bluuebunny/crossref_metadata_2025 huggingface dataset:
Hierarchical modelling approach to estimate the abundance of data-limited cetacean species and its application to fishery-targeted and rarely seen delphinid species off Japan
Authors: Kanaji Y , Sasaki H , Hakamada T , Okamura H
Published: June 2023

An assessment of the abundances and their trends is urgently needed for the conservation and management of fishery-targeted and rarely seen cetacean species (FTCS and RSCS, respectively); however, such assessment is often challenging because of the paucity of available data. In particular, the number of sightings is smaller than the general requirement for the reliable estimation of a detection function, and the spatial coverage of many cetacean surveys is insufficient. To address these issues, we propose a Bayesian approach that uses the previous abundance estimation of the same species or a species with similar biological traits as prior information. Therefore, we obtained the latest abundance estimates for six FTCS and two RSCS. For FTCS, we also estimated abundance trends by fitting an exponential population dynamics model with random effects accounting for interannual changes in animal distributions to the posterior samples of the Bayesian abundance estimates. Our approach enables us to (1) facilitate stakeholders’ consensus by maintaining previously agreed abundances while updating the conservation information; (2) identify the species of greater concern and prioritize conservation efforts towards those species; and (3) monitor the abundance and trends of data-limited cetacean species.
The role of the radiologist in diagnosing placenta percreta: a case report and review of the literature
Authors: Elharras Yahya , Choayb Safaa , Lrhorfi Najlae , Allali Nazik , Chat Latifa , Elhaddad Siham
Published: June 2023

Placenta percreta is the most severe and least common form of placental insertion abnormalities. The increasing frequency of C-Section deliveries has led to more of these abnormalities. Ultrasound and magnetic resonance imaging (MRI) have a key role in diagnosing these abnormal adherences since it shows best transmural extension of the placental tissue. We report a case of a woman with a previous cesarean delivery who had been diagnosed with a placenta preavia on ultrasound and a suspicion of transmural extension with her MRI later showing a placenta percreta.
Bivalves Present the Largest and Most Diversified Repertoire of Toll-Like Receptors in the Animal Kingdom, Suggesting Broad-Spectrum Pathogen Recognition in Marine Waters
Authors: Saco Amaro , Novoa Beatriz , Greco Samuele , Gerdol Marco , Figueras Antonio
Published: June 2023

Toll-like receptors (TLRs) are the most widespread class of membrane-bound innate immune receptors, responsible of specific pathogen recognition and production of immune effectors through the activation of intracellular signaling cascades. The repertoire of TLRs was analyzed in 85 metazoans, enriched on molluscan species, an underrepresented phylum in previous studies. Following an ancient evolutionary origin, suggested by the presence of TLR genes in Anthozoa (Cnidaria), these receptors underwent multiple independent gene family expansions, the most significant of which occurred in bivalve molluscs. Marine mussels (Mytilus spp.) had the largest TLR repertoire in the animal kingdom, with evidence of several lineage-specific expanded TLR subfamilies with different degrees of orthology conservation within bivalves. Phylogenetic analyses revealed that bivalve TLR repertoires were more diversified than their counterparts in deuterostomes or ecdysozoans. The complex evolutionary history of TLRs, characterized by lineage-specific expansions and losses, along with episodic positive selection acting on the extracellular recognition domains, suggests that functional diversification might be a leading evolutionary force. We analyzed a comprehensive transcriptomic data set from Mytilus galloprovincialis and built transcriptomic correlation clusters with the TLRs expressed in gills and in hemocytes. The implication of specific TLRs in different immune pathways was evidenced, as well as their specific modulation in response to different biotic and abiotic stimuli. We propose that, in a similar fashion to the remarkable functional specialization of vertebrate TLRs, the expansion of the TLR gene family in bivalves attends to a functional specification motivated by the biological particularities of these organisms and their living environment.
Not Quite Lost in Translation: Mistranslation Alters Adaptive Landscape Topography and the Dynamics of Evolution
Authors: Schmutzer Michael , Wagner Andreas
Published: June 2023

Mistranslation—the erroneous incorporation of amino acids into nascent proteins—is a source of protein variation that is orders of magnitude more frequent than DNA mutation. Like other sources of nongenetic variation, it can affect adaptive evolution. We study the evolutionary consequences of mistranslation with experimental data on mistranslation rates applied to three empirical adaptive landscapes. We find that mistranslation generally flattens adaptive landscapes by reducing the fitness of high fitness genotypes and increasing that of low fitness genotypes, but it does not affect all genotypes equally. Most importantly, it increases genetic variation available to selection by rendering many neutral DNA mutations nonneutral. Mistranslation also renders some beneficial mutations deleterious and vice versa. It increases the probability of fixation of 3–8% of beneficial mutations. Even though mistranslation increases the incidence of epistasis, it also allows populations evolving on a rugged landscape to evolve modestly higher fitness. Our observations show that mistranslation is an important source of nongenetic variation that can affect adaptive evolution on fitness landscapes in multiple ways.
A HEAD-TO-HEAD COMPARISON OF PULSE TRANSIT TIME USING SECOND-DERIVATIVE AND INTERSECTING TANGENTS METHODS
Authors: Tairi Amira , Obeid Hasan , Khataei Sanam , Fortier Catherine , Agharazii Mohsen
Published: June 2023

Objective:

Determination of aortic stiffness as measured by carotid-femoral pulse wave velocity (CFPWV) is based on pulse transit time (PTT). PTT is determined by identification of the foot of the pressure wave using either the peak of the second-derivative or the intersecting tangents algorithm. The aim of this study was to examine if there are any differences when these algorithms are performed on the same arterial pressure waveforms.

Design and method:

Carotid and femoral arterial pressure waveforms were simultaneously recorded using the piezoelectric sensors of the Complior Analyse system. Waveforms were extracted and imported into In-house software (MATLAB; MathWorks, Natick, Massachusetts, USA) to calculate the PTT only on valid pressure waveforms without artifacts that are due to movements.

