pressure Monitoring (1993-1994) lacked a prospective dimension. We are constructing a new resource of longitudinal population studies to investigate with great precision to what extent the ambulatory blood pressure improves risk stratification., Methods: The acronym IDACO refers to the new International Database of Ambulatory blood pressure in relation to Cardiovascular Outcome. Eligible studies are population based, have fatal as well as nonfatal outcomes available for analysis, comply with ethical standards, and have been previously published in peer-reviewed journals. In a meta-analysis based on individual patient data, composite and cause-specific cardiovascular events will be related to various indexes derived by ambulatory blood pressure monitoring. The analyses will be stratified by cohort and adjusted for the conventional blood pressure and other cardiovascular risk factors., Results: To date, the international database includes 7609 patients from four cohorts recruited in Copenhagen, Denmark (n=2311), Noorderkempen, Belgium (n=2542), Ohasama, Japan (n=1535), and Uppsala, Sweden (n=1221). In these four cohorts, during a total of 69,295 person-years of follow-up (median 9.3 years), 1026 patients died and 929 participants experienced a fatal or nonfatal cardiovascular event. Follow-up in five other eligible cohorts, involving a total of 4027 participants, is still in progress. We expect that this follow-up will be completed by the end of 2007., Conclusion: The international database of ambulatory blood pressure in relation to cardiovascular outcome will provide a shared resource to investigate risk stratification by ambulatory blood pressure monitoring to an extent not possible in any earlier individual study.

The 825T allele of the G-protein beta(3)-subunit is associated with increased intracellular signalling. Its association with hypertension is inconsistent. We, therefore, studied the C825T polymorphism in relation to ambulatory blood pressure as well as left ventricular structure and function in two European populations. We genotyped 248 parents and 318 offspring, enrolled in the European Project on Genes in Hypertension in Cracow, Poland (n=286) and in Novosibirsk, Russian Federation (n=280). The 24-h ambulatory blood pressure was recorded using oscillometric SpaceLabs 90207 monitors. Within each centre, a single observer performed two-dimensionally guided M-mode echocardiography and Doppler sonography to measure left ventricular structure (American Society of Echocardiography conventions) and diastolic function: early (E) and late (A) peak diastolic inflow velocities. We used analysis of covariance and generalized estimating equations to allow for covariables and nonindependence among related subjects. Genotype frequencies were similar (P=0.25) in Cracow and Novosibirsk and amounted to 44.7% for CC, 47.2% for CT, and 8.1% for TT. Among parents (mean age: 51.3 years)-but not among offspring (mean age 25.1 years)-24-h, daytime and night time systolic blood pressures were 5-6 mmHg higher in TT homozygotes than in C allele carriers. In TT homozygous parents (-8.2 cm/sec, P=0.004) as well as in TT homozygous offspring (-7.5 cm/sec, P=0.02), the E-wave was significantly reduced, which in offspring also resulted in a lower E/A ratio (-0.25, P=0.002). Neither in parents nor in offspring, left ventricular mass index was associated with the C825T polymorphism. In conclusion, in TT homozygotes of both generations, early left ventricular relaxation was reduced. In TT homozygous parents, the latter observation might be because of the higher systolic pressure associated with the TT genotype.

Objective: To describe the distributions of the ambulatory blood pressure in a sample drawn from the Siberian population., Methods: In the European Project On Genes in Hypertension (EPOGH), a random population sample of 162 persons (72 men and 90 women) was investigated in Novosibirsk, Russia. Mean age (+/-SD) was 40.6+/-15.3 years. Validated oscillometric 90207 SpaceLabs monitors were programmed to obtain ambulatory blood pressure readings at intervals of 15min from 0800h to 2200h and at 30min intervals from 2200h to 0800h. Daytime and nighttime were defined using short fixed-clock time intervals, which ranged from 1000h to 2000h and from midnight to 0600h, respectively., Results: In the 162 participants, of whom 54 were hypertensive, 24-h clocktime day and clocktime night blood pressures averaged 120/73, 126/79 and 110/60mmHg, respectively. Compared with daytime values, blood pressures at the clinic were 5.7/1.1mmHg lower in 108 normotensive people, but 17.0/13.1mmHg higher in 54 hypertensive patients. In the normotensive subgroup, the 95th percentiles of the 24-h clocktime day and clocktime night blood pressures were 128/81, 136/86 and 118/72mmHg, respectively., Conclusion: In comparison with other population surveys, the present interim report on the EPOGH study produced consistent results with respect to the distributions of the ambulatory measurements both in normotensive subjects and in the overall study population.