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Whether extreme dipping is associated with cardiovascular events (CVE) is unclear. The present study was conducted to test the hypothesis that the prognostic role of extreme dipping varies as a function of age. The analysis was performed in 10 868 participants (53% men) aged 53±15 (mean±SD) years enrolled in 8 prospective studies. Using the ambulatory systolic blood pressure nocturnal decline, we identified 4 groups: dippers (>10%-20%), nondippers (>0%-10%), reverse dippers (≤0%), and extreme dippers (>20%). The association between dipping category and CVE was estimated as a function of age using Cox models adjusted for sex, average 24-hour systolic blood pressure, and traditional risk factors. During a median follow-up of 5.7 years, there were a total of 829 CVE (168 fatal). For extreme dippers, no increase in risk of CVE was observed among the participants <70 years (hazard ratio, 0.99 [95% CI, 0.73-1.34]; P =0.93) compared with dippers. In contrast, among the participants ≥70 years, there was a significant increase in risk (hazard ratio, 1.88 [95% CI, 1.14-3.11]; P =0.013). Among the octogenarians, the hazard ratio (95% CI) for CVE were 2.34 (1.12-4.93) for nondippers ( P =0.024), 3.91 (1.75-8.73) for reverse dippers ( P =0.001), and 4.12 (1.64-10.37) for extreme dippers ( P =0.003) compared with dippers. These data show that extreme dipping is not associated with poorer outcome in people younger than 70 years. A U-shaped relationship between nocturnal blood pressure dipping and adverse outcome is present in subjects older than 70 years. In the octogenarian extreme dippers, the risk of CVEs was 4× higher than in the dippers and similar to that in the reverse dippers.

The prognostic value of uric acid (UA) for cardiovascular events (CVE) is still debated. Our purpose was to investigate the association between UA and CVE in 5243 participants of the ABP-International study with the main aim of identifying optimal sex-specific cut-points. In multivariable Cox analyses, the relationship between CVE and UA as a continuous variable was modeled by including both linear and nonlinear terms. Survival models were also estimated with UA as a categorical variable. Optimal UA cut-points were determined using an outcome-oriented approach. During a median follow-up of 5.9 years, there were 423 CVE (93 fatal). In age- and sex-adjusted Cox models, UA as a continuous variable was a significant predictor of CVE in all individuals and in men and women considered separately. The relationship between UA and CVE was linear (P-value for nonlinearity 0.54 and 0.80 for men and women, respectively). For each 1 mg/dL increase in UA, the relative hazard increase was 16% in men and 19% in women. In fully adjusted models, UA remained a significant predictor of CVE in the whole study cohort. The optimal cut-point best separating patients at low and high risk of CVE was 6.3 mg/dL for men and 4.4 mg/dL for women. Subjects with high UA had a 38% greater risk of CVE. In a sex-specific analysis, the association remained significant only in men (hazard ratio, 1.47; P < 0.01). In conclusion, high UA is an independent predictor for subsequent CVE and significantly improves risk discrimination and reclassification over the baseline multivariable model., (©2019 Wiley Periodicals, Inc.)

The prognostic relevance of masked uncontrolled hypertension (MUCH) is incompletely clear, and its global impact on cardiovascular outcomes and mortality has not been assessed. The aim of this study was to perform a meta-analysis on the prognostic value of MUCH. We searched for articles assessing outcome in patients with MUCH compared with those with controlled hypertension (CH) and reporting adjusted hazard ratio and 95% CI. We identified 6 studies using ambulatory blood pressure monitoring (12 610 patients with 933 events) and 5 using home blood pressure measurement (17 742 patients with 394 events). The global population included 30 352 patients who experienced 1327 events. Selected studies had cardiovascular outcomes and all-cause mortality as primary outcome, and the main result is a composite of these events. The overall adjusted hazard ratio was 1.80 (95% CI, 1.57-2.06) for MUCH versus CH. Subgroup meta-analysis showed that adjusted hazard ratio was 1.83 (95% CI, 1.52-2.21) in studies using ambulatory blood pressure monitoring and 1.75 (95% CI, 1.38-2.20) in those using home blood pressure measurement. Risk was significantly higher in MUCH than in CH independently of follow-up length and types of studied events. MUCH was at significantly higher risk than CH in all ethnic groups, but the highest hazard ratio was found in studies, including black patients. Risk of cardiovascular events and all-cause mortality is significantly higher in patients with MUCH than in those with CH. MUCH detected by ambulatory or home blood pressure measurement seems to convey similar prognostic information.