Results:

In 105 human subjects (59 ± 18 years; 64% men) including a mix of 59% hypertensive, 34% with chronic kidney disease, 16% diabetic and 13% with cardiovascular disease, the average brachial blood pressure was 125 ± 18/73 ± 10 mmHg. A total of 6 203 pairs of simultaneous carotid and femoral arterial pressure waveforms were analysed. The PTT using the second-derivative algorithm was 68.4 ± 18.6 ms (CFPWV: 9.48 ± 3.18 m/s), similar to PTT using the intersecting tangents method that was 68.6 ± 18.8 (CFPWV: 9.45 ± 3.12). This difference while statistically significant given the high number of observation points (P < 0.001), is not considered to be clinically significant.

Conclusions:

Based on our findings, both algorithms perform similarly and can be used interchangeably when high quality acquisition are used. However, device-based algorithms may perform differently given variabilities in quality assessment criteria.
DASH VS. MEDITERRANEAN DIET ON A SALT RESTRICTION BACKGROUND IN ADULTS WITH HIGH NORMAL BLOOD PRESSURE OR GRADE 1 HYPERTENSION: A RANDOMIZED CONTROLLED TRIAL
Authors: Filippou Christina , Thomopoulos Costas , Konstantinidis Dimitrios , Siafi Eirini , Tatakis Fotis , Manta Eleni , Drogkaris Sotiris , Polyzos Dimitrios , Kyriazopoulos Konstantinos , Grigoriou Kalliopi , Tousoulis Dimitrios , Tsioufis Konstantinos
Published: June 2023

Objective:

Non-pharmacological measures are recommended as the first-line treatment for individuals with high-normal blood pressure (BP) or mild hypertension. Studies directly comparing the BP effects of the Dietary Approaches to Stop Hypertension (DASH) vs. the Mediterranean diet (MedDiet) on a salt restriction background are currently lacking. Thus, our purpose was to assess the BP effects of a 3-month intensive dietary intervention implementing salt restriction either alone or in the context of the DASH, and the MedDiet compared to no/ minimal intervention in adults with high normal BP or grade 1 hypertension.

Design and method:

We randomly assigned never drug-treated individuals to a control group (CG, n = 60), a salt restriction group (SRG, n = 60), a DASH diet with salt restriction group (DDG, n = 60), or a MedDiet with salt restriction group (MDG, n = 60). The primary outcome was the attained office systolic BP difference among the randomized arms at the end of the study.

Results:

A total of 240 patients were enrolled, while 204 (85%) completed the study. According to the intention-to-treat analysis, compared to the CG, office and 24h ambulatory systolic and diastolic BP were reduced in all intervention groups. A greater reduction in the mean office systolic BP was observed in the MDG compared to all other study groups (MDG vs. CG: mean difference = -15.1 mm Hg; MDG vs. SRG: mean difference = -7.5 mm Hg, and MDG vs. DDG: mean difference = -3.2 mm Hg, all P-values < 0.001). The DDG and the MDG did not differ concerning the office diastolic BP and the 24h ambulatory systolic and diastolic BP; however, both diets were more efficient in BP-lowering compared to the SRG.

Conclusions:

On a background of salt restriction, the MedDiet was superior in office systolic BP-lowering, but the DASH and MedDiet reduced BP to an extent higher than salt restriction alone.

Registration number: NCT05669404
PROGNOSTIC IMPACT OF RENIN ANGIOTENSIN ALDOSTERONE SYSTEM INHIBITOR IN HYPERTENSIVE PATIENTS UNDERGOING TRANSCATHETER AORTIC VALVE IMPLANTATION
Authors: Mancusi Costantino , Basile Christian , Fucile Ilaria , Luca Nicola De , Franzone Anna , Esposito Giovanni
Published: June 2023

Objective:

The purpose of this study was to determine the prognostic impact of baseline treatment with RAAS inhibitors (RAASi) on all-cause mortality in a population of patients with severe AS who underwent transcatheter aortic valve implantation (TAVI).

Design and method:

The study included 373 patients with AS who had undergone TAVI. Analyses were undertaken on the subgroup of hypertensive individuals (n 327) with 2 years of follow-up. Clinical characteristics were compared using Kruskal-Wallis non-parametric test for independent samples and study-stratified multivariable Cox proportional hazards regression models was built according to baseline RAASi therapy status. A second analysis was undertaken by categorizing patients receiving RAASi medication (n 222) into those receiving angiotensin II receptor blockers (ARBs) (n 110) and those receiving angiotensin-converting enzyme inhibitors (ACEi) (n 112).

Results:

Taking RAASi at baseline in the hypertensive patients group was significantly related to gender (Women 56,8%), heart failure (25,7%), chronic kidney disease (CKD) (25,7%), atrial fibrillation (AF) (19,4), being on calcium-channel blocker (26,6%) or anti-platelet therapy (68,5%) (all p < 0,05). All-cause mortality occurred in 23 (10,4%) of the patients on RAASi, 9 (8,2%) on ARBs and 14 (12,4%) on ACEi.

In univariate COX regression model treatment with a RAASi was related with a reduction in 2-year all-cause mortality (EXP 0.46, p 0.011). After multivariable correction for significant confounders the association was not statistically significant (p = 0.08). Analyzing ACEi ARBs separately baseline ARB therapy was associated with significant reduction in all-cause mortality (EXP 0.44, p 0.028) (Figure) that was confirmed in multivariate analysis (EXP 0.42, p 0.038) with no impact in baseline ACEi use (Table).

Heart failure (EXP 2.87, p < 0.001), atrial fibrillation (EXP 2.39, p 0.005) and chronic kidney disease (EXP 2.08, p 0.02) were all related with an increased 2-year all-cause mortality, but after multivariable correction only heart failure remained statistically significant.

