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Background: Emerging evidence suggests that a hypertensive response to exercise (HRE) during dynamic or isometric stress tests assessing cardiac function is predictive of hypertension and cardiovascular events such coronary artery disease, heart failure and stroke. Whether HRE represents a marker of masked hypertension (MH) in individuals with no prior history of hypertension is still unclear. This is also the case for the association between MH and hypertension-mediated organ damage (HMOD) in the HRE setting., Methods: We addressed this issue through a review and a meta-analysis of studies providing data on this topic in normotensive individuals undergone both to dynamic or static exercise and to 24-h blood pressure monitoring (ABPM). A systematic search was performed using Pub-Med, OVID, EMBASE and Cochrane library databases from inception up to February 28th 2023., Results: Six studies including a total of 1,155 untreated clinically normotensive individuals were considered for the review. Data provided by the selected studies can be summarized as follows: (i) HRE is a BP phenotype linked to a high prevalence of MH (27.3% in the pooled population); (ii) MH is, in turn, associated with a greater, consistent likelihood of echocardiographic left ventricular hypertrophy (OR: 4.93, CI: 2.16-12.2, P < 0.0001) and vascular organ damage, as assessed by pulse wave velocity, (SMD: 0.34 ± 0.11, CI: 0.12-0.56, P = 0002)., Conclusions: On the basis of this, albeit limited, evidence, the diagnostic work-up in individuals with HRE should primarily be addressed to look for MH as well as for markers of HMOD, a highly prevalent alteration in MH., (© The Author(s) 2023. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: Gender-based evidence on the association between serum uric acid (SUA) and left ventricular hypertrophy (LVH), as assessed by echocardiography, is still based on single studies. Thus, we performed a systematic meta-analysis of echocardiographic studies in order to provide an updated and comprehensive information on this issue., Methods: The PubMed, OVID-MEDLINE, and Cochrane library databases were analyzed to search English-language articles published from the inception up to March 31, 2023. Studies were identified by using MeSH terms and crossing the following search items: 'uric acid', 'hyperuricemia', 'left ventricular mass', 'left ventricular hypertrophy', 'echocardiography', 'female', 'male'., Results: Six studies including 2791 normotensive and hypertensive individuals were considered for the analysis. In women, increasing values of SUA were associated with progressively higher values of age, body mass index (BMI) and systolic blood pressure (SBP). This was not the case for men. In women, the meta-analysis comparing LV mass index (LVMI) in low versus high SUA group showed a greater pooled LVMI in the high SUA group [standard means difference (SMD): 0.81 ± 0. 24, confidence interval (CI) 0.34-1.27, P  < 0.0001]. On the contrary, in men no statistical difference was found between the low group and high SUA group (SMD: 0.27 ± 0.27, CI: -0.27/0.81, P  = 0.32)., Conclusions: Our meta-analysis suggests that hyperuricemia portends the likely presence of increased LVMI in women but not in men. However, as hyperuricemia in the female pooled population, different from men, was associated with older age, higher BMI and SBP, the present findings do not support an independent role of the SUA in LV remodelling process in women., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Hypertension-mediated organ damage (HMOD) at cardiac level include a variety of abnormal phenotypes of recognized adverse prognostic value. Although the risk of cardiac HMOD is related with the severity of BP elevation, the interaction of numerous non-hemodynamic factors plays a relevant role in this unfavorable dynamic process. In particular, sex-related differences in cardiovascular (CV) risk factors and HMOD have been increasingly described. The objective of the present review is to provide comprehensive, updated information on sex-related differences in cardiac HMOD, focusing on the most important manifestations of subclinical hypertensive heart disease such as left ventricular hypertrophy (LVH), LV systolic and diastolic dysfunction, left atrial and aortic dilatation. Current evidence, based on cross-sectional and longitudinal observational studies as well as real-world registries and randomized controlled trials, suggests that women are more at risk of developing (and maintaining) LVH, concentric remodeling and subclinical LV dysfunction, namely the morpho-functional features of heart failure with preserved ejection fraction. It should be pointed out, however, that further studies are needed to fill the gap in defining gender-based optimal therapeutic strategies in order to protect women's hearts., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: There is evidence that a reduced nocturnal fall in blood pressure (BP) entails an increased risk of hypertensive-mediated organ damage (HMOD) and cardiovascular events. Most studies focusing on left ventricular (LV) systolic function, assessed by conventional LV ejection fraction (LVEF) in non-dippers compared to dippers failed to detect significant differences. To provide a new piece of information on LV systolic dysfunction in the non-dipping setting, we performed a meta-analysis of speckle tracking echocardiography (STE) studies investigating LV global longitudinal strain (GLS), a more sensitive index of LV systolic function., Methods: A computerized search was performed using PubMed, OVID, EMBASE, and Cochrane library databases from inception until 31 July, 2022. Full articles reporting data on LV GLS and LVEF in non-dippers and dippers were considered suitable., Results: A total of 648 non-dipper and 530 dipper individuals were included in 9 studies. LV GLS was worse in non-dipper than in their dipper counterparts (-18.4 ± 0.30 vs. -20.1 ± 0.23%, standard means difference [SMD]: 0.73 ± 0.14, confidence interval [CI]: 0.46/1.00, P < 0.0001) whereas this was not the case for LVEF (61.4 ± 0.8 and 62.0 ± 0.8%, respectively), SMD: --0.15 ± 0.09, CI: -0.32/0.03, P = 1.01). A meta-regression analysis between nighttime systolic BP and myocardial GLS showed a significant, relationship between these variables (coefficient 0.085, P < 0.0001)., Conclusions: Our findings suggest that early changes in LV systolic function not detectable by conventional echocardiography in the non-dipping setting can be unmasked by STE; implementation of STE in current practice may improve the detection of HMOD of adverse prognostic significance in individuals with altered circadian BP rhythm., (© The Author(s) 2022. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The authors investigated the association between obstructive sleep apnea (OSA) and right ventricular (RV) systolic dysfunction trough a meta-analysis of echocardiographic studies providing data on RV mechanics as assessed by longitudinal strain (LS). A systematic search was conducted using PubMed, OVID-MEDLINE, and Cochrane library databases to search English-language review papers published from inception to March 31, 2022. Only studies reporting data on RV free-wall or global LS in patients with OSA of different severity and non-OSA controls were reviewed. Data of interest were pooled to obtain standard means difference (SMD) with 95% confidence interval (CI). The meta-analysis included 628 participants (436 with OSA and 192 controls) from eight studies. Compared to controls, RV free wall LS was significantly reduced in the pooled OSA group (SMD 1.02 ± .33, CI:.17/1.24, P < .002); this was also the case for RV global LS (SMD: .72 ± .11, CI: .50/.93, P < .0001). Notably, compared to patients with mild-OSA those with moderate and severe OSA exhibited significantly lower RV free-wall LS and global LS values; this was not the case for tricuspid annular plane excursion. In conclusions, both RV free-wall and global LS are impaired in patients with OSA; deterioration of these indices, unlike TAPSE, was already evident in the early stages and was related to the severity of the syndrome. Thus, RV myocardial strain should be considered to be included in echocardiographic evaluation of OSA patients in order to detect subclinical cardiac damage in these patients regardless of its degree of severity., (© 2022 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Current evidence on the effects of continuous positive airway pressure (CPAP) on cardiac mechanics in patients with obstructive sleep apnea (OSA) is based on a few single studies. The authors investigated this topic through a meta-analysis of speckle tracking echocardiography (STE) studies that provided data on left ventricular (LV) and right ventricular (RV) mechanics as assessed by global longitudinal strain (GLS). The PubMed, OVID-MEDLINE, and Cochrane library databases were systematically analyzed to search English-language review papers published from inception to January 31, 2022. Studies were identified by crossing the following terms: "obstructive sleep apnea", "sleep quality", "sleep disordered breathing", "continuous positive airway pressure therapy", "noninvasive ventilation", "left ventricular hypertrophy", "systolic dysfunction", "global longitudinal strain", "left ventricular mechanics", "right ventricular mechanics", "echocardiography" and "STE echocardiography". The meta-analysis, including a total of 337 patients with OSA from nine studies (follow-up 2-24 months) showed a significant GLS improvement in both LV and RV after CPAP, standard mean difference (SMD) being 0.51±0.08, CI:0.36-0.66, p = .0001 and 0.28±0.07, CI:0.15-0.42, p = .0001), respectively. Corresponding SMD values for LV ejection fraction (LVEF) and tricuspid annular plane systolic excursion (TAPSE) were 0.20±0.06, CI:0.08-0.33, p = .001 and 0.08±0.06, CI: -0.04/0.20, p = .21. Our meta-analysis suggests that: I) CPAP treatment exerts beneficial effects on biventricular function in patients with OSA; II) the assessment of cardiac mechanics by STE should be routinely recommended for monitoring cardiac function in this setting, due to limitations of conventional echocardiography in evaluating biventricular performance., (© 2022 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

