bluuebunny/crossref_metadata_2025 huggingface dataset:
CORRELATION OF ANKLE-BRACHIAL INDEX WITH SEVERITY OF CORONARY ARTERY DISEASE IN PATIENTS HOSPITALIZED FOR ACUTE MYOCARDIAL INFARCTION
Authors: Koumelli A. , Tsioufis K. , Konstantinou K. , Mantzouranis E. , Kasiakogias A. , Dimitriadis K. , Milk A. , Konstantinidis D. , Leontsinis I. , Tousoulis D.
Published: April 2021

Objective:

Ankle-brachial index (ABI) is an stablished predictor of cardiovascular events in different clinical setting including hypertension

Purpose:

To assess the usefulness of ABI evaluation for identifying multivessel CAD in patients with acute myocardial infraction (AMI).

Design and method:

We studied 101 patients [77.2% male; mean age 60.9 years; 63.4% hypertensives; 24.8% with diabetes mellitus (DM)] who were hospitalized because of ST-elevation MI (STEMI, 51.5%) and Non-ST–elevation MI (NSTEMI). All patients underwent baseline estimation of clinical and laboratory parameters during their hospitalization. The ABI was measured according to established methodology using a certified automated device and abnormal ABI was defined as a value <0.9. Severity of CAD was estimated by the number of affected main vessels.

Results:

In the entire population, mean ABI was 1.11 ± 0.17, while 15.8% of patients had abnormal ABI. NSTEMI patients compared to those with STEMI demonstrated a trend forlower ABI (1.07 ± 0.18 vs 1.12 ± 0.16; p = 0.144) and more often abnormal ABI (22.4% vs 9.6%; p = 0.103). Using univariate analysis in the entire population, severity of CAD was correlated with age (r = 0.133; p = 0.053), history of DM (r = 0.225; p = 0.01), ABI value (r = 0.214; p = 0.029) and abnormal ABI (r = 0.242; p = 0.015). In multivariate regression models, both ABI value (b = 0.258; p = 0.014) and abnormal ABI (b = 0.218; p = 0.036) remained significant predictors of CAD severity independently of gender, age, DM, smoking, low density lipoprotein (LDL-C), 24-h systolic blood pressure and the type of MI.

Conclusions:

An impaired ABI is associated with greater risk of multivessel CAD in patients with AMI. This finding in patients with acute coronary syndromes may thusraise the suspicion of advanced disease, alerting to the need for moreaggressive diagnostic and therapeutic strategies.
ROLE OF ATYPICAL CHEMOKINE RECEPTOR 2 IN PERIVASCULAR ADIPOSE TISSUE INFLAMMATION IN ANGIOTENSIN II DEPENDENT HYPERTENSION
Authors: Mikolajczyk Tomasz , Skiba Dominik , Vidler Francesca , Love Samantha , Justo-Junior Amauri , Nosalski Ryszard , Graham Delyth , Maffia Pasquale , Graham Gerard , Guzik Tomasz
Published: April 2021

Objective:

Hypertension (HT) is associated with perivascular adipose tissue (PVAT) inflammation in which chemokines play a crucial role. Atypical chemokine receptor 2 (ACKR2) is essential for CC-chemokine ligand binding and their degradation resulting in regulation of inflammation. We hypothesized that ACKR2 is important for immune cell recruitment into PVAT.

Design and method:

Using flow cytometry we analysed the numbers of leukocytes infiltrating PVAT in ACKR2-/- mice and WT (wild-type, C57BL/6J) infused for 14 days with Ang II (angiotensin II, 490ng/min/kg).

Results:

Chronic infusion of Ang II caused increased of leukocyte (CD45+) content in PVAT in both WT and ACKR2-/- mice. This increase was particularly evident for T cell subsets in WT but not in ACKR2-/-. However the number of macrophages (F4/80+CD11b+) was increased in both groups. Interestingly, ACKR2-/- revealed decreased T cell number infiltrating PVAT upon Ang II infusion in comparison to WT. Hypertension was associated with increased CCR1, CCR2 and CCR3 expression in PVAT in both WT and ACKR2-/-. However, ACKR2-/- revealed higher expression of CCR1 and CCR2 but not CCR3 in comparison to WT. Interestingly, increased expression of CCR5 in PVAT upon Ang II infusion in WT was not observed in ACKR2-/-. Hypertension resulted in increased RANTES level in aorta and PVAT to the same extent in both WT and ACKR2-/-. However, MCP-1, MIP-1 alpha and MIP-1 beta level was higher in ACKR2-/- aorta than in WT aorta upon Ang II infusion. ACKR2 expression was lower in PVAT than in aorta. Interestingly, Ang II administration decreased the expression of ACKR2 in aorta but increased ACKR2 level in thoracic PVAT. RNAscope analysis revealed ACKR2 expression in vascular smooth muscle cells (VSMC). Vessels isolated from ACKR2-/- were protected from vascular dysfunction and revealed reduced ROS production in comparison to WT upon Ang II administration. ACKR2-/- mice developed similar extent of blood pressure increase as WT in hypertension.

Conclusions:

In hypertension, ACKR2-/- is associated with decreased T cell content and reduced CCR5 expression in PVAT. This is accompanied by improved vascular function and diminished ROS production, independently of blood pressure regulation.
TRPM7 IS PROTECTIVE AGAINST CARDIOVASCULAR DAMAGE INDUCED BY ALDOSTERONE AND SALT
Authors: Rios Francisco J. , Zou Zhi -Guo , Harvey Adam P. , Harvey Katie Y. , Neves Karla B. , Alves-Lopes Rheure , Nichol Sarah Ef , Camargo Livia L. , Chubanov Vladimir , Gudermann Thomas , Montezano Augusto C. , Touyz Rhian M.
Published: April 2021

Objective:

TRPM7 is a channel-kinase that regulates cellular signaling and Mg2+ homeostasis. We demonstrated that TRPM7 is protective against cardiac inflammation and dysfunction. Since hyperaldosteronism causes hypertension and Mg2+ wasting, we questioned whether TRPM7 plays a role in aldosterone-induced hypertension and fibrosis.

