Ambulatory hypertension subtypes and 24-hour systolic and diastolic blood pressure as distinct outcome predictors in 8341 untreated people recruited from 12 populations.

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.

Opposing Age-Related Trends in Absolute and Relative Risk of Adverse Health Outcomes Associated With Out-of-Office Blood Pressure.

Participant-level meta-analyses assessed the age-specific relevance of office blood pressure to cardiovascular complications, but this information is lacking for out-of-office blood pressure. At baseline, daytime ambulatory (n=12 624) or home (n=5297) blood pressure were measured in 17 921 participants (51.3% women; mean age, 54.2 years) from 17 population cohorts. Subsequently, mortality and cardiovascular events were recorded. Using multivariable Cox regression, floating absolute risk was computed across 4 age bands (≤60, 61-70, 71-80, and >80 years). Over 236 491 person-years, 3855 people died and 2942 cardiovascular events occurred. From levels as low as 110/65 mm Hg, risk log-linearly increased with higher out-of-office systolic/diastolic blood pressure. From the youngest to the oldest age group, rates expressed per 1000 person-years increased (P<0.001) from 4.4 (95% CI, 4.0-4.7) to 86.3 (76.1-96.5) for all-cause mortality and from 4.1 (3.9-4.6) to 59.8 (51.0-68.7) for cardiovascular events, whereas hazard ratios per 20-mm Hg increment in systolic out-of-office blood pressure decreased (P≤0.0033) from 1.42 (1.19-1.69) to 1.09 (1.05-1.12) and from 1.70 (1.51-1.92) to 1.12 (1.07-1.17), respectively. These age-related trends were similar for out-of-office diastolic pressure and were generally consistent in both sexes and across ethnicities. In conclusion, adverse outcomes were directly associated with out-of-office blood pressure in adults. At young age, the absolute risk associated with out-of-office blood pressure was low, but relative risk high, whereas with advancing age relative risk decreased and absolute risk increased. These observations highlight the need of a lifecourse approach for the management of hypertension.

Diagnostic thresholds for ambulatory blood pressure monitoring based on 10-year cardiovascular risk.

BACKGROUND: Current diagnostic thresholds for ambulatory blood pressure (ABP) mainly rely on statistical parameters derived from reference populations. We determined an outcome-driven reference frame for ABP measurement. METHODS AND RESULTS: We performed 24-hour ABP monitoring in 5682 participants (mean age 59.0 years; 43.3% women) enrolled in prospective population studies in Copenhagen, Denmark; Noorderkempen, Belgium; Ohasama, Japan; and Uppsala, Sweden. In multivariate analyses, we determined ABP thresholds, which yielded 10-year cardiovascular risks similar to those associated with optimal (120/80 mm Hg), normal (130/85 mm Hg), and high (140/90 mm Hg) blood pressure on office measurement. Over 9.7 years (median), 814 cardiovascular end points occurred, including 377 strokes and 435 cardiac events. Systolic/diastolic thresholds for optimal ABP were 116.8/74.2 mm Hg for 24 hours, 121.6/78.9 mm Hg for daytime, and 100.9/65.3 mm Hg for nighttime. Corresponding thresholds for normal ABP were 123.9/76.8, 129.9/82.6, and 110.2/68.1 mm Hg, respectively, and those for ambulatory hypertension were 131.0/79.4, 138.2/86.4, and 119.5/70.8 mm Hg. After rounding, approximate thresholds for optimal ABP amounted to 115/75 mm Hg for 24 hours, 120/80 mm Hg for daytime, and 100/65 mm Hg for nighttime. Rounded thresholds for normal ABP were 125/75, 130/85, and 110/70 mm Hg, respectively, and those for ambulatory hypertension were 130/80, 140/85, and 120/70 mm Hg. CONCLUSIONS: Population-based outcome-driven thresholds for optimal and normal ABP are lower than those currently proposed by hypertension guidelines.

Prognostic accuracy of day versus night ambulatory blood pressure: a cohort study.

