Identifying people with chronic obstructive pulmonary disease (COPD) who are at high risk of significant health events such as exacerbations and hospital admissions is clinically important to guide optimisation of preventative interventions. We evaluated the utility of the Global Initiative for Obstructive Lung Disease (GOLD) 2026 ABE assessment tool which stratifies based on exacerbations or symptoms to distinguish these patients at high risk. Methods 664 participants from the ERICA ( E valuation of the R ole of I nflammation in C hronic A irways Disease) COPD cohort were classified into GOLD ABE groups using both the Chronic Airways Assessment Tool (CAAT) score and the modified Medical Research Council (mMRC) breathlessness scale to define the degree of symptoms. National Health Service hospital episode statistics data were prospectively collected for a median follow-up of 4.75 years. Hospital admissions, including for acute exacerbations of COPD (H-AECOPD (hospitalised acute exacerbations of COPD)), were evaluated. Logistic regression analyses with ORs adjusted for potential confounding factors were performed. Results Using CAAT, n=43/182/439 (7%/27%/66%) of participants were in groups A, B and E, respectively. By mMRC, n=144/81/439 (22%/12%/66%) were in groups A, B and E. The ABE tool derived using both CAAT and mMRC predicted H-AECOPD over follow-up. For group B versus group A by CAAT, the OR was 3.72 (95% CI 1.09 to 12.73, p=0.04), and for group E versus group A the OR was 8.13 (95% CI 2.45 to 26.92, p<0.001). By mMRC, for group B versus group A the OR was 2.69 (95% CI 1.36 to 5.32, p=0.005) and for group E versus group A the OR was 4.05 (95% CI 2.38 to 6.05, p<0.001). Conclusions In this prospective real-world UK cohort, the simple GOLD 2026 ABE tool identified patients with high-risk COPD for severe exacerbations (H-AECOPD). The differences in groups A and B classification depending on whether the CAAT score or mMRC scale is used have clinical implications that need consideration.

Aim – GLP-1 and glucagon dual receptor agonists are under clinical development for a range of metabolic conditions including as type 2 diabetes and obesity. The cardiovascular actions of GLP-1 and glucagon receptor agonism are well studied, however less is known about their combination. The aim of this study was to explore the haemodynamic effects of dual agonism at the GLP-1 and glucagon receptor. Methods – Healthy male participants attended a series of randomised, saline-controlled intravenous infusion studies using glucagon [low] (25 ng/kg/min), glucagon [high] (50 ng/kg/min), exenatide (loading dose 50 ng/min for 30 minutes then 25 ng/min) and exenatide:glucagon co-infusion for 120 minutes (Part A, glucagon dose-ranging study), or 60 minutes (Part B, dual-agonism study). Results – In Part A (n=7, 25±7 years), glucagon dose-dependently increased heart rate by 3 bpm with glucagon [low] (p=0.407) and 11 bpm with glucagon [high] (95% CI 4-17 bpm, p<0.01). In Part B (n=12, 25±3 years), exenatide increased heart rate by 4 bpm (95% CI 2-6 bpm, p<0.001). Glucagon [low] increased heart rate by 4 bpm (95% CI 1-7 bpm, p<0.001). Co-infusion increased heart rate by 7 bpm (95% CI 4-9 bpm, p<0.001). There were no differences in stroke volume, cardiac output, blood pressure, or heart rate variability. Conclusion – With the exception of an increase in heart rate, no concerning haemodynamic signals have been detected in studies with GLP-1 and glucagon dual receptor agonists. Our data are consistent with these findings, showing dual agonism acutely increases heart rate in healthy male participants.

