Risk of heart failure in ambulatory resistant hypertension: a meta-analysis of observational studies.

The impact of ambulatory resistant hypertension (ARH) on the occurrence of heart failure (HF) is not yet completely known. We performed for the first time a meta-analysis, by using published data or available data from published databases, on the risk of HF in ARH. Patients with ARH (24-h BP ≥ 130/80 mmHg during treatment with ≥3 drugs) were compared with those with controlled hypertension (CH, clinic BP < 140/90 mmHg and 24-h BP < 130/80 mmHg regardless of the number of drugs used), white coat uncontrolled resistant hypertension (WCURH, clinic BP ≥ 140/90 mmHg and 24-h BP < 130/80 mmHg in treated patients) and ambulatory nonresistant hypertension (ANRH, 24-h BP ≥ 130/80 mmHg during therapy with ≤2 drugs). We identified six studies/databases including 21,365 patients who experienced 692 HF events. When ARH was compared with CH, WCURH, or ANRH, the overall adjusted hazard ratio for HF was 2.32 (95% confidence interval (CI) 1.45-3.72), 1.72 (95% CI 1.36-2.17), and 2.11 (95% CI 1.40-3.17), respectively, (all P < 0.001). For some comparisons a moderate heterogeneity was found. Though we did not find variables that could explain the heterogeneity, sensitivity analyses demonstrated that none of the studies had a significant influential effect on the overall estimate. When we evaluated the potential presence of publication bias and small-study effect and adjusted for missing studies identified by Duval and Tweedie's method the estimates were slightly lower but remained significant. This meta-analysis shows that treated hypertensive patients with ARH are at approximately twice the risk of developing HF than other ambulatory BP phenotypes.

Ambulatory Resistant Hypertension and Risk of Heart Failure in the Elderly.

(1) Background: The aim of the study was to assess the risk of heart failure (HF) in elderly treated hypertensive patients with white coat uncontrolled hypertension (WUCH), ambulatory nonresistant hypertension (ANRH) and ambulatory resistant hypertension (ARH), when compared to those with controlled hypertension (CH). (2) We studied 745 treated hypertensive subjects older than 65 years. CH was defined as clinic blood pressure (BP) < 140/90 mmHg and 24-h BP < 130/80 mmHg; WUCH was defined as clinic BP ≥ 140/90 mmHg and 24-h BP < 130/80 mmHg; ANRH was defined as 24-h BP ≥ 130/80 mmHg in patients receiving ≤2 antihypertensive drugs; ARH was defined as 24-h BP ≥ 130/80 mmHg in patients receiving ≥3 antihypertensive drugs. (3) Results: 153 patients had CH, 153 had WUCH, 307 had ANRH and 132 (18%) had ARH. During the follow-up (8.4 ± 4.8 years), 82 HF events occurred. After adjustment for various covariates, when compared to CH, the hazard ratio (95% confidence interval) for HF was 1.30 (0.51-3.32), 2.14 (1.03-4.43) and 3.52 (1.56-7.96) in WUCH, ANRH and ARH, respectively. (4) Conclusions: among elderly treated hypertensive patients, those with ARH are at a considerably higher risk of developing HF when compared to CH.

Prognostic Impact of 24-Hour Pulse Pressure Components in Treated Hypertensive Patients Older Than 65 Years.

(1) Background: The aim of this study was to assess the prognostic impact of 24-hour pulse pressure (PP), elastic PP (elPP) and stiffening PP (stPP) in elderly treated hypertensive patients; (2) Methods: In this retrospective study, we evaluated 745 treated hypertensive subjects older than 65 years who underwent ambulatory blood pressure monitoring to assess 24-hour PP and 24-hour elPP and stPP, as calculated by a mathematical model. The association of these PP components with a combined endpoint of cardiovascular events was investigated; (3) Results: The 24-hour PP, elPP and stPP were 59 ± 12.5, 47.5 ± 9.5 and 11.5 ± 6.5 mmHg, respectively. During the follow-up (mean 8.4 years), 284 events occurred, including coronary events, stroke, heart failure hospitalization and peripheral revascularization. In the univariate Cox regression analysis, 24-hour PP, elPP and stPP were associated with the combined outcome. After the adjustment for covariates, per one standard deviation increase, 24-hour PP had a borderline association with risk (hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.00-1.34), 24-hour elPP remained associated with cardiovascular events (HR 1.20, 95% CI 1.05-1.36) and 24-hour stPP lost its significance. (4) Conclusions: 24-hour elPP is a predictor of cardiovascular events in elderly treated hypertensive patients.

Prediction of Masked Uncontrolled Hypertension Detected by Ambulatory Blood Pressure Monitoring.