We sought to investigate echocardiography-derived myocardial work in hypertensive patients with different left ventricular (LV) geometric patterns. This cross-sectional study included 211 hypertensive patients (74 with normal LV geometry, 53 with concentric remodeling, 46 with eccentric LV hypertrophy (LVH) and 38 with concentric LVH) who underwent complete two-dimensional echocardiographic examination including two-dimensional speckle-tracking echocardiography. Pressure-strain curve was used to determine parameters of myocardial work. Our findings showed that multidirectional LV strain was lower in patients with eccentric and concentric LVH than in those with normal LV geometry and concentric remodeling. Global myocardial work index and global constructive work were higher in patients with eccentric and concentric LVH than in those with normal LV geometry and concentric remodeling. Global wasted work and global efficacy work were similar between groups with different LV geometry. E/e' and LV mass index were associated with global myocardial work index and global constructive work independently of clinical and echocardiographic parameters. In conclusion, myocardial work was higher in patients with eccentric and concentric LVH than in patients with normal LV geometry and concentric remodeling. Increased blood pressure in patients with concentric LVH in comparison with other LV geometric patterns has significant impact on the final result. LV geometry has significant impact on myocardial work in hypertensive patients., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Aim: Information on systolic dysfunction, as assessed by left ventricular (LV) mechanics in secondary hypertension is still largely limited. We performed a systematic meta- analysis of 2D/3D speckle tracking studies in order to provide an updated comprehensive information on this topic., Methods: The PubMed, OVID-MEDLINE, and Cochrane library databases were analysed to search for articles published from the inception up to March 31st 2021. Studies were identified by using MeSH terms and crossing the following search items: "myocardial strain" "left ventricular mechanics", "speckle tracking echocardiography", "systolic dysfunction", "hypertensive heart disease", "left ventricular hypertrophy", "secondary hypertension", "primary aldosteronism", "pheochromocytoma", "Cushing disease", "renal artery stenosis"., Results: On the whole, 515 patients with secondary hypertension (169 pheochromocytoma, 165 primary aldosteronism, 144 renal artery stenosis and 37 Cushing's syndrome) and 601 essential hypertensive patients from 11 studies were considered. Pooled ejection fraction (EF) was similar in essential hypertensive controls and in patients with secondary hypertension (SMD 0.12±0.06, CI: 0.001/0.25, p=0.05). Of note, EF was higher in patients with pheochromocytoma than in essential hypertensives (0.50±0.11, CI: 0.27/0.73, p<0.001). In contrast, pooled GLS was impaired in patients with secondary hypertension compared to their essential hypertensive counterparts (SMD 0.83±0.26, CI: 0.32/1.30, p< 0.001)., Conclusions: The present meta-analysis adds a new piece of evidence by showing that GLS performs better than EF in identifying systolic dysfunction in the setting of secondary hypertension. In particular, this is true in patients with pheochromocytoma in whom conventional EF suggests a normal or even super-normal systolic function., (Copyright © 2021. Published by Elsevier B.V.)

