bluuebunny/crossref_metadata_2025 huggingface dataset:
EFFECT OF RENAL DENERVATION ON BLOOD PRESSURE IN PATIENTS WITH CHRONIC KIDNEY DISEASE AND UNCONTROLLED HYPERTENSION: RESULTS OF A PROSPECTIVE RANDOMIZED SHAM-CONTROLLED STUDY
Authors: Schmieder Roland , Kannenkeril Dennis , Böhm Michael , Mahfoud Felix , Rump Lars C. , Stegbauer Johannes , Van Der Giet Markus , Schiffer Mario , Veelken Roland , Uder Michael , Schmid Axel
Published: May 2024

Objective:

The activity of the sympathetic nervous system (SNS) is increased in patients with chronic kidney disease (CKD) and endovascular renal denervation (RDN) offers the opportunity to modulate SNS activity and thereby blood pressure.

Hypothesis: In patients with CKD stage 3 and uncontrolled hypertension, endovascular ultrasound-based RDN (uRDN) reduces 24-hour ambulatory BP without adverse safety events.

Design and method:

In a multicenter prospective randomized clinical trial, following the criteria of a blinded sham-controlled design, patients with CKD stage 3 and uncontrolled hypertension despite prescription of 1-5 antihypertensive medications were enrolled. Patients were randomly allocated to either endovascular uRDN using the Paradise™ Renal Denervation System (ReCor Medical, Inc., Palo Alto, CA, USA) or a sham procedure restricted to renal angiopgraphy alone. The primary endpoint was the change in mean 24-hour ambulatory systolic BP at 6 months while on stable medication. Secondary endpoints were changes of other 24h ambulatory BP values, office BP and safety parameters of uRDN. Blinding was to be maintained through 6 months. Due to slow recruitment through 2 years, the trial was prematurely stopped.

Results:

Of 25 randomized patients (mean age 67yrs), 20 subjects had a 6 month visit per protocol. Major cause of CKD was hypertension and/or type-2 diabetes (N=13). There was no difference in clinical characteristics (eGFR, UACR, BMI, HbA1c, comorbidities), pretreatment 24 hour/day/night ambulatory and office BP between the uRDN (N=10) and the sham group (N=10). After 6 months the decrease in 24h(and day) ambulatory diastolic BP was significantly greater in the RDN compared with the sham group (p=0.035 (and 0.030)). Within the uRDN group, 24 hour (and day) ambulatory diastolic BP decreased over time compared to pretreatment values, whereas in the sham group no changes occurred. Systolic ambulatory BP decreased numerically in the uRDN group, but was not significant. No safety concerns related to uRDN emerged.

Conclusions:

In this randomized sham-controlled blinded study, despite its premature stop leading to a small study cohort, we observed a decrease of diastolic BP after endovascular uRDN and no safety signals in these hypertensive patients with CKD.
FEASIBILITY STUDY TO ASSESS THE DELIVERY OF A NOVEL ISOMETRIC EXERCISE INTERVENTION FOR PEOPLE WITH STAGE 1 HYPERTENSION
Authors: Farmer Chris , Rees-roberts Melanie , Santer Ellie , O’Driscoll Jamie , Macinnes Douglas , Short Vanessa , Pellatt-higgins Tracy , Mills Ashley , Gousia Katerina , West Alan , Darby John , Borthwick Rachel , Doulton Timothy , Swift Pauline , Wiles Jim
Published: May 2024

Objective:

Adherence is low to the lifestyle changes recommended by NICE for patients with hypertension. More easily adopted, effective and manageable exercise interventions are needed. This study determined the feasibility of personalised isometric exercise (IE) for patients with Stage (grade) 1 hypertension in the National Health Service (NHS) in England.

Design and method:

We conducted a multicentre randomised controlled feasibility study delivered through NHS primary/secondary care. Patients included were 18+, with clinic systolic BP (SBP)140-159mmHg, not on anti-hypertensive medication and without significant medical contraindications. Participants were randomised to standard lifestyle advice (control) or standard lifestyle advice plus wall squat IE for a 6-month period (intervention). After excluding people with average home systolic <135mmHg, 41 participants were included (control n=19, IE n=22) (aged 57 ± 15.15yrs). Participants were followed up at 4-weeks, 3-months, and 6-months.