OBJECTIVE:To investigate the prevalence of hypertension and cardiovascular dysfunction 1 year postpartum in Black African women who experienced pre-eclampsia in a low-resource setting in Uganda. DESIGN:Prospective cohort study. SETTING:Tertiary referral hospital in urban Uganda. POPULATION:Pregnant women who developed pre-eclampsia between 2019 and 2021, matched to normotensive controls with maternal and gestational age. METHODS:Sociodemographic, clinical and laboratory data were collected at recruitment and 1 year postpartum. Baseline characteristics and incidence rate ratios were calculated to assess risk factors for developing hypertension. Multivariable conditional Poisson regression adjusted for matched study design was used to analyse outcomes. MAIN OUTCOME MEASURES:The primary outcome was hypertension (≥ 140/≥ 90 mmHg) at 1 year postpartum. Secondary outcomes included aortic pulse wave velocity, left ventricular mass index, and left ventricular ejection fraction at 1 year postpartum. RESULTS:At one-year postpartum, hypertension prevalence was higher among women with pre-eclampsia than controls (36.4% (96/264) versus 4.5% (12/264); aIRR 1.26, 95% CI 1.16-1.36, p < 0.001). Postpartum median aortic pulse wave velocity was increased in women with pre-eclampsia (6.45 ± 0.76 m/s vs. 5.67 ± 0.22 m/s, p < 0.001). Left ventricular mass indexed to body surface area was increased in women with pre-eclampsia (71.7 ± 19.6 g vs. 76.5 ± 23.2 g, p < 0.01). Left ventricular ejection fraction was not influenced by pre-eclampsia (p = 0.35). CONCLUSIONS:In this low-resource setting, black African women with pre-eclampsia had increased cardiovascular risk markers at one year postpartum. Over one-third of women with pre-eclampsia developed hypertension at one year postpartum, emphasising the need for postpartum blood pressure monitoring and early intervention to mitigate long-term cardiovascular risk in this high-risk population.

Specialised pro-resolving mediators (SPMs) are endogenously produced lipid mediators that regulate the propagation of inflammation and promote tissue repair. We hypothesised that SPM production is dysregulated in COPD; and associated with disease severity, defined by patients with stable COPD (no exacerbations)versuspatients with frequent exacerbations.MethodsLipid mediators were measured in plasma samples from patients with COPD (stable and frequent exacerbators) and age, sex, BMI-matched healthy controls using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Lipid mediator (LM) profiles were compared between controls and stable COPD patients, and stable COPD patients compared with frequent exacerbators. Exploratory association with ever occurrence of severe exacerbation over 4.1 years of follow up was examined. Data are presented as mean±semin pg·mL−1for LMs, or mean±sd.ResultsForty-nine stable COPD patients had increased levels of pro-inflammatory mediators and some SPMs compared with 28 controls (prostaglandin (PG)D2: 13.97±2.44versus0.53±0.13, p<0.001, lipoxins: 226.83±23.84versus59.84±20.25, p<0.01, respectively). Fifty-two frequent exacerbators had lower PGD2(3.07±0.97versus13.97±2.44, p<0.01) and SPMs (D-resolvins: 8.73±1.25versus34.53±8.95, p<0.01, lipoxins: 53.93±9.23versus226.83±23.84, p<0.01, respectively) compared with stable COPD patients, despite a higher neutrophil count (5.28±2.16versus4.28±1.60×109/L, p=0.004).In exacerbators, D-resolvins levels were independently, inversely associated with occurrence of severe exacerbation (OR:0.88 (95%CI: 0.79,0.97), p=0.03, over follow-up.ConclusionThese findings demonstrate distinct LM profiles of stable COPD and frequent exacerbator patients. In exacerbators, D-resolvins were downregulated compared with stable COPD patients and associated with future risk of severe exacerbations over follow up. Further work is needed to understand these findings.