Conclusions:

ARBs, but not ACEi, are independently associated with a decreased risk of 2-year all-cause death in a cohort of hypertensive patients with severe AS who underwent TAVI. While it is true that these results have molecular basis, additional research is required to corroborate these findings.
IDENTIFYING HYPERTENSION IN TEENAGERS: DIFFERENCES BETWEEN EUROPEAN AND AMERICAN GUIDELINES
Authors: Eason Stephen , Sayers Merlyn
Published: June 2023

Objective:

Since the measurement of blood pressure is an element in the qualification of volunteers presenting for blood donation, there is an opportunity to identify, in these ostensibly healthy individuals, those who might be at heightened risk of hypertensive heart disease. Since the classification of blood pressure differs when using the American College of Cardiology/American Heart Association and European Society of Cardiology/European Society of Hypertension guidelines, we took this opportunity to compare the prevalence of suspected hypertension in teenagers as differently identified by the two systems.

Design and method:

Participants in the study were American volunteer blood donors, age 16 to 19, who donated between the years 2015 and 2021 at an independent, community blood program serving some 200 hospitals. There were 87,051 females and 59,498 males. Systolic (SBP) and diastolic (DBP) blood pressures were measured using automated equipment (Welch Allyn, ProBP). The cut points chosen for hypertension were, by ACC/AHA criteria, > = 130 (SBP) or > = 80 mmHg (DBP). The ESC/ESH criteria for hypertension were > = 140 (SBP) and/or > = 90 mmHg (DBP).

Results:

The table shows percentages of male and female teenagers considered hypertensive by American and European guidelines.

Conclusions:

There are significant differences between the American and European guidelines in the diagnosis of hypertension in teenagers, with a higher prevalence by American guidelines. The risk for hypertension is higher in males than females by both guidelines.
ASSOCIATIONS OF LONG-TERM VISIT-TO-VISIT BLOOD PRESSURE VARIABILITY WITH SUBCLINICAL KIDNEY DAMAGE AND ALBUMINURIA IN ADULTHOOD: A 30-YEAR PROSPECTIVE COHORT STUDY
Authors: Wang Yang , Zhao Peng , Chu Chao , Du Ming -Fei , Zhang Xiao -Yu , Zou Ting , Hu Gui -Lin , Jia Hao , Liao Yue -Yuan , Ma Qiong , Wang Dan , Desir Gary V. , Delles Christian , Chen Fang -Yao , Mu Jian -Jun
Published: June 2023

Objective:

Recent evidence indicates that long-term visit-to-visit blood pressure variability (BPV) may be associated with the risk of cardiovascular disease. We therefore aimed to determine the potential associations of long-term BPV from childhood to middle age with subclinical kidney damage (SKD) and albuminuria in adulthood.

Design and method:

Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, which recruited children and adolescents aged 6 to 18 years at baseline, we assessed BP variability by standard deviation (SD) and average real variability (ARV) for 30 years (6 visits). Presence of SKD was defined as estimated glomerular filtration rate (eGFR) between 30 and 60 ml/min/ 1.73 m2 or elevated urinary albumin-to creatinine ratio (uACR) at least 30 mg/g. Albuminuria was defined as uACR greater than 30 mg/g.

Results:

During a follow-up of 30 years, of the 1771 participants, 204 SKD events occurred. After adjustment for demographic, clinical characteristics and mean BP during 30 years, higher SDSBP, ARVSBP, SDDBP, ARVDBP, SDMAP, ARVMAP and ARVPP were significantly associated with higher risk of SKD [ORs (95% CIs) were 1.14(1.06 - 1.23), 1.15(1.08 - 1.21), 1.12(1.06 - 1.17), 1.16(1.08 - 1.25), 1.12(1.07 - 1.17), 1.18(1.10 - 1.27) and 1.11(1.03 - 1.21), respectively]. When we used cumulative exposure to BP from childhood to adulthood instead of mean BP as adjustment factors, results were similar. In addition, greater long-term BPV was also associated with the risk of albuminuria [ORs (95% CIs) were 1.07(1.03 - 1.10) for SDSBP, 1.13(1.06 - 1.20) for ARVSBP, 1.11(1.06 - 1.17) for SDDBP, 1.14(1.06 - 1.23) for ARVDBP, 1.18(1.09 - 1.27) for ARVMAP and 1.08(1.01 - 1.17) for ARVPP]. Long-term BP variability for 30 years from childhood to middle age was associated with higher risk of SKD and albuminuria in adulthood, independent of mean BP or cumulative exposure to BP during follow-up.

Conclusions:

Identifying long-term BP variability from early age may assist in predicting kidney disease and cardiovascular disease in later life.
THE ASSOCIATION BETWEEN BLOOD PRESSURE VARIABILITY AND DEMENTIA: A TWO-SAMPLE MENDELIAN RANDOMIZATION STUDY
Authors: Jia Pingping , Tsoi Kelvin
Published: June 2023

Objective:

This study aims to investigate the causal inference by applying a mendelian randomization (MR) study using single-nucleotide polymorphisms (SNPs) from the genome-wide association study (GWAS) based on the UK biobank.

Design and method:

The genetic instruments were chosen from BPV GWAS based on UK Biobank data. Four GWA studies were used for the genetic evaluation of dementia, including (1) The International Genomic of Alzheimer's Project (IGAP) GWAS for dementia; (2) and (3) UK Biobank GWAS for proxy phenotypes of Alzheimer's dementia: the maternal and paternal family history (MFH and PFH-UKBB); (4) A combined GWAS meta-analysis from the abovementioned three GWAS results. The following exclusion criteria were applied for SNPs: (1) confounding SNPs by searching hypertension and artery stiffness GWAS; (2) significant SNPs that are associated with dementia in the datasets; (3) palindromic SNPs with an effect allele frequency between 0.4 and 0.7. Proxy SNPs were manually selected for some SNPs. (4) only SNPs with linkage disequilibrium r2 < 0.01 were selected as genetic instruments, also known as independent SNPs. The effect/reference alleles were checked to ensure the consistency of the base pair between BPV and dementia GWAS, which is also known as data harmonization. After data harmonization, four MR methods were employed to measure the causal effect: IVW-MR with random effect, IVW-MR with fixed effect, MR-Egger, and weighted median MR.