Results:

Healthcare professionals were able to deliver the intervention with high fidelity (100% passed independent delivery check and 84.6% of participants recorded at least 2/3 of exercise heart rates within their target range over 6 months). A sample size for an efficacy trial (primary objective), was determined n= 542, based upon the 35% attrition rate and 14.4mmHg SD of change of SBP from baseline. Qualitative work provided valuable insights into acceptability, feasibility, delivery, and implementation in an NHS setting and for improved follow-on studies. Whilst the study was not powered to detect BP changes, reductions in SBP were observed at all time points.

Figure 1. Marginal means and 95% CI from ANCOVA (Per-protocol population)

Difference between means at each time point were:

4-weeks -2.31 mmHg (95% CI -11.29 to 6.67),

3 months -4.07 mmHg (95% CI, -10.28 to 2.15)

6 months -2.35 (95% CI -11.70-6.99).

Pilot economic analyses suggested the intervention is cost-effective.

Conclusions:

Feasibility of IE has been demonstrated, but deliverability without significant modifications to the wall squat IE prescription protocol due to current NHS constraints would not be possible. Findings support investigating effectiveness of the intervention and justify a full RCT. A sample size of n=542 is needed to establish effectiveness.
POTASSIUM-ENRICHED SALT EFFECTIVELY REDUCES SODIUM INTAKE IN THE NURSING HOME POPULATION OF NORTHERN CHINA: THE CHINA SALT TRIAL
Authors: Meng Xianmin , Dou Xiangfeng , Wei Hua , Li Weiwei , Zhao Jinguo , Zhao Sufang , Liu Yongjuan , Zhang Hongye , Liu Lisheng
Published: May 2024

Objective:

to explore the promoting effect of long-term consumption of potassium-enriched salt (KCL/NACL=1:1) on dietary salt restriction in the nursing home population.

Design and method:

In northern China, a total of 29 nursing homes were selected using cluster random sampling. The nursing homes were divided into intervention group (using potassium-enriched salt in the dining room) and control group (using regular salt in the dining room). The usage of salt and high-sodium condiments in the dining room was recorded, including the amount of salt used and the number of diners. The average per capita daily sodium intake from condiments (TNA/PD) in the nursing home was calculated, as well as the average per capita daily sodium intake from dietary salt (SNA/PD). The two values were added together to calculate the total per capita daily sodium intake (ANA/PD).

Results:

Over 6 years, a total of 18,046 meals were consumed in the dining room. The intervention group demonstrated a significant reduction in per capita daily sodium intake (ANA/PD) compared to the control group (3.0 vs 5.0g). There was no statistically significant difference in per capita daily sodium intake from condiments (TNA/PD) between the two groups, but the intervention group exhibited a significantly lower per capita daily sodium intake from dietary salt (SNA/PD) compared to the control group (2.2 vs 4.1g). Furthermore, the intervention group consistently maintained a lower urine sodium-to-potassium ratio than the control group. By incorporating potassium-enriched salt, the intervention group achieved an average increase of 1.2±0.31g in daily potassium intake. Subgroup analysis of 24-hour urine results indicated that the intervention group had significantly lower urinary sodium excretion and higher potassium excretion. Following one year of using potassium-enriched salt, the estimated dietary salt intake in the intervention group decreased from approximately 15g to around 9g based on urinary sodium excretion.

Conclusions:

These findings suggest that the utilization of potassium-enriched salt can effectively reduce sodium intake without necessitating alterations in dietary habits.
ASSESSMENT AND MANAGEMENT OF PATIENTS WITH OBESITY AND HYPERTENSION IN EUROPEAN SOCIETY OF HYPERTENSION EXCELLENCE CENTRES. A SURVEY FROM THE ESH WORKING GROUP ON DIABETES AND META
Authors: Antza Christina , Grassi Guido , Weber Thomas , Persu Alexandre , Jordan Jens , Nilsson Peter , Redon Josef , Stabouli Stella , Kreutz Reinhold , Kotsis Vasilios
Published: May 2024

Objective:

Healthcare providers are faced with an increasing number of patients with obesity and arterial hypertension. Preventing obesity-associated hypertension and appropriately managing patients with established disease are both important. Hence, the aim of our study was to evaluate the clinical care of patients with obesity and hypertension among ESH Excellence Centres (ECs).

