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Mesenchymal stem cells (MSCs) treatment has been widely explored as a therapy for myocardial infarction, peripheral ischemic vascular diseases, dilated cardiomyopathy, and pulmonary hypertension. Latest in vitro studies suggest that MSCs can differentiate into contractile cardiomyocytes. One of the best‐characterized MSCs products are MSCs‐derived extracellular vesicles (EVs). EVs are crucial paracrine effectors of MSCs. Based on previous works, paracrine effects of MSCs play a primary role in the regenerative ability. Hence, in the current paper, we focused our attention on an alternative approach, exploiting products derived from human dental pulp stem cells (hDPSCs) rather than MSCs themselves, which may denote a cost‐effective and safer approach. The focus has been on EVs and the bioactive molecules they contain to evaluate their ability to influence the differentiation process toward cardiomyogenic lineage. The expression of GATA4, ACTC1, CX43, and Nkx2.5 was evaluated using Immunofluorescence, real time‐PCR, and Western blotting analyses. Furthermore, the expression profiling analysis of the microRNA hsa‐miR‐200c‐3p, targeting the GATA4 gene, was studied. The hsa‐miR‐200c‐3p was found significantly down‐regulated in both c‐hDPSCs + EVs‐hDPSCs and c‐hDPSCs + EVs‐HL‐1 compared to untreated c‐hDPSCs underlying a possible epigenetic mechanism behind the prevalent up‐regulation of its targeted GATA4 gene. The aim of the present work was to develop an in vitro model of hDPSCs able to differentiate into cardiomyocytes in order to investigate the role of EVs derived from hDPSCs and derived from HL‐1 cardiomyocyte cell line in modulating the differentiation process toward cardiomyogenic lineage. [ABSTRACT FROM AUTHOR]

Hypoxia signaling plays an important role in physiological and pathological conditions. Hypoxia in the heart tissue can produce different consequences depending on the duration of exposure to the hypoxic state. While acute hypoxic exposure leads to a reversible acclimatization in heart tissue with normal systemic oxygen supply, chronic hypoxia exacerbates cardiac dysfunction, leads to a destruction of the tissue. Extracellular vesicles (EVs) are small membrane vesicles that act as mediators of intercellular communication. EVs are secreted by different cell types and those produced by oral cavity-derived mesenchymal stem cells (MSCs), including human gingival MSCs (hGMSCs), have pro-angiogenic and anti-inflammatory effects and showed therapeutic role in tissue regeneration. The aim of the present work was to evaluate the potential protective and regenerative role of EVs produced by hGMSCs, in an in vitro model of hypoxia-conditioned HL-1 cardiomyocytes through the expression analysis of following inflammatory, oxidative stress, angiogenesis, cell survival and apoptotic markers: HIF-1α, P300, NFkB, CCL2, IL1B, IL6, NRF2, CASP-3, BAX and VEGF. Results showed that hGMSCs-derived EVs exerted protection HL-1 cardiomyocytes exposed to both pre and post hypoxic conditions. Moreover, modulation of CASP3 and BAX expression demonstrated that EVs reduced the apoptosis. The analysis of microRNAs in EVs derived from hGMSCs was performed to assess the epigenetic regulation of the presented markers. The following microRNAs: hsa-miR-138-5p, hsa-miR-17-5p, hsa-miR-18a-5p, hsa-miR-21-5p, hsa-miR-324-5p, hsa-miR-133a-3p, hsamiR-150-5p, hsa-miR-199a-5p, hsa-miR-128-3p and hsa-miR-221-3p can directly or indirectly target the studied genes by determining their modulation obtained in our study. The data from this study suggested that EVs obtained from hGMSCs may be considered for the cell free treatment option in hypoxia-driven cardiac tissue dysfunction. [ABSTRACT FROM AUTHOR]

(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. [ABSTRACT FROM AUTHOR]

