Targeting Hypertensive Response to Exercise and the Association of Masked Hypertension With Subclinical Organ Damage: A Mini-Review and Meta-Analysis.

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 ±â€…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.

Masked Hypertension and Exaggerated Blood Pressure Response to Exercise: A Review and Meta-Analysis.

AIM: Whether exaggerated blood pressure response (EBPR) to exercise represents a marker of masked hypertension (MH) in individuals with no prior history of hypertension is still unclear. We investigated this issue through a review and a meta-analysis of studies providing data on this association in normotensive individuals undergone both to dynamic or static exercise and to 24 h blood pressure monitoring (ABPM). DESIGN: A systematic search was performed using Pub-Med, OVID, EMBASE, and Cochrane library databases from inception up to 31 December 2022. Studies were identified by using the following search terms: "masked hypertension", "out-of-office hypertension", "exercise blood pressure", "exaggerated blood pressure exercise", "exercise hypertension". RESULTS: Nine studies including a total of 387 participants with MH and 406 true normotensive controls were considered. Systolic BP (SBP) and diastolic BP (DBP) at rest were significantly higher in MH individuals than in sustained normotensives: 126.4 ± 1.4/78.5 ± 1.8 versus 124.0 ± 1.4/76.3 ± 1.3 mmHg (SMD: 0.21 ± 0.08, CI: 0.06-0.37, p = 0.007 for SBP; 0.24 ± 0.07, CI: 0.08-0.39, p = 0.002 for DBP). The same was true for BP values at peak exercise: 190.0 ± 9.5/96.8 ± 3.7 versus 173.3 ± 11.0/88.5 ± 1.8 mmHg (SMD 1.02 ± 0.32, CI: 0.39-1.65, p = 0.002 for SBP and 0.97 ± 0.25, CI: 0.47-1.96, p < 0.0001 for DBP). The likelihood of having an EBPR was significantly greater in MH than in their normotensive counterparts (OR: 3.33, CI: 1.83-6.03, p < 0.0001). CONCLUSIONS: Our meta-analysis suggests that EBPR reflects an increased risk of MH and that BP measurement during physical exercise aimed to assess cardiovascular health may unmask the presence of MH. This underscores the importance of BP measured in the medical setting at rest and in dynamic conditions in order to identify individuals at high cardiovascular risk due to unrecognized hypertension.

Unmasking left ventricular systolic dysfunction in masked hypertension: looking at myocardial strain. A review and meta-analysis.

BACKGROUND AND AIM: A growing body of evidence supports the view that masked hypertension (MH) (i.e. normal office and elevated out-of-office BP) is a blood pressure (BP) phenotype associated with increased risk of subclinical organ damage, cardiovascular disease and death as compared to true normotension. Whether left ventricular (LV) systolic function is impaired in individuals with MH is still a poorly defined topic. Therefore, we aimed to provide a new piece of information on LV systolic dysfunction in the untreated MH setting, focusing on speckle tracking echocardiography (STE) studies investigating LV global longitudinal strain (GLS), a more sensitive index of systolic function than conventional LV ejection fraction (LVEF). METHODS: A computerized search was performed using Pub-Med, OVID, EMBASE and Cochrane library databases from inception until June 30, 2022. Full articles reporting data on LV GLS in MH, as assessed by ambulatory BP monitoring (ABPM), and normotensive controls were considered suitable for the purposes of review and meta-analysis. RESULTS: A total of 329 untreated individuals with MH and 376 normotensive controls were included in six studies. While pooled average LVEF was not different between groups [64.5 ±â€Š1.5 and 64.5 ±â€Š1.3%, respectively, standard means difference (SMD): -0.002 ±â€Š0.08, confidence interval (CI): 0.15/-0.15, P = 0.98), LV GLS was worse in MH patients than in normotensive counterparts (-18.5 ±â€Š0.70 vs. -20.0 ±â€Š0.34%, SMD: 0.68 ±â€Š0.28, CI: 0.12/1.24, P < 0.01). CONCLUSIONS: Our findings suggest that early changes in LV systolic function not detectable by conventional echocardiography in the MH setting can be unmasked by STE and that its implementation of STE in current practice may improve the detection of subclinical organ damage of adverse prognostic significance.