Introduction Specialised pro-resolving mediators (SPMs) are endogenously produced lipid mediators (LMs) that regulate the propagation of inflammation and promote tissue repair. We hypothesised that SPM production is dysregulated in COPD and is associated with disease severity, defined by patients with stable COPD (no exacerbations) versus patients with frequent exacerbations. Methods LMs were measured in plasma samples from patients with COPD (stable patients and patients with frequent exacerbations) and from healthy controls, matched for age, sex and body mass index, using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The LM profiles of controls were compared with those of stable COPD patients, and the LM profiles of stable COPD patients were compared with those of COPD patients with frequent exacerbations. We explored whether or not there was an association between LM profile and ever having a severe COPD exacerbation over 4.1 years of follow-up. Data are presented as mean +/- sem in pgmL(-1) for LMs, or mean +/- sd. Results 49 stable COPD patients had increased levels of pro-inflammatory mediators and some SPMs, compared with 28 controls (prostaglandin (PG)D-2: 13.97 +/- 2.44 versus 0.53 +/- 0.13; p<0.001; lipoxins: 226.83 +/- 23.84 versus 59.84 +/- 20.25; p<0.01, respectively). 52 patients with frequent exacerbations had lower levels of PGD(2) (3.07 +/- 0.97 versus 13.97 +/- 2.44; p<0.01) and SPMs (D-resolvins: 8.73 +/- 1.25 versus 34.53 +/- 8.95; p<0.01; lipoxins: 53.93 +/- 9.23 versus 226.83 +/- 23.84; p<0.01) than stable COPD patients, despite having a higher neutrophil count (5.28 +/- 2.16x10(9) L-1 versus 4.28 +/- 1.60x10(9) L-1; p=0.004). Among patients with frequent exacerbations, D-resolvin levels were independently inversely associated with occurrence of severe exacerbation (OR 0.88, 95% confidence interval (CI) 0.79-0.97; p=0.03) during follow-up. Conclusion These findings demonstrate distinct LM profiles of stable COPD patients and patients with frequent exacerbations. In those with exacerbations, D-resolvins were downregulated, compared with stable COPD patients, and associated with future risk of severe exacerbations during follow-up. Further work is needed to understand these findings.

BACKGROUND:Essential hypertension is often treated as a uniform condition. However, it encompasses distinct patterns of blood pressure elevation such as isolated systolic, systolic diastolic, and isolated diastolic hypertension, which vary in prevalence according to age and sex. We hypothesized that different hemodynamic mechanisms account for the age- and sex-related differences in these hypertensive phenotypes. METHODS:In this cross-sectional analysis of the ACCT (Anglo-Cardiff Collaborative Trial), 5371 individuals (2402 male), aged 18 to 92 years, free of cardiovascular disease and medication were included. Blood pressure, cardiac output, stroke volume, peripheral vascular resistance (PVR), and aortic pulse wave velocity were measured. Within each sex, subjects were stratified according to age (<30, 30-60, and >60 years), and blood pressure phenotype based on clinic (seated) blood pressure. RESULTS:Isolated systolic hypertension was the most common hypertensive phenotype in young men and characterized by an elevated cardiac output and stroke volume. In contrast, systolic diastolic hypertension and isolated diastolic hypertension were more common in younger females, with systolic diastolic hypertension associated with elevated PVR and aortic pulse wave velocity, and isolated diastolic hypertension with increased PVR. Systolic diastolic hypertension was the most common phenotype in middle age and accompanied by increased PVR in both sexes. Isolated systolic hypertension was again the most common phenotype in older individuals. However, in contrast to younger adults, isolated systolic hypertension affected both men and women equally (~1:1) and was characterized by elevated aortic pulse wave velocity and PVR. CONCLUSIONS:Different hypertensive phenotypes are characterized by distinct hemodynamic mechanisms in an age- and sex-dependent manner. Targeting therapy toward primary hemodynamic abnormalities could lead to more effective interventions in essential hypertension.