Objective: The relative role of office heart rate (HR) and ambulatory HR for predicting major adverse cardiovascular events (MACEs) and mortality is not well known. Aim of this study was to investigate the association of white-coat tachycardia and masked tachycardia with MACE and mortality in hypertensive patients., Methods: We performed 24-h ambulatory blood pressure and HR monitoring in 7602 hypertensive patients (4165 men) aged 52 ± 16 years enrolled in six prospective studies in Italy, Japan, and Australia. Participants were divided into four groups: normal office and normal night-time HRs (N = 5238), white-coat tachycardia (N = 998), masked tachycardia (N = 796), and sustained tachycardia (N = 570). Median follow-up was 5.0 years., Results: In age-and-sex-adjusted Cox model, using the normal HRs group as a reference, white-coat tachycardia was not a significant predictor of excess MACEs or all-cause death. In contrast, both masked tachycardia [hazard ratio, 95% confidence interval (CI); 1.40, 1.11-1.77] and sustained tachycardia (1.86, 1.44-2.40) were associated with risk of excess MACE. In addition, masked tachycardia (hazard ratio, 95% CI; 1.62, 1.14-2.29) but not sustained tachycardia (1.35, 0.83-2.19) was a significant predictor of excess mortality. These relationships held true in multivariable parsimonious Cox models including major risk factors. In these models, masked tachycardia remained an independent predictor of excess MACE (hazard ratio, 95% CI; 1.34, 1.06-1.71) and all-cause mortality (1.68, 1.18-2.41)., Conclusion: The current study confirms that measurement of HR adds to the risk stratification for MACE and mortality and shows that an elevated night-time HR confers an increased mortality risk to hypertensive patients who have normal office HR.

The independent prognostic significance of circadian blood pressure (BP) changes is unclear. We investigated the association between circadian BP changes and cardiovascular risk among elderly-treated hypertensive patients. The occurrence of a composite end point (that is, stroke, coronary events, heart failure and peripheral revascularization) was evaluated among 1191 elderly-treated hypertensive patients (age range 60-90 years). According to the nighttime change and the morning surge (MS) of systolic BP, subjects were divided into groups of dippers with a normal or high MS (DNMS and DHMS, respectively), non-dippers (ND), reverse dippers (RD) and extreme dippers with a normal or high MS (EDNMS and EDHMS, respectively). During the follow-up (9.1±4.9 years, range 0.4-20 years), 392 events occurred. The event rate was 3.63 per 100 patient-years. After adjustment for various covariates, including 24-h BP, the DHMS (hazard ratio (HR) 1.49, 95% confidence interval (CI) 1.02-2.16, P=0.04), ND (HR 1.71, 95% CI 1.28-2.27, P=0.0001), RD (HR 2.05, 95% CI 1.44-2.93, P=0.0001) and EDHMS (HR 3.40, 95% CI 1.96-5.90, P=0.001) were at higher cardiovascular risk than the DNMS. The population attributable risk was 0.6, 7.1, 7.3 and 1.4% for the DHMS, ND, RD and EDHMS, respectively. In elderly-treated hypertensive patients, circadian BP changes were independently associated with increased cardiovascular risk. At the patient level, the highest risk was observed among the EDHMS, followed by the RD, ND and DHMS. At the population level, the highest risk was observed among the RD, followed by the ND, EDHMS and DHMS.