Aim: Evidence on systolic dysfunction, as assessed by left ventricular (LV) mechanics, in hypertensive heart disease phenotyped by abnormal LV geometric patterns is still limited. Thus, we performed a systematic meta-analysis of 2D/3D speckle-tracking studies in order to provide an updated comprehensive information on this topic., Methods: The PubMed, OVID-MEDLINE, and Cochrane library databases were analyzed to search for articles published from the inception up to 31 January 2021. Studies were identified by using MeSH terms and crossing the following search items: 'myocardial strain', 'left ventricular mechanics', 'speckle tracking echocardiography', 'systolic dysfunction', 'hypertensive heart disease', 'left ventricular hypertrophy', left ventricular remodeling", 'concentric hypertrophy', 'eccentric hypertrophy'., Results: Overall, data of 267 normotensive controls and 712 hypertensive patients (234 normal geometry, 97 LV concentric remodeling, 176 eccentric LVH, and 205 concentric LVH) from eight studies were considered. Pooled ejection fraction was similar in normotensives and in the whole group of hypertensive patients: (SMD 0.037 ± 0.05, confidence interval (CI): 0.14/0.07, P = 0.51) as well as in hypertensive subgroups. LVMI, and E/e' gradually increased from hypertensive patients with normal geometry and concentric remodeling, to patients with eccentric and concentric LVH. LV global longitudinal strain (GLS) was lower in all hypertensive groups compared with normotensive controls, in particular, in the eccentric (SMD 1.14 ± 0.22, CI: 0.69/1.59, P < 0.0001) and concentric LVH group (SMD 1.37 ± 0.21, CI: 0.95/1.79, P < 0.0001). The meta-analysis restricted to hypertensive patients showed that GLS gradually deteriorated from hypertensive patients with normal LV geometry, across those with concentric remodeling, to participants with eccentric and concentric LVH (-19.5 ± 0.6 versus -18.8 ± 0.73 versus -17.6 ± 0.66 versus -16.5 ± 0.6%, P < 0.001 for trend). Statistical significance was reached when GLS of the concentric and eccentric LVH group but not the concentric remodeling was compared with the normal geometry one., Conclusion: The present meta-analysis confirms that GLS performs better than ejection fraction in identifying systolic dysfunction in the hypertension setting. More importantly, it suggests that this occurs in patients with altered LV structure and geometry, such as LVH., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: Available evidence on systolic dysfunction in systemic hypertension, as assessed by left ventricular (LV) mechanics, is still based on single studies. Thus, we performed a systematic meta-analysis of two-dimensional speckle-tracking studies in order to provide an updated comprehensive information on this issue., Methods: The PubMed, OVID-MEDLINE, and Cochrane library databases were analyzed to search English language articles published from the inception up to 31 December 2020. Studies were identified by using MeSH terms and crossing the following search items: 'myocardial strain', 'left ventricular mechanics', 'speckle tracking echocardiography', 'systolic dysfunction', 'hypertensive heart disease', 'systemic hypertension', 'essential hypertension'., Results: Data from 4276 individuals (2089 normotensive controls and 2187 mostly uncomplicated hypertensive patients) were included. Left ventricular (LV) mass index, relative wall thickness, left atrial volume index and E/e' ratio were significantly higher in hypertensive patients than in normotensive controls. LV ejection fraction did not differ in the two pooled groups (SMD -0.048 ± 0.054, 95% CI -0.20 to 0.10, P = 0.30), whereas LV global longitudinal strain (GLS) was significantly impaired in the hypertensive group (SMD: 1.07 ± 0. 15, 95% CI 0.77-1.36, P < 0.0001). Similar findings were obtained in a sub-analysis restricted to 15 studies in which mean age was similar in cases and controls (SMD 1.21 ± 0.23, 95% CI 0.76-1.67, P = 0.002)., Conclusion: The present meta-analysis suggests that GLS assessment unmasks systolic dysfunction undetected by conventional ejection fraction in the uncomplicated hypertension setting and that this parameter should be incorporated into routine work-up aimed to identify hypertension-mediated cardiac damage., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: Available evidence on the association between reverse dipping pattern and subclinical cardiac damage is scanty. We performed a systematic meta-analysis of echocardiographic studies in order to provide an updated and comprehensive information on this issue., Methods: The PubMed, OVID-MEDLINE, and Cochrane library databases were analyzed to search English-language articles published from January from the inception up to 31 July 2020. Studies were identified by using MeSH terms and crossing the following search items: 'reverse dipping', 'nondipping', 'inverted dipping', 'ambulatory blood pressure', 'cardiac damage', 'hypertensive heart disease', 'left ventricular mass', 'left ventricular hypertrophy', and 'echocardiography'., Results: Data from 14 studies including 1429 patients with reverse dipping, 2584 dippers and 3508 nondippers were considered. Left ventricular (LV) mass index and relative wall thickness were greater in reverse dippers than in dippers (SMD: 0.40 ± 0.04 g/m2, P < 0.0001; 0.31 ± 0.07, P < 0.0001) and nondippers (SMD: 0.25 ± 0.04 g/m2, P < 0.0001; 0.21 ± 0.07, P = 0.004). The reverse dipping group had an increased risk of LV hypertrophy compared with dipping (OR = 1.85, CI 1.47-2.32, P < 0.0001) and nondipping group (OR = 1.45, CI 1.19-1.78, P < 0.0001). A significant progressive reduction in the E/A ratio, paralleled by an increase in left atrium diameter occurred from dippers, to nondippers and reverse dippers., Conclusion: The present meta-analysis provides a novel piece of information about the unfavourable association between the reverse dipping pattern and subclinical cardiac alterations and suggests that the detection of this blood pressure phenotype may identify individuals at increased risk for subclinical organ damage., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: Available evidence on regression of left ventricular (LV) hypertrophy in patients with primary aldosteronism after unilateral adrenalectomy is scanty. We performed a systematic meta-analysis of echocardiographic studies to provide an updated and comprehensive information on this issue., Methods: The PubMed, OVID-MEDLINE and Cochrane library databases were analyzed to search English-language articles published from 1 January 1990 up to 30 June 2020. Studies were identified by using MeSH terms and crossing the following search items: 'primary aldosteronism' 'Conn's syndrome' 'adrenalectomy', with 'cardiac damage', 'hypertensive heart disease' 'left ventricular mass', 'left ventricular hypertrophy', 'left ventricular hypertrophy regression', 'echocardiography'., Results: A total of 629 hypertensive patients with primary aldosteronism (mean age 49 years, 45% men) were included in 14 studies. Baseline and postintervention pooled mean LV mass/BSA values were 134 ± 4 and 108 ± 3 g/m2 [standard means difference (SMD) -0.42 ± 0.05, confidence interval (CI) -0.52/-0.32, P < 0.0001]; corresponding values for LV mass/h2.7 were 56 ± 2 and 49 ± 1 g/h2.7 (SMD -0.45 ± 0.06, CI -0.52/-0.36, P < 0.0001). Adrenalectomy, followed by a marked decrease in blood pressure, was associated with a decrease in relative wall thickness (SMD -0.17 ± 0.06, CI -0.31/-0.03, P < 0.01) as well as in the number of antihypertensive drugs (SMD -0.45 ± 0.04, CI -0.50-0.32, P < 0.0001)., Conclusion: The present meta-analysis suggests that adrenalectomy in patients with primary aldosteronism exerts a beneficial effect on LV structure and geometry by reducing the burden of LV hypertrophy and LV concentric geometry., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: Few echocardiographic studies have focused on regression of left ventricular hypertrophy (LVH) in patients with renal artery stenosis after revascularization, with inconsistent results. We performed a systematic meta-analysis of these studies in order to offer a comprehensive information on this topic., Methods: The PubMed, OVID-MEDLINE, and Cochrane library databases were analyzed to search English-language articles published from 1 January 1990 up to 31 March 2020. Studies were identified by crossing the following terms: 'renal artery stenosis', 'renovascular hypertension', 'fibromuscular dysplasia', 'renal artery stenting', 'renal artery surgery' with 'cardiac damage', 'hypertensive heart disease' 'left ventricular mass', 'left ventricular hypertrophy', 'echocardiography'., Results: A total of 726 hypertensive patients with renal artery stenosis (mean age 61 years, 64% men, 98% treated, 10% with fibromuscular dysplasia) were included in 13 studies. Baseline and postintervention pooled mean LVM values were 220 ± 15 and 203 ± 19 g, respectively (SMD -0.24 ± 0.06, CI -0.37 to -0.21, P<0.0001); corresponding values for LV mass index were 129.0 ± 6 and 115 ± 7 g/m, respectively (SMD -0.28 ± 0.04, CI -0.36 to 0.21, P < 0.0001). Renal revascularization was associated with a 40% lower risk of LVH. This trend was accompanied by a reduction in the number of antihypertensive drugs (SMD -0.27 ± 0.04, CI -0.37 to 0.17, P < 0.0001)., Conclusion: The present meta-analysis suggests that renal artery revascularization added to antihypertensive therapy promotes a favourable effect on LV structure, as reflected by a significant decrease in absolute and indexed LV mass index as well by a lower risk of LVH. Limitations include: high prevalence of modest renal artery stenosis (≥50%); small sample of fibromuscular dysplasia; lack of randomized design of most studies.

Subclinical abnormalities in cardiac and vascular structure reflect the adverse effects triggered by a variety of risk factors on the cardiovascular (CV) system thereby representing an intermediate step in the cardiovascular continuum; such alterations are recognized as reliable markers of increased cardiovascular risk in different clinical settings including obstructive sleep apnea (OSA). The mechanisms underlying subclinical organ damage (OD) in the OSA setting are multifactorial. Hypoxemia and hypercapnia, induced by repeated collapses of upper airways, have been suggested to trigger a cascade of events such as activation of the sympathetic tone, renin-angiotensin-aldosterone system leading to endothelial dysfunction, vasoconstriction, myocardial and vascular remodeling, and hypertension. Furthermore, coexisting non-haemodynamic alterations such as increased oxidative stress, release of inflammatory substances, enhanced lipolysis and insulin resistance have been reported to play a role in the pathogenesis of both cardiac and extra-cardiac OD. In this article we reviewed available evidence on the association between OSA and subclinical cardiac (i.e., left and right ventricular hypertrophy, left atrial dilatation) and extra-cardiac organ damage (i.e., carotid atherosclerosis, arterial stiffness, microvascular retinal changes, and microalbuminuria). This association is apparently stronger for cardiac and carotid subclinical damage than for other markers (i.e., arterial stiffness and retinal changes) and mostly evident in the setting of severe OSA.