Results:

Finally, six independent SNPs were chosen as instrument variants for SBPV, and five for DBPV. Significant causal effects of SBPV on dementia were found in the PFH-UKBB dataset, and the odds ratio of dementia per 10-unit increase in SBPV was 1.028, 1.015, and 1.015 for MR-Egger, weighted median, and IVW-MR, respectively (Table 1). In contrast, only one significant result was found for DBPV in MFH-UKBB. No significant results were found on other datasets.

Conclusions:

Along with the evidence from different observational studies, this GWAS study demonstrates that systolic blood pressure variability is a potential causal risk factor for Alzheimer's dementia, while the evidence from diastolic blood pressure variability is still uncertain.
PATIENTS WITH VERY HIGH RISK OF CARDIOVASCULAR ADVERSE EVENTS DURING CARFILZOMIB THERAPY: PREVENTION AND MANAGEMENT OF EVENTS IN A SINGLE CENTER EXPERIENCE
Authors: Mingrone Giulia , Astarita Anna , Colomba Anna , Catarinella Cinzia , Cesareo Marco , Airale Lorenzo , Paladino Arianna , Leone Dario , Vallelonga Fabrizio , Bringhen Sara , Gay Francesca , Veglio Franco , Milan Alberto
Published: June 2023

Objective:

Carfilzomib (CFZ) improves the prognosis of multiple myeloma (MM) patients, but has shown cardiovascular toxicity. The cardiovascular adverse events (CVAEs) risk stratification now seems well established, while little is known about the course and management of patients with high risk or CVAEs during therapy. So, we aimed to describe our specialistic experience in decision-making to support health professionals in selecting the best management strategies to prevent and treat CVAEs.

Design and method:

From January 2015 to September 2022, 194 patients with indication to CFZ underwent baseline evaluation of CVAEs risk and were prospectively followed. We proposed a novel approach with inducible ischemia imaging tests for patients at high baseline CV risk to rule out clinical conditions that could contraindicate the starting of CFZ.

Results:

After baseline evaluation, 16 (8.2%) patients resulted at high risk of CVAEs: 13 (6.7%) patients performed inducible myocardial ischemia imaging test and 3 (1.5%) could not receive CFZ for CV contraindications. 178 (91.7%) patients started CFZ: 82 (46%) experienced arterial hyperten-sion-related events and 37 (20.8%) major CVAEs (Fig. 1); 19 (10.7%) patients had to suspend or remodulate CFZ.

Conclusions:

Together with baseline risk stratification also subsequent cardiovascular clinical and diagnostic follow-up appeared critical to identify clinical conditions that could contraindicate the anti-cancer therapy.
EARLY LIFE CARDIOVASCULAR RISK FACTOR TRAJECTORIES AND VASCULAR AGING IN MIDLIFE: A 30-YEAR PROSPECTIVE COHORT STUDY
Authors: Wang Yang , Wang Jie , Du Ming -Fei , Zhang Xi , Chu Chao , Wang Dan , Liao Yue -Yuan , Ma Qiong , Jia Hao , Hu Gui -Lin , Yan Yu , Sun Yue , Chang John , Delles Christian , Lu Yao , Mu Jian -Jun
Published: June 2023

Objective:

Vascular aging, as assessed by structural and functional arterial properties, is an independent predictor of cardiovascular outcomes. We aimed to explore the associations of individual cardiovascular risk factors from childhood to midlife and their accumulation over a 30-year span with vascular aging in midlife.

Design and method:

Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, 2180 participants aged 6 to 18 years at baseline were followed for over 30 years. Distinct trajectories of systolic blood pressure (SBP), body mass index (BMI), and heart rate (HR) from childhood to midlife were identified by group-based trajectory modeling. Vascular aging was assessed by carotid intima–media thickness (cIMT) or brachial-ankle pulse wave velocity (baPWV).

Results:

We identified 4 distinct SBP trajectories, 3 distinct BMI trajectories and 2 distinct HR trajectories from childhood to midlife. Persistently-increasing SBP, high-increasing BMI, and high-stable HR were all shown to have a positive association with baPWV in midlife. For cIMT, similar associations were observed for persistently-increasing SBP and high-increasing BMI. After further adjustment for SBP, BMI and HR at the time of vascular assessment in 2017, associations were also observed for cardiovascular risk factor trajectories accumulation with baPWV (↓ = 0.656 (95%CI, 0.265 - 1.047)] and with cIMT [↓ = 0.045 (95%CI, 0.011 - 0.079)] in adulthood.

Conclusions:

Longitudinal exposure to individual cardiovascular risk factors from childhood to midlife and cardiovascular risk factor accumulation were associated with an increased risk of vascular aging in midlife. Our study lends support for early targeting of risk factors in order to prevent cardiovascular disease later in life.
ASSOCIATION OF HIGH BLOOD PRESSURE WITH POST-TRAUMATIC STRESS DISORDER IN UKRAINIAN WOMEN SEEKING ASYLUM IN POLAND: A PILOT STUDY
Authors: Shalimova Anna , Stoenoiu Maria Simona , Cubala Wieslaw , Burnier Michel , Persu Alexandre , Narkiewicz Krzysztof
Published: June 2023

Objective:

Post-traumatic stress disorder (PTSD) and its components have been associated with hypertension, particularly in military servants, war veterans and more recently in populations exposed to chronic violence. However, to our knowledge, this association has not been investigated in refugees. The objective of this study was to explore the potential association between high blood pressure and PTSD in Ukrainian women seeking asylum in Poland.