The prognostic importance of the nocturnal systolic blood pressure (SBP) fall, adjusted for average 24-hour SBP levels, is unclear. The Ambulatory Blood Pressure Collaboration in Patients With Hypertension (ABC-H) examined this issue in a meta-analysis of 17 312 hypertensives from 3 continents. Risks were computed for the systolic night-to-day ratio and for different dipping patterns (extreme, reduced, and reverse dippers) relative to normal dippers. ABC-H investigators provided multivariate adjusted hazard ratios (HRs), with and without adjustment for 24-hour SBP, for total cardiovascular events (CVEs), coronary events, strokes, cardiovascular mortality, and total mortality. Average 24-hour SBP varied from 131 to 140 mm Hg and systolic night-to-day ratio from 0.88 to 0.93. There were 1769 total CVEs, 916 coronary events, 698 strokes, 450 cardiovascular deaths, and 903 total deaths. After adjustment for 24-hour SBP, the systolic night-to-day ratio predicted all outcomes: from a 1-SD increase, summary HRs were 1.12 to 1.23. Reverse dipping also predicted all end points: HRs were 1.57 to 1.89. Reduced dippers, relative to normal dippers, had a significant 27% higher risk for total CVEs. Risks for extreme dippers were significantly influenced by antihypertensive treatment (P<0.001): untreated patients had increased risk of total CVEs (HR, 1.92), whereas treated patients had borderline lower risk (HR, 0.72) than normal dippers. For CVEs, heterogeneity was low for systolic night-to-day ratio and reverse/reduced dipping and moderate for extreme dippers. Quality of included studies was moderate to high, and publication bias was undetectable. In conclusion, in this largest meta-analysis of hypertensive patients, the nocturnal BP fall provided substantial prognostic information, independent of 24-hour SBP levels., (© 2016 American Heart Association, Inc.)

Background and Method: To determine which SBP measure best predicts cardiovascular events (CVEs) independently, a systematic review was conducted for cohorts with all patients diagnosed with hypertension, 1+ years follow-up, and coronary artery disease and stroke outcomes. Lead investigators provided ad hoc analyses for each cohort. Meta-analyses gave hazard ratios from clinic SBP (CSBP), daytime SBP (DSBP), and night-time SBP (NSBP). Coefficients of variation of SBP measured dispersion. Nine cohorts (n = 13,844) were from Europe, Brazil, and Japan. For sleep-wake SBP classification, seven cohorts used patient-specific information., Results: Overall, NSBP's dispersion exceeded DSBP's dispersion by 22.6% with nonoverlapping confidence limits. Within all nine cohorts, dispersion for NSBP exceeded that for CSBP and DSBP. For each comparison, P = 0.004 that this occurred by chance. Considered individually, increases in NSBP, DSBP, and CSBP each predicted CVEs: hazard ratios (95% confidence intervals) = 1.25 (1.22-1.29), 1.20 (1.15-1.26), and 1.11 (1.06-1.16), respectively. However, after simultaneous adjustment for all three SBPs, hazard ratios were 1.26 (1.20-1.31), 1.01 (0.94-1.08), and 1.00 (0.95-1.05), respectively. Cohorts with baseline antihypertensive treatment and cohorts with patient-specific information for night-day BP classification gave similar results. Within most cohorts, simultaneously adjusted hazard ratios were greater for NSBP than for DSBP and CSBP: P = 0.023 and 0.012, respectively, that this occurred by chance., Conclusion: In hypertensive patients, NSBP had greater dispersion than DSBP and CSBP in all cohorts. On simultaneous adjustment, compared with DSBP and CSBP, increased NSBP independently predicted higher CVEs in most cohorts, and, overall, NSBP independently predicted CVEs, whereas CSBP and DSBP lost their predictive ability entirely.

The association of ambulatory blood pressure (BP) variability with mortality and cardiovascular events is controversial. To investigate whether BP variability predicts cardiovascular events and mortality in hypertension, we analyzed 7112 untreated hypertensive participants (3996 men) aged 52±15 years enrolled in 6 prospective studies. Median follow-up was 5.5 years. SD of night-time BP was positively associated with age, body mass index, smoking, diabetes mellitus, and average night-time BP (all P<0.001). In a multivariable Cox model, night-time BP variability was an independent predictor of all-cause mortality (systolic, P<0.001/diastolic, P<0.0001), cardiovascular mortality (P=0.008/<0.0001), and cardiovascular events (P<0.001/<0.0001). In contrast, daytime BP variability was not an independent predictor of outcomes in any model. In fully adjusted models, a night-time systolic BP SD of ≥12.2 mm Hg was associated with a 41% greater risk of cardiovascular events, a 55% greater risk of cardiovascular death, and a 59% increased risk of all-cause mortality compared with an SD of <12.2 mm Hg. The corresponding values for a diastolic BP SD of ≥7.9 mm Hg were 48%, 132%, and 77%. The addition of night-time BP variability to fully adjusted models had a significant impact on risk reclassification and integrated discrimination for all outcomes (relative integrated discrimination improvement for systolic BP variability: 9% cardiovascular events, 14.5% all-cause death, 8.5% cardiovascular death, and for diastolic BP variability: 10% cardiovascular events, 19.1% all-cause death, 23% cardiovascular death, all P<0.01). Thus, addition of BP variability to models of long-term outcomes improved the ability to stratify appropriately patients with hypertension among risk categories defined by standard clinical and laboratory variables., (© 2014 American Heart Association, Inc.)