INTRODUCTION:Normal pregnancy is associated with cardiovascular changes that enable adaptation to the pregnancy state. We sought to describe the haemodynamic changes from prepregnancy to very early pregnancy in women planning to conceive in southwestern Uganda. METHODS:In this prospective cohort study, we enrolled women in southwestern Uganda planning to conceive. Brachial and central blood pressure, heart rate, cardiac output, stroke volume, and peripheral vascular resistance were assessed prepregnancy and repeated in very early pregnancy. RESULTS:We studied 86 women with a mean age of 27.8 years (SD ± 4.4). The mean gestational age was 7 (±2) weeks at the time of repeat blood pressure measurement. Brachial systolic and diastolic blood pressure decreased in very early pregnancy (116 ± 11 to 114 ± 8 mmHg and 68 ± 6 to 65 ± 5 mmHg, respectively; P  < 0.001). Central systolic and diastolic blood pressure also decreased (112 ± 10 to 109 ± 8 mmHg, P  = 0.003 and 68 ± 6 to 65 ± 5 mmHg, P  < 0.001, respectively), as did peripheral vascular resistance (1450 ± 581 to 1311 ± 276 dyn/s/cm 5P  = 0.038). There was no significant difference in cardiac output (5.3 ± 1.2 vs 5.5 ± 1.1 l/min P  = 0.146) or stroke volume (64 ± 13 to 66 ± 12 ml, P  = 0.172). CONCLUSION:Significant haemodynamic changes occur in very early pregnancy. Using late first trimester measurements as a baseline for pregnancy induced changes may not be suitable for understanding the full extent of pregnancy induced haemodynamic changes, or provide a reliable substitute for prepregnancy states.

Background: Recognising the importance of patient-reported outcomes in assessing COPD severity, the GOLD ABE assessment tool highlights the clinical priority of exacerbations and in those with infrequent exacerbations, symptoms. It has the potential to identify high-risk individuals with COPD which may be important for disease progression and to guide treatments. However, the GOLD ABE tool has not been validated in clinical research studies. Aim: To evaluate the utility of GOLD ABE assessment to predict severe exacerbations in a UK COPD cohort. Firstly, to evaluate across A-B-E within the cohort and then compare the tool to other established COPD severity indices (GOLD grade and BODE quartiles). Methods:664 participants from the ERICA (Evaluation of the Role of Inflammation in Chronic Airways Disease) COPD cohort with complete data to enable classification based on GOLD ABE, GOLD grade (2-4) and BODE quartiles were selected. The COPD Assessment Test (CAT) score was used to assess symptoms for A-B and repeat analysis with mMRC was also undertaken. NHS hospital episode statistics (HES) data were prospectively collected for a median 4.75 years of follow-up and hospital admissions for acute exacerbations of COPD (severe exacerbations, H-AECOPD) were extracted from hospital episode primary position ICD-10 codes. Cox proportional hazards regression, logistic regression and ROC analyses were undertaken. Models were performed unadjusted and then adjusted for age and sex (and FEV1 for ABE). Data are presented as median (IQR), average±SD, n (%). Results: Out of 664 participants, GOLD ABE stratification was as follows: A=60 participants (9%), B=277 (42%), E=327 (49%), 324 (49%) were on triple inhaled therapy. A total of 225 participants (34%) in the cohort had H-AECOPD over follow up with median time to first H-AECOPD being 525 (205-1071) days. 46% of group E, 25% in group B and 10% in group A had a H-AECOPD over follow-up. Group B had a higher risk of H-AECOPD and time to first H-AECOPD compared with group A (p<0.01 for both), despite both groups being infrequent exacerbators at baseline. Table 1 shows further data for ABE, GOLD grade and BODE quartiles. Conclusion: ABE was not more strongly associated with H-AECOPD than other COPD severity indices. Its utility from these data, however, seems to be across the A-B-E comparison to identify individuals at higher risk for future H-AECOPD. Table 1