(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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The aim of this mini-review is to report current knowledge about the association between ambulatory blood pressure and risk of heart failure in hypertension. We conducted a literature search through PubMed, Web of science and Cochrane Library by using terms such as ambulatory blood pressure, 24-hour blood pressure, daytime blood pressure, nighttime blood pressure, hypertension, heart failure. We identified 4 studies including 7891 patients who developed 260 cases of heart failure during the follow-up. The evaluation of published studies indicates that ambulatory blood pressure is superior to clinic blood pressure in predicting the occurrence of heart failure. Particularly, it has been reported that 24-hour blood pressure values, nighttime nondipping blood pressure pattern and ambulatory resistant hypertension are associated with increased risk of heart failure above clinic blood pressure. Nevertheless, there are still few data in the literature on this topic. Therefore, further studies are needed to broaden our knowledge on this matter to improve our therapeutic approach to prevent HF in hypertensive patients. [ABSTRACT FROM AUTHOR]

The aim of this mini-review is to report current knowledge about left ventricular systolic function assessed by global longitudinal strain in hypertensive patients with and without left ventricular hypertrophy, that is, stage A and B heart failure. We conducted a literature search through PubMed, Web of science and Cochrane Library by using terms such as myocardial strain, speckle tracking echocardiography, systolic dysfunction, left ventricular hypertrophy, left ventricular geometry, essential hypertension. We identified 2 meta-analyses including 30 studies, 1 review including 8 studies and 5 other studies. The evaluation of published studies suggests that global longitudinal strain is significantly reduced in hypertensive patients than in normotensive subjects, despite normal ejection fraction. This alteration may be present in both patients with and without left ventricular hypertrophy, though it is more relevant in those with left ventricular hypertrophy. Global longitudinal strain is a more sensitive marker for early abnormalities of left ventricular function and can be of greater help than conventional methods in predicting hypertensive disease progression and outcomes. However, the prevalence of left ventricular longitudinal dysfunction in hypertension, its predicting factors and its clinical relevance are not yet completely clear. Thus, other studies are needed to shed further light on this topic. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Atrial cardiopathy, encompassing chamber enlargement, wall structural changes, electrical remodeling, functional impairment, and prothrombotic predisposition,[[1], [3]] may be detected in individuals in the general population, including those with normotension and hypertension. The individuals with concomitant atrial cardiopathy and elevated, stage 1 or 2 hypertension also had higher cardiovascular mortality rates (22.3, 25.7, and 33.9 per 1,000 person-years, respectively) compared with their counterparts in the same hypertension categories without atrial cardiopathy (7.8, 8.1, and 17.8 per 1,000 person-years, respectively). All-cause death rates were almost double among subjects with concomitant atrial cardiopathy and elevated blood pressure (120-129/<80), stage 1 (130-139/80-89) or stage 2 hypertension (>=140/>=90) compared with their counterparts in the same hypertension stages without atrial cardiopathy (47.8, 61.3, and 80.2 vs. 23, 24.7, and 44.8 per 1,000 person-years, respectively). [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

After oral mucosal injury, the healing response following specific steps that lead to wound closure and to tissue repair. Multiple cell populations are involved in this process; in particular, fibroblasts play a key role in the production of extracellular matrix (ECM). During wound healing the remodeling of ECM is a key stage to restore the tissue functionality through multifunctional fibroblast populations that are placed in the connective tissues of gingiva and periodontal ligament. Notably, a fibroblast sub-type (myofibroblast) is centrally involved in collagen synthesis and fibrillar remodeling. The present work evidenced the role of Transforming Growth Factor-beta1 (TGF-β1) to mediate human gingival fibroblasts (hGFs) differentiation into myofibroblasts derived from gingival fibroblasts (myo-hGFs). The morphological and functional features were analyzed through Confocal Laser Scanning Microscopy (CLSM), flow cytometry, and western blotting analyses. The specific markers, such as alpha-Smooth Muscle Actin (α-SMA), Vimentin, E-cadherin, β-catenin, and Smad 2/3, were modulated in myo-hGFs after the induction with TGF-β1, at different time points (24, 48, and 72 h). After 72 h of treatment TGF-β1 operates as an inducer of hGFs into myo-hGFs differentiation. We propose that TGF-β1 may promote in vitro the fibroblasts-to-myofibroblasts transition via the morphological and molecular modifications, as the induction of α-SMA, Vimentin, E-cadherin, β-catenin, and Smad 2/3. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]