Design and method:

Wild-type (WT) and TRPM7-deficient (M7+/δ) mice were treated with aldosterone (600 μg/Kg/day) and/or 1% NaCl (drinking water) (aldo, salt or aldo/salt) for 4 weeks. Blood pressure (BP) was evaluated by tail-cuff. Vascular function was investigated by wire myography. Inflammatory infiltrate was investigated by flow cytometry. Molecular mechanisms of fibrosis and inflammation were investigated in cardiac fibroblasts (CF) isolated from WT and M7+/δ mice. Protein expression was assessed by western-blot and histology.

Results

: Aldo/salt reduced TRPM7-phosphorylation (62%) and expression (30%) in WT, similarly to reduced levels observed in M7+/δ-veh. M7+/δ exhibited increased BP by aldo (140mmHg), salt (135mmHg) and aldo/salt (137mmHg) vs M7+/δ-veh (117mmHg) (p < 0.05), whereas in WT, BP was increased only by aldo/salt (134mmHg). All treatments induced endothelial dysfunction in M7+/δ as observed in acetylcholine-relaxation curves [Emax% M7+/δ: aldo (81±4), salt (69 ± 4) and aldo/salt (75 ± 3.0), p < 0.05], whereas in WT, Emax% was reduced after aldo (68 ± 4) and aldo/salt (80 ± 3). Phenylephrine-contraction and SNP-relaxation curves were similar among groups. In kidneys from WT, aldo/salt increased numbers of macrophages (47% vs 32% WT-veh) and CD4+T cells (33% vs 22% WT-veh) (p < 0.05), effects observed in M7+/δ-veh (macrophages: 42%, CD4+T cells: 34%). Aldosterone increased CD8+T cells in kidneys from M7+/δ (16% vs M7+/δ-veh 9%). Collagen was increased only in aortas from M7+/δ-aldo (31%) and M7+/δ-aldo/salt (45%). Aldo/salt induced higher collagen deposition in hearts (68%) and kidneys (126%) from vs WT. Hearts from M7+/δ-veh exhibited increased p-Stat1 and p-Smad3 (1.5-fold), whereas tissues from WT exhibited 3-fold increase only after treatments. CF from M7+/δ showed increased activation of Stat1 (2-fold), Smad3 (9-fold), ERK1/2 (8-fold) and reduced pStat3 (70%) vs WT. These effects were ameliorated by Mg2+ supplementation (p < 0.05).

Conclusions:

We define a novel protective role of TRPM7 in aldosterone-salt induced cardiovascular damage, which when downregulated, facilitates hypertension, vascular remodeling and cardiac fibrosis through Mg2+-dependent mechanisms.
UNCOVERING ASSOCIATIONS BETWEEN BLOOD PRESSURE PHENOTYPES AND IMMUNE TRAITS IN TWINSUK
Authors: Christofidou Paraskevi , Menni Christina , Liechti Thomas , Roederer Mario , Spector Tim , Mangino Massimo
Published: April 2021

Objective:

The primary aim of this work was to define the contribution of both the innate and adaptive immune system arms to blood pressure changes.

Design and method:

In order to define the inter-relationships between immune cell subtypes, blood pressure (BP) and susceptibility to hypertension (HT), we carried out association analyses between 23,394 immune phenotypes and blood pressure measures [systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP)] and HT.

After calculating the mean SBP and DBP values from two BP measurements, we adjusted for medication use by adding 15- and 10-mm Hg to SBP and DBP respectively for individuals reported to be on BP-lowering treatment. PP was calculated as SBP minus DBP according to medication adjusted traits. HT was defined as (i) SBP>=140 mm Hg, (ii) DBP>=90 mm Hg or taking BP-lowering medication.

We undertook a comprehensive and high-resolution deep immunophenotyping flow-cytometry approach, to examine immune traits in 502 female twins from TwinsUK. The platform used covered all major lymphocyte and myeloid subsets in peripheral blood. A linear/logistic mixed model regression analysis adjusted for family structure, age and BMI was used to examine the associations between immune traits and blood pressure phenotypes and HT status respectively.

Results:

We observed statistically significant associations (Bonferroni P-value < 1.71x10–4) between blood pressure phenotypes and immune cell subtypes. In particular, DBP showed 47 significant associations with distinct myeloid cell types of CD8 differentiation T cells. SBP showed 59 significant associations with both CD8 differentiation T cells and specific myeloid subpopulations such as monocytes. PP showed 4 significant associations with monocyte subpopulations. Analysis of HT revealed 7 associations with monocytes, CD8 T cells and dendritic cells.

Conclusions:

The results reported in this study provide preliminary evidence of an inter-relationship between blood pressure and human immune cell profile associations. We have shown for the first time that change in the proportions of immune cells correlates with blood pressure measurements.
EFFECTS OF FEBUXOSTAT ON CAROTID INTIMA-MEDIA THICKNESS IN ASYMPTOMATIC HYPERURICEMIA: A RANDOMIZED CLINICAL TRIAL (PRIZE)
Authors: Tanaka Atsushi , Taguchi Isao , Teragawa Hiroki , Ishizaka Nobukazu , Murohara Toyoaki , Node Koichi
Published: April 2021

Objective:

Elevated levels of serum uric acid (SUA) increase the risk of gout and may be associated with the risk of cardiometabolic disorders and subsequent cardiovascular disease. Clinical evidence regarding the effects of xanthine oxidase (XO) inhibitors on atherosclerosis is lacking. The purpose of the study was to test whether treatment with febuxostat, a non-purine selective inhibitor of XO, delays carotid intima-media thickness (IMT) progression in patients with asymptomatic hyperuricemia.

Design and method:

This was an investigator-initiated, multicenter, randomized, controlled, open-label clinical trial undertaken at 48 Japanese sites. A total of 514 adults, who had both asymptomatic hyperuricemia with SUA >7.0 mg/dL and maximum IMT of the common carotid artery (CCA) 1.1 mm or greater at screening, were equally allocated to receive either dose-titrated febuxostat (10–60 mg daily) or non-pharmacological lifestyle modification for hyperuricemia as a control-arm. The primary endpoint was the percentage change from baseline in mean IMT of the CCA at 24 months. Key secondary outcomes included other carotid ultrasonographic parameters, SUA, and adverse events.

