Blood pressure response during exercise testing in individuals with and without hypertension: The value of the recovery phase.

BACKGROUND: Hypertension and exercise testing are essential for cardiovascular risk assessment. However, an exact description of blood pressure (BP) in patients with a hypertensive response during exercise (HRE), especially in the recovery phase is lacking. Herein, we aimed to analyse BP and heart rate during exercise testing and recovery in patients with an HRE. METHODS: 800 patients aged 17-90 with an HRE during a standardized bicycle ergometry test were recruited. The BP behaviour during exercise testing was correlated with clinical data. Furthermore, data were analysed according to the presence of pre-existent hypertension. RESULTS: Of the 800 patients included in this study 497 (62%) were previously diagnosed with hypertension. Analysis of covariance showed a significantly faster systolic (ß [95% CI] 8.0 [4.9-11.1]) and diastolic (2.4 [0.4-4.4]) BP recovery 3 min after maximal exercise in patients without hypertension in univariable models. These results remained robust in fully adjusted models taking into account age, sex, body mass index, cardiovascular disease, and antihypertensive treatment for systolic (5.3 [1.2-9.4]) and diastolic BP (4.5 [1.9-7.0]). Furthermore, patients with hypertension displayed higher systolic BP during maximal exercise in univariable (3.8 [0.1-7.5]) and fully adjusted (5.5 [1.1-10.0]) models. There was no difference in maximum diastolic BP between groups. CONCLUSION: In this large cohort study, patients without hypertension showed a faster systolic and diastolic BP recovery and lower maximal systolic BP compared to patients with hypertension. Overall, this study provides new insights into cardiovascular health during recovery phase.

Effect of a Hypertensive Response During Exercise on Growth Rates of Aortic Diameters.

BACKGROUND: Aortic diameters are related to age, sex, and body size. There is a scarcity of data on the long-term sequelae of a hypertensive response to exercise (HRE) on aortic diameters. In this retrospective cohort study, we aimed to evaluate the relationship between the growth rates of the aorta in individuals with a HRE. METHODS: Our analysis included follow-up data of 649 patients recruited between January 2009 and December 2014 with a HRE. Participants with known connective tissue disease or a history of acute aortic syndrome were excluded. Sinus of Valsalva (SoV) and ascending aorta (AscAo) diameters were measured by transthoracic echocardiography using leading edge to leading edge convention at end-diastole. RESULTS: At baseline, median age, maximum systolic blood pressure (BP), body mass index (BMI), diameter of the SoV, and AscAo were 62 years, 208 mm Hg, 26.9 kg/m2, 35 mm, and 35 mm respectively. 32% of patients were female and 67% had hypertension. After a median follow-up of 7.1 years, mean yearly growth rates (±SD) of the SoV and AscAo were 0.09 (0.41) mm and 0.13 (0.56) mm, respectively. No significant associations were observed between growth rates of aortic diameters and maximum systolic and diastolic BP or when considering only individuals with a baseline diameter >40 mm. CONCLUSIONS: In this large cohort study, maximum systolic and diastolic BP during exercise showed no association with growth rates of aortic diameters. Furthermore, the mean growth rates of aortic diameters in this population were in line with growth rates in a normal population.

CAVI (Cardio-Ankle Vascular Index) as an independent predictor of hypertensive response to exercise.

OBJECTIVES: Hypertensive response to exercise (HRE) is related to the development of future hypertension, cardiovascular morbidity, and mortality, independent of resting blood pressure. We hypothesized that arterial stiffness as measured by cardio-ankle vascular index (CAVI) could be an independent predictor of HRE. MATERIALS AND METHODS: Retrospective chart review of patients participated in the preventive health program at the Bangkok Heart Hospital who underwent both CAVI and treadmill stress testing on the same day between June and December 2018 were performed. Variables for the prediction of HRE were analyzed using univariate analysis, and significant variables were entered into multiple logistic regression. An ROC curve was created to test the sensitivity and specificity of CAVI as a predictor of HRE. RESULTS: A total of 285 participants (55.1% female) were enrolled in this study. There were 58 patients (20.4%) who met the HRE definition (SBP > 210 mmHg in males, SBP > 190 mmHg in females, or DBP > 110 mmHg in both males and females), with a mean age of 46.4 12.8 years. In univariate analysis, age, systolic blood pressure at rest, diastolic blood pressure at rest, pulse pressure at rest, diabetes mellitus, hypertension, dyslipidemia, history of beta-blocker, and CAVI results were statistically significant. Multiple logistic regression revealed that CAVI and systolic blood pressure were statistically significant predictors of HRE with OR of 5.8, 95%CI: 2.9-11.7, P < 0.001 and OR 1.07, 95%CI: 1.03-1.10, P = 0.001 respectively. ROC curve analysis of the CAVI revealed an AUC of 0.827 (95%CI: 0.76-0.89, p < 0.001), and the sensitivity and specificity of cut-point CAVI > 8 were 53% and 92%, respectively. CONCLUSION: This study demonstrated that CAVI is an independent predictor of hypertensive response to exercise. Additionally, the findings suggest that CAVI > 8 can be a valuable tool in identifying individuals at risk for hypertensive responses during exercise.