Aim: Findings regarding the association of left ventricular mass (LVM) and new-onset hypertension are based on blood pressure measured in the office. We sought to assess the value of LVM in predicting in-office and out-of-office incident hypertension in members of the general population enrolled in the Pressioni Monitorate E Loro Associazioni study., Methods: The study included participants with normal office (n = 792), home (n = 714) and 24-h (n = 825) ambulatory blood pressure (ABP) at baseline evaluation who had a readable echocardiogram at entry and at the end of follow-up. Each normotensive group was divided into quartiles of LVM indexed (LVMI) to height., Results: Over a follow-up of 148 months cumulative incidence of new office, home and 24-h ABP hypertension were 35.9, 30.7 and 36.1%, respectively. In fully adjusted models (including age, sex, BMI change during follow-up, baseline serum glucose, creatinine, total cholesterol office, home and 24-h SBP and DBP). higher LVMI values (i.e. the highest vs. the lowest quartile) were independently associated with an increased risk of home [odds ratio (OR) = 2.14, 95% confidence interval (CI) 1.21-3.77, P = 0.008] and 24-h ABP hypertension (OR = 1.70, 95% CI 1.05-2.76, P = 0.03). This was not the case for new-onset office hypertension (OR = 1.61, 95% CI 0.94-2.74, P = 0.07)., Conclusion: Our study provides the first evidence that in normotensive individuals the magnitude of LVMI is independently associated with the risk of incident out-of-office hypertension.

We sought to assess functional capacity in recently diagnosed untreated hypertensive patients with different 24-hour blood pressure (BP) patterns (dipping, non-dipping, extreme dipping, and reverse dipping). This cross-sectional study involved 164 untreated hypertensive patients who underwent 24-hour ambulatory BP monitoring and cardiopulmonary exercise testing. Our findings showed that 24-hour and daytime BP values did not differ between four groups. Nighttime BP significantly and gradually increased from extreme dippers to reverse dippers. There was no significant difference in BPs at baseline and at the peak of exercise among four observed groups. Peak oxygen consumption (peak VO2) was significantly lower in reverse dippers than in dippers and extreme dippers. Heart rate recovery was significantly lower among reverse dippers than in dippers and extreme dippers. Ventilation/carbon dioxide slope (VE/VCO2) was significantly higher in reverse dippers and non-dippers in comparison with dippers and extreme dippers. Non-dipping BP pattern (non-dippers and reverse dippers together) was independently and negatively associated lower heart rate recovery in the first minute and peak VO2. Reverse dipping BP pattern was independently associated not only with heart rate recovery in the first minute and peak VO2, but also with VE/VCO2. In conclusion, untreated hypertensive patients with reverse dipping BP patterns showed significantly worse functional capacity than those with dipping and extreme dipping BP patterns. Circadian BP rhythm is related with functional capacity and should be taken into account in the risk assessment of hypertensive patients., (©2019 Wiley Periodicals, Inc.)

Aim: Although nocturnal hypotension is considered the key factor responsible for the increased cardiovascular risk associated with the extreme dipping (ED) pattern, no information is available on its prevalence in this setting. Therefore, we have assessed this topic in a cohort of patients referred to a single out-patient hypertension center., Methods: A large database of individual 24-hour ambulatory BP recordings from untreated individuals with a history of hypertension and treated individuals with hypertension was analyzed., Results: A total of 339 of 7,074 patients (4.5%) exhibited an ED pattern (207 had a nighttime reduction in both systolic and diastolic BP ≥ 20% compared to daytime values and 132 a nighttime reduction in diastolic BP ≥ 20%). Among patients with ED, the prevalence of nocturnal hypotension varied from 9.1% to 45.0% depending on the criteria used (i.e., mean nighttime BP < 90/50 mm Hg or < 100/60 mm Hg), and the prevalence of nocturnal hypertension (i.e., mean nighttime BP ≥ 120/70 mm Hg) was 19.5%. Compared with untreated patients, those taking antihypertensive drugs were more likely to have nocturnal hypotension and less likely to have nocturnal hypertension., Conclusions: Our findings support the view that ED pattern is a condition not always associated with nocturnal hypotension because a large fraction of ED patients has normal or elevated mean BP nocturnal values., (© American Journal of Hypertension, Ltd 2019. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Aim: The association between prehypertension (pre-HTN) and abnormal left ventricular (LV) geometric patterns is unclear. We performed a meta-analysis of echocardiographic studies aimed to provide a new piece of information on LV geometric alterations in untreated pre-HTN individuals., Design: Studies were identified by crossing the following search terms: 'prehypertension,' 'high normal blood pressure,' 'heart,' 'LV hypertrophy' (LVH), 'LV geometry,' 'LV mass,' and 'echocardiography.', Results: A total 60 949 participants (38 536 normotensive, 14 453 pre-HTN, and 7960 HTN individuals) were included in six studies. LV concentric remodelling was the most common abnormal pattern in pre-HTN participants followed by eccentric and concentric LVH. Compared with normotensive group, pre-HTN exhibited a higher risk of LV concentric remodelling (OR 1.89, CI 1.70-2.10, P < 0.001), eccentric LVH (OR 1.65, CI 1.40-1.90, P < 0.001) and concentric LVH (OR 2.09, CI 1.50-3.00, P < 0.001). The likelihood of having abnormal LV patterns in HTN was significantly higher (P < 0.001 for all) than in pre-HTN participants., Conclusion: Our meta-analysis shows that alterations in LV geometry in pre-HTN individuals are intermediate between normotensive and HTN individuals. These findings suggest that pre-HTN is associated to early changes in LV structure and geometry, and preventive strategies may have a protective impact on development of subclinical cardiac damage in this setting.

Cross-sectional and longitudinal data analysis of the PAMELA (Pressioni Monitorate E Loro Associazioni) population was performed to assess the association between prehypertension and left ventricular hypertrophy (LVH) at entry and the risk of new-onset LVH associated to this condition in the subset of participants with normal LV mass index (LVMI). A total of untreated 1397 participants with measurable echocardiographic parameters at baseline were considered in the cross-sectional analysis. The longitudinal analysis included 880 participants without LVH at baseline and with measurable LVMI at follow-up examination performed 10 years later. At entry, after adjustment for major confounders LVH prevalence rates (LVM/body surface area) showed a significant, progressive increase from the normotensive (2.1%), to prehypertension (6.7%), and hypertension group (18.3%). The incidence of LVH increased progressively from the normotensive to prehypertension and hypertension group (9.0%, 23.2%, and 36.5%, respectively). The risk of new LVH was significantly greater in prehypertension who progressed to sustained hypertension (odds ratio, 4.21; CI, 1.64-10.83; P=0.003) than in those with persistent prehypertension (odds ratio, 1.89; CI, 0.77-5.11; P=0.21) compared with persistent normotensive participants after adjustment for age, sex, baseline LVMI, obesity, glucose, creatinine, total cholesterol and the use of antihypertensive drugs at follow-up. Further adjustments for changes in body mass index, metabolic variables, and creatinine during the follow-up did not modify the strength of association between prehypertension and new-onset LVH. Our findings offer a new piece of evidence on the association of prehypertension with LVH and support the view that preventive actions for this condition affecting a large fraction of the general population should be intensified.