Background: The independent prognostic value of blood pressure (BP) variability in treated hypertension is not yet clear. We investigated the relationship between BP variability, evaluated by noninvasive monitoring, and cardiovascular outcome in treated hypertensive patients., Methods: The occurrence of fatal and nonfatal cardiovascular events was evaluated in 1472 treated patients. Subjects with the standard deviation of daytime or night-time systolic BP below or above the median of the population were classified as having low or high BP variability. Specifically, 738 and 734 patients had low and high daytime BP variability, respectively, and 739 and 733 subjects had low and high night-time BP variability, respectively., Results: During follow-up (4.88 +/- 2.9 years, range 0.2-11.6 years) there were 119 events. The event rates per 100 patient-years in subjects with low and high BP variability according to daytime BP were 1.18 and 2.01, respectively, and in those with low and high BP variability according to night-time BP were 1.2 and 2.05, respectively. Event-free survival was significantly different between the low and high BP variability groups (P = .006 for both daytime and night-time BP). However, after adjustment for other covariates in a Cox multivariate analysis, the adverse prognostic relevance of high BP variability was no longer detectable, whereas age, smoking habit, LDL cholesterol, diabetes, previous events, LV hypertrophy, and daytime or night-time systolic BP resulted independent predictors of risk., Conclusions: Increased BP variability is associated with higher incidence of cardiovascular events, but also with other relevant prognostic factors. Indeed, in multivariate analysis the possible adverse prognostic impact of BP variability is no longer evident. Thus, in treated hypertension, BP variability evaluated by noninvasive monitoring is not an independent predictor of outcome.

Background: The aim of this study was to evaluate the cardiovascular outcome in apparently responder hypertensive patients with responder and masked hypertension, and in apparently resistant hypertensive patients with false and true resistant hypertension., Methods: The occurrence of fatal and nonfatal cardiovascular events was evaluated in 340 patients with responder hypertension (clinic blood pressure [BP] <140/90 mm Hg and daytime BP <135/85 mm Hg), 126 with masked hypertension (clinic BP <140/90 mm Hg and daytime BP >135 or 85 mm Hg), 146 with false resistant hypertension (clinic BP >or=140 or 90 mm Hg and daytime BP <135/85 mm Hg), and 130 with true resistant hypertension (clinic BP >or=140 or 90 mm Hg and daytime BP >135 or 85 mm Hg)., Results: During follow-up period (4.98 +/- 2.9 years), the event-rate per 100 patient-years was 0.87, 2.42, 1.2, and 4.1 in patients with responder, masked, false resistant, and true resistant hypertension, respectively. After adjustment for several covariates, including clinic BP (forced into the model), Cox regression analysis showed that cardiovascular risk was significantly higher in masked hypertension (masked versus responder hypertension, relative risk [RR] 2.28, 95% confidence interval [CI] 1.1-4.7, P < .05) and in true resistant hypertension (true resistant versus responder hypertension, RR 2.94, 95% CI 1.02-8.41, P < .05), whereas there was no significant difference between false resistant and responder hypertension., Conclusions: This study shows that patients with masked hypertension are at higher risk than those with responder hypertension, and that those with false resistant hypertension are at lower risk than those with true resistant hypertension. Ambulatory BP monitoring should be performed in treated hypertensive patients to obtain a better prognostic stratification.