Results:

Compared with the control group, febuxostat had no significant effect on the primary endpoint (1.2% [95% CI, -0.6% to 3.0%] in the febuxostat group vs 1.4% [95% CI, -0.5% to 3.3%] in the control group; between-group difference [febuxostat-control], -0.2% [95% CI, -2.3% to 1.9%]; P = 0.83) and any other carotid ultrasonographic parameters. At 24 months, the between-group difference [febuxostat-control] in the SUA change from baseline was significant (-2.65 mg/dL [95% CI, -2.93 mg/dL to -2.37 mg/dL]; P < 0.001), and gout arthritis occurred only in the control group (4 patients [1.6%]). There were three deaths in the febuxostat group and seven in the control group during follow-up.

Conclusions:

In Japanese patients with asymptomatic hyperuricemia, 24 months of febuxostat treatment did not delay carotid atherosclerosis progression, compared with non-pharmacological care. These findings do not support the use of febuxostat for delaying carotid atherosclerosis in this population. However, febuxostat treatment was tolerable and did not increase the incidence of cardiovascular and all-cause mortality.
OPTIMAL DRUGS FOR MEDICATION REDUCTION: SECONDARY ANALYSIS OF THE OPTIMISE MEDICATION REDUCTION TRIAL
Authors: Sheppard James , Lown Mark , Burt Jenni , Temple Eleanor , Ford Gary , Hobbs Richard , Little Paul , Mant Jonathan , Payne Rupert , McManus Richard
Published: April 2021

Objective:

Deprescribing of antihypertensive medications is recommended in some elderly patients with polypharmacy and multi-morbidity. The OPTiMISE trial demonstrated that antihypertensive medication reduction can be achieved in two thirds of patients without changes in systolic blood pressure (SBP) control or serious adverse events at 12-week follow-up. The present analyses aimed to examine whether specific drug types were associated with more successful medication reduction in the intervention arm of the trial.

Design and method:

A total of 282 participants, aged at least 80 years with SBP < 150 mmHg and receiving 2 or more antihypertensive medications were randomised to medication reduction and included in the present analyses. Successful medication reduction was defined by the proportion of participants maintaining reduced medications. Secondary outcomes examined the association between drug class and change in SBP and adverse events. Multivariate regression analyses were conducted to examine associations adjusted for age, sex, systolic blood pressure, cardiovascular disease, multimorbidity, polypharmacy and frailty.

Results:

Participants included in the analysis were aged 84.6 years, with controlled hypertension (mean SBP 129.4 mmHg), polypharmacy (mean 5.4 medications) and multimorbidity (98.8% participants had 2 or more morbidities). More participants withdrawing ACE inhibitors (79.4%) and beta-blockers (80.6%) were able to maintain medication reduction more than any other drug throughout 12-week follow-up. Half (50.0%) of participants who had these medications removed experienced no increase in SBP at follow-up. In multivariate analyses, calcium channel blockers were less likely to remain withdrawn at follow-up (OR 0.31, 95% CI 0.12 to 0.86), whilst withdrawal of beta-blockers was associated with a significant reduction in SBP (-9.5 mmHg, 95% CI -16.8 to -2.1 mmHg). There was no association between removal of specific drug classes and subsequent adverse events.

Conclusions:

In the OPTiMISE medication reduction trial, beta-blockers were more likely to be successfully reduced and have little impact of follow-up blood pressure than any other antihypertensive drug class. When considering reducing antihypertensive medications due to polypharmacy, beta-blockers should be targeted as a first-line therapy for deprescribing, followed by ACE inhibitors in older patients with controlled hypertension.
STRATIFIED EFFECTS OF BLOOD PRESSURE-LOWERING TREATMENT ON LONG-TERM BLOOD PRESSURE: A META-ANALYSIS OF INDIVIDUAL-LEVEL DATA OF 334,219 PARTICIPANTS FROM 50 RANDOMIZED TRIALS
Authors: Canoy Dexter , Copland Emma , Ramakrishnan Rema , Pinho-Gomes Ana -Catarina , Nazarzadeh Milad , Bidel Zeinab , Salimi-Khorshidi Gholamreza , Woodward Mark , Davis Barry R. , Pepine Carl J. , Chalmers John , Teo Koon , Rahimi Kazem
Published: April 2021

Objective:

Evidence on the magnitude of blood pressure (BP)-lowering treatment effects in large-scale randomised clinical trials is limited but is pertinent for explaining treatment effects on cardiovascular outcomes and for policy planning. We determined the effects of BP-lowering treatment on long-term BP overall and across important patient subgroups defined by their characteristics.

Design and method:

We conducted a one-stage individual patient-level data meta-analysis (N = 50 trials). We analysed data separately by trial design, and fitted mixed models (with fixed treatment effects, fixed time effect, random intercepts at trial and participant level, and a random slope for time at participant level). Models were adjusted for age, sex and baseline BP (except when used as stratification factor) and compared using likelihood ratio test and Akaike information criterion.

Results:

The analysis included 334,219 (42% women) participants with mean age = 65 years, and among whom 18% were current smokers, 47% had CVD, 29% had diabetes, and 73% were previously on BP-lowering medication. Over 4 years of follow-up, participants had an average of 8 BP measurements. For BP-lowering intensity trials (N = 8), mean differences (95% confidence interval) in systolic BP (SBP) and diastolic BP (DBP) between comparison arms were 8.2 (8.0 to 8.4) mmHg and 3.7 (3.6 to 3.9) mmHg, respectively, for placebo-controlled trials (N = 21) the SBP and DBP differences were 4.2 (4.0 to 4.3) mmHg and DBP 1.9 (1.9 to 2.0) mmHg, respectively, and for drug comparison trials (N = 28) the SBP and DBP differences were 1.3 (1.2 to 1.3) mmHg and 0.5 (0.5 to 0.5) mmHg, respectively. The reduction in BP differed by follow-up duration and patient characteristics, particularly for placebo-controlled and BP-lowering intensity trials, which showed substantial heterogeneity in BP reductions according to baseline BP, age, sex, prior CVD, diabetes and non-randomised anti-hypertensive use.