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.

Deep phenotype characterization of hypertensive response to exercise: implications on functional capacity and prognosis across the heart failure spectrum.

AIMS: Limited evidence is available regarding the role of hypertensive response to exercise (HRE) in heart failure (HF). We evaluated the systolic blood pressure (SBP) to workload slope during exercise across the HF spectrum, investigating haemodynamic and prognostic correlates of HRE. METHODS AND RESULTS: We prospectively enrolled 369 patients with HF Stage C (143 had preserved [HFpEF], and 226 reduced [HFrEF] ejection fraction), 201 subjects at risk of developing HF (HF Stages A-B), and 58 healthy controls. We performed a combined cardiopulmonary exercise stress echocardiography testing. We defined HRE as the highest sex-specific SBP/workload slope tertile in each HF stage. Median SBP/workload slope was 0.53 mmHg/W (interquartile range 0.36-0.72); the slope was 39% steeper in women than men (p < 0.0001). After adjusting for age and sex, SBP/workload slope in HFrEF (0.47, 0.30-0.63) was similar to controls (0.43, 0.35-0.57) but significantly lower than Stages A-B (0.61, 0.47-0.75) and HFpEF (0.63, 0.42-0.86). Patients with HRE showed significantly lower peak oxygen consumption and peripheral oxygen extraction. After a median follow-up of 16 months, HRE was independently associated with adverse outcomes (all-cause mortality and hospitalization for cardiovascular reasons: hazard ratio 2.05, 95% confidence interval 1.81-5.18), while rest and peak SBP were not. Kaplan-Meier analysis confirmed a worse survival probability in Stages A-B (p = 0.005) and HFpEF (p < 0.001), but not HFrEF. CONCLUSION: A steeper SBP/workload slope is associated with impaired functional capacity across the HF spectrum and could be a more sensitive predictor of adverse events than absolute SBP values, mainly in patients in Stages A-B and HFpEF.

Relationship Between Cardiorespiratory Fitness, Baseline Blood Pressure and Hypertensive Response to Exercise in the Ferrari Corporate Population.

AIM: To evaluate the incidence and clinical significance of impaired cardiorespiratory fitness (CRF) and the association with baseline blood pressure (BP) levels and hypertensive response to exercise (HRE). METHODS: A cross-sectional study was conducted on a total sample of 2058 individuals with a mean age of 38 ± 9 years, enrolled for the first time at the Ferrari corporate wellness program "Formula Benessere", including a maximal exercise stress testing (EST). BP and heart rate (HR) values were obtained from EST at rest, during exercise and recovery time. CRF was arbitrarily classified according to estimated VO2 max in optimal, normal, mildly and moderately reduced. RESULTS: One-hundred and thirty-nine individuals of 2058 (6.7%) showed a moderate CRF reduction assessed by EST. Subjects with elevated resting and/or exercise BP showed a worse CRF than those with normal BP levels, also after the adjustment for age, sex, body mass index, smoking habits, peak SBP and DBP. Seventy-seven individuals (3.7%) showed an HRE during EST, with normal baseline BP levels. CONCLUSION: About 7% of a corporate population showed a significantly reduced CRF, assessed by EST. Individuals with lower levels of CRF have higher resting and/or peak exercising BP values after adjusting for co-variables. This study expands the role of EST outside of traditional ischemic CVD evaluation, towards the assessment of reduced CRF and HRE in the general population, as a possible not evaluated CV risk factor.

The association of exaggerated hypertensive response to exercise and beta-blockers use in hypertensives.