Background: The prognostic value of white coat hypertension (WCH) in uncomplicated patients with mild hypertension is not yet completely clear. We investigated cardiovascular outcomes in patients with mild hypertension and without left ventricular hypertrophy, diabetes mellitus, and associated cardiovascular and renal disease, with sustained hypertension (SH) and WCH., Methods: The occurrence of fatal and nonfatal cardiovascular events was evaluated in 1038 patients with mild hypertension and 241 normotensive subjects. The presence of WCH was defined as clinic hypertension and daytime blood pressure <135/85 mm Hg., Results: During follow-up (4.5 +/- 2.3 years, range 0.5 to 9.2 years) the event rates per 100 patient-years in subjects with normotension, WCH, and SH were 0.27, 0.38, and 1.39, respectively. After adjustment for other covariates, Cox regression analysis showed that SH was an independent predictor of cardiovascular events (SH versus WCH, RR 5.17, 95% CI 2.04 to 13.1, P = 0 .001), whereas there was no significant difference between normotension and WCH (normotension versus WCH, RR 0.93, 95% CI 0.22 to 3.98, P = .92). At the end of follow-up, drug therapy was less frequent and intensive in WCH than in SH., Conclusions: In this study of individuals with mild hypertension and without left ventricular hypertrophy, diabetes mellitus, and associated cardiovascular and renal disease, subjects with WCH, despite less frequent and intensive drug therapy, had a significantly better prognosis than those with sustained hypertension.

BACKGROUND Masked uncontrolled hypertension (MUCH), that is, nonhypertensive clinic but high out-of-office blood pressure (BP) in treated patients is at increased cardiovascular risk than controlled hypertension (CH), that is, nonhypertensive clinic and out-of-office BP. Using ambulatory BP, MUCH can be defined as daytime and/or nighttime and/or 24-hour BP above thresholds. It is unclear whether different definitions of MUCH have similar prognostic information. This study assessed the prognostic value of MUCH defined by different ambulatory BP criteria. METHODS Cardiovascular events were evaluated in 738 treated hypertensive patients with nonhypertensive clinic BP. Among them, participants were classified as having CH or daytime MUCH (BP ≥135/85 mm Hg) regardless of nighttime BP (group 1), nighttime MUCH (BP ≥120/70 mm Hg) regardless of daytime BP (group 2), 24-hour MUCH (BP ≥130/80 mm Hg) regardless of daytime or nighttime BP (group 3), daytime MUCH only (group 4), nighttime MUCH only (group 5), and daytime + nighttime MUCH (group 6). RESULTS We detected 215 (29%), 357 (48.5%), 275 (37%), 42 (5.5%),184 (25%) and 173 (23.5%) patients with MUCH from group 1 to 6, respectively. During the follow-up (10 ± 5 years), 148 events occurred in patients with CH and MUCH. After adjustment for covariates, compared with patients with CH, the adjusted hazard ratio (95% confidence interval) for cardiovascular events was 2.01 (1.45–2.79), 1.53 (1.09–2.15), 1.69 (1.22–2.34), 1.52 (0.80–2.91), 1.15 (0.74–1.80), and 2.29 (1.53–3.42) from group 1 to 6, respectively. CONCLUSIONS The prognostic impact of MUCH defined according to various ambulatory BP definitions may be different. [ABSTRACT FROM AUTHOR]

BACKGROUND Prognosis of masked and white coat uncontrolled hypertension (MUCH and WCUCH, respectively) detected by ambulatory blood pressure (BP) monitoring is incompletely clear in elderly treated hypertensive patients. We evaluated prognosis of MUCH and WCUCH identified by ambulatory BP monitoring in this setting. METHODS The occurrence of a composite endpoint was evaluated in 1,191 elderly treated hypertensive patients. Controlled hypertension (CH) was defined as clinic BP <140/90 mm Hg and 24-hour BP <130/80 mm Hg, MUCH as clinic BP <140/90 mm Hg and 24-hour BP ≥130 and/or ≥80 mm Hg, WCUCH as clinic BP ≥140 and/or ≥90 mm Hg and 24-hour BP <130/80 mm Hg and sustained uncontrolled hypertension (SUCH) as clinic BP ≥140 and/or ≥90 mm Hg and 24-hour BP ≥130 and/or ≥80 mm Hg. RESULTS MUCH was identified in 142 patients (12% of all the population, 34% of those with normal clinic BP) and WCUCH in 230 patients (19% of all the population, 30% of those with high clinic BP). During the follow-up (9.1 ± 4.9 years, range 0.4-20 years), 392 events occurred. After adjustment for various covariates, patients with MUCH (hazard ratio (HR) 1.60, 95% confidence interval (CI) 1.12-2.29, P = 0.01) and SUCH (HR 1.81, 95% CI, 1.35-2.42, P < 0.001) had significantly higher cardiovascular risk than those with CH, whereas those with WCUCH (HR 1.09, 95% CI, 0.74-1.60, P = 0.66) had not significantly higher risk. CONCLUSIONS In elderly treated hypertensive patients evaluated by ambulatory BP monitoring, compared to individuals with CH, those with MUCH have significantly higher risk and those with WCUCH have slightly and not significantly higher risk. [ABSTRACT FROM AUTHOR]