Design and method:

We conducted a cross-sectional, worldwide 30-item survey through e-mails.

Results:

In total, 70 representatives of ECs participated (78% men) with 66% of them practicing medicine for more than 30 years and working in well-equipped clinics. Most were internists (41%) and cardiologists (37%) and 73% reported training on the management of obese patients with hypertension. A majority weigh their patients (77%) and evaluate patients for sleep disorders (93%). However, only 47% spend more than 5 min to advise for lifestyle modification in general, 59% for weight loss, 56% for salt intake and 64% for exercise. Finally, a minority of participants ask patients if they like their body (6%) or about previous attempts to lose weight (28%), evaluate 24h urinary sodium excretion rate (22%) and provide written (15%) or personalized (10%) dietary advices. If the patient suffers also from type 2 diabetes mellitus, 66% switch treatment to GLP1 receptor agonists and 60% to SGLT2 inhibitors.

Conclusions:

Most clinicians in ESH ECs are well educated regarding obesity-associated hypertension, and clinics are sufficiently equipped to manage these patients, as well. However, several deficits were reported regarding efforts to address and implement obesity specific aspects and interventions to improve care in patients with obesity and hypertension.
SINGLE-PILL COMBINATION ANTIHYPERTENSIVE THERAPY IN HYPERTENSIVE, OBESE PATIENTS: A PROSPECTIVE, EPIDEMIOLOGICAL STUDY IN ROMANIA
Authors: Vintila Ana -Maria , Dolofan Bogdan , Trambitas Nicoleta , Vittos Oana
Published: May 2024

Objective:

To assess the blood pressure (BP) management in obese, hypertensive patients under treatment with single-pill combination (SPC) antihypertensive therapy.

Design and method:

Prospective, observational, multicenter study, involving 192 investigators (85 cardiologists and 107 general practitioners) randomly selected from Romanian healthcare system, which included 1299 obese, hypertensive patients (Body Mass Index (BMI) of 30 kg/m2 or higher); 56.22±11years; 53.89% females) (1-month recruitment). The total study duration was 5 months (May-Aug 2023), while the patient observational period was 12 weeks (including 3 visits: baseline, at one month and at three months after inclusion). At enrolment visit each patient received a SPC antihypertensive therapy as per investigator’s decision, based on his/her own best medical judgement and in line with the current practice guidelines. Demographic data, comorbidities and data regarding hypertension and evolution of BP values in relation to the antihypertensive treatments were collected.

Results:

The study population had the following characteristics: BMI 34.35±4.21 kg/m2; 20.94% smokers, 56.81% with CV family history, and 52.12% had comorbidities. Among the patients with comorbidities the most frequently identified were diabetes mellitus type 2 (37.37%), valvular heart disease (20.97%), angina (19.35%) and heart failure (16.24%). At study inclusion the investigators’ perception regarding the cardiovascular (CV) risk was that only 27.02% of patients are in “very high” risk category, while according to SCORE2 and SCORE2-OP the actual calculated CV “very high” risk, was identified in 68.82% of patients.

The most frequent recommended double SPC at study inclusion were perindopril/indapamide (81.68%) and olmesartan/amlodipine (5%).

Hypertension was treated in all patients and systolic and diastolic BP values (SBP and DBP) and heart rate (HR) decreased significantly throughout the study (p<0.001) (Fig. 1).

Analyzing the patients treated with different double SPC a significant decrease in BP and HR values was observed (p<0.001) for the perindopril/indapamide SPC, and olmesartan/amlodipine, respectively (Fig. 2).

Conclusions:

This study showed that single pill antihypertensive combinations are effective in decreasing BP and HR values in hypertensive obese patients, while correct CV risk estimation by clinicians remains challenging in their daily practice, with the tendency of underestimation.
THE ASSOCIATION OF LONG-TERM TRAJECTORIES OF BMI, ITS VARIABILITY, AND METABOLIC SYNDROME: A 30-YEAR PROSPECTIVE COHORT STUDY
Authors: Guo Tongshuai , Zheng Sirui , Chen Tao , Chu Chao , Ren Jie , Sun Yue , Wang Yang , He Mingjun , Yan Yu , Jia Hao , Liao Yueyuan , Cao Yumeng , Du Mingfei , Wang Dan , Yuan Zuyi , Wang Duolao , Mu Jianjun
Published: May 2024

Objective:

Data on the association between the longitudinal patterns of weight change in early life and the incidence of metabolic syndrome (MetS) in midlife are limited. This study aims to investigate the association of long-term trajectories of body mass index (BMI), its variability, and the risk of MetS in Chinese subjects.