The aim of this study was to provide prediction models for masked uncontrolled hypertension (MUCH) detected by ambulatory blood pressure (BP) monitoring in an Italian population. We studied 738 treated hypertensive patients with normal clinic BPs classified as having controlled hypertension (CH) or MUCH if their daytime BP was < or ≥135/85 mmHg regardless of nighttime BP, respectively, or CH or MUCH if their 24-h BP was < or ≥130/80 mmHg regardless of daytime or nighttime BP, respectively. We detected 215 (29%) and 275 (37%) patients with MUCH using daytime and 24-h BP thresholds, respectively. Multivariate logistic regression analysis showed that males, those with a smoking habit, left ventricular hypertrophy (LVH), and a clinic systolic BP between 130−139 mmHg and/or clinic diastolic BP between 85−89 mmHg were associated with MUCH. The area under the receiver operating characteristic curve showed good accuracy at 0.78 (95% CI 0.75−0.81, p < 0.0001) and 0.77 (95% CI 0.73−0.80, p < 0.0001) for MUCH defined by daytime and 24 h BP, respectively. Internal validation suggested a good predictive performance of the models. Males, those with a smoking habit, LVH, and high-normal clinic BP are indicators of MUCH and models including these factors provide good diagnostic accuracy in identifying this ambulatory BP phenotype.

Prognostic value of non-resistant and resistant masked uncontrolled hypertension detected by ambulatory blood pressure monitoring.

Masked uncontrolled hypertension (MUCH) is at higher cardiovascular risk than controlled hypertension (CH). In previous studies, patients with MUCH were considered as a unique group though those receiving ≤2 drugs could be defined as having nonresistant MUCH (NRMUCH) and those receiving ≥3 drugs as having resistant MUCH (RMUCH). The aim of this study was to assess the prognostic value of NRMUCH and RMUCH detected by ambulatory blood pressure (BP) monitoring. Cardiovascular risk was evaluated in 738 treated hypertensive patients with normal clinic BP. Patients were classified as having CH or MUCH if daytime BP < or ≥ 135/85 mmHg, respectively, regardless of nighttime BP, or CH or MUCH if 24-h BP < or ≥ 130/80 mmHg, respectively, regardless of daytime or nighttime BP. By daytime or 24-h BP, the authors detected 523 (71%), 178 (24%), and 37 (5%) or 463 (63%), 231 (31%), and 44 (6%) patients with CH, NRMUCH, and RMUCH, respectively. During the follow-up (median 10 years), 148 events occurred. After adjustment for covariates, compared to CH, the hazard ratio (HR), 95% confidence interval (CI), for cardiovascular events was 1.81, 1.27-2.57, and 2.99, 1.73-5.16, in NRMUCH and RMUCH defined by daytime BP, respectively, and 1.58, 1.12-2.23, and 2.21, 1.27-3.82, in NRMUCH and RMUCH defined by 24-h BP, respectively. If RMUCH was compared with NRMUCH, the risk tended to be higher in RMUCH but did not attain statistical significance (P = .08 and P = .23 by daytime and 24-h BP thresholds, respectively). In conclusion, both NRMUCH and RMUCH are at increased cardiovascular risk than CH.

Association of clinic and ambulatory blood pressure with new-onset atrial fibrillation: A meta-analysis of observational studies.

The aim of this study was to perform a meta-analysis of studies evaluating the association of clinic and daytime, nighttime, and 24-h blood pressure with the occurrence of new-onset atrial fibrillation. We conducted a literature search through PubMed, Web of science, and Cochrane Library for articles evaluating the occurrence of new-onset atrial fibrillation in relation to the above-mentioned blood pressure parameters and reporting adjusted hazard ratio and 95% confidence interval. We identified five studies. The pooled population consisted of 7224 patients who experienced 444 cases of atrial fibrillation. The overall adjusted hazard ratio (95% confidence interval) was 1.05 (0.98-1.13), 1.19 (1.11-1.27), 1.18 (1.11-1.26), and 1.23 (1.14-1.32), per 10-mmHg increment in clinic, daytime, nighttime, and 24-h systolic blood pressure, respectively. The degree of heterogeneity of the hazard ratio estimates across the studies (Q and I-squared statistics) were minimal. The results of this meta-analysis strongly suggest that ambulatory systolic blood pressure prospectively predicts incident atrial fibrillation better than does clinic systolic blood pressure and that daytime, nighttime, and 24-h systolic blood pressure are similarly associated with future atrial fibrillation.

Ambulatory blood pressure and risk of new-onset atrial fibrillation in treated hypertensive patients.