BACKGROUND: Few studies have formally compared the predictive value of the blood pressure at night over and beyond the daytime value. We investigated the prognostic significance of the ambulatory blood pressure during night and day and of the night-to-day blood pressure ratio. METHODS: We did 24-h blood pressure monitoring in 7458 people (mean age 56.8 years [SD 13.9]) enrolled in prospective population studies in Denmark, Belgium, Japan, Sweden, Uruguay, and China. We calculated multivariate-adjusted hazard ratios for daytime and night-time blood pressure and the systolic night-to-day ratio, while adjusting for cohort and cardiovascular risk factors. FINDINGS: Median follow-up was 9.6 years (5th to 95th percentile 2.5-13.7). Adjusted for daytime blood pressure, night-time blood pressure predicted total (n=983; p<0.0001), cardiovascular (n=387; p<0.01), and non-cardiovascular (n=560; p<0.001) mortality. Conversely, adjusted for night-time blood pressure, daytime blood pressure predicted only non-cardiovascular mortality (p<0.05), with lower blood pressure levels being associated with increased risk. Both daytime and night-time blood pressure consistently predicted all cardiovascular events (n=943; p<0.05) and stroke (n=420; p<0.01). Adjusted for night-time blood pressure, daytime blood pressure lost prognostic significance only for cardiac events (n=525; p> or =0.07). Adjusted for the 24-h blood pressure, night-to-day ratio predicted mortality, but not fatal combined with non-fatal events. Antihypertensive drug treatment removed the significant association between cardiovascular events and the daytime blood pressure. Participants with systolic night-to-day ratio value of 1 or more were older, at higher risk of death, and died at an older age than those whose night-to-day ratio was normal (> or =0.80 to <0.90). INTERPRETATION: In contrast to commonly held views, daytime blood pressure adjusted for night-time blood pressure predicts fatal combined with non-fatal cardiovascular events, except in treated patients, in whom antihypertensive drugs might reduce blood pressure during the day, but not at night. The increased mortality in patients with higher night-time than daytime blood pressure probably indicates reverse causality. Our findings support recording the ambulatory blood pressure during the whole day.

Is blood pressure during the night more predictive of cardiovascular outcome than during the day?

The objective of this study was to investigate the prognostic significance of the ambulatory blood pressure (BP) during night and day and of the night-to-day BP ratio (NDR). We studied 7458 participants (mean age 56.8 years; 45.8% women) enrolled in the International Database on Ambulatory BP in relation to Cardiovascular Outcome. Using Cox models, we calculated hazard ratios (HR) adjusted for cohort and cardiovascular risk factors. Over 9.6 years (median), 983 deaths and 943 cardiovascular events occurred. Nighttime BP predicted mortality outcomes (HR, 1.18-1.24; P<0.01) independent of daytime BP. Conversely, daytime systolic (HR, 0.84; P<0.01) and diastolic BP (HR, 0.88; P<0.05) predicted only noncardiovascular mortality after adjustment for nighttime BP. Both daytime BP and nighttime BP consistently predicted all cardiovascular events (HR, 1.11-1.33; P<0.05) and stroke (HR, 1.21-1.47; P<0.01). Daytime BP lost its prognostic significance for cardiovascular events in patients on antihypertensive treatment. Adjusted for the 24-h BP, NDR predicted mortality (P<0.05), but not fatal combined with nonfatal events. Participants with systolic NDR of at least 1 compared with participants with normal NDR (> or = 0.80 to <0.90) were older, at higher risk of death, but died at higher age. The predictive accuracy of the daytime and nighttime BP and the NDR depended on the disease outcome under study. The increased mortality in patients with higher NDR probably indicates reverse causality. Our findings support recording the ambulatory BP during the whole day.

Diagnostic thresholds for ambulatory blood pressure moving lower: a review based on a meta-analysis-clinical implications.