Design and method:

The prospective Hanzhong Adolescent Hypertension study began in 1987, and the present study included 1824 participants with at least five BMI measurements available from 1987 to 2017. We used group-based trajectory modeling to identify different BMI patterns over time. To assess BMI variability, we calculated Standard Deviation (SD), Variability Independent of the Mean (VIM), and Average Real Variability (ARV). We then used a logistic regression model to estimate how BMI patterns and variability relate to the occurrence of MetS in midlife.

Results:

The BMI trajectories were grouped as low-increasing (34·4%), moderate-increasing (51·8%), and high-increasing (13·8%). Compared with the low-increasing group, the RRs (95% CIs) of MetS in moderate- and high-increasing groups were 4·33 [2·68-6·97] and 13·48 [6·54-27·79] (P <0·0001), respectively. Additionally, higher BMI variabilities (SDBMI, VIMBMI, and ARVBMI) were also associated with a higher risk of MetS (all P <0·0001).

Conclusions:

Our study suggests that both early-life BMI trajectories and BMI variability could be predictive of incident MetS. Early detection and intervention of overweight or obesity in BMI is crucial.
EXPLORING THE BIDIRECTIONAL CAUSAL ASSOCIATION BETWEEN FRAILTY AND CARDIOVASCULAR DISEASES: INSIGHTS FROM A BIDIRECTIONAL MENDELIAN RANDOMIZATION STUDY
Authors: Yin Zheng , Miao Huanhuan , Yang Shijie , Zhou Zhanyang , Zhang Yuqing
Published: May 2024

Objective:

Observational studies have consistently shown a robust association between frailty and cardiovascular diseases. However, it remains uncertain whether this association reflects causality. We performed a bidirectional Mendelian randomized (MR) study to assess the bidirectional causality between frailty, as measured by the frailty index (FI), and hypertension(HTN), atrial fibrillation(AF), coronary artery disease (CAD) and heart failure(HF).

Design and method:

Using the latest genome-wide association study (GWAS) summary data on individuals of European descent, we extracted independent single nucleotide polymorphisms (SNPs) for each phenotype at genome-wide significance levels as instrument variables, including FI (N=175,226), HTN (N=462,933), AF (N=138,994) and HF (N= 977,323). The inverse variance weighting method in two-sample MR analysis was primarily used, followed by various sensitivity and validation analyses such as MRPRESSO.

Results:

Higher FI significantly increased the risk of HTN (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.07-1.16 P<0.001) and CAD (OR 2.57, 95% CI 1.72-3.84 P<0.001). FI was suggestively associated with a higher risk of AF (OR 1.83 95%CI 1.11-3.01 P<0.05). No association between FI and HF was observed (OR 1.30, 95% CI 1.00-1.71 P>0.05). In the reverse analysis, genetic predisposition to HTN (OR 1.94 95% CI 1.71, 2.19 P<0.001) and CAD (OR 1.07 95% CI 1.05-1.09 P<0.001) was significantly associated with higher FI. A suggestive correlation between genetic susceptibility to HF (OR 1.09 95% CI 1.00-1.19 P<0.05) and higher FI was also observed. No association between AF and FI was observed (OR 1.01 95% CI 1.00-1.03 P>0.05). Results of sensitivity and validation analyses were stable.