AIMS:Glucagon-like peptide-1 (GLP-1) and glucagon dual receptor agonists are in clinical development for a range of metabolic conditions, including type 2 diabetes and obesity. The cardiovascular actions at these receptors are well studied, but less is known about their combination. The aim was to explore the acute haemodynamic effects of dual agonism at the GLP-1 and glucagon receptor. METHODS:Healthy male participants attended randomized, saline-controlled intravenous infusion studies using glucagon (low, 25 ng/kg/min), glucagon (high, 50 ng/kg/min), exenatide (loading dose 50 ng/min for 30 min then 25 ng/min) and exenatide:glucagon co-infusion for 120 min in Part A (glucagon dose-comparison study) and 60 min in Part B (dual-agonism study). RESULTS:In Part A (n = 7, median age 21 years, interquartile range 21-32 years), glucagon (high) increased heart rate by 11 beats per minute (bpm) (95% confidence interval [CI] 4-17 bpm, P < .01). In Part B (n = 12, median age 24 years, interquartile range 22-26 years), exenatide increased heart rate by 4 bpm (95% CI 2-6 bpm, P < .001). Glucagon (low) increased heart rate by 4 bpm (95% CI 1-7 bpm, P < .001). Co-infusion of glucagon (low) and exenatide increased heart rate by 7 bpm (95% CI 4-9 bpm, P < .001) and the rate pressure product by 793 mmHg*bpm (95% CI 460-1127 mmHg*bpm, P < .001). There were no differences in cardiac output, blood pressure or heart rate variability. CONCLUSIONS:In healthy males, exenatide and glucagon co-infusion acutely increases the rate pressure product, an indirect measure of cardiac work. This increase is driven by an increase in heart rate, rather than any change in systolic blood pressure.

[This corrects the article DOI: 10.1016/j.xagr.2023.100163.].

Previous studies demonstrated that placental syndromes, including pre-eclampsia, gestational hypertension and fetal growth restriction are associated with an increased risk of maternal hypertension, diabetes and cardiovascular disease (CVD) both in the year after giving birth and in later life. Meanwhile, it is known that pre-pregnancy cardiometabolic risk factors are associated with an increased risk of placental syndromes. Whether placental syndromes simply unmask women with pre-conception poor cardiometabolic health or cause later maternal diabetes and CVD remains unknown due to the modest patient number or the lack of detail in studies with pre-conception measures of cardiometabolic risk factors to date. The POPPY study, coordinated by the University of Cambridge and funded by Wellcome Trust, is to test definitively if placental syndromes adversely affect cardiometabolic health post-partum, independent of women's pre-conception cardiometabolic health through an observational and prospective study of healthy, nulliparous women. Assessment of the participant's cardiometabolic risk factors and validated intermediate phenotypes for CVD will be undertaken pre, during and post pregnancy. Early maternal haemodynamic adaptation to pregnancy will also be assessed to determine whether it can serve as a biomarker for the later development of placental syndromes and the extent to which pre-pregnancy cardiovascular health is linked to cardiovascular maladaptation. Finally, the study will include women who do not intend to conceive during their involvement in the study to test definitively whether pregnancy per se has any effect on future cardiometabolic health. The POPPY study aims to open 6 sites across UK and to recruit a total of 3000 participants to the pregnancy arm and 500 to the non-pregnancy arm based on the confirmed feasibility through two pilot studies IMPOST and CONCEIVE, which share the similar protocol as POPPY. Currently, Cambridge, Glasgow and London each has one site open to recruitment, with the 4th site to come on line 2024.

National and international hypertension guidelines recommend that adults with young-onset hypertension (aged <40 years at diagnosis) are reviewed by a hypertension specialist to exclude secondary causes of hypertension and optimise therapeutic regimens. A recent survey among UK secondary care hypertension specialist physicians highlighted variations in the investigation of such patients. In this position statement, the British and Irish Hypertension Society seek to provide clinicians with a practical approach to the investigation and management of adults with young-onset hypertension. We aim to ensure that individuals receive consistent and high-quality care across the UK and Ireland, to highlight gaps in the current evidence, and to identify important future research questions.