Upper limits of normal ambulatory blood pressure (ABP) have been a matter of debate in recent years. Current diagnostic thresholds for ABP rely mainly on statistical parameters derived from reference populations. Recent findings from the International Database of Ambulatory Blood Pressure in Relation to Cardiovascular Outcome (IDACO) provide outcome-driven thresholds for ABP. Rounded systolic/diastolic thresholds for optimal ABP were found to be 115/75 mm Hg for 24 hours, 120/80 mm Hg for daytime, and 100/65 mm Hg for nighttime. The corresponding rounded thresholds for normal ABP were 125/75 mm Hg, 130/85 mm Hg, and 110/70 mm Hg, respectively, and those for ambulatory hypertension were 130/80 mm Hg, 140/85 mm Hg, and 120/70 mm Hg. However, in clinical practice, any diagnostic threshold for blood pressure needs to be assessed in the context of the patient's overall risk profile. The IDACO database is therefore being updated with additional population cohorts to enable the construction of multifactorial risk score charts, which also include ABP.

Prognostic superiority of daytime ambulatory over conventional blood pressure in four populations: a meta-analysis of 7,030 individuals.

OBJECTIVE: To investigate the multivariate-adjusted predictive value of systolic and diastolic blood pressures on conventional (CBP) and daytime (10-20 h) ambulatory (ABP) measurement. METHODS: We randomly recruited 7,030 subjects (mean age 56.2 years; 44.8% women) from populations in Belgium, Denmark, Japan and Sweden. We constructed the International Database on Ambulatory blood pressure and Cardiovascular Outcomes. RESULTS: During follow-up (median = 9.5 years), 932 subjects died. Neither CBP nor ABP predicted total mortality, of which 60.9% was due to noncardiovascular causes. The incidence of fatal combined with nonfatal cardiovascular events amounted to 863 (228 deaths, 326 strokes and 309 cardiac events). In multivariate-adjusted continuous analyses, both CBP and ABP predicted cardiovascular, cerebrovascular, cardiac and coronary events. However, in fully-adjusted models, including both CBP and ABP, CBP lost its predictive value (P >or= 0.052), whereas systolic and diastolic ABP retained their prognostic significance (P or= 0.21). In adjusted categorical analyses, normotension was the referent group (CBP < 140/90 mmHg and ABP < 135/85 mmHg). Adjusted hazard ratios for all cardiovascular events were 1.22 [95% confidence interval (CI) = 0.96-1.53; P = 0.09] for white-coat hypertension (>or= 140/90 and < 135/85 mmHg); 1.62 (95% CI = 1.35-1.96; P < 0.0001) for masked hypertension (< 140/90 and >or= 135/85 mmHg); and 1.80 (95% CI = 1.59-2.03; P < 0.0001) for sustained hypertension (>or= 140/90 and >or= 135/85 mmHg). CONCLUSIONS: ABP is superior to CBP in predicting cardiovascular events, but not total and noncardiovascular mortality. Cardiovascular risk gradually increases from normotension over white-coat and masked hypertension to sustained hypertension.

Diagnostic thresholds for ambulatory blood pressure monitoring based on 10-year cardiovascular risk.

Current diagnostic thresholds for ambulatory blood pressure (ABP) mainly rely on statistical parameters derived from reference populations. We determined an outcome-driven reference frame for ABP measurement. We performed 24-h ABP monitoring in 5682 participants (mean age 59.0 years; 43.3% women) enrolled in prospective population studies in Copenhagen, Denmark; Noorderkempen, Belgium; Ohasama, Japan; and Uppsala, Sweden. In multivariate analyses, we determined ABP thresholds, which yielded 10-year cardiovascular risks similar to those associated with optimal (120/80 mmHg), normal (130/85 mmHg), and high (140/90 mmHg) blood pressure on office measurement. Over 9.7 years (median), 814 cardiovascular end points occurred, including 377 strokes and 435 cardiac events. Systolic/diastolic thresholds for optimal ABP were 118.3/74.2 mmHg for 24 h, 121.6/78.9 mmHg for daytime, and 104.7/65.3 mmHg for nighttime. Corresponding thresholds for normal ABP were 124.3/76.8, 129.9/82.6, and 111.6/68.1 mmHg, respectively, and those for ambulatory hypertension were 130.3/79.4, 138.2/86.4, and 118.5/70.8 mmHg. After rounding, approximate thresholds for optimal ABP amounted to 115/75 mmHg for 24 h, 120/80 mmHg for daytime, and 105/65 mmHg for nighttime. Rounded thresholds for normal ABP were 125/75, 130/85, and 110/70 mmHg, respectively, and those for ambulatory hypertension were 130/80, 140/85, and 120/70 mmHg. In conclusion, population-based outcome-driven thresholds for optimal and normal ABP are lower than those currently proposed by hypertension guidelines.