Carotid intima-media thickness (CIMT), as assessed by ultrasonography, has been shown to be directly related to cardiovascular (CV) morbidity and mortality independently of conventional risk factors. Thus, CIMT has been proposed as a marker of CV risk and a surrogate end-point for therapeutic interventions. In the present article we will review available literature about CIMT clinical/prognostic significance in order to offer an updated comprehensive information on this topic. In particular, the anti-atherosclerotic effect of angiotensin II receptor blockers (ARBs) in the hypertensive setting will be addressed, based on findings provided by double blind, randomized, prospective studies comparing CIMT longitudinal changes. Our review, including 8 studies totaling 1154 hypertensive participants, shows that ARBs are as effective as the other classes of antihypertensive drugs in preventing/regressing subclinical carotid damage and that findings supporting their superiority in this field are limited and not univocal. Future studies aimed to clarify the therapeutic impact of ARBs on CIMT changes and their prognostic implications are warranted., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Blockade of the renin-angiotensin-aldosterone system is a cornerstone in cardiovascular disease prevention and hypertension treatment. The relevance of ambulatory blood pressure monitoring (ABPM) has been widely confirmed for both increasing the accuracy of blood pressure (BP) measurements, particularly in pharmacological trials, and focusing on 24 h BP prognostic parameters. The aim of this study was to assess the effects of canrenone addition on ambulatory BP in uncontrolled hypertensive patients already treated with the highest tolerated dose of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1 receptor (AT1R) antagonists plus hydrochlorothiazide (HCT)., Methods: ABPM was performed at baseline and after 3 months of combination therapy in 158 outpatients with stage 1 or 2 hypertension who were randomized to add canrenone (50 or 100 mg) to the pre-existing therapy with ACE inhibitors or AT1R antagonists plus HCT. Twenty-four-hour systolic and diastolic BPs were considered normalized when the values were <130 and <80 mmHg, respectively., Results: The addition of canrenone was associated with a reduction in systolic and diastolic BPs (24 h and daytime and nighttime; P <0.001), mean arterial pressures ( P <0.001), and pulse pressures ( P <0.01). The Δ 24 h systolic/diastolic BPs were -13.5±11.2/-8±8 mmHg and -16.1±13.5/-11.2±8.3 mmHg (50 and 100 mg/day, respectively). In the 50 mg arm, the 24 h systolic and diastolic BPs were normalized in 67.5% and 74% of the patients, respectively, and in 61.6% and 68.5% of the patients in the 100 mg arm, respectively ( P <0.05; P = not significant for 50 vs 100 mg). The percentage of patients whose nocturnal decrease was >10% with respect to diurnal values did not change during combination therapy., Conclusion: Canrenone addition to ACE inhibitors or AT1R antagonists plus HCT was associated with a significant reduction of 24 h BP and to an increased number of patients meeting 24 h ABPM targets in a clinical setting of uncontrolled stage 1 or 2 hypertension., Competing Interests: Disclosure Massimo Vanasia is employed by Direzione Medica THERABEL GiEnne Pharma, Italy. The other authors report no conflicts of interest in this work.

Reverse or inverted dipping (ie, the phenomenon characterized by higher nighttime compared with daytime blood pressure values) is an alteration of circadian blood pressure rhythm frequently documented in hypertension, type 2 diabetes mellitus, chronic kidney disease, and sleep apnea syndrome, and generally regarded as a harmful condition. Available literature on the clinical and prognostic implications of reverse dipping is scanty. The present article will review a number of relevant issues concerning reverse dipping, in particular: (1) its possible mechanisms; (2) prevalence and clinical correlates, (3) concomitant cardiac and extracardiac subclinical organ damage; (4) association with acute and chronic cardiovascular diseases; (5) prognostic value in predicting cardiovascular events and mortality; and (6) therapeutic interventions aimed at reverting this abnormal circadian blood pressure rhythm., (©2017 Wiley Periodicals, Inc.)

Because subclinical alterations in cardiovascular structure reflect cumulative damage induced by risk factors and represent an intermediate stage between risk factor exposure and cardiovascular events, this damage is regarded as a marker of increased cardiovascular risk in different clinical settings, including the general population. The Pressioni Monitorate e Loro Associazioni (PAMELA) is an originally designed research study aimed at assessing the normal values and prognostic significance of ambulatory and home blood pressure in a representative sample of the Northern Italian general population. Because the study protocol included the collection of electrocardiographic (ECG) and echocardiographic (ECHO) data, the prevalence and clinical correlates, as well as the prognostic value of subclinical cardiac alterations, have been extensively investigated. This article is a review of the findings of the PAMELA study regarding the clinical aspects and prognostic significance of cardiac abnormal phenotypes such as left ventricular hypertrophy, left atrial dilatation and aortic root dilation.

Aim: Scanty information is available about the association of isolated daytime hypertension (IDH) and isolated night-time hypertension (INH) with subclinical cardiac damage in the general population. We examined this issue in patients enrolled in the Pressioni Arteriose Monitorate E Loro Associazioni study., Methods: The analysis included 2021 participants with valid ambulatory blood pressure (BP) monitoring at baseline evaluation. IDH and INH were defined according to current guidelines. Subclinical organ damage was assessed by validated electrocardiographic and echocardiographic criteria., Results: A total of 1258 patients (62.3%) had daytime/night-time normotension, 376 (18.6%) daytime/night-time hypertension, 231 (11.4%) INH and 156 (7.7%) IDH, respectively. Participants with hypertension, compared with their normotensive counterparts were older, included a higher fraction of men, had higher BMI, LDL cholesterol, triglyceride and glucose levels and exhibited a greater subclinical cardiac involvement. Furthermore, INH and IDH patients showed a similar degree of cardiac damage (i.e. left ventricular mass index: 89 ± 18 vs 90 ± 20 g/m), intermediate between normotensive (82 ± 19 g/m) and day-night hypertensive patients (99 ± 24 g/m)., Conclusion: The present study shows that IDH and INH exert similar detrimental effects on cardiac structure. In a practical perspective, appropriate antihypertensive chrono-therapeutic approaches in these opposite ambulatory hypertensive subtypes may have important implications in cardiovascular prevention.

Aim: To evaluate the effects of canrenone as add-on therapy in patients already treated with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II receptor blockers (ARBs) and hydrochlorothiazide at the maximum dosage (25 mg/d)., Method: In this randomized, open-label, controlled trial, we enrolled 175 Caucasian patients with essential hypertension not well controlled by concomitant ACE-I or ARBs and hydrochlorothiazide. At baseline, 87 patients (57 males and 30 females) were randomized to add canrenone 50 mg, and 88 (56 males and 32 females) patients to canrenone 100 mg, once a day, for 3 months. At baseline and after 3 months, we evaluated blood pressure (BP), pulse pressure (PP), heart rate (HR), fasting plasma glucose (FPG), homeostasis model assessment insulin (HOMA Index), lipid profile, electrolytes, uric acid, estimated glomerular filtration rate (eGFR), plasma urea, aldosterone, B-type natriuretic peptide (BNP), and galectin-3., Results: Blood pressure decreased with both dosages of canrenone, with a better effect with canrenone 100 mg (-20.26 vs -23.68 mm Hg for SBP, and -10.58 vs -12.38 mm Hg for DBP), without a clinically relevant increase in potassium levels. We did not observe any differences regarding FPG or HOMA Index, nor of lipid profile, with the exception of triglycerides, which increased compared to baseline with canrenone 50 mg (+0.25 vs +0.34 mEq/L). Creatinine slightly increased with canrenone 100 mg (+0.02 vs +0.05 mg/dL), although no variations of eGFR were observed in neither groups. There was an increase in aldosterone levels with canrenone 50 mg. No changes in BNP or galectin-3 were recorded., Conclusion: Both canrenone dosages gave a decrease in blood pressure, with a better effect with the higher dose, with only a slight increase in potassium and creatinine levels, which were not clinically relevant. Clinical Trials Registration Eudract number: 2010-023606-13; ClinicalTrials.gov NCT02687178., (© 2016 The Authors. Cardiovascular Therapeutics Published by John Wiley & Sons Ltd.)