Conclusions:

Our findings support a bidirectional causal association between frailty and HTN and CAD and a possible causal association between frailty and the development of AF and HF. A deeper exploration of this association is imperative to optimize the management of elderly patients.
A EUROPEAN SURVEY TO IDENTIFY CURRENT PRACTICES ON THE TREATMENT OF HYPERTENSION IN ADULTS >75 YEARS IN ESH EXCELLENCE CENTRES
Authors: Camafort Miguel , Bahat Gülistan , Bogaert Jonathan , Rojas Dhayana E. Dallmeier , De Backer Tine , Desideri Giovambattista , Kenny Rose , Protogerou Athanasios , Rajzer Marek , Ribeiro Heloise , Sheppard James , Ungar Andrea , Virdis Agostino , Labat Carlos , Weber Thomas , Persu Alexandre , Benetos Athanase
Published: May 2024

Objective:

Treatment specificities of hypertension in older adults remains a matter of debate. We therefore investigated the clinical practices on the treatment of hypertension in adults >75 years in ESH Excellence Centres (EC).

Design and method:

A survey with 24 questions was developed by the Working Group Hypertension in Older Adults and addressed to ESH-EC. The survey was questioning therapeutic strategies in treating hypertension in 4 groups of frailty/functionality status: Group 1: Fit, Group 2: Frail and Independent, Group 3: Frail and Dependent Group 4: End of Life.

Results:

Responses were received from 50 ESH excellence centres. The representatives of these centers who answered (one person per center) were mostly internists (42%), cardiologists (32%) and nephrologists (18%). A total of 48% of respondents stated that they always considered frailty status, whilst a further 48% said that they frequently consider frailty, usually based on general appearance of the patient (68%).

The preferable SBP range was considered for the 4 groups. A SBP range of 130-139 mm Hg for Groups 1 and 2 was considered as optimal by 56% of respondents whereas for Group 3, 48% considered a SBP range of 140-149 mmHg and for Group 4, 56% considered SBP 150 mmHg or more as optimal.

For Group 1, 46% and 48% of respondents respectively proposed combination therapy in all hypertensives and in grade 2-3 hypertensives. These percentages were respectively 8% and 66% for Group 2, 4%and 34% for Group 3, 2% and 12% for Group 4.

When considering a reduction in antihypertensive treatment, 57% did not specify any tool, and 34% used START/STOPP criteria. For Group 1, 42% proposed treatment reduction when SBP was between 100-120 mmHg whereas 40% of the respondents reduced treatment only if SBP <100mmHg. In the 3 other groups about 74-80% proposed to reduce treatment when SBP<120 mmHg.

Conclusions:

As frailty increases, higher SBP targets are considered optimal; Nevertheless the use of validated tools to improve frailty stratification, is still not standardized.
PLASMA EXOSOMES FROM HYPERTENSIVE PATIENTS WITH RENAL DYSFUNCTION ARE ENRICHED IN SPECIFIC REDOXIMIRS AND FIBROMIRS
Authors: Redon Josep , Martinez-arroyo Olga , Flores-chova Ana , Debacts Marta Mendez , Martinez-hervas Sergio , Forner Maria J , Ortega Ana , Cortes Raquel
Published: May 2024

Objective:

Several microRNAs (miRNAs) have emerged as powerful regulators of fibrotic processes and have been termed “fibromiRs”. In addition, miRNAs can also influence the expression of genes responsible for the generation of reactive oxygen species and antioxidant defense and are termed “redoximiRs”. Both biological processes are present in the development and progression of renal damage. Frequently, miRNAs are enclosed inside exosomes, which have evolved as novel specific targets for pathogenic mechanisms and therapy search. We aimed to investigate whether plasma exosomes from hypertensive and diabetes patients are enriched in fibromiRs and redoximiRs using deep sequencing technology.

Design and method:

: In a cohort of hypertensive and diabetic patients with nephropathy (n=15) and a control group (n=20), we analyzed by next generation sequencing (RNA-Seq) the miRNA profile in plasma exosomes. Then, we validated miR-21-5p by RT-qPCR such as relevant “redoxifibromiR” and their target predictions and molecular pathways analysis were performed through GO terms and KEGG pathways.

Results:

RNA-Seq analysis from plasma exosomes identified 32 differentially expressed (DE) miRNAs in patients compared to controls, of which 75% are biofluid specific. In addition, the majority of the exosomal DE miRNAs were identified as fibromiRs (17 miRNAs, 53%) or redoximiRs (8 miRNAs, 25%). One of the most representative miRNAs identified was miR-21-5p, whose levels in plasma exosomes were increased 23.5 fold-change (p<0.05), validated by qPCR, and were highly associated with UAE/U-Creatinine (r Spearman=0.96, p<0.001). Bioinformatic analysis revealed that within the top 20 terms of this pro-fibrotic “redoximiR”, miR-21-5p is implicated in molecular functions such as growth factor and cytokine activity, and cytokine receptor binding and regulates key signalling pathways with specific relevance in the context of organ fibrosis, such as chemokine, Ras, Rap1, TNF and MAPK signalling pathways.