Conclusions:

Pharmacologic agents are effective in reducing long-term BP across individuals with different characteristics. In large-scale trials, the magnitude of BP reduction varied by several patient characteristics, which could have implications on interpretation of any differential effects of BP treatment on major clinical outcomes.
OPTIMAL THRESHOLDS FOR AMBULATORY BLOOD PRESSURE IN PATIENTS WITH HIGH CARDIOVASCULAR RISK
Authors: Jaehyung Ha , Chanjoo Lee , Hyoeun Kim , Kyeong-Hyeon Chun , Jaewon Oh , Sang-Hak Lee , Seok-Min Kang , Sungha Park
Published: April 2021

Objective:

Recent 2017 American College of Cardiology/American Heart Association hypertension guideline suggested new ambulatory blood pressure (ABP) thresholds, however there are arguments whether it is optimal for defining hypertension. The objective of this study was to find optimal ABP thresholds for outcomes especially in patients with high cardiovascular risk.

Design and method:

From the Cardiovascular and Metabolic Disease Etiology Research Center – High Risk Cohort (CMERC-HI), 2026 patients who had 24-hour ABP monitoring data were selected. Baseline 24-hour ABP, daytime ABP, nighttime ABP, morning ABP threshold were determined separately using Cox proportional hazard model with propensity scores adjustment. The composite of cardiovascular disease (CVD) outcomes (hospitalization with MI, stroke, or heart failure) and all-cause mortality were primary end-points of this study.

Results:

A total of 2026(median age, 60 years, 52.6% male) subjects were analyzed in this study. Median follow-up was 3.4 years. There were 54 CVD outcomes and all-cause mortality (8.1 per 1000 person-years). Compared to 24-hour ABP <135/85 mmHg, 24-hour ABP more than 135/85 mmHg was associated with significantly poor outcomes (HR 1.49, 95% CI, 1.02–2.17). However, 24-hour ABP more than 130/80 mmHg and 24-hour ABP more than 125/75 were not associated with significantly higher risk. For daytime ABP, the threshold of 140/90 mmHg was significantly related to higher risk of CVD outcomes or death, (HR 1.78, 95% CI, 1.04–3.05) rather than ABP 135/85 mmHg or 130/80 mmHg. For nighttime ABP, no cut-off level other than 125/75 mmHg (HR 1.58, 95% CI, 1.08–2.32) was statistically meaningful. There was no adequate threshold for morning ABP in this analysis.

Conclusions:

In patients with high risk for CVD, 135/85mmHg for 24hr-ABP, 140/90 mmHg for daytime ABP, 125/75 mmHg for nighttime ABP seemed to be the threshold associated with increased outcomes. The BP threshold suggested by the ACC/AHA guideline was not significantly associated with increased outcomes.
GENETIC BACKGROUND DOMINATES FIBROTIC AORTIC REMODELING DURING ANGIOTENSIN-INDUCED HYPERTENSION IN MICE
Authors: Spronck Bart , Caulk Alexander W. , Ramachandra Abhay B. , Murtada Sae -Il , Rojas Alexia , He Chang -Shun , Bersi Matthew R. , Tellides George , Humphrey Jay D.
Published: April 2021

Objective:

Many induced genetic mutations affect aortic structure and function in mice, but less is known about the influence of background strain. This study quantifies and compares the aortic phenotype in angiotensin II (AngII)-induced hypertension across different strains of wild-type mice.

Design and method:

Adult C57BL/6J and 129SvEv mice were studied before and after induction of hypertension via subcutaneous infusion of AngII (1000 ng/kg/min) for two weeks, which elevated blood pressure similarly in both strains (+34% vs. +32%, systolic). Excised descending thoracic aortas were subjected to a series of isobaric vasocontraction and vasorelaxation tests as well as novel biaxial stiffness testing. Immuno-histological studies quantified medial and adventitial composition as well as CD45+ cellular infiltration.

Results:

Baseline aortic geometry and biomechanical properties were similar across strains, consistent with the existence of general homeostatic mechanical targets. Nevertheless, aortic remodeling due to AngII-induced hypertension differed dramatically between strains, with gross over-adaptive remodeling (exuberant thickening of the media and adventitia) in C57BL/6J (+89% thickness increase) but under-adaptive remodeling in 129SvEv mice (+12% thickness increase). Importantly, vasoconstrictive strength was lower in C57BL/6J than 129SvEv mice, both before (-4% vs. -11% contractile change in outer diameter (δOD), p = 0.020; -8 vs. -24% contractile change in circumferential stress (δσ), p = 0.023) and after (-10% vs. -22% contractile δOD, p < 0.001; -24 vs. -46% contractile δσ, p < 0.001) hypertension. CD45+ cell content was markedly higher in C57BL/6J than 129SvEv mice following hypertension (p < 0.001). When considering individual vessels, wall thickness correlated with both CD45+ content (p = 0.034) and total contractility (p = 0.001), with contractility the strongest predictor statistically. Finally, layer-specific biomechanical analyses revealed increased adventitial load bearing in the hypertensive 129SvEv aorta under passive conditions, which, however, it is able to normalize by its increased contractility.

Conclusions:

Genetic modifiers play key roles in the different hypertensive aortic remodeling between C57BL/6J and 129SvEv mice (Figure) as well as mixed C57BL/6;129SvEv mice. The lower fibrotic response in 129SvEv mice results from their lower inflammatory state but also their greater aortic vasoresponsiveness to AngII, which lowers the wall-stress associated mechano-stimulus for remodeling. Remodeling in mixed-background mice was dominated by the 129SvEv strain.
ARTERIAL STIFFNESS AND ORTHOSTATIC BLOOD PRESSURE CHANGES IN HYPERTENSIVE ADULTS – RESULTS FROM SEPHAR III SURVEY
Authors: Fronea Oana Florentina Gheorghe , Darabont Roxana , Pop Calin , Dorobantu Maria
Published: April 2021

Objective:

To evaluate the relationship between orthostatic hypotension (OH) and arterial stiffness in controlled and uncontrolled hypertensive adults

Design and method:

Eight hundred eighty-nine hypertensive subjects identified in SEPHAR III national-representative survey (aged 18 to 80 years; mean age 48.5 ± 17.5 years, 52.5%females, 81,3% treated, 30,8% controlled) were studied. BP in both sitting and at 1 and 3 minutes after standing up was measured. Arterial stiffness was assessed by PWVao measured by a sphygmomanometric method (Arteriograph). Orthostatic hypotension (OH) was defined by SBP decrease of at least 20mmHg and/or DBP decrease of at least 10mmHg at 3 minutes after standing.