Design and method:

From September to December 2022, 55 Ukrainian women refugees were enrolled in dormitories from Sopot (Poland). Blood pressure (BP) was measured using validated oscillometric devices. Hypertension was defined as systolic BP > = 140 mmHg, diastolic BP > = 90 mmHg or being on antihypertensive treatment. Relevant demographic and clinical data were obtained. Furthermore, subjects filled validated questionnaires for depression, stress and anxiety (DASS) and post-traumatic stress disorder (PTSD) (PCL-5). Subjects with and without hypertension were compared for both general and psychological characteristics.

Results:

Thirty out of 55 subjects were found to be hypertensive. Compared to subjects with normal BP in absence of drugs (mean BP: 117.8/75.6 mmHg, n = 25), hypertensive subjects (mean BP: 138.1/85.8 mmHg, n = 30) were older (57.2 ± 11.1 vs. 39.1 ± 0.8 years, p < 0.00001) and had a higher BMI (29.0 ± 5.4 vs. 23.8 ± 4.4 kg/m2, p = 0.003). Furthermore, despite a similar personal situation (socio-economic background, direct exposure to war, time since arrival in Poland, with or without children/relatives), hypertensive subjects were more often feeling unsafe at the time of examination (4-items scale, p = 0.001) and scored higher for PTSD score (24.9 ± 17.0 vs. 16.3 ± 12.9, p = 0.038), particularly regarding intrusion (cluster B, p = 0.039) and hyper-arousal (cluster E, p = 0.002) dimensions, but not for DASS score (22.4 ± 14.2 vs. 17.2 ± 11.5, p = 0.14).

Conclusions:

This preliminary analysis is consistent with an association between high BP and both feeling of being unsafe and PTSD score in Ukrainian women refugees. Our results need confirmation using 24-hour BP monitoring and in a larger sample. In the absence of difference in personal background and exposure to war, these associations may reflect underlying differences in expression of emotions and coping abilities, as previously shown in other populations exposed to violence or with difficult-to-treat hypertension.
CORRELATION BETWEEN LOW DIASTOLIC BLOOD PRESSURE AND SEVERITY OF CORONARY ARTERY DISEASE USING SYNTAX SCORE
Authors: Amrawy Ahmed Mahmoud El , Zaki Amr Mahmoud , Azeem Ahmed Mokhtar Abd El
Published: June 2023

Objective:

Hypertension remains a leading cause of morbidity and mortality, and the optimum blood pressure target remains debated, especially in coronary artery disease, given concerns for reduced myocardial perfusion if diastolic blood pressure is too low. The aim of this work was to study the relationship between diastolic blood pressure (DBP) and severity, and burden of coronary artery disease (CAD) as quantified by SYNTAX Score.

Design and method:

Six hundred consecutive stable patients with signs or symptoms of CAD who underwent elective coronary angiography were included in the study. Patients were divided into three groups according to SYNTAX Score as low, intermediate, and high.

Results:

Patients were predominantly males (72%), their age ranged from 35 - 82 years, with mean age of 59.55 ± 9.44 years. 426 patients (71%) were hypertensive, 82.1%,69.4%,70% of high, intermediate, and low SYNTAX groups respectively had hypertension.

SYNTAX score ranged from 2.0 – 53.0 with a mean of 17.32 ± 9.87. In DBP group <60 mmHg, SYNTAX score ranged from 8.0 – 53.0 with a mean of 26.47 ± 10.59. In DBP group 60 – 69 mmHg, SYNTAX score ranged from 5.0 – 45.50 with a mean of 22.13 ± 7.77. In DBP group 70 – 79 mmHg, SYNTAX score ranged from 3.0 - 34.0 with a mean of 13.91 ± 7.09. In DBP group > = 80 mmHg, SYNTAX score ranged from 2.0 – 46.50 with a mean of 12.90 ± 8.21, SYNTAX score was significant higher in DBP groups <60 and 60 – 69 mmHg than other groups (p < 0.001).

High atherosclerotic burden was identified by the presence of intermediate or high SYNTAX score. The frequency of high atherosclerotic burden was significantly increased with decreasing DBP, for mean SYNTAX Scores of 41.1, 35.6, 10 and 13.3 in DBP <60, 60 – 69, 70 – 79, and > = 80 mmHg; p < 0.0001 for all. There was negative significant correlation between diastolic blood pressure and SYNTAX score (rs = -0.471, p < 0.001).

Conclusions:

A low DBP level had an independent association with high SYNTAX Score. Lower DBP, particularly <60 mmHg, may be important to recognize a potential pathophysiological contribution of too low DBP in the development of complexity and increased atherosclerotic burden, which is identified by the presence of intermediate or high SYNTAX Score in stable patients with obstructive CAD.
ASSOCIATION OF CUMULATIVE SYSTOLIC BLOOD PRESSURE LOAD AND STROKE IN PATIENTS WITHOUT DIABETES
Authors: Zhao Yifan , Li Moran , Zhang Yi
Published: June 2023

Objective:

The purpose of this study was to assess the association between cumulative systolic blood pressure (SBP) load and risk of stroke in patients without previous stroke and diabetes.

Design and method:

The present study was a post hoc analysis of patients enrolled in the SPRINT study. Cumulative SBP load was defined as the area under curve for SBP values >120 or 130 or 140mmHg respectively (named SBP load120, SBP load130 and SBP load 140 respectively) divided by the area under curve for all measured SBP values over a 48-month exposure period. Hazard ratios for the association between cumulative SBP load with stroke were estimated using Cox models.

Results:

Only SBP load130, but not mean SBP, SBP standard deviation (SBP SD), time at therapeutic range (TTR); had a well-correlation with the incidence of stroke according to the restricted cubic spline curve (RCS). Grouping participants with tertiles of cumulative SBP load130 distinguished the incidence of stroke by K-M curve. Different Cox models indicated SBP load130 was an independent risk factor for stroke. For the prediction of stroke, only cumulative SBP load130, but not SBP load120 and SBP load140, outperformed mean SBP, TTR, SBP SD in terms of C-statistics and net reclassification indexes.