Evidence on the association of nocturnal hypertension (NH) with subclinical cardiac and vascular damage is scanty. The authors performed a meta-analysis to provide comprehensive information on this clinically relevant issue. Full articles providing data on subclinical cardiac and carotid damage as assessed by ultrasonographic methods in patients with NH as compared with patients with nocturnal normotension (NN) were considered. A total of 3657 patients (NH=2083, NN=1574) of both sexes were included in seven studies. Left ventricular mass index was higher in individuals with NH than in those with NN (112±4.7 g/m(2) vs 98±4.8 g/m(2) ; standard mean difference [SMD], 0.54±0.16; confidence interval [CI], 0.23-0.85; P<.01). Similarly, common carotid intima-media thickness was greater in patients with NH than in those with NN (751±34 μm vs 653±14 μm; SMD, 0.44±0.08; CI, 0.29-0.59; P<.01). The present meta-analysis shows an association between NH pattern and increased likelihood of cardiac and carotid structural alterations., (© 2016 Wiley Periodicals, Inc.)

Evidence on the association of nondipping pattern with carotid atherosclerosis is scarce. We performed a meta-analysis in order to provide comprehensive information on subclinical carotid alterations in nondipping as compared with dipping individuals. A computerized search was performed using PubMed, OVID, EMBASE and Cochrane library databases from 1 January 1990 up to 31 March 2015. Full articles providing data on carotid intima-media thickness (IMT) and plaque in nondipping and dipping individuals, as assessed by ultrasonography, were analyzed. A total of 2753 adult individuals (1003 nondipping and 1750 dipping) included in 13 studies were considered. Common carotid IMT was higher in nondipping than in dipping individuals [807 ± 36  μm vs. 746 ± 28  μm, standard means difference, SMD: 0.37 ± 0.09, confidence interval (CI): 0.19-0.56, P < 0.01]. From data on plaque prevalence provided by five studies, the odds ratio for carotid plaques resulted 67% higher in nondipping (95% CI: 1.26-2.21, P < 0.01) than in dipping individuals. Our findings support an association between nondipping pattern and increased risk of subclinical carotid alterations. In a practical perspective, the present meta-analysis reinforces the view that an effective blood pressure control over the entire 24-h period, in particular at night, may prevent the progression of vascular damage associated with nondipping phenotype.

Aim: The association of non-dipping (ND) pattern with cardiac damage is debated. We performed a meta-analysis in order to provide comprehensive information on subclinical cardiac alterations in untreated ND hypertensives., Design: A computerized search was performed using PubMed, OVID, EMBASE, and Cochrane library databases from 1 January 1990 up to 31 October 2014. Full articles published in English language providing data on subclinical cardiac damage in ND as compared to dipper (D) hypertensives, as assessed by echocardiography, were considered., Results: A total of 3,591 untreated adult subjects (1,291 ND and 2,300 D hypertensives) included in 23 studies were considered. Left ventricular (LV) mass index (LVMI) was higher in ND than in D hypertensives (122±3.8 g/m2 vs. 111±3.3 g/m2, standardized mean difference, SMD: 0.40±0.07, confidence interval (CI): 0.26-0.53, P < 0.001); relative wall thickness (RWT) and left atrium (LA) diameter were greater (SMD: 0.14±0.005, CI: 0.05-0.23, P = 0.002; 0.36±0.10, CI: 0.16-0.56, P < 0.001, respectively), while mitral E/A ratio was lower in ND than in D counterparts (SMD: -0.23±0.08, CI: -0.39 to -0.08, P = 0.003). After assessing data for publication bias, the difference between groups was still significant, with the exception of E/A ratio., Conclusions: Our meta-analysis supports an association between ND pattern and increased risk of LV structural alterations in untreated essential hypertensives. This observation supports the view that an effective BP control throughout the entire 24-hour cycle may have a key role in preventing or regressing subclinical cardiac damage associated to ND pattern., (© American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Scientific authorities recommend that patients with arterial hypertension should be managed not only on the basis of blood pressure (BP) levels, but also on the assemement of total cardiovascular risk. In particular, evaluation of target organ damage (TOD) is of major relevance for identifying hypertensive individuals at high cardiovascular risk independently of clinic BP levels. Evidence of cardiac and extra-cardiac TOD has been consistently associated with worse cardiovascular prognosis. Unfortunately, detection of TOD markedly depends on sensitivity of diagnostic tools, at difference from evaluation of risk factors and associated diseases, usually reliably provided by accurate clinical examination and routine investigation. The purpose of this paper was to provide an updated, comprehensive review on the role of echocardiography in identifying hypertensive patients apparently uncomplicated, but exposed to a high cardiovascular risk due to the presence of subclinical structural and functional cardiac alterations of adverse prognostic significance.

Aim: Diastolic dysfunction related to hypertensive left ventricular hypertrophy (LVH) has been shown to affect right-sided cardiac morphology and haemodynamics. As left atrial enlargement (LAE) is a marker of chronically elevated left ventricular (LV) filling pressure and diastolic dysfunction, we investigated the relationship between LAE and right ventricular hypertrophy (RVH) in systemic hypertension., Methods: A total of 330 essential hypertensives, categorized according to tertiles of left atrial (LA) diameter indexed to body surface area were considered for the analysis. All subjects underwent a quantitative echocardiographic examination as well as extensive clinical and laboratory investigations. RVH was defined as anterior right ventricular (RV) wall thickness ≥ 6.0/5.5 mm in men and women, respectively, and LVH as LV mass index ≥ 51/47 g/m(2.7) in men and women, respectively., Results: The prevalence of LVH increased across LA diameter tertiles from 21.0% to 50% and that of RVH from 26.3% to 41.8% (p < 0.01for both). This was also the case for biventricular hypertrophy (from 10.0% to 26.0%, p < 0.01). Differences in both LV and RV structure across LA diameter tertiles remained significant after adjusting for age, office systolic/diastolic blood pressure and duration of hypertension. Similar results were obtained when study population was divided according to absolute LA diameter tertiles., Conclusions: Our findings provide further evidence of an interaction between left and right chambers in systemic hypertension by showing that LAE is associated with RVH. The clinical and prognostic implications of such observation remain be evaluated in future prospective studies.

Background: The influence of gender on the association between metabolic syndrome (MS) and subclinical organ damage (OD) has been poorly investigated. The aim of this study was to investigate whether the risk of developing left ventricular hypertrophy (LVH) and carotid atherosclerosis is different in men and women with MS., Methods: A total of 3752 untreated and treated hypertensive patients (mean age 53.3 ± 12.6, 52.7% men) were considered for this analysis. All patients underwent standard ultrasonographic investigations searching for LVH and carotid atherosclerosis. The MS was defined according to ATP III criteria., Results: LVH was more prevalent in women and men with the MS compared with their counterparts (58% vs 34% and 48% vs 33%, respectively, p < 0.001). This was also the case for carotid plaque prevalence (61% vs 42% and 57% vs 44%, p < 0.001). The prevalence of OD was not different between men and women with MS, after adjusting for confounders. In multivariate analysis, abdominal obesity was the most important MS component independently related to LVH in both genders, followed by blood pressure. As for carotid plaques, blood pressure, hyperglycemia and hypertriglyceridemia turned out to be independent correlates regardless of gender., Conclusions: Our data indicate that MS is associated with a higher risk of LVH and carotid atherosclerosis irrespective of gender; these findings do not support a gender influence in the association between MS and subclinical OD.