The aim of this study was to evaluate the influence of clinic and ambulatory blood pressure (BP) on the occurrence of new-onset atrial fibrillation (AF) in treated hypertensive patients. We studied 2135 sequential treated hypertensive patients aged >40 years. During the follow-up (mean 9.7 years, range 0.4-20 years), 116 events (new-onset AF) occurred. In univariate analysis, clinic, daytime, nighttime, and 24-h systolic BP were all significantly associated with increased risk of new-onset AF, that is, hazard ratio (95% confidence interval) per 10 mm Hg increment 1.22 (1.11-1.35), 1.36 (1.21-1.53), 1.42 (1.29-1.57), and 1.42 (1.26-1.60), respectively. After adjustment for various covariates in multivariate analysis, clinic systolic BP was no longer associated with increased risk of new-onset AF, whereas daytime, nighttime, and 24-h systolic BP remained significantly associated with outcome, that is, hazard ratio (95% confidence interval) per 10 mm Hg increment 1.09 (0.97-1.23), 1.23 (1.10-1.39), 1.16 (1.03-1.31), and 1.22 (1.06-1.40), respectively. Daytime, nighttime, and 24-h systolic BP are superior to clinic systolic BP in predicting new-onset AF in treated hypertensive patients. Future studies are needed to evaluate whether a better control of ambulatory BP might be helpful in reducing the occurrence of new-onset AF.

Risk of Atrial Fibrillation in Masked and White Coat Uncontrolled Hypertension.

BACKGROUND: Risk of atrial fibrillation (AF) in masked and white coat uncontrolled hypertension (MUCH and WUCH, respectively) has not yet been investigated. We assessed the risk of new-onset AF in MUCH and WUCH detected by ambulatory blood pressure (BP) monitoring. METHODS: The occurrence of AF was evaluated in 2,135 treated hypertensive patients aged >40 years, with baseline sinus rhythm, by electrocardiogram. Controlled hypertension (CH) was defined as clinic BP <140/90 mm Hg and daytime BP, regardless of nighttime BP, <135/85 mm Hg, MUCH as clinic BP <140/90 mm Hg and daytime BP ≥135 and/or ≥85 mm Hg, WUCH as clinic BP ≥140 and/or ≥90 mm Hg and daytime BP <135/85 mm Hg, and sustained uncontrolled hypertension (SUCH) as clinic BP ≥140 and/or ≥90 mm Hg and daytime BP ≥135 and/or ≥85 mm Hg. RESULTS: MUCH was identified in 203 patients (9.5% of all the population, 29% of those with normal clinic BP) and WUCH in 503 patients (23.5% of all the population, 35% of those with high clinic BP). During the follow-up (mean 9.7 years), 116 cases of AF occurred. After adjustment for covariates, patients with MUCH (hazard ratio 2.02, 95% confidence interval, 1.06-3.85) and SUCH (hazard ratio 1.83, 95% confidence interval, 1.04-3.21) had higher risk of new-onset AF than those with CH, whereas those with WUCH (hazard ratio 1.12, 95% confidence interval, 0.59-2.13) did not. CONCLUSIONS: When compared with patients with CH, those with MUCH and SUCH are at higher risk (approximately doubled) of new-onset AF, whereas those with WUCH are not.

Prognostic Value of Masked Uncontrolled Hypertension Defined by Different Ambulatory Blood Pressure Criteria.

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.

Prognostic value of daytime and nighttime blood pressure in treated hypertensive patients according to age and sex.

The authors assessed the prognostic value of daytime and nighttime blood pressure (BP) in adult (≤65 years) or old (> 65 years) women or men with treated hypertension. Cardiovascular outcomes were evaluated in 2264 patients. During the follow-up (mean 10 years), 523 cardiovascular events occurred. After adjustment for covariates, both daytime and nighttime systolic BP were always associated with outcomes, that is, hazard ratio (95% confidence interval per 10 mm Hg increment) 1.22 (1.04-1.43) and 1.20 (1.04-1.37), respectively, in adult women, 1.30 (1.18-1.43) and 1.21 (1.10-1.33), respectively, in adult men, 1.21 (1.10-1.33) and 1.18 (1.07-1.31), respectively, in old women, and 1.16 (1.01-1.33) and 1.28 (1.14-1.44), respectively, in old men. When daytime and nighttime systolic BP were further and mutually adjusted, daytime and nighttime BP had comparable prognostic value in adult and old women, daytime BP remained associated with outcomes in adult men (hazard ratio 1.40, 95% confidence interval 1.13-1.74 per 10 mm Hg increment), and nighttime BP remained associated with outcomes in old men (hazard ratio 1.35, 95% confidence interval 1.11-1.64 per 10 mm Hg increment). Daytime and nighttime systolic BP have similar prognostic impact in adult and old women with treated hypertension, whereas daytime BP is a stronger predictor of risk in adult men and nighttime BP is a stronger predictor of risk in old men.