Incident Left Ventricular Hypertrophy in Masked Hypertension.

In the PAMELA study (Pressioni Arteriose Monitorate e Loro Associazioni), clinical variables, an echocardiogram, as well as office and ambulatory blood pressure (ABP) were simultaneously measured at baseline and after a 10-year follow-up. The study design allowed us to assess the value of masked hypertension (MH) as a predictor of new-onset left ventricular hypertrophy (LVH). The present analysis included 803 participants without LVH at baseline (left ventricular mass index <115 g/m2 in men and <100 g/m2 in women). Based on office and 24-hour mean ABP values, subjects were divided into 3 groups: normal subjects (normotensive, office blood pressure [BP] <140/90 mm Hg and 24-hour mean ABP <130/80 mm Hg), MH (office BP, normal, and 24-hour mean ABP, elevated), and sustained hypertension (office and 24-hour BP, both elevated). At entry, 57 of 803 subjects fulfilled diagnostic criteria for MH (7.1%); 182 participants developed LVH (22.6%). Compared with subjects with normal in-office and out-of-office BP, the risk of new-onset LVH was greater in MH (odds ratio, 2.22; CI, 1.11-4.46, P=0.0250) after adjustment for potential confounders. This was also the case for the absolute increase of left ventricular mass index. Our study provides a new piece of evidence that MH, identified by office and ABP values, is associated with an increased risk of new-onset LVH. Moreover, our findings convey the notion that office BP may inaccurately estimate the risk of incident LVH in the general population.

When Office Blood Pressure Is Not Enough: The Case of Masked Hypertension.

An increasing attention has been devoted in the last two decades to masked hypertension (MH), a condition characterized by the fact that classification of a normal blood pressure (BP) status by office measurements is not confirmed by home and/or ambulatory BP monitoring (ABPM). MH definition (i.e., normal office BP, but high out-of-office BP) should be restricted to untreated subjects (true MH) whereas masked uncontrolled hypertension (MUCH) reserved to treated patients previously classified as hypertensives, presenting normal office BP and high ABPM or home values. Both MH and MUCH are associated with metabolic alterations, comorbidities, and hypertension-mediated organ damage (HMOD). Furthermore, the risk of cardiovascular events related to these conditions has been shown to be close or greater than that of sustained hypertension. This review discusses available evidence about MH and MUCH by focusing on its prevalence, clinical correlates, association with HMOD, prognostic significance, and their therapeutic implications.

Untreated masked hypertension and carotid atherosclerosis: a meta-analysis.

AIM: Masked hypertension (MH) is recognized as a clinical entity with an unfavorable cardiovascular prognosis; a limited number of reports, however, investigated the impact of this condition on subclinical vascular damage. We performed a meta-analysis aimed at evaluating the association of MH with subclinical carotid atherosclerosis in initially untreated subjects. DESIGN: Studies were identified by the following search terms: "masked hypertension", "isolated clinic normotension", "white coat normotension", "carotid artery", "carotid atherosclerosis", "carotid intima-media thickness", "carotid damage" and "carotid thickening". Full articles published in English language reporting data from studies performed in untreated adult individuals were considered. RESULTS: Overall, 2752 untreated subjects (1039 normotensive, 497 MH and 766 hypertensive individuals) of both genders were included in five studies (sample size range 18-222 for MH participants). Common carotid intima-media thickness (IMT) showed a progressive increase from normotensive (681 ± 24 µm) to MH (763 ± 57 µm) (standardized mean difference, SMD: 0.51 ± 0.19, 95% CI 0.13-0.89, p < 0.01) and to sustained hypertensive subjects (787 ± 58 µm) (SMD: 0.33 ± 0.07, 95% CI 0.20-0.46, p < 0.01). The statistical difference between MH and NT became borderline after correction for publication bias. A sensitivity analysis showed that the final result was not substantially affected by a single study effect. CONCLUSIONS: Our findings support the view that MH subjects tend to have a higher risk of developing early carotid atherosclerosis than their true normotensive counterparts. From a practical perspective, the ultrasound search of preclinical carotid disease may improve cardiovascular risk stratification and decision making strategies in these subjects.