The International Database of Ambulatory Blood Pressure in relation to Cardiovascular Outcome (IDACO): protocol and research perspectives.

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.

Diurnal blood pressure pattern and risk of congestive heart failure.

CONTEXT: High blood pressure is the most important risk factor for congestive heart failure (CHF) at a population level, but the relationship of an altered diurnal blood pressure pattern to risk of subsequent CHF is unknown. OBJECTIVES: To explore 24-hour ambulatory blood pressure characteristics as predictors of CHF incidence and to investigate whether altered diurnal blood pressure patterns confer any additional risk information beyond that provided by conventional office blood pressure measurements. DESIGN, SETTING, AND PARTICIPANTS: Prospective, community-based, observational cohort in Uppsala, Sweden, including 951 elderly men free of CHF, valvular disease, and left ventricular hypertrophy at baseline between 1990 and 1995, followed up until the end of 2002. Twenty-four-hour ambulatory blood pressure monitoring was performed at baseline, and the blood pressure variables were analyzed as predictors of subsequent CHF. MAIN OUTCOME MEASURE: First hospitalization for CHF. RESULTS: Seventy men developed heart failure during follow-up, with an incidence rate of 8.6 per 1000 person-years at risk. In multivariable Cox proportional hazards models adjusted for antihypertensive treatment and established risk factors for CHF (myocardial infarction, diabetes, smoking, body mass index, and serum cholesterol level), a 1-SD (9-mm Hg) increase in nighttime ambulatory diastolic blood pressure (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.02-1.55) and the presence of "nondipping" blood pressure (night-day ambulatory blood pressure ratio > or =1; HR, 2.29; 95% CI, 1.16-4.52) were associated with an increased risk of CHF. After adjusting for office-measured systolic and diastolic blood pressures, nondipping blood pressure remained a significant predictor of CHF (HR, 2.21; 95% CI, 1.12-4.36 vs normal night-day pattern). Nighttime ambulatory diastolic blood pressure and nondipping blood pressure were also significant predictors of CHF after exclusion of all participants who had an acute myocardial infarction before baseline or during follow-up. CONCLUSIONS: Nighttime blood pressure appears to convey additional risk information about CHF beyond office-measured blood pressure and other established risk factors for CHF. The clinical value of this association remains to be established in future studies.

The Cardiovascular Risk of White-Coat Hypertension.