PURPOSE: An elevation in blood pressure (BP) during exercise is the normal physiological response, however an abnormally exaggerated rise in BP, in terms of hypertensive response to exercise (HRE), is seen as a prognostic factor for end-organ damage and mortality. HRE is more common in hypertensive (HT) patients and data are lacking on the effect of antihypertensive medication on HRE. In this study, we evaluated patients who underwent treadmill exercise testing (TET) to reveal the effect of antihypertensive medication on HRE. MATERIALS AND METHODS: A cohort of 2970 individuals underwent TET and data were evaluated for HRE development. HRE has been defined as a systolic BP>210 mmHg in males and >190 mmHg in females throughout the TET. To reveal the effects of antihypertensive medication on HRE, 992 HT patients were analyzed. RESULTS: HRE was observed in 11.4% (n = 113) of HT patients and 5.9% (n = 107) of non-HT individuals(p < .001). HRE was observed significantly more in males (57.6% vs. 67.3%;p = .033), and in patients with higher body mass index BMI (29.1 ± 4.5 vs. 30.3 ± 5.2;0.033). There was no significant association between medication and HRE development apart from beta-blockers. Also, gender (odds ratio:1.787; 95%CI:1.160-2.751;p = .008), BMI (odds ratio:1.070;95%CI:1.025-1.116;p = .002) and being under beta-blocker treatment (odds ratio:0.637;95%CI:0.428-0.949;p = .026) were found to be independent predictors of HRE in multivariate logistic regression analysis. CONCLUSION: HRE was associated with gender, BMI and beta-blocker use in hypertensive with male gender and higher BMI associated with higher HRE, while beta-blocker-based treatment, either mono- or combination therapy, associated with lower HRE.

Blood pressure response to exercise in young athletes aged 10 to 18 years.

The aim of the study was to determine arterial blood pressure response to exercise in young athletes. The study group comprised 711 young athletes (457 boys, 254 girls) aged 10 to 18 years (mean 13.41 ± 3.12 years) who had been training for an average of 7.62 ± 4.2 h per week for an average of 4.01 ± 2.5 years. Participants with elevated arterial blood pressure above the 90th percentile at rest were excluded from investigation. A symptom-limited, multistage exercise test to exhaustion was performed using a Monark cycle ergometer. Arterial blood pressure was measured with an aneroid manometer in the third minute of each stage of the test. Mean systolic arterial blood pressure during peak exercise was significantly higher in boys than in girls: 183.21 ± 27.97 mm Hg and 170.97 ± 21.4 mm Hg, respectively (p = 0.03). Multivariate linear regression analysis showed that age and workload had significant effects on arterial blood pressure during the test. Systolic arterial blood pressure during the exercise can be described with the following equations: boys, SBPex (mm Hg) = -1.92 × age (years) + 0.55 × workload (W) + 120.84; girls, SBPex (mm Hg) = -0.88 × age (years) + 0.48 × workload (W) + 111.22. The study results describe reference values of arterial blood pressure during the exercise test. The presented equations and figures can help to assess whether the arterial blood pressure at each stage of the exercise test exceeds the normal range or not.

Hypertensive response to exercise in dipper and non-dipper normotensive diabetics.

Non-dipper blood pressure (NDP) as an indicator of autonomic dysfunction could be associated with hypertensive response to exercise (HRE) in diabetic patients. HRE was determined as a predictor of development of unborn hypertension. We aimed to investigate if any correlation among NDP and HRE in normotensive type 2 diabetic patients. A total of 59 consecutive type 2 diabetic patients without history of hypertension and with normal blood pressure (BP) on ambulatory blood pressure monitoring (ABPM) were enrolled to the study. We divided the study population in to two groups depending on their BP on ABPM as dipper (group 1) or non-dipper (group 2). There were 22 patients (mean age 49.5 ± 7 and 10 male) in group 1 and 37 patients (mean age 53.1 ± 10 and 14 male) in group 2. Daytime diastolic and mean BP of dippers and night time systolic and mean BP of non-dippers were significantly higher. HRE was not significantly different between groups (59% vs. 62%, p = 0.820). Hemodynamic parameters during the exercise test were similar. At multivariate linear regression analysis, resting office systolic blood pressure (SBP) (r = 0.611, p < 0.001), male sex (r = 0.266, p = 0.002) and age (r = 0.321, p = 0.010) were independently correlated with peak exercises SBP. Logistic regression analyses identified the resting office SBP (OR 1.191, 95% CI 1.080-1.313; p < 0.001) and age (OR 1.161, 95% CI 1.038-1.298; p = 0.012) were independent predictors of HRE. This study revealed that HRE is not related with non-dipper BP in diabetic patients. This study could inspire to further studies to explore the main reasons of HRE in diabetes mellitus.

Exercise Hypertension.