Conclusions:

Cumulative SBP load may provide better prediction of stroke compared with traditional BP measures among patients without previous stroke and diabetes. 130mmHg could be the best cutoff value for predicting incidence of stroke by SBP load.
ASSOCIATION BETWEEN LONG-TERM EXPOSURE TO ANTIHYPERTENSIVE DRUGS AND RISK OF CANCER: A LARGE POPULATION-BASED RETROSPECTIVE COHORT STUDY
Authors: Franchi Matteo , Torrigiani Ginevra , Kjeldsen Sverre E. , Corrao Giovanni , Mancia Giuseppe
Published: June 2023

Objective:

Several meta-analyses have examined whether antihypertensive drugs alter the risk of cancer. However, in most studies follow-up was relatively short and adherence to antihypertensive drugs was not accounted for. We analysed the relationship between long-term exposure to antihypertensive drugs and risk of cancer.

Design and method:

Retrospective population-based cohort study based on healthcare utilization databases of Lombardy Region (Italy). We selected all individuals aged 40 - 85 years newly dispensed with at least one antihypertensive drug from between 2009 and 2011, and with no previous history of cancer. Exposure to angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), calcium channel blockers (CCB), beta-blockers (BB), thiazides/thiazide-likes, loop diuretics and mineralocorticoid receptor antagonists (MRA) was evaluated by using an “as-treated” approach, according to which each cohort member was classified based on the duration of exposure to each class of drugs. Patients were followed-up from the date of the first dispensation of antihypertensive drug and ended at the earliest date between onset of cancer, migration, death or December 31, 2020. The association between the duration of exposure to each class of drug (considered as a time-dependent covariate) and cancer risk was evaluated by Cox regression models, adjusted for sex, age and the Multisource Comorbidity Score, and mutually adjusted for the exposure to each class of drugs.

Results:

The study cohort included 339,842 new users of antihypertensive drugs (median age 59 years, 49.5% males). During a median follow-up of 10.2 years, 36,778 cancers occurred. There was no evidence of consistent significant associations of the risk of cancer with ACEI, ARB and thiazides. An increasing but weak risk was associated to a medium-long term exposure to CCB and with a long-term exposure to BB. With the limit that the number of users was much smaller, exposure to MRA was associated to a significant increase in the risk of cancer at all exposure levels.

Conclusions:

In our study, treatment adherence allowed a more accurate evaluation of true exposure to a potentially carcinogenic drug influence. The results showed an increased risk with the exposure to some antihypertensive agents, in particular with the MRA.
LONG-TERM EVENT RATES, RISK FACTORS, AND TREATMENT PATTERN IN PATIENTS QUALIFYING FOR DUAL BLOOD PRESSURE-LOWERING THERAPY: AN OBSERVATIONAL STUDY IN 1.4 MILLION INDIVIDUALS
Authors: Coca Antonio , Borghi Claudio , Stergiou George S. , Blacher Jacques , Lee Christopher , Tricotel Aurore , Castelo-Branco Anna , Khan Irfan , Abdel-Moneim Mohamed
Published: June 2023

Objective:

Elevated blood pressure (BP) is a major risk factor for cardiovascular (CV) morbidity and mortality. This study assessed CV event rates, their predictive factors, and treatment patterns for BP-lowering therapy in a population qualifying for dual BP-lowering therapy, over a long-term follow-up.

Design and method:

This study utilized the Clinical Practice Research Datalink, Hospital Episode Statistics, and Office for National Statistics databases in England. Individuals aged > = 18 years with hypertension, qualifying for dual BP-lowering therapy as per the European Society of Cardiology/European Society of Hypertension (ESC/ESH) guidelines were identified during a 15-year period (2005 to 2019). Primary endpoint was composite of non-fatal myocardial infarction (MI), non-fatal stroke, hospitalization for heart failure, and CV death. Secondary endpoint was all-cause death. Main subgroups of interest were atherosclerotic cardiovascular disease (ASCVD) and diabetes. Event rates and association of risk factors with primary endpoint and all-cause death were evaluated using Kaplan-Meier method and Cox-proportional hazards model, respectively. Treatment patterns were summarized via percent of patient-time on a given therapy during each year of follow-up.

Results:

Overall, 1,426,079 patients were included. The mean (SD) age was 62.9 (14.1) years and ∼50% were male. The 15-year event rates for the primary composite endpoint and all-cause death were 27.1% and 32.6%, respectively (Table 1) with CV event rates being ∼2.5-fold and ∼1.5-fold in those with ASCVD and diabetes, respectively (unadjusted analyses). Risk factors strongly associated with primary composite endpoint (hazard ratio >1.50) were age > = 65 years, heart failure, atrial fibrillation, chronic kidney disease 4 – 5, chronic obstructive pulmonary disease, coronary heart disease, stroke, and peripheral arterial disease (P < 0.0001 for all). At variance with guidelines, BP-lowering monotherapy was the most common treatment pattern (42.6% – 56.7% of patient-time) over 5–year follow-up period.

Conclusions:

Patients with hypertension qualifying for dual BP-lowering therapy are at high risk of major CV events and death, with the risk being substantially elevated in those with ASCVD or diabetes. These findings highlight an opportunity for further risk reduction in this population via timely initiation of dual BP-lowering therapy, especially in patients with comorbidities.
SERUM ACID URIC AND HYPERTRIGLYCERIDEMIA AND CAROTID PLAQUES: A SUB-ANALYSIS OF THE URIC ACID RIGHT FOR HEART HEALTH (URRAH) STUDY
Authors: Muiesan Maria Lorenza , Paini Anna , Rosei Claudia Agabiti , Maloberti Alessandro , Giannattasio Cristina , Salvetti Massimo , Cirillo Massimo , Ferri Claudio , Galletti Ferruccio , Grassi Guido , Iaccarino Guido , Palatini Paolo , Parati Gianfranco , Pontremoli Roberto , Tikhonoff Valerie , Verdecchia Paolo , Volpe Massimo , Casiglia Edoardo , Virdis Agostino , Borghi Claudio
Published: June 2023