Prognostic value of morning surge of blood pressure in middle-aged treated hypertensive patients.

We investigated the prognostic value of morning surge (MS) of blood pressure (BP) in middle-aged treated hypertensive patients. The occurrence of a composite end point (coronary events, stroke, and heart failure requiring hospitalization) was evaluated in 1073 middle-aged treated hypertensive patients (mean age 49 years). Patients with preawakening MS of BP above the 90th percentile (27/20.5 mm Hg for systolic/diastolic BP) were defined as having high MS of BP. During the follow-up (mean 10.9 years), 131 cardiovascular events occurred. After adjustment for various covariates, including known risk markers and ambulatory BP parameters, patients with high MS of systolic BP (hazard ratio 1.81, 95% confidence interval 1.10-2.96) and those with high MS of diastolic BP (hazard ratio 1.98, 95% confidence interval 1.19-3.28) were at higher cardiovascular risk than those with normal MS. In middle-aged treated hypertensive patients, high MS of systolic and diastolic BP is independently associated with increased cardiovascular risk.

Prognostic value of average real variability of systolic blood pressure in elderly treated hypertensive patients.

OBJECTIVE: The independent prognostic significance of ambulatory blood pressure variability in the elderly is incompletely clear. We investigated the prognostic value of average real variability of 24-hour blood pressure in elderly treated hypertensive patients. METHODS: The occurrence of a combined end-point including stroke, coronary events, heart failure requiring hospitalization and peripheral revascularization was evaluated in 757 elderly treated hypertensive patients. According to tertiles of average real variability of 24-hour systolic blood pressure patients were classified as having low (≤8.66 mmHg; n = 252), medium (8.67-10.05 mmHg; n = 252) or high (>10.05 mmHg; n = 253) average real variability. RESULTS: During the follow-up (6.9 ± 3.4 years, range 0.4-12.9 years), 195 events occurred. The event rate of the population was 3.74 per 100 patient-years. After adjustment for age, sex, previous events, diabetes, estimated glomerular filtration rate, left ventricular hypertrophy, left atrial enlargement, asymptomatic left ventricular systolic dysfunction at baseline, 24-hour systolic blood pressure, non-dipping and dipping with high morning surge of blood pressure, patients with high average real variability were at higher cardiovascular risk than those with low average real variability (hazard ratio 1.64, 95% confidence interval 1.12-2.40). CONCLUSIONS: In elderly treated hypertensive patients, high average real variability of 24-hour systolic blood pressure is associated with higher cardiovascular risk independently of other risk markers, average 24-hour systolic blood pressure and circadian blood pressure changes.

Prognostic Value of Masked Uncontrolled Hypertension.

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.

Prognosis of Masked and White Coat Uncontrolled Hypertension Detected by Ambulatory Blood Pressure Monitoring in Elderly Treated Hypertensive Patients.

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.

Prognostic Value of Nondipping and Morning Surge in Elderly Treated Hypertensive Patients With Controlled Ambulatory Blood Pressure.

BACKGROUND: The independent prognostic significance of nondipping and morning surge (MS) of blood pressure (BP) in treated hypertensive patients with controlled ambulatory BP is not yet clear. We investigated the association between the aforesaid ambulatory BP parameters and cardiovascular risk in elderly treated hypertensive patients with normal achieved ambulatory BP. METHODS: The occurrence of a composite end-point (stroke, coronary events, heart failure, and peripheral revascularization) was evaluated in 391 elderly treated hypertensive patients (age range 60-90 years) with controlled ambulatory BP (both daytime BP <135/85 mm Hg and nighttime BP <120/70 mm Hg). According to nighttime change and MS of systolic BP, subjects were divided in dippers with normal or high MS (>23 mm Hg) and nondippers. RESULTS: During the follow-up (9.3 ± 4.6 years, range 0.5-20 years), 76 events occurred. The event-rate was 2.09 per 100 patient-years. After adjustment for age, gender, left ventricular (LV) hypertrophy, asymptomatic LV systolic dysfunction at baseline and left atrial enlargement, dippers with high MS (hazard ratio 2.45, 95% confidence interval 1.27-4.73, P = 0.007) and nondippers (hazard ratio 2.04, 95% confidence interval 1.18-3.53, P = 0.01) were at higher cardiovascular risk than dippers with normal MS. CONCLUSIONS: In elderly treated hypertensive patients with normal achieved ambulatory BP, dippers with high MS and nondippers are at increased cardiovascular risk.