Conclusions:

Our study found an enrichment of fibromiRs and RedoximiRs in plasma exosomal biofluid from hypertensive/diabetic patients with renal dysfunction and are closely related with relevant signaling pathways implicated in fibrogenesis.

FUNDING: Health Institute Carlos III [PI19/01796; PI21/00249; PI23/01179 (National Health Research Projects); FI20/00096 FI22/00032 (PFIS Grants); CD00069 (Miguel Servet Contract)]; IJC2020-045308-I, by MCIN/AEI. European Regional Development Fund (ERDF).
HYPERTENSIVE EMERGENCIES AND URGENCIES: ADHERENCE TO GUIDELIENS AND RELATIONSHIP BETWEEN BLOOD PRESSURE MANAGEMENT AND IN-HOSPITAL MORTALITY
Authors: Maloberti Alessandro , Valobra Tommaso , Giani Valentina , Garofani Ilaria , De Censi Lorenzo , Galasso Michele , Colombo Valentina , Menna Alessandro , Annalisa Giacalone , Ferretti Cecilia , Sultana Andrea , Gheda Silvia , Capsoni Nicolò , Galbiati Filippo , Bombelli Michele , Giannattasio Cristina
Published: May 2024

Objective:

Data regarding prevalence and clinical management of hypertensive emergencies and urgencies are lacking and heterogeneous. Our goal is to characterize patients with hypertensive emergencies and urgencies admitted to the Emergency Department (ED) of Niguarda hospital and Pio XI Hospital of Desio. In this population we also want to evaluate factors associated with organ damage, adherence to guidelines and the impact of Blood Pressure (BP) management on in-hospital mortality.

Design and method:

We performed a multi-centre retrospective study collecting data about all adult patients with systolic BP > 180 mmHg and/or diastolic BP >120 mmHg admitted to our hospitals’ ED during 2017 and 2019.

Results:

Admission to ED for BP elevation were 1838 (0.95% of total admission to ED), of whom 38% were hypertensive emergencies and 62% were hypertensive urgencies. Patients with hypertensive emergencies were older, mainly male, with more comorbidities and more symptomatic at ED admission. In the emergencies group, we observe a SBP mean reduction of 39.50 mmHg (±26.35) and a DBP mean lowering of 16.28 mmHg (±17.57); the most used drugs were furosemide, nitroglycerin and parenteral labetalol. In the urgencies group, the mean reduction was 39.09 mmHg (±22.46) for SBP and 15.34 mmHg (±16.07) for DBP. The most used drug was short-acting nifedipine benzodiazepine and amlodipine in this group. Age, sex, clinical history of heart failure and chronic obstructive pulmonary disease, symptoms at ED admission ad eGFR have been recognised as factors associated with organ damage. Instead, BP at ED admission and its management didn’t appear to have a significant impact on outcomes.

Conclusions:

Our study demonstrated better adherence to guidelines in the treatment of hypertensive emergency than of hypertensive urgencies. Furthermore, no significant association were found between the BP management in the ED and in-hospital mortality
THE MEDICAL IMPACT OF EMERGENT BANNING OF N-NITROSODIMETHYLAMINE (NDMA)- CONTAMINATED ANTIHYPERTENSIVE DRUG: A NATIONWIDE LONGITUDINAL COHORT STUDY
Authors: Lee Hae -YOUNG , Cho Myung -Chan
Published: May 2024

Objective:

Concerns exist regarding the potential carcinogenic effect of N-nitrosodimethylamine (NDMA) as a contaminant of the antihypertensive medication, valsartan. This study evaluated the association of NDMA-contaminated generic valsartan with cancer incidence.