Results:

Orthostatic Hypotension was identified in 161 subjects, representing 19% of the sample., with significantly higher prevalence among uncontrolled hypertensive subjects (21,3% vs. 10.9%, p = 0,001)

In uncontrolled hypertensive subjects, the orthostatic alterations in systolic, but not in diastolic blood pressure (DBP), were inversely related to PWV, independently from age, gender, mean BP, and diabetes mellitus.

In uncontrolled hypertensive subjects the greater the aortic stiffness the larger was the systolic blood pressure (SBP) decrease after assuming orthostatic position. On the contrary, no such association was found between PWV and orthostatic changes of BP in controlled hypertensive subjects.

Conclusions:

Our results suggest the presence of a pathophysiological association between arterial stiffening and BP postural changes in hypertensive adults. Antihypertensive drug treatment, as well as other factors that have not been evaluated in the present study, might have modulated this association.
DIFFERENCE BETWEEN CHRONOLOGICAL AND VASCULAR AGE AS A PREDICTOR FOR CARDIOVASCULAR EVENTS - IDENTIFICATION OF PATIENTS WITH SUPERNORMAL VASCULAR AGING (SUPERNOVA)
Authors: Bruno Rosa Maria , Nilsson Peter , Engsrtöm Gunnar , Wadström Benjamin , Empana Jean -Philippe , Boutouyrie Pierre , Laurent Stéphane
Published: April 2021

Objective:

Pulse wave velocity (PWV) is an established marker of early vascular aging (EVA), but may also help identifying individuals with supernormal vascular aging (SUPERNOVA). Aim of this study is to test the hypothesis that individuals with the largest difference between chronological and vascular age (Delta-age), calculated from classical CV risk factors and PWV, show the lowest rate of CV events, and may thus be defined SUPERNOVA.

Design and method:

Vascular age was calculated according to the best fitting model for chronological age prediction, in the cross-sectional Reference Values for Arterial stiffness Collaboration Database (n = 11,406), for different age categories. The risk of fatal and non-fatal CV events associated with Delta-age was investigated in the longitudinal Malmö Diet and Cancer Study cohort (n = 2642). Delta-age deciles were used to define EVA (<3.0 years), normal vascular ageing (VA, 3.0 to 8.8 years) and SUPERNOVA (>8.8 years).

Results:

In the Reference Values Database, the most significant predictor of vascular age (full model r2 = 0.598) was PWV. In the Malmö Diet and Cancer Study Cohort (6.6-year follow-up, 286 events). Delta-age was significantly and inversely associated with CV events. Compared to normal VA, SUPERNOVA had lower risk [HR 0.55 (95%CI 0.36–0.82)], whereas EVA had higher risk [HR 2.88 (95%CI 1.88–4.40)]. There was no significant association with all-cause mortality.

Conclusions:

PWV proved to be useful to identify SUPERNOVA individuals. Further characterization of this extreme phenotype may help discovering novel protective molecular pathways and providing preventive strategies for successful vascular aging.
CAROTID-TO-FEMORAL PULSE TRANSIT TIME VARIABILITY PREDICTS ALL-CAUSE AND CARDIOVASCULAR MORTALITY IN CHINESE AND SWEDISH ELDERLY
Authors: An Dewei , Muhammad Iram Faqir , Guo Qian -Hui , Borné Yan , Sheng Chang -Sheng , Persson Margaretha , Cheng Yi -Bang , Wang Ji -Guang , Engström Gunnar , Li Yan , Nilsson Peter
Published: April 2021

Objective:

Acquisition of pulses at carotid and femoral arteries allows measurement of carotid-femoral pulse wave velocity (cf-PWV) via determination of pulse transit time (PTT) and pulse travelled distance. PWV predicts adverse outcome and contributes to risk stratification. However, little is known about the PTT variability during the cf-PWV measurement and its predictive value.

Design and method:

Community-based prospective cohorts of elderly population from Shanghai, China and Malmö, Sweden were included in the study. The cf-PWV, cf-PTT and its coefficient of variation (CV) were measured with the Sphygmocor device. Vital status in both cohorts and cause of death in the Malmö subjects were ascertained. Cox proportional hazard model and Fine-Gray competing risk model were applied for analysis.

Results:

Of the 1249 (median age, 75.6 years; 42.5% men) and 2999 (72.4 years; 39.6% men) participants from Shanghai and Malmö who were followed up for a median of 8.9 and 6.6 years, respectively, 292 (23.3%) and 388 (12.9%) died, respectively. The cf-PWV (median: 9.4 vs. 8.7 m/s in Shanghai and 11.2 vs. 9.9 m/s in Malmö) and CV of cf-PTT (median: 8.6 vs. 7.4 % in Shanghai and 9.0 vs. 7.9 % in Malmö) were significantly higher in the deceased people compared to those survived. Age, body mass index, heart rate, mean blood pressure and pulse pressure were determinants (P < 0.05) of the CV of PTT in both cohorts. Each 1-standard deviation increase in the log-transformed CV of cf-PTT was associated with a 14% (95% CI, 1–28%) increased risk of all-cause mortality in Shanghai subjects and 25% (13–37%) and 59% (34–89%) increased risk of all-cause and cardiovascular mortality in Malmö subjects. Adding the CV of cf-PTT to the models including cf-PWV had significant net reclassification improvement (0.202 [0.062–0.321]; P = 0.007) and integrated discrimination improvement (0.013[0.001–0.039]; P = 0.02) for cardiovascular mortality in Malmö subjects.