Objective:

High levels of serum uric acid (SUA) and triglycerides (TG) might promote high-cardiovascular risk phenotypes, including subclinical atherosclerosis. An interaction between plaques Xanthine Oxidase (XO) expression, SUA, and HDL-C has been recently postulated

Design and method:

N = 6211 patients from the URic acid Right for heArt Health (URRAH) study with carotid ultrasound and without previous cardiovascular diseases (CVD), followed over 20 years, were included in the analysis. Hypertriglyceridemia (hTG) was defined as TG > = 150 mg/dL. Higher levels of SUA (hSUA) were defined as > = 5.6 mg/dL in men and 5.1 mg/dl in women

Results:

A carotid plaque was identified in 1742 subjects (28 %). SUA and TG predicted carotid plaque (HR 1.09 [1.04 - 1.27], p < 0.001 and HR 1.25 [1.09 - 1.45], p < 0.001) in the whole population, independently of age, sex, diabetes, systolic blood pressure, HDL and LDL cholesterol and treatment.

Four different groups were identified (normal SUA and TG, hSUA and normal TG, normal SUA and hTG, hSUA and hTG). The prevalence of plaque was progressively greater in subjects with normal SUA and TG (23%), hSUA and normal TG (31%), normal SUA and hTG (34%), hSUA and hTG (38%) chisquare 0,0001) Logistic regression analysis showed that hSUA and normal TG [HR 1.159 (1.002 to 1,341); P = 0.001], normal SUA and hTG [HR 1. 305 (1.057 to 1.611); P = 0.001], and the combination of hUA and hTG [HR 1. 539 (1.274 to 1.859); P = 0.001], were associated with a higher risk of plaque

Conclusions:

Our findings demonstrate that SUA is independently associated with the presence of carotid plaque and suggest that the combination of hyperuricemia and hypertriglyceridemia is a stronger determinant of carotid plaque than hSUA or hTG taken as single wisk factors. The association between SUA and CVD events may be explained in part because of a direct association of UA with carotid plaqu
SHOULD MIDDLE-AGED AND OLDER HIGH-RISK HYPERTENSIVE PATIENTS WITH DIABETES BE TREATED TO TARGET BT <130/80 MMHG?
Authors: Olsen Eirik , Søraas Camilla Lund , Mancia Giuseppe , Heimark Sondre , Mehlum Maria H. , Liestöl Knut , Kjeldsen Sverre E. , Høieggen Aud , Rostrup Morten , Mo Rune , Julius Stevo , Weber Michael
Published: June 2023

Objective:

Diabetes Mellitus Type-2 (DM2) is common in hypertensive patients, increasing the risk of cardiovascular disease. Current guidelines recommend targeting systolic BP (SBP) to 130 - 139 mmHg in diabetic patients >65 years. We investigated whether the middle-aged and elderly hypertensive DM2 patients in the VALUE Trial had reduced risk of cardiovascular disease and death if SBP was lowered to <130 mmHg.

Design and method:

Of the 15,245 participants, there were 13,803 patients without cardiovascular events during the first six months after randomization, roll-over from previous medication and up-titration of study drugs. Of these 2,458 patients had left ventricular hypertrophy by electrocardiogram. These patients were excluded from analyses due to increased mortality when SBP is lowered to <130 mmHg (submitted).

Of the remaining 11,345 patients, 3,932 had DM2. Cox analyses adjusted for age, gender, and baseline variables compared cardiac and all-cause mortality and other pre-specified endpoints for patients achieving average SBP 130 - 139 mmHg (DM2 group 1,605, non-DM2 group 3,260) and SBP <130 mmHg (DM2 group 600, non-DM2 group 1,546). Reference groups were patients achieving average SBP > = 140 mmHg.

Results:

Mean age in DM2 patients was 66.9 years. The DM2 group achieving average SBP <130 mmHg did not have significant changes in primary cardiac endpoint, all-cause mortality, or stroke (Table). However, DM2 had lower incidence of reduced kidney function (increase in serum creatinine of 50% compared to baseline, HR = 0.43, p = 0.008). In the DM2 group achieving average SBP 130 - 139 mmHg there were significant reductions in cardiovascular events and kidney function.

Conclusions:

Our findings suggest that lowering systolic BP <130 mmHg in DM2 has little effect on reducing cardiovascular events compared to systolic BP 130 - 139 mmHg. However, we did find an effect on kidney function. In conclusion, our data suggest that treating middle-aged and elderly DM2 patients <130/80 mmHg can prevent reduction of renal function which is an endpoint of high importance in DM2 patients.
NEW SCREENING CUTOFF VALUES FOR DETECTION OF ALDOSTERONOMA EXAMINED BY LC-MS/MS AND NEWLY DEVELOPED NON-COMPETITIVE CLEIA
Authors: Satoh Fumitoshi , Ono Yoshikiyo , Tezuka Yuta , Omata Kei , Takase Kei , Sato Akihiro , Suzuki Takashi , Sasano Hironobu
Published: June 2023

Objective:

Thinking of the poor accuracy of conventional CLEIA measurements of aldosterone, liquid chromatography-tandem mass spectrometry (LC-MS/MS) is the ideal method but it is costly, labor intensive and time consuming. A novel non-competitive chemiluminescent enzyme immunoassay (sandwich assay) (NC-CLEIA) for measuring aldosterone was recently developed. We validated the accuracy and diagnostic ability of the NC-CLEIA and compared the results obtained with those by LC-MS/MS and also determined the new screen cutoffs by both measurements, respectively, detecting aldosterone-prodcuing adenoma (APA) in hypertensive patients.

Design and method:

We measured plasma renin activity by enzyme assay and plasma aldosterone concentrations (PAC) using LC-MS/MS and NC-CLEIA in 133 APA, 100 bilateral hyperaldosteronism and 111 essential hypertension patients to examine the accuracy of the values of PAC measured by this new NC--CLEIA as compared with those by LC-MS/MS, and determine the new screen cutoff values by both measurements to detect APA, respectively.