Untreated Masked Hypertension and Subclinical Cardiac Damage: A Systematic Review and Meta-analysis.

AIM: Data on the association of masked hypertension (MH) (i.e., normal office and elevated out-of-office blood pressure (BP)) with cardiac damage are scanty. We performed a meta-analysis in order to provide a comprehensive information on subclinical cardiac alterations in subjects with MH. DESIGN: Studies were identified by the following search terms: "masked hypertension," "white coat normotension," "isolated ambulatory hypertension," "left ventricular mass," "left ventricular hypertrophy," "cardiac damage," and "echocardiography." Full articles published in English language providing data on left ventricular (LV) mass and/or prevalence of LV hypertrophy in MH, as assessed by ambulatory BP monitoring, were considered. RESULTS: Overall, 4,884 untreated subjects (2,467 normotensive, 776 MH, and 1,641 sustained hypertensive individuals) of both genders included in 12 studies were analyzed. LV mass index showed a progressive increase from normotensive (79.2 ± 0.35 g/m(2)) to MH (91.6 ± 4.0 g/m(2)) (standard difference in means (SDM): 0.50 ± 0.11, confidence interval (CI): 0.28-0.73, P < 0.01) and to hypertensive subjects (102.9 ± 3.3g/m(2)) (SDM: 0.22 ± 0.07, CI: 0.09-0.35, P < 0.01). After assessing data for publication bias, the difference between groups was still significant. CONCLUSIONS: Our findings support an association between MH and increased risk of LV structural alterations compared to true normotensive individuals. Due to the worse cardiovascular prognosis associated with subclinical cardiac damage, subjects with MH should be carefully screened in order to detect hypertensive organ damage and provide appropriate therapeutic interventions.

Masked hypertension and echocardiographic left ventricular hypertrophy: an updated overview.

Masked hypertension (MH) is an emerging clinical entity predisposing to subclinical organ damage and to increased cardiovascular risk. We sought to review the recent literature focusing on the association between MH and echocardiographic left ventricular hypertrophy (LVH). A MEDLINE search was performed in order to identify relevant papers using the key words such as 'masked hypertension', 'ambulatory hypertension', 'left ventricular hypertrophy', 'cardiac damage', 'target organ damage', 'left ventricular dysfunction'. Full articles published in English language in the last decade, namely from 1 December 1999 to 31 July 2011, reporting studies in adult or elderly individuals, were considered. Checks of the reference lists of selected papers complemented the electronic search. A total of 13 studies, including 966 patients with MH (sample size range 17-222 patients, mean age range 30-70 years; men 71%) and 2640 controls with sustained normotension, controlled hypertension, and white coat hypertension were considered. The prevalence of LVH, defined according to six criteria, ranged from 7 to 66% in MH and from 0.4 to 42% in non-MH counterparts (average 29 vs. 9%, P<0.01). In conclusion, available evidence linking a selective blood pressure elevation outside office to echocardiographic LVH in clinically normotensive individuals is supported by limited evidence. Further studies are needed to expand our knowledge in this area and to explore the beneficial effects of antihypertensive treatment on subclinical cardiac damage in patients with MH.

The Hyper-Pract Study : a multicentre survey on the accuracy of the echocardiographic assessment of hypertensive left ventricular hypertrophy in clinical practice.

Left ventricular hypertrophy (LVH) assessed by echocardiography has a relevant impact in clinical decision making in hypertensive patients. We investigated the precision and accuracy of hypertensive LVH determination in current clinical practice by a regional-based survey. The study included 211 patients with essential hypertension consecutively attending six hospital outpatient hypertension clinics in the northern Italian region of Lombardy; all subjects had undergone an echocardiographic examination for hypertension-related problems in a non-academic or research ultrasound laboratory within 2 years. The original echocardiographic report was examined to ascertain whether the diagnosis of LVH was based on calculation of left ventricular (LV) mass according to validated formulae and indexed to body size (primary outcome) and whether LV geometrical patterns and indices of diastolic function were provided (secondary outcome). A total of 211 echocardiograms performed by 120 physicians operating in 73 different hospital and out-of-hospital ultrasound laboratories were collected. Absolute LV mass, LV mass index and relative wall thickness were calculated in 45.5%, 24.6% and 12.3% of the cases, respectively. Parameters of LV diastolic filling were measured in two-thirds of the cases and estimation of E/A ratio was provided by less than 20% of the examinations. This study shows that a large majority of echocardiographic examinations, routinely performed in hypertensive subjects in order to detect cardiac damage, do not report qualifying data on LV mass, LV geometry and diastolic function. These results indicate that a quantitative assessment of LVH and LV function is rarely provided in clinical practice.