Conclusions:

The variability of cf-PTT during the cf-PWV measurement was predictive of mortality and improved risk prediction in the elderly.
EVALUATION OF CENTRAL HEMODYNAMICS USING THE RADIAL ARTERIAL PULSE WAVE IN CHILDREN AND YOUNG ADULTS
Authors: Murakami Tomoaki , Shiraishi Masahiro , Takeda Atsuhito
Published: April 2021

Objective:

Evaluation of central hemodynamics is useful in prevention and treatment of cardiovascular diseases. In this study, we examined the accuracy of non-invasively measured central hemodynamics in children and young adults.

Design and method:

This study enrolled 19 patients who had undergone a cardiac catheterization below 28 years old (9.7 ± 7.3 years). Ascending aortic blood pressure was measured recorded using a pressure sensor-mounted catheter (model SPC-454D, Millar Instrument, Inc., Houston, Texas). Radial artery pulse waves were simultaneously measured non-invasively by tonometry (HEM-9000AI, Omron Healthcare Co., Ltd., Kyoto, Japan). We analyzed the degree of coincidence between ascending aortic systolic blood pressure (aSBP) and estimated central systolic blood pressure by tonometry (estCBP) using 36 simultaneous recording of aSBP and estCBP. We also analyzed the relationship between aortic augmentation index (aAI) and radial augmentation index (rAI).

Results:

The aSBP was 95.5 ± 13.1 mmHg and estCBP was 88.5 ± 19.9mmHg. There was a significant relationship between aBP and estCBP (aSBP = 0.78 (estCBP) + 22.7, r = 0.82, p < 0.01). The mean difference of the aSBP minus eCBP was 2.6 ± 8.0 mmHg by Bland-Altman analysis. The rAI was 64.0 ± 15.1% and aAI was 14.9 ± 10.0%. There was a significant correlation between two parameters (r = 0.40, p = 0.015).

Conclusions:

The estimation of central hemodynamics by the radial artery tonometry is useful for children and young adults.
SYSTOLIC BLOOD PRESSURE AT BIRTH: THE IMPACT OF MOTHEŔS OBESITY
Authors: Alvarez Julio , Torro Maria Isabel , Redon Pau , Aguilar Francisco , Redon Josep , Lurbe Empar
Published: April 2021

Objective:

Rates of overweight and obesity are high in the obstetric population, and this is of particular importance because being overweight prior to pregnancy increases, among others, the risk for infants being large for gestational age. The impact of motheŕs weight condition on BP at birth has not been previously analyzed.

Design and method:

Three hundred and twenty one newborns (160 females) born at term (gestational age > 36 weeks) after uncomplicated pregnancies and in the absence of perinatal illness were included. Subjects were divided according to size at birth in small, appropriate, and large for gestational age. Anthropometric parameters were obtained at birth and BP was measured on the second day of life. Motheŕs characteristics were obtained.

Results:

Among mother's characteristics were: age (mean age 32.0 ± 4.6 years), smoking habits (no smokers 70.7%, heavy smokers 4.6%) weight gain during pregnancy (mean 12.8 ± 5.9 kg) and normal weight, overweight and obese (32.4%, 28%, 39.6% respectively). Subjects according to size at birth were small, appropriate, and large for gestational age, 6.9%, 74.5% and 18.6%, respectively. Motheŕs weight was positively related with birth weight (r = 0.212, p < 0.001), length (r = 0.132, p = 0.03) and head circumference (r = 0.194, p = 0.01). Likewise, a positive relationship between SBP and birth weight (r = 0.43, p < 0.001), and SBP with motheŕs weight (r 0.22, <0.001), were observed. When gestational age, sex, length, head circumference and motheŕs characteristics were considered, birth weight was the main and positive determinant of SBP at birth. In addition, motheŕs weight condition assessed by BMI (kg/m2) was also an independent determinant. The concurrent influence of both birth weight and motherś BMI is shown in the table.

Conclusions:

Systolic BP at birth depends of birth weight and motheŕs weight categories. The increment on the prevalence of obesity before pregnancy may contribute to future BP elevation in the offspring.
METHODS TO RECTIFY DISCREPANCIES WITH ADULT BLOOD PRESSURE GUIDELINES
Authors: Larkins Nicholas , Mori Trevor , Choong Cathy , Schlaich Markus , Beilin Laurence
Published: April 2021

Objective:

The American Academy of Pediatrics (AAP) guidelines for screening and managing high blood pressure (BP) for children and adolescents are commonly used for Australian children. These were updated in 2017 to remain consistent with recommendations for adults in the United States (hypertension defined as >=130/80mmHg), which differ from guidelines for Australian adults (>=140/90mmHg). We sought to investigate the applicability of the AAP guidelines to define BP thresholds for Australian children.

Design and method:

The West Australian Pregnancy Cohort (Raine) Study has followed since birth a cohort of 2868 children born between 1989–1991. BP was measured at 3/5/8/10/14/17 years, in the seated position after 5 minutes rest, using an oscillometric sphygmomanometer (Dinamap™). Three readings were taken every 2 minutes until the 10-year visit, and subsequently 6 readings every 2 minutes, with the first measurement discarded and mean of following results calculated to give the BP value. Centile curves were constructed by the LMS method, adjusted for height and stratified by sex, and then compared to the published AAP centile curves. In this analysis we focus on systolic BP (SBP).

Results:

2202 participants were included, contributing 7850 observations (1127 males, 51.2%). The 95th SBP centile according to the fitted curves for a child on the 50th height centile are displayed in Fig. 1, along with equivalent AAP curves. The fitted were higher than the AAP curves for both sexes in early and mid-childhood, before converging in adolescence for females but not males in whom the fitted curve approached 140mmHg at 18 years. Comparing absolute BP thresholds, 13.5% of children had an SBP >=130mmHg between 14 and 18 years of age, but only 3.0% had an SBP >=140mmHg.