BACKGROUND: The role of white-coat hypertension (WCH) and the white-coat-effect (WCE) in development of cardiovascular disease (CVD) risk remains poorly understood. OBJECTIVES: Using data from the population-based, 11-cohort IDACO (International Database on Ambulatory Blood Pressure Monitoring in Relation to Cardiovascular Outcomes), this study compared daytime ambulatory blood pressure monitoring with conventional blood pressure measurements in 653 untreated subjects with WCH and 653 normotensive control subjects. METHODS: European Society Hypertension guidelines were used as a 5-stage risk score. Low risk was defined as 0 to 2 risk factors, and high risk was defined as ≥3 to 5 risk factors, diabetes, and/or history of prior CVD events. Age- and cohort-matching was done between 653 untreated subjects with WCH and 653 normotensive control subjects. RESULTS: In a stepwise linear regression model, systolic WCE increased by 3.8 mm Hg (95% confidence interval [CI]: 3.1 to 4.6 mm Hg) per 10-year increase in age, and was similar in low- and high-risk subjects with or without prior CVD events. Over a median 10.6-year follow-up, incidence of new CVD events was higher in 159 high-risk subjects with WCH compared with 159 cohort- and age-matched high-risk normotensive subjects (adjusted hazard ratio [HR]: 2.06; 95% CI: 1.10 to 3.84; p = 0.023). The HR was not significant for 494 participants with low-risk WCH and age-matched low-risk normotensive subjects. Subgroup analysis by age showed that an association between WCH and incident CVD events is limited to older (age ≥60 years) high-risk WCH subjects; the adjusted HR was 2.19 (95% CI: 1.09 to 4.37; p = 0.027) in the older high-risk group and 0.88 (95% CI: 0.51 to 1.53; p = 0.66) in the older low-risk group (p for interaction = 0.044). CONCLUSIONS: WCE size is related to aging, not to CVD risk. CVD risk in most persons with WCH is comparable to age- and risk-adjusted normotensive control subjects.

Blood pressure load does not add to ambulatory blood pressure level for cardiovascular risk stratification.

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.

How many measurements are needed to estimate blood pressure variability without loss of prognostic information?

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.

Risk stratification by ambulatory blood pressure monitoring across JNC classes of conventional blood pressure.

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.

Outcome-driven thresholds for ambulatory pulse pressure in 9938 participants recruited from 11 populations.

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.

Setting thresholds to varying blood pressure monitoring intervals differentially affects risk estimates associated with white-coat and masked hypertension in the population.

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.

Age-specific differences between conventional and ambulatory daytime blood pressure values.

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.

Risk stratification by 24-hour ambulatory blood pressure and estimated glomerular filtration rate in 5322 subjects from 11 populations.

No previous study addressed whether in the general population estimated glomerular filtration rate (eGFR [Chronic Kidney Disease Epidemiology Collaboration formula]) adds to the prediction of cardiovascular outcome over and beyond ambulatory blood pressure. We recorded health outcomes in 5322 subjects (median age, 51.8 years; 43.1% women) randomly recruited from 11 populations, who had baseline measurements of 24-hour ambulatory blood pressure (ABP(24)) and eGFR. We computed hazard ratios using multivariable-adjusted Cox regression. Median follow-up was 9.3 years. In fully adjusted models, which included both ABP(24) and eGFR, ABP(24) predicted (P≤0.008) both total (513 deaths) and cardiovascular (206) mortality; eGFR only predicted cardiovascular mortality (P=0.012). Furthermore, ABP(24) predicted (P≤0.0056) fatal combined with nonfatal events as a result of all cardiovascular causes (555 events), cardiac disease (335 events), or stroke (218 events), whereas eGFR only predicted the composite cardiovascular end point and stroke (P≤0.035). The interaction terms between ABP(24) and eGFR were all nonsignificant (P≥0.082). For cardiovascular mortality, the composite cardiovascular end point, and stroke, ABP(24) added 0.35%, 1.17%, and 1.00% to the risk already explained by cohort, sex, age, body mass index, smoking and drinking, previous cardiovascular disease, diabetes mellitus, and antihypertensive drug treatment. Adding eGFR explained an additional 0.13%, 0.09%, and 0.14%, respectively. Sensitivity analyses stratified for ethnicity, sex, and the presence of hypertension or chronic kidney disease (eGFR <60 mL/min per 1.73 m(2)) were confirmatory. In conclusion, in the general population, eGFR predicts fewer end points than ABP(24). Relative to ABP(24), eGFR is as an additive, not a multiplicative, risk factor and refines risk stratification 2- to 14-fold less.

Masked hypertension in diabetes mellitus: treatment implications for clinical practice.