Left ventricular hypertrophy and cardiovascular risk stratification: impact and cost-effectiveness of echocardiography in recently diagnosed essential hypertensives.

BACKGROUND: Echocardiography is more accurate than electrocardiography in the assessment of cardiac target organ damage related to hypertension, thus leading to a more precise stratification of total cardiovascular risk. However, ultrasound examination of the heart on a routine basis remains a matter of debate. OBJECTIVE: To evaluate the impact and cost-effectiveness of echocardiographic examination on global risk stratification in low and medium-risk hypertensive patients in relation to age and sex. METHODS: A total of 580 untreated hypertensive individuals (355 men and 225 women, mean age 47.8 +/- 11.4 years), classified at low to medium risk, according to routine clinical work-up suggested by the 2003 European Society of Hypertension/European Society of Cardiology guidelines, were included in the study. Total risk was reassessed by adding the results of ultrasound examination of the heart. Left ventricular hypertrophy (LVH) was defined as a left ventricular mass index of 125 g/m2 or more in men and 110 g/m2 or more in women. The impact of LVH in stratifying risk was assessed according to age (< 50 and > or = 50 years) and sex. RESULTS: According to routine classification, 16.3% (n = 93) of the 580 patients were considered to be at low added risk and 83.7% (n = 487) at medium added risk. In the whole population, echocardiographic LVH was found in 86 patients (14.8%) who were then reclassified in the high-risk stratum. The prevalence rates of patients reclassified in the high-risk class as a consequence of LVH detection, according to age and sex, were as follows: 8.9% in men under 50 years, 12.3% in women under 50 years, 26.7% in men aged 50 years and over and 15.3% in women aged 50 years and over. The cost per detected case of LVH was 595 euros in patients under 50 years of age and 290 euros in those 50 years of age and older. CONCLUSIONS: Our findings indicate that the prevalence of LVH, and consequently the probability of upgrading the total cardiovascular risk profile, is highest in the group of old hypertensive men; echocardiography has a limited impact on the risk reclassification in younger patients and an unfavourable cost-effectiveness profile. Our data thus do not support the systematic ultrasound assessment of the heart in all uncomplicated hypertensive individuals.

Carotid atherosclerosis and cardiovascular risk stratification: role and cost-effectiveness of echo-Doppler examination in untreated essential hypertensives.

OBJECTIVE: To investigate the impact and cost-effectiveness of carotid ultrasonographic examination on total risk stratification in low-medium risk hypertensive patients in relation to age (< 50 and > 50 years) and gender. METHODS: Five hundred and eighty untreated hypertensives classified at low-medium risk, after the routine work-up recommended by the 2003 ESH/ ESC guidelines, were included in the study and total risk was reassessed by adding the results of carotid ultrasonography. RESULTS: According to the stratification based on routine work-up 16.3% of the whole population was considered at low added risk and 83.7% at medium added risk. Carotid subclinical damage was found in 158 patients (27.0%), who were then reclassified in the high-risk stratum. Prevalence rates of patients reclassified in the high-risk stratum as a consequence of carotid damage were as follows: 12.6% in men < 50 years, 14.1% in women < 50 years, 53.0% in men > or = 50 years and 40.1% in women > or = 50 years. The cost per detected case of carotid atherosclerosis was 473 euro in patients < 50 years and 133 euro in those > or = 50 years. CONCLUSIONS: Our results show that: (i) the use of carotid ultrasonography allows a much more accurate identification of high-risk individuals; (ii) its impact and cost-effectiveness on the risk stratification process differs markedly according to the age and gender; (iii) the selective use of this procedure in subjects at high risk of target organ damage may substantially improve the cost of primary prevention.