Aim: Experimental and clinical evidence supports the view that right ventricular hypertrophy (RVH) may parallel left ventricular hypertrophy in systemic hypertension; a comprehensive analysis of this issue, however, is lacking. Thus, we analyzed the literature in order to provide an updated information on the right ventricular structural changes associated to systemic hypertension., Design: A literature search using the key words 'right ventricle' 'right ventricular hypertrophy', 'biventricular hypertrophy' 'right and left ventricular hypertrophy'. 'hypertension', 'echocardiography' was performed in order to identify relevant articles. Full articles published in English language in the last three decades reporting studies in adult hypertensive individuals were considered., Results: A total of 13 studies, including 1290 untreated (45%) and treated hypertensive patients and 259 normotensive controls, were considered. Overall, in hypertensive individuals right ventricular wall was thicker than in normotensive counterparts (standardized difference 1.3 mm, P < 0.001). RVH prevalence consistently varied among studies (17.0-80.0%) with an average of 28.6% in the pooled population. This was also the case for LVH prevalence rates (9.0-100%) with an average value of 30.6%., Conclusion: Clinical studies consistently indicate that RVH is a common cardiac phenotype in systemic hypertension. As this finding is based on a limited number of cross-sectional studies including small population samples, further investigations are needed to determine the clinical utility and prognostic value of this phenotype in clinical practice.

Background: Left atrial enlargement (LAE) is a marker of hypertensive heart disease associated with increased cardiovascular risk. We reviewed recent literature about the prevalence of LAE, as assessed by echocardiography, to update our information about the clinical relevance of this cardiac phenotype in human hypertension., Methods: We performed a search of MEDLINE using the key words "left atrial enlargement," "left atrial dilatation," "left atrial size," "hypertension," "echocardiography," and "atrial fibrillation" to identify relevant papers. We considered full articles published in English from January 1, 2000 to July 1, 2012 reporting studies involving adult individuals., Results: We analyzed a total of 15 studies, including 10,141 untreated and treated subjects. LAE was defined according to 11 different criteria (4 studies applied two or three criteria), and its prevalence consistently varied among studies, from 16.0-83.0%, with a prevalence in the pooled population of 32%. A gender-based analysis of 9 studies (8,588 patients) showed the prevalence of LAE as being similar in women and men (OR, 1.23; 95% CI, 0.83-1.83; P = 0.30). Data provided by 10 studies (n = 9,354 patients) showed the prevalence of left-ventricular hypertrophy as being significantly higher in patients with LAE (68.2%) than in their counterparts without LAE (41.8%) (OR, 2.97; 95% CI, 2.68-3.29; P < 0.01)., Conclusions: Our analysis shows that LAE is present in a relevant fraction of the hypertensive population. Because LAE is an independent predictor of cardiovascular events, the accurate detection of this phenotype may improve the evaluation of risk in hypertensive patients.

Introduction: The electrocardiogram (ECG) is listed among the routine diagnostic examinations for hypertensive patients according to international guidelines., Objective: The aim of this survey was to investigate whether an ECG is routinely prescribed before an echocardiographic examination by general practitioners for the evaluation of subclinical cardiac damage in uncomplicated hypertensive patients in a suburban area of Italy., Methods: A total of 60 consecutive hypertensive patients (45% men, mean age 60 ± 14 years) referred to a single out-patient cardiology service by their general practitioners for the assessment of cardiac organ damage by echocardiography were enrolled in the study. Patients' demographic data and medical history were collected at the echocardiographic laboratory on a questionnaire administered by the attending physician., Results: Less than 40% of the study sample had undergone an ECG during the 12-month period preceding the echocardiographic examination. Notably, only 60% of newly diagnosed hypertensive patents had an ECG done after the discovery of their hypertensive status., Conclusions: These findings show that an ECG is not routinely prescribed as a first-line examination in the assessment of cardiac organ damage related to hypertension by a large fraction of general practitioners in current clinical practice in a northern area of Italy. This contrasts with available evidence that the combined assessment of left ventricular hypertrophy by ECG and echocardiogram provides the best evaluation of cardiac damage and stratification of cardiovascular risk in hypertension.

Background and Aim: The impact of aging on the relationship between left ventricular (LV) mass/geometry and diastolic function as assessed by updated echocardiographic methods, such as tissue Doppler, is poorly defined. We investigated this issue in a cohort of hypertensive patients., Methods: A total of 660 hypertensives (mean age 65 ± 13 years, 48% men) with preserved LV systolic function underwent a comprehensive echo-Doppler examination for routine clinical indications. For the present analysis, the subjects have been divided in two age groups (<65 or ≥65 years)., Results: Overall, 61% of subjects fulfilled the criteria for LVH, 18% for left atrial (LA) enlargement and 11% for altered LV filling index. Concentric LV geometry was 1.4-fold higher in older hypertensives than in younger counterparts; also the prevalence of LA enlargement and altered LV filling was 2.0- and 1.9-fold higher in the former group, respectively. In older hypertensives, at variance from younger ones, neither LV mass nor relative wall thickness (RWT), a continuous index of LV geometry, were independently correlated to conventional as well as tissue Doppler LV diastolic indexes., Conclusions: Our findings suggest the relationship between cardiac hypertrophy and diastolic function in hypertensive subjects is affected by aging-associated factors unrelated to the amount of LV mass as assessed by standard echocardiography.

Aim: Left ventricular hypertrophy (LVH) is a strong predictor of cardiovascular events in different clinical settings. We reviewed recent studies on the prevalence of hypertensive LVH, as assessed by ECG, in order to update our knowledge about this marker of cardiac organ damage in human hypertension., Design: A MEDLINE search using the key words ' LVH ', 'hypertension', 'ECG', 'cardiac organ damage' and 'cardiac hypertrophy' was performed in order to identify relevant articles. Full articles published in English language in the last decade (1 January 2000 to 31 December 2010) reporting studies in adult or elderly individuals, were considered., Results: A total of 26 studies, including 40 444 untreated and treated individuals (85% whites, 47% men, 32% obese, 28% diabetics and 22% patients with cardiovascular disease) were considered. LVH was defined by 15 criteria (seven studies used two or more criteria, range 2-7); LVH prevalence consistently varied among studies (0.6-40.0%) with an average of 18% in the pooled population. A sex-based analysis in five out of 26 studies (12 084 patients) showed an average prevalence of LVH of 24% in men and 16% in women (odds ratio 1.38, 95% CI 0.91-2.09, P  =  0.11)., Conclusion: Our analysis shows that LVH, as assessed by ECG, is present in a relevant fraction of the hypertensive population; these data highlight the role of ECG as a first-line examination for identifying subclinical organ damage and optimizing blood pressure control in hypertensive patients.