Irrespective of apparent 'normal' resting blood pressure (BP), some individuals may experience an excessive elevation in BP with exercise (i.e. systolic BP ≥210 mm Hg in men or ≥190 mm Hg in women or diastolic BP ≥110 mm Hg in men or women), a condition termed exercise hypertension or a 'hypertensive response to exercise' (HRE). An HRE is a relatively common condition that is identified during standard exercise stress testing; however, due to a lack of information with respect to the clinical ramifications of an HRE, little value is usually placed on such a finding. In this review, we discuss both the clinical importance and underlying physiological contributors of exercise hypertension. Indeed, an HRE is associated with an increased propensity for target organ damage and also predicts the future development of hypertension, cardiovascular events and mortality, independent of resting BP. Moreover, recent work has highlighted that some of the elevated cardiovascular risks associated with an HRE may be related to high-normal resting BP (pre-hypertension) or ambulatory 'masked' hypertension and that an HRE may be an early warning signal of abnormal BP control that is otherwise undetected with clinic BP. Whilst an HRE may be amenable to treatment via pharmacological and lifestyle interventions, the exact physiological mechanism of an HRE remains elusive, but it is likely a manifestation of multiple factors including large artery stiffness, increased peripheral resistance, neural circulatory control and metabolic irregularity. Future research focus may be directed towards determining threshold values to denote the increased risk associated with an HRE and further resolution of the underlying physiological factors involved in the pathogenesis of an HRE.

Endothelial Nitric Oxide Synthase Glu298Asp Gene Polymorphism is Associated with Hypertensive Response to Exercise in Well-Controlled Hypertensive Patients

PURPOSE: Hypertensive response to exercise (HRE) is known to be an adverse prognostic factor for future cardiovascular events and may be associated to endothelial dysfunction. Previous studies regarding endothelial nitric oxide synthase (eNOS) Glu298Asp polymorphism focused upon its relation to hypertension. In this study, we hypothesize that the polymorphism may be associated with inherent difference in endothelial response to exercise. PATIENTS AND METHODS: Two hundred sixty nine patients who underwent treadmill test were enrolled in this study; 77 patients (mean age 55.8 +/- 9.4 years) had hypertensive response (peak systolic BP of > 210mmHg in men and > 190mmHg in women). Pulse wave velocity (PWV) was measured on 153 patients of them. The Glu298Asp exchange in exon 7 was determined by the methods of single base extension with amplifying primers and probes for TaqMan. RESULTS: The percentages of the GG, GT and TT genotypes were 81.0, 18.6 and 0.4 %, respectively. The presence of GT or TT genotype was independently associated with prevention of HRE when controlled for age, sex, baseline systolic BP and homeostatic model assessment (HOMA) index (OR=0.35, p=0.016). Subgroup analysis showed that preventive effect for HRE of T allele was significant in females (p < 0.001) and patients without insulin resistance (p=0.009). CONCLUSION: In our study, eNOS Glu298Asp polymorphism was significantly associated with HRE. This result suggests that the presence of T allele of the Glu298Asp polymorphism may be a favorable factor to in preventing HRE, especially in female and patients without insulin resistance.

Endothelial Nitric Oxide Synthase Glu298Asp Gene Polymorphism is Associated with Hypertensive Response to Exercise in Well-Controlled Hypertensive Patients

PURPOSE: Hypertensive response to exercise (HRE) is known to be an adverse prognostic factor for future cardiovascular events and may be associated to endothelial dysfunction. Previous studies regarding endothelial nitric oxide synthase (eNOS) Glu298Asp polymorphism focused upon its relation to hypertension. In this study, we hypothesize that the polymorphism may be associated with inherent difference in endothelial response to exercise. PATIENTS AND METHODS: Two hundred sixty nine patients who underwent treadmill test were enrolled in this study; 77 patients (mean age 55.8 +/- 9.4 years) had hypertensive response (peak systolic BP of > 210mmHg in men and > 190mmHg in women). Pulse wave velocity (PWV) was measured on 153 patients of them. The Glu298Asp exchange in exon 7 was determined by the methods of single base extension with amplifying primers and probes for TaqMan. RESULTS: The percentages of the GG, GT and TT genotypes were 81.0, 18.6 and 0.4 %, respectively. The presence of GT or TT genotype was independently associated with prevention of HRE when controlled for age, sex, baseline systolic BP and homeostatic model assessment (HOMA) index (OR=0.35, p=0.016). Subgroup analysis showed that preventive effect for HRE of T allele was significant in females (p < 0.001) and patients without insulin resistance (p=0.009). CONCLUSION: In our study, eNOS Glu298Asp polymorphism was significantly associated with HRE. This result suggests that the presence of T allele of the Glu298Asp polymorphism may be a favorable factor to in preventing HRE, especially in female and patients without insulin resistance.