Conclusions:

Using data from Australian children and adolescents to define the threshold for hypertension led to curves more congruous with current Australian adult hypertension guidelines. Sex stratification better represents physiologic changes in BP, but again leads to inconsistencies between paediatric and adult guidelines. A better method would be to develop net-benefit or risk-based guidelines based on future clinical events or phenotypes, which we aim to do in future work.
TRENDS IN OFFICE AND AMBULATORY BP ACROSS PEDIATRIC AGE
Authors: Lurbe Empar , Alvarez Julio , Torro Maria Isabel , Redon Josep , Aguilar Francisco , Redon Pau
Published: April 2021

Objective:

ABPM is gaining ground in the assessment of BP in children and adolescents, becoming an aid for diagnosis and management of HTN. The 24-hours ABPM values obtained have generally been higher than those of their office BP counterparts, however the differences across the pediatric age have not been analyzed. The objective of the present study was to assess trends in office and 24-hours in children and adolescents.

Design and method:

Two thousand two hundred and sixty-four BP assessments (office and 24h-ABPM) were performed in 778 Caucasians youth of both sexes (387 females), of European origin, from 5 to 18 years of age (mean age 10.9 3.3 years) in the absence of antihypertensive treatment. Office BP was measured in the non-dominant arm and the three measurements were averaged for analysis. The same day, 24h-ABPM was performed and the averages of the valid readings for 24 h, daytime and nighttime, respectively, were calculated. Differences in trends of office and 24-hours ABPM, according to age and sex were analyzed using the slope of the regression lines.

Results:

Total ABPM measurements were 72+/- 14. Overall 24-hour SBP was higher than the office counterparts, however the magnitude of the differences changes according to age and sex (figure). In girls, the gap between office SBP and 24-hour SBP slightly reduces over the years, in contrast in boys the gap disappears at 15 years and thereafter. The slope of the regression lines was not significant in girls (ß 0.736 0.078 vs 1.199 0.284) while achieving statistically significance in boys (ß 0.395 0.0022 vs 0.759 0.062).

Conclusions:

Differences in trends between office and ABPM are observed across age in both sexes. The reasons that fully explain this, need to be clarified. Disparities in trends may impact on the diagnosis of white-coat and masked HTN.
ACE2 AND ANGIOTENSIN-(1-7) AND ALDOSTERONE BIOSYNTHESIS IN HUMAN ADRENOCORTICAL TISSUES
Authors: Caroccia Brasilina , Vanderriele Paul -Emmanuel , Seccia Teresa Maria , Piazza Maria , Lenzini Livia , Prisco Selene , Torressan Francesca , Domening Oliver , Poglitsch Marko , Iacobone Maurizio , Rossi Gian Paolo
Published: April 2021

Objective:

The angiotensin converting enzyme 2 (ACE2) and its product angiotensin-(1–7) (Ang-(1–7)) were suggested to play cardiovascular protective effects via angiotensin type 2 (AT2R), MasR and alamandine receptors. Whether this involves blunting of aldosterone biosynthesis in humans remains unknown.

Design and method:

We quantified ACE2 mRNA in human aldosterone-producing adenoma (APA) and APA-adjacent tissue obtained ex vivo from primary aldosteronism (PA) patients with real-time and ddPCR. We also investigated the effects of Ang-(1–7) and diminazene aceturate (DIZE), a putative ACE2 activator, on aldosterone synthase (CYP11B2) and 11b-hydroxylase (CYP11B1) as proxy for aldosterone and cortisol secretion, respectively, in the absence and presence of the AT1R antagonist irbesartan, or the MasR antagonist A779.

Results:

We detected ACE2 mRNA at higher amounts in APA-adjacent tissue than in APA. Functional in vitro studies with LC-MS showed active conversion of Ang II into Ang 1–7, albeit at low level, through ACE-2-independent mechanisms. At [10–8 M] Ang-(1–7) did not affect CYP11B1 and CYP11B2 gene transcripts, while at high concentration [10–6 M] it increased both mRNAs (p < 0.001 vs vehicle) through an AT1-R-mediated mechanism as these stimulatory effects were abolished by irbesartan. To investigate if Ang-(1–7) could blunt aldosterone production when CYP11B2 is upregulated, we exposed H295 cells to [10–8 M] Ang II and found that Ang-(1–7) did not blunt Ang II-induced expression of CYP11B1 and CYP11B2 mRNA. Moreover, we discovered that [10–7 M] DIZE increased ACE2 mRNA by 1.5 fold from baseline (p = 0.01) but left CYP11B1 or CYP11B2 mRNA levels unaffected. DIZE did not blunt the AT1R mediated stimulatory effect of [10–6 M] Ang-(1–7) on CYP11B1 and CYP11B2 mRNA.

Conclusions:

Thus, although Ang-(1–7) can be locally generated at low levels and MasR and ACE2 mRNAs are detectable in APA and APA-adjacent tissue, neither Ang-(1–7) nor DIZE were able to blunt Ang II-mediated aldosterone synthase expression. Collectively these results suggest that the ACE2/Ang-(1–7)/MasR axis is unlikely to counteract aldosterone biosynthesis under conditions of enhanced aldosterone secretion as PA and heart failure.
EFFECTS OF THE MTORC1 INHIBITOR EVEROLIMUS ON HEMODYNAMIC CHARACTERISTICS OF PATIENTS WITH PRIMARY ALDOSTERONISM
Authors: Burkard Thilo , Trinh Beckey
Published: April 2021

Objective:

We recently showed that treatment with the mTORC1 inhibitor everolimus lowers home measured blood pressure (BP) and improves renin suppression in subjects with primary aldosteronism (PA). Aldosterone levels were markedly reduced in a subset of subjects. The aim of this study was to perform an explorative, secondary analysis of hemodynamic parameters acquired during this trial.

Design and method:

Design and Methods:

This is an explorative, secondary analysis of an open-label proof-of-concept trial. Fourteen adult patients with PA diagnosed according to the current guidelines of the American Endocrine Society were recruited between June 2017 and June 2018 at our institution. Subjects were treated with everolimus 0.75 mg orally twice daily for 2 weeks. Peripheral and central BP, heart rate, pulse wave velocity, cardiac index, inotropic state index, left stroke work index, stroke systemic vascular resistance and system-integrated hemodynamic maps were measured at baseline, after the treatment and after a 2-week washout. Hemodynamic profiles were generated by thoracic electrical bioimpedance method using the HOTMAN® System. Central BP and pulse wave velocity (PWA) where estimated using Mobil-O-Graph PWA.