Results:

Passing-Bablok analysis revealed that NC-CLEIA (regression slope, intercept and correlation coefficient were 0.962, -0.043, and 0.994, respectively), was significantly correlated and equivalent to LC-MS/MS than RIA. Bland-Altman plot analysis of NC-CLEIA by LC-MS/MS also demonstrated much smaller systemic errors (a bias of -0.348 ng/dL with limits of agreement of -4.390 and 3.694 and 95% confidence interval). The receiver-operating characteristics analysis demonstrated that cut-off values of aldosterone/renin activity ratio obtained by LC-MS/MS and NC-CLEIA were 31.2 and 31.5 (ng/dL per ng/mL/hr) with a sensitivity of 91.0% and 90.2%, and a specificity of 75.4% and 76.8%, respectively, in terms of discriminating APA from non-APA. Therefore, we can recommend an ARR > 30.0 ng/dL per ng/mL/hr as a screening cut-off by both LC-MS/MS and NC-CLEIA, which would discriminate APA with a sensitivity of 91.7% in both assays, and with a specificity of 73.0% and 73.9 %, respectively.

Conclusions:

This novel NC-CLEIA assay for PAC could serve as a clinically reliable alternative to LC-MS/MS to detect APA among hypertensive patients with more accuracy than the conventional methods.
ASSESSMENT OF LEFT ATRIAL FUNCTION IN INDIVIDUALS WITH RESISTANT HYPERTENSION BY ADVANCED ECHOCARDIOGRAPHY
Authors: Laurinavicius Antonio Gabriele , Souza Jonathan Batista , Sousa Marcio Gonçalves , Colombo Fernanda Consolim , Assef Jorge Eduardo
Published: June 2023

Objective:

Resistant hypertension is a challenging phenotype within the hypertension (HTN) spectrum, requiring careful assessment and follow-up. Evaluation of left atrial function may be clinically informative, but is commonly neglected. Strain and three-dimensional echocardiography (3D ECHO) may be useful complementary tools for assessing atrial function among hypertensive patients.

Design and method:

96 eligible adult patients were categorized into three groups: resistant hypertensive (RH), controlled hypertensive (CH), and normotensive (N), and underwent advanced echocardiography techniques to identify specific morphofunctional changes in the left atrium (LA) throughout different HTN phenotypes.

Results:

As shown in Figure 1, LA reservoir strain was significantly lower among RH than N and CH patients (p < 0.001). Accordingly, LA conduit strain showed a gradient through the groups: higher among N, followed by CH and RH (p = 0.015). LA contraction strain was higher among CH than N and RH (p = 0.02). Maximum indexed, pre-A, and minimum atrial volumes obtained by 3D ECHO showed differences between N and the others (p < 0.001), but not between CH and RH. N showed higher fraction of passive emptying of the LA than the others (p = 0.02), with no difference between CH and RH. Total emptying of the LA only differed between the extreme groups N and RH, being lower in the latter, while active emptying of the LA showed no difference between the groups (p = 0.82).

Conclusions:

Advanced echocardiography measures, especially LA strain, proved to be early markers of atrial myocardial damage in both RH and CH. We demonstrated for the first time that morphofunctional changes in the LA due to resistant hypertension may occur concomitantly and even independently from those observed in the left ventricle.
POOLED, 6-MONTH SAFETY AND EFFICACY RESULTS USING THE SYMPLICITY SPYRAL RADIOFREQUENCY RENAL DENERVATION CATHETER
Authors: Mahfoud Felix , Mancia Giuseppe , Townsend Raymond , Kandzari David , Whitbourn Robert , Böhm Michael
Published: June 2023

Objective:

Over 1,200 patients received renal denervation (RDN) to reduce high blood pressure using the current generation, multi-electrode, radiofrequency Symplicity SpyralTM catheter as part of the SPYRAL HTN Global Clinical Program. The Spyral FIM was a prospective, single-arm study to assess feasibility. The SPYRAL HTN-OFF MED and -ON MED studies were randomized, sham controlled, blinded trials assessing the safety and efficacy of RDN in the absence and presence of antihypertensive medications, respectively. The Global SYMPLICITY Registry is an all-comer, global, single-arm study assessing safety and efficacy of RDN in a real-world setting with patients on various medication regimens. Here, we present the pooled, 6-month efficacy and safety results of RDN using the Spyral catheter.

Design and method:

At each follow-up, including at 6 months, office systolic and diastolic blood pressures and 24-h ambulatory systolic and diastolic were collected. Adverse safety events and other indicators including estimated glomerular filtration rate (eGFR) and incidence of renal artery stenosis were recorded. GSR was an all-comer registry for patients with uncontrolled hypertension, whereas patients in the SPYRAL HTN-OFF and ON MED trials were required to have an OSBP > = 150 and <180 mmHg and ODBP > = 90 mmHg.

Results:

As of December 19, 2022, 1,298 patients have received RDN therapy using the Spyral catheter, including eligible control patients from the randomized trials who elected to cross over to receive RDN after unblinding. Mean, 6-month reductions in office and 24-h ambulatory BP from baseline are shown in the Figure. Patients had similar, significant reductions in diastolic blood pressure from baseline through 6 months. Including crossover patients, eGFR decreased by 1.5 mL/min/1.73 m2 through 6 months in RDN patients using the SPYRAL catheter (n = 962; 95% CI: -2.27,-0.74; p < 0.001). There have been no recorded instances of renal artery stenosis >70% through 6 months.

Conclusions:

Patients receiving RDN had significant and consistent 6-month reductions in BP compared to baseline measures. There have been no incidences of renal artery stenosis, and reductions in eGFR are consistent with natural progression with age. These results highlight the efficacy and safety of RDN using the current generation Spyral catheter.