Objective: Obesity and hypertension share a well known association. However, the mechanisms underlying their relationship are not well understood. Our goal was to assess the feasibility of a longitudinal, interventional weight gain study with detailed cardiovascular measurements in humans. Methods: Sixteen healthy, normotensive, young, male volunteers (28 ± 7 years) were enrolled. Body composition, biochemical and cardiovascular data were obtained at baseline, and after an 8-week period of overfeeding (800–1000 kcal/day). Blood pressure (BP), cardiac output (CO) and peripheral vascular resistance (PVR) were determined, as were the minimum forearm vascular resistance (MFVR), forearm blood flow (FBF) response to mental stress and heart rate variability (HRV) parameters. Results: Overfeeding resulted in a median weight gain of 5.6 kg [interquartile range (IQR) 4.6–6.4 kg; P < 0.001]. Seated systolic and diastolic BP were significantly increased by 10 ± 9 and 4 ± 6 mmHg, respectively, after weight gain (P < 0.001 and P = 0.011, respectively). CO also increased and PVR decreased significantly as a result of weight gain (P = 0.032 and P = 0.044, respectively). MFVR was also significantly decreased after weight gain (P = 0.023). The FBF response to mental stress was blunted significantly (P = 0.002), and sympathovagal balance and responsiveness to orthostatic challenge altered moderately after weight gain. Conclusion: Our overfeeding regimen resulted in moderate weight gain and significant increases in BP. An increase in CO is likely to be the dominant mechanism underlying the observed BP changes, with decreases in PVR partially compensating for these effects. Experimental weight gain, coupled with detailed cardiovascular phenotyping, is a feasible model to examine potential mechanisms underlying obesity-associated hypertension in young adults.

Introduction: Unattended (UA) office blood pressure (BP) measurements have been proposed as better substitutes for attended (AT) BP readings for the diagnosis and monitoring of patients with hypertension (HTN). A superior correlation of UA over AT BP measurements with Left Ventricular Hypertrophy (LVH), an early marker of hypertensive organ damage has not been conclusively demonstrated. We hypothesized that in a group with untreated HTN, UA BP would correlate more strongly with left ventricular hypertrophy than AT BP. Methods: Newly diagnosed untreated patients with HTN presenting newly to an outpatient clinic in Nigeria were consented as part of a larger study. Three sets of AT and UA seated BP readings were carried out using a validated device followed by same-day echocardiographic assessment of their Left Ventricular Mass Indexed to Body surface area (LVMI). Pearson’s coefficient (r) was determined and a 2-tailed significance was defined by a two-tailed P value (P) less than 0.05. Coefficients were compared using Fisher r to z transformation. Results: A total of 49 participants (female=25) were recruited with a mean age of 46.2 +/- 9 years. The mean of the AT BP in the cohort (mAT) was 157.1 +/- 13.5mmHg, while the mean of the UA BP was 151.9 +/- 15.7 with no significant difference in both (P=0.085). The mean LVMI of the cohort was 102.3 +/- 28.7 mg/m2. Both the mAT BP (r= 0.304, P= 0.034) and the mUA BP (r=0.354, P=0.013) positively correlated with LVMI, with no significant difference in the strength of both correlations with r to z transformation (z=0.27, P=0.394 ). Conclusion: In a small cohort of newly diagnosed Nigerian hypertensives, both attended and unattended systolic office blood pressure readings correlated positively with left ventricular mass indexed to body surface area, with no significant difference in the strength of their correlation. Having failed to demonstrate a superior correlation of unattended blood pressure readings with LVH, our findings support the continued use of attended office blood pressure readings for clinical monitoring in busy time-constrained office settings where unattended office blood pressure monitoring may not be feasible. Larger studies are however required to confirm these findings.