BACKGROUND The prognostic impact of masked hypertension is not yet completely clear. The aim of this study was to evaluate the prognostic relevance of masked hypertension in subjects with prehypertension. METHODS The occurrence of fatal and nonfatal cardiovascular events was evaluated in 591 subjects with prehypertension defined as clinic blood pressure (BP) in the range of 120-139 mm Hg for systolic BP and 80-89 mm Hg for diastolic BP. Among them, 471 were classified as having true prehypertension (clinic BP <140/90 mm Hg and daytime BP <135/85 mm Hg) and 120 as having masked hypertension (clinic BP <140/90 mm Hg and daytime BP ≥135 or 85 mm Hg). RESULTS During the follow-up (6.6 ± 4.3 years, range 0.5-15.5 years), 29 cardiovascular events occurred. In subjects with true prehypertension and masked hypertension the event-rates per 100 patient-years were 0.57 and 1.51, respectively. Event-free survival was significantly different between the groups (P < 0.005). After adjustment for other covariates, including clinic BP (forced into the model), Cox regression analysis showed that cardiovascular risk was significantly higher in masked hypertension than in true prehypertension (masked vs. true prehypertension, relative risk 2.65, 95% confidence interval 1.18-5.98, P = 0.018). CONCLUSIONS Among subjects with prehypertension, those with masked hypertension are at higher cardiovascular risk than those with true prehypertension. Out-of-office BP should be known in individuals with prehypertension, preferably by ambulatory BP monitoring or alternatively by home BP measurement, to obtain a better prognostic stratification. [ABSTRACT FROM AUTHOR]

BACKGROUND There is still ambiguity about the prognostic relevance of regression of left ventricular hypertrophy (LVH) (as revealed by echocardiography) in a large population of subjects with hypertension, with and without evidence of LVH in their electrocardiograms (ECGs). This holds true even after adjusting for various confounders including in treatment ambulatory blood pressure (BP). The most suitable time point for a follow-up echocardiography also remains a matter for debate. In this study, we investigated the prognostic relevance of regression of LVH after 2 years of therapy, in a large population of subjects with hypertension, and possessing the aforesaid characteristics. METHODS The occurrence of adverse cardiovascular events was evaluated in 387 patients with LVH shown by echocardiography at baseline, and these patients were studied again after 2 years of therapy. At the second examination, 245 subjects showed regression of LVH, whereas 142 did not. RESULTS During the time period before the subsequent follow up (6.2 ± 3 years, range 1.9-12.9 years), 59 first adverse events (26 cardiac and 33 cerebrovascular) had occurred among these subjects. The event rates per 100 patient-years in patients with and without LVH regression were 1.06 and 4.4, respectively. After adjusting for several covariates at the 2-year visit, including in treatment ambulatory BP, Cox regression analysis showed that cardiovascular risk was significantly lower in patients with LVH regression than in those without (RR 0.36, 95% CI 0.19-0.68, P = 0.002). When left ventricular (LV) mass index reduction was analyzed instead of LVH status, it was found to be significantly associated with reduced risk (RR 0.62 per 1-s.d. decrease, 95% CI 0.44-0.88, P = 0.01). CONCLUSIONS Regression of LVH, as revealed by echocardiography after 2 years of therapy, is associated with reduced cardiovascular risk in patients with hypertension, whether or not LVH was revealed in their ECGs. This holds true even after adjusting for various confounders including in treatment ambulatory BP. [ABSTRACT FROM AUTHOR]

The article presents a commentary on the study of S. L. Shuger on body mass index and risk of future hypertension in women. It is noted that the risk of future hypertension has been associated with the continuous increase of body fat and fat mass. The author implies that abdominal obesity has been considered as more powerful predictor of disease in cardiovascular system.