Background: The relationship between high nocturnal blood pressure (BP), organ damage and the dipping/nondipping status is poorly defined. We investigated whether a consistent dipping/nondipping pattern defined on the basis of two 24-h ambulatory BP monitorings (ABPMs) is associated with subclinical organ damage in untreated hypertensive patients with elevated nighttime BP., Methods: All subjects underwent the following procedures: cardiac and carotid ultrasonography, 24-h urine collection for microalbuminuria (MA), and ABPM over two 24-h periods within 4 weeks. Nocturnal hypertension was defined according to current guidelines (i.e., nighttime systolic BP (SBP) ≥120 and/or diastolic BP ≥70 mm Hg) and nondipping status as an average reduction in SBP at night <10% compared with day-time values., Results: Among 343 subjects, 199 were dippers and 144 nondippers. No differences were found in clinical variables, average 48-h BP, left ventricular mass, carotid intima-media (IM) and urinary albumin excretion between the groups. This was also the case for prevalence rates of left ventricular hypertrophy, carotid IM thickening or plaque and MA. Finally, no relationship was found between the markers of organ damage and BP fall at night., Conclusions: In the presence of nocturnal hypertension, dippers have a similar subclinical cardiac and extra-cardiac organ damage as their nondipper counterparts. These data suggest that therapeutic strategies only addressing the nondipper pattern may be insufficient to protect hypertensive subjects against the dangerous effects of elevated nocturnal BP.American Journal of Hypertension, (2012); doi:10.1038/ajh.2012.49.

Aim: We sought to investigate the prevalence and correlates of severe left ventricular hypertrophy (LVH) in relation to age in a large cohort of essential hypertensives referred to a single outpatient hypertension clinic., Methods: A total of 3752 (mean age 53±13 years, 53% men) untreated (29.5%) and treated hypertensive patients categorized in three age groups (I: 18-40 years; II: 41-64 years; III: ≥65 years) were considered for this analysis. All patients underwent extensive investigations searching for target organ damage. LVH, defined as LV mass ≥49/45 g/m(2.7) in men/women, respectively, was graded as mild, moderate and severe according to Lang's report., Results: LVH prevalence was 29.4% in group I, 48.2% in group II and 63.6% in group III. Overall, more than one fourth of patients with LVH had a severely increased LV mass index; the likelihood of having severe LVH was two- and four-fold higher in elderly hypertensives than in their middle-aged and young counterparts, respectively. Increasing age and LVH degree were both associated with a greater prevalence of concentric LV geometry as well as of extra-cardiac organ damage (i.e. carotid intima-media thickness)., Conclusions: LVH is a highly prevalent organ damage in essential hypertensives, particularly in the elderly, who exhibited a more severe increase of LV mass index, higher relative wall thickness and extra-cardiac organ damage compared with young and middle-aged sub-groups. Our findings suggest that the assessment of cardiovascular risk by grading LVH rather than simply defining the presence/absence of this cardiac phenotype could improve therapeutic strategies in the hypertensive population, particularly in the elderly.

Left-ventricular hypertrophy (LVH) is a cardinal manifestation of hypertensive organ damage associated with an increased cardiovascular (CV) risk. We reviewed recent literature on the prevalence of LVH, as assessed by echocardiography, in order to offer an updated information on the magnitude of subclinical alterations in LV structure in contemporary human hypertension. A MEDLINE search using key words 'left ventricular hypertrophy', 'hypertension', 'echocardiography' and 'cardiac organ damage' was performed in order to identify relevant papers. Full articles published in English language in the last decade, (1 January 2000-1 December 2010), reporting studies in adult or elderly individuals, were considered. A total of 30 studies, including 37,700 untreated and treated patients (80.3% Caucasian, 52.4% men, 9.6% diabetics, 2.6% with CV disease) were considered. LVH was defined by 23 criteria; its prevalence ranged from 36% (conservative criteria) to 41% (less conservative criteria) in the pooled population. LVH prevalence was not different between women and men (range 37.9-46.2 versus 36.0-43.5%, respectively). Eccentric LVH was more frequent than concentric hypertrophy (range 20.3-23.0 versus 14.8-15.8, respectively, P<0.05); concentric phenotype was found in a consistent fraction (20%) of both genders. Despite the improved management of hypertension in the last two decades, LVH remains a highly frequent biomarker of cardiac damage in the hypertensive population. Our analysis calls for a more aggressive treatment of hypertension and related CV risk factors leading to LVH.

Background: Left atrial (LA) enlargement is a powerful risk factor for cardiovascular diseases; little information is available about its prevalence and correlates in subjects free of overt cardiac disease seen in echocardiographic practice., Aim: We evaluated the prevalence of LA enlargement (LAE) and the relationship with left ventricular (LV) mass and diastolic function in subjects with preserved LV systolic function referred to an echocardiographic study for routine clinical indications., Methods: 1104 subjects (mean age 58 ± 16 years, 46% men, 57% hypertensives) underwent a comprehensive echo-Doppler examination. LAE and LV hypertrophy (LVH) were defined as LA volume index (LAVI) >29 ml/m(2) and LV mass index (LVMI) >50 g/h(2.7), respectively. Abnormalities of LV relaxation and LV filling were diagnosed by age-related thresholds of lateral annular velocity (Ei) and by early mitral flow velocity to Ei ratio (E/Ei) ≥16, respectively., Results: Overall, 10% of echocardiographic examinations fulfilled the criteria for LAE, 46% for LVH, 45% for altered LV relaxation and 5% for altered LV filling index. LVH progressively increased from 25% to 75% across LAVI quartiles. More patients in the highest quartile exhibited abnormal indexes of LV relaxation and LV filling compared with lower quartiles. In multivariate analysis, LV mass index (β = 0.408), age (β = 0.188), E/Ei ratio (β = 0.140) and Ei (β = 0.140) emerged as major correlates of LAE (p at least <0.01 for all)., Conclusions: LAE is a frequent finding in patients with preserved systolic function seen in current practice; this abnormality is strongly related to LVH and to diastolic dysfunction. Early detection of LAE may identify patients at higher cardiovascular risk and promote appropriate prevention strategies.

AIM. Prevalence, correlates and reproducibility of nocturnal hypertension (NH) as defined by fixed cut-off limits in uncomplicated essential hypertension are poorly defined. Therefore, we assessed such issue in a cohort of 658 untreated hypertensives. METHODS. All subjects underwent procedures including cardiac and carotid ultrasonography, 24-h urine collection for microalbuminuria, ambulatory blood pressure monitoring (ABPM), over two 24-h periods within 4 weeks. NH was defined according to current guidelines (i.e. night-time blood pressure, BP ? 120/70 mmHg) and non-dipping status as a reduction in average systolic (SBP) and diastolic BP (DBP) at night lower than 10% compared with daytime values. RESULTS. A total of 477 subjects showed NH during the first and second ABPM period; 62 subjects had normal nocturnal BP (NN) in both ABPM sessions. Finally, 119 subjects changed their pattern from one ABPM session to the other. Overall, 72.5% of subjects had reproducible NH, 18% variable pattern (VP) and 9.5% reproducible NN. In the same group, figures of reproducible non-dipping, variable dipping and reproducible dipping pattern were 24%, 24% and 52%, respectively. Among NH patients, 56% of whom were dippers, subclinical cardiac organ damage was more pronounced than in their NN counterparts. CONCLUSIONS. In uncomplicated essential hypertensives, NH is a more frequent pattern than non-dipping; NH is associated with organ damage, independently of dipping/non-dipping status. This suggests that options aimed at restoring a blunted nocturnal BP fall may be insufficient to prevent cardiovascular complications unless night-time BP values are fully normalized.