Objective: There is considerable controversy concerning the physiology and prognostic significance of isolated systolic hypertension (ISH) in youth. We sought to address this by pooling hemodynamic and echocardiographic data from participants up to 40 years in a large international academic research consortium. Design and method: In all 18 centers, 24-hour blood pressure (24hBP) was measured with the same validated oscillometric upper arm device (Mobil-O-Graph, I.E.M., Germany), using a transfer function and ARCSolver algorithms for determination of central pressures (using mean/diastolic BP calibration), pulsatile (Pressure Augmentation-AP, amplitudes of Forward (Pf) and Backward (Pb) wave) and steady state (Cardiac Output-CO, Total Peripheral Resistance-TPR) hemodynamics. Hypertension phenotypes were defined according to average 24h brachial BP as normotension (NTN), isolated systolic (ISH) and diastolic (IDH) hypertension, and systolic/diastolic hypertension (SDH). Left ventricular mass was determined by echocardiography, and indexed to body surface area (LVMi). Results: Overall, 675 participants were included. 52.3, 5.9, 19.1 and 22.7% were classified as NTN, ISH, IDH, and SDH, with average 24h brachial BPs of 117/71, 134/75, 124/85 and 140/93 mmHg, respectively. Participants with ISH were the youngest and tallest among all 4 groups, and had the highest proportion of men. Average 24h central SBP and PP were 121/49, 143/66, 125/38 and 140/46 mmHg in NTN, ISH, IDH, and SDH, respectively. Participants with ISH had highest average 24h values for pulsatile hemodynamics (AP, Pf, Pb) and cardiac output (CO), and participants with SDH had highest average 24h values for TPR, respectively (see Table). LVMi was 76.9, 84.8, 78.2 and 96.3 g/m2 in participants with NTN, ISH, IDH, and SDH, respectively (p<0.0001). Conclusions: In this cohort of younger individuals, ISH was an infrequent condition with specific clinical and hemodynamic characteristics. The relatively high LVMi and central BPs in those with ISH as compared to IDH and NTN is a suspicious prognostic sign.

Objective: To describe the prevalence of systolic hypertension phenotypes based on simultaneous 24hr ambulatory blood pressure monitoring (ABPM) of the brachial (br) and aortic (ao) systolic pressure, as well as their association with left ventricular hypertrophy (LVH), using data from the international 24hr aortic blood pressure consortium (i24ABC). Design and method: Participants with 24hr br & ao ABPM (Mobil-O-Graph, IEM Germany) and echocardiography data from 21 centers worldwide were analyzed and categorized into the following 4 phenotypes: sustained [br & ao] systolic normotension (SSN), isolated br systolic hypertension (IbrSH), isolated ao systolic hypertension (IaoSH), and sustained [br & ao] systolic hypertension (SSH). These phenotypes were generated using 2 different calibration (C) methods and various proposed 24hr ao systolic pressure cut-off values (mmHg) (C1: systolic /diastolic pressure [120 and 114]; C2: mean/diastolic [135 and 132]). Results: We analysed 2367 individuals (49.5 ± 16.1 years, 54.5% men, 55.8% hypertensives). Depending on both cut-off values as well as on calibration method the phenotypes prevalence ranged: IaoSH 5.8% - 24.2%; IbrSH: 0.2% - 8.7%; SSN: 41.9% - 60.3%; SSH: 29.2% - 33.9%. In comparison to the SSN and after adjustment for age, sex and diastolic blood pressure: the SSH phenotype had 2.4 to 3.2 times more often LVH (statistically significant irrespectively of calibration and cut-off); the IaoSH had 1.7 to 2.4 times more often LVH (statistically significant with both C1 and C2); the IbrSH had 2.1 times more often LVH only with C1 and 120 mmHg cut-off. Conclusions: Individuals with the novel herein defined phenotype of 24hr IaoSH constitute a non-neglectable percentage of the population that cannot be identified by brachial arm ABPM, possibly carrying high cardiovascular risk as suggested by the more frequent LVH. Outcome studies are needed to verify these results.