Results:

Full hemodynamic data with good recording quality were available for 7 patients, central BP and PWV data for 10 patients, respectively. After treatment with everolimus, we found a significant decrease in peripheral (median 94 mmHg [IQR 85–104] to 88 mmHg [IQR 78–96], p = 0.049, N = 10) and central diastolic blood pressure (median 95 mmHg [IQR 87–106] to 89 mmHg [IQR 82–97], p = 0.037, N = 10), a trend towards decreased peripheral (median 149 mmHg [IQR 130–165] to 144 [IQR 124–149], p = 0.073, N = 10) and central systolic blood pressure (median 138 mmHg [IQR 121–157] to 137 mmHg [IQR 117–141], p = 0.166, N = 10) and significantly reduced hypervolemia (p = 0.008, N = 7). Other hemodynamic parameters of the system-integrated hemodynamic maps remained unchanged (Figure).

Conclusions:

Everolimus decreases central and peripheral diastolic blood pressure in subjects with primary aldosteronism which is possibly mediated by a decrease in preload and primary aldosteronism-induced hypervolemia.
PREVALENCE OF PRIMARY ALDOSTERONISM AND HYPOKALEMIA IN 5,100 PATIENTS REFERRED TO A TERTIARY HYPERTENSION UNIT
Authors: Burrello Jacopo , Monticone Silvia , Losano Isabel , Cavaglia’ Giovanni , Buffolo Fabrizio , Tetti Martina , Covella Michele , Rabbia Franco , Veglio Franco , Pasini Barbara , Williams Tracy Ann , Mulatero Paolo
Published: April 2021

Objective:

Primary aldosteronism (PA) was considered a rare disorder almost always associated with hypokalemia. After the introduction of aldosterone-to-renin ratio, the widespread screening of hypertensive patients unveiled a higher prevalence of normokalemic PA, which now represents the prevailing phenotype. Many studies have described the prevalence of hypokalemia in patients with PA, conversely the prevalence of PA in patients with hypokalemia is unknown. In this retrospective observational study, we define the prevalence of hypokalemia in referred patients with hypertension and the prevalence of PA in patients with hypokalemia and hypertension.

Design and method:

For each patient, medical records were reviewed by three independent reviewers, who were blinded to patients’ identification and diagnosis. Hypokalemia was defined for potassium levels lower than 3.7 mmol/L. PA was diagnosed according to the Endocrine Society guideline. Multivariate logistic regression analysis was used to assess the association of hypokalemia and PA with cardiovascular risk indicators.

Results:

Hypokalemia was present in 15.8% of 5,100 patients with hypertension whereas 76.9% of these patients were normokalemic. PA prevalence in this cohort was significantly higher than in a cohort of 1,672 unselected patients with hypertension in primary care from the PATO study (7.8% vs. 5.9%, P = 0.011). The prevalence of PA in patients with hypokalemia was 28.1% and increased with decreasing serum potassium concentrations up to 88.5% of patients with spontaneous hypokalemia and serum potassium concentrations below 2.5 mmol/L. A multivariate regression analysis demonstrated the association of hypokalemia with the occurrence of cardiovascular events independent of PA diagnosis. An association of PA with the occurrence of cardiovascular events and target organ damage independent of hypokalemia was also demonstrated.

Conclusions:

Our results confirm that PA is a frequent cause of secondary hypertension in patients with hypokalemia and the presence of hypertension and spontaneous hypokalemia are strong indications for a diagnosis of PA. Finally, we show that PA and hypokalemia are associated with an increased risk of cardiovascular events.
THE 2020 ITALIAN SOCIETY OF HYPERTENSION (SIIA) PRACTICAL GUIDELINES FOR THE MANAGEMENT OF PRIMARY ALDOSTERONISM
Authors: Rossi Gian Paolo , Bisogni Valeria , Cesari Maurizio , Maiolino Giuseppe , Seccia Teresa M.
Published: April 2021

Objective:

Considering the amount of novel knowledge generated in the last five years, a team of experienced hypertensiologists was assembled to furnish updated clinical practice guidelines for the management of primary aldosteronism (PA).

Design and method:

They were asked to undertake a systematic review of the literature in international databases by using the PICO strategy, to identify the most relevant studies and to grade their quality. Predefined quality criteria were in compliance with STARD (Standards for Reporting of Diagnostic Accuracy) recommendations. Each section of the guidelines was then jointly prepared by at least two coauthors, who provided, whenever possible, a Class of Recommendation and Level of Evidence, following the American Heart Association (AHA) methodology. The resulting guidelines underwent two rounds of revision, followed by review by an External Committee, two face-to-face meetings with all coauthors to clarify standing queries, a joint presentation on occasion of the 36th SIIA Conference to gather further feedbacks by the all Society members and, on these bases, a further conclusive peer review.

Results:

As a potentially curable cause of hypertension, PA should always be suspected in hypertensive patients and identified in a cost-effective manner by physicians dealing with these patients. Screening for PA is particularly beneficial when hypertension is severe and/or resistant to treatment, because target treatment and/or surgery allows to control BP, to withdraw or markedly reduce the number and dosage of antihypertensive medications, and to prevent or regress organ damage and associated comorbidities. Subtyping should be performed at third level referral centers that are proficient in performing and interpreting AVS. Adrenalectomy usually cure hyperaldosteronism and hypokalemia when a unilateral cause of PA is discovered; BP can also be normalized or considerably reduced in a substantial proportion of patients. Even when subtyping is unfeasible/failed, identification of PA allows undertaking a target treatment, which will provide better control of high BP.

Conclusions:

The proposed guidelines, offering substantial updated information, could simplify the diagnosis of PA and assist practicing physicians in the optimization of treatment and follow-up of patients with one of the most common curable causes of arterial hypertension.