Although distinguishing features of masked hypertension in diabetics are well known, the significance of antihypertensive treatment on clinical practice decisions has not been fully explored. We analyzed 9691 subjects from the population-based 11-country International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcomes. Prevalence of masked hypertension in untreated normotensive participants was higher (P<0.0001) among 229 diabetics (29.3%, n=67) than among 5486 nondiabetics (18.8%, n=1031). Over a median of 11.0 years of follow-up, the adjusted risk for a composite cardiovascular end point in untreated diabetic-masked hypertensives tended to be higher than in normotensives (hazard rate [HR], 1.96; 95% confidence interval [CI], 0.97-3.97; P=0.059), similar to untreated stage 1 hypertensives (HR, 1.07; CI, 0.58-1.98; P=0.82), but less than stage 2 hypertensives (HR, 0.53; CI, 0.29-0.99; P=0.048). In contrast, cardiovascular risk was not significantly different in antihypertensive-treated diabetic-masked hypertensives, as compared with the normotensive comparator group (HR, 1.13; CI, 0.54-2.35; P=0.75), stage 1 hypertensives (HR, 0.91; CI, 0.49-1.69; P=0.76), and stage 2 hypertensives (HR, 0.65; CI, 0.35-1.20; P=0.17). In the untreated diabetic-masked hypertensive population, mean conventional systolic/diastolic blood pressure was 129.2 ± 8.0/76.0 ± 7.3 mm Hg, and mean daytime systolic/diastolic blood pressure 141.5 ± 9.1/83.7 ± 6.5 mm Hg. In conclusion, masked hypertension occurred in 29% of untreated diabetics, had comparable cardiovascular risk as stage 1 hypertension, and would require considerable reduction in conventional blood pressure to reach daytime ambulatory treatment goal. Importantly, many hypertensive diabetics when receiving antihypertensive therapy can present with normalized conventional and elevated ambulatory blood pressure that mimics masked hypertension.

Double product reflects the predictive power of systolic pressure in the general population: evidence from 9,937 participants.

BACKGROUND: The double product (DP), consisting of the systolic blood pressure (SBP) multiplied by the pulse rate (PR), is an index of myocardial oxygen consumption, but its prognostic value in the general population remains unknown. METHODS: We recorded health outcomes in 9,937 subjects (median age, 53.2 years; 47.3% women) randomly recruited from 11 populations and enrolled in the International Database on Ambulatory blood pressure in relation to Cardiovascular Outcomes (IDACO) study. We obtained the SBP, PR, and DP for these subjects as determined through 24-hour ambulatory monitoring. RESULTS: Over a median period of 11.0 years, 1,388 of the 9,937 study subjects died, of whom 536 and 794, respectively, died of cardiovascular (CV) and non-CV causes, and a further 1,161, 658, 494, and 465 subjects, respectively, experienced a CV, cardiac, coronary, or cerebrovascular event. In multivariate-adjusted Cox models, not including SBP and PR, DP predicted total, CV, and non-CV mortality (standardized hazard ratio [HR], ≥ 1.10; P ≤ 0.02), and all CV, cardiac, coronary, and stroke events (HR, ≥ 1.21; P < 0.0001). For CV mortality (HR, 1.34 vs. 1.30; P = 0.71) and coronary events (1.28 vs. 1.21; P = 0.26), SBP and the DP were equally predictive. As compared with DP, SBP was a stronger predictor of all CV events (1.39 vs. 1.27; P = 0.002) and stroke (1.61 vs. 1.36; P < 0.0001), and a slightly stronger predictor of cardiac events (1.32 vs. 1.22; P = 0.06). In fully adjusted models, including both SBP and PR, the predictive value of DP disappeared for fatal endpoints (P ≥ 0.07), coronary events (P = 0.06), and stroke (P = 0.12), or DP was even inversely associated with the risk of all CV and cardiac events (both P ≤ 0.01). CONCLUSION: In the general population, we did not observe DP to add to risk stratification over and beyond SBP and PR.