Design and method:

Nationwide longitudinal observational cohort of 3,231,212 participants with satisfactory minimal adherence, followed up from January 1, 2013 until December 31, 2020 from the National Health Insurance Service of South Korea consisted. We performed 1:1:1 pairwise propensity score matching (PSM) of NDMA-uncontaminated original, NDMA-contaminated generic, and initially-suspended-but-finally confirmed as NDMA-uncontaminated generic valsartan user-groups. Time-dependent Cox models and dose-response evaluation were used to evaluate carcinogenicity. The primary outcome was any primary cancer incidence. The secondary outcome was the incidences of 12 organ-specific cancers. The risks of all-cause and cardiovascular deaths were estimated before and after the withdrawal of valsartan.

Results:

Among participants (mean age 59.5±13.1 years; male, 53.5%), valsartan new users had adjusted hazard ratios and 95% confidence intervals (CI) of 1.069 (1.054 to 1.085) and 1.172 (1.128 to 1.216) for any cancer in the NDMA-exposed period (versus NDMA-unexposed) before and after 1:1:1 PSM, respectively. Regardless of PSM, prostate cancer risk increased significantly during the NDMA-exposed period and did not increase in the eventually-NDMA-uncontaminated group in valsartan new users. All-cause and cardiovascular mortality did not differ significantly with NDMA exposure before and after emergent banning.

Conclusions:

NDMA-contaminated valsartan increased cancer risk, especially of prostate cancer. All-cause and cardiovascular mortality did not evidently increase following banning. This supports emergent health-policy action against potentially carcinogenic drugs.
BLOOD PRESSURE AND RENAL FUNCTION RESPONSES IN WORKERS EXPOSED TO LEAD FOR UP TO SIX YEARS
Authors: Yu Yuling , An Dewei , Yang Wenyi , Verhamme Peter , Allegaert Karel , Nawrot Tim , Staessen Jan
Published: May 2024

Objective:

As the contemporary environmental lead exposure is comparable to the pre-industry levels in developed countries, whether lead exposure still contributes to the hypertension and renal impairment is controversial. We aimed to assess the association between blood pressure, renal function and lead exposure at contemporary low level in a longitudinal occupational cohort.

Design and method:

The Study for Promotion of Health in Recycling Lead assessed the blood pressure (BP) including the incidence of hypertension and renal function (RF) responses for up to six years in the workers without previous occupational exposure. BP averaged by 5 consecutive readings and the estimated glomerular filtration rate (eGFR) derived from serum creatinine and cystatin C (eGFRcrt and eGFRcys). Blood lead (BL) was measured by inductively coupled plasma mass spectrometry (detection limit 0.5 mg/dL). The statistical methods included multivariable-adjusted mixed models and interval-censored Cox regression analysis.

Results:

The 234 workers analysed were on average 28.5 years old and included 91.9% men. The baseline BL concentration was 4.35 microgram/dL and increased 3.17-fold over follow-up (median: 2.03 years; range: 0.92-6.45 years). The changes in BP and RF were not significantly correlated with the follow-up-to-baseline BL ratio (p >= 0.51 and p >= 0.18, respectively). The fully-adjusted changes in systolic/diastolic BP associated with a doubling of BL were -0.25/-0.12 mm Hg (CI: -0.94 to 0.44/-0.66 to 0.42 mm Hg). Accordingly, the incidence of stage-1 or stage-2 hypertension was not associated with the BL change (p >= 0.063). Similarly, the changes in eGFRcrt and eGFRcys associated with a 2 fold BL increment were not significant, amounting to -0.70 mL/min/1.73 m2 (CI: -1.70 to 0.30 mL/min/1.73 m2) and 1.06 ml/min/1.73 m2 (-2.16 to 0.03 mL/min/1.73 m2).

Conclusions:

The BP and RF responses to an over 3-fold BL increment were small and not significant confirming the safety of modern lead-handing facilities operating under current safety rules.
CALCIUM INTAKE IS INVERSELY ASSOCIATED WITH PERIPHERAL BLOOD PRESSURE: POSSIBLE INTERACTION WITH SERUM CALCIUM
Authors: Pont Chiara Dal , Giontella Alice , Sartorio Andrea , Minuz Pietro , Ericson Ulrika , Melander Olle , Fava Cristiano
Published: May 2024

Objective:

Serum calcium has been directly associated with blood pressure (BP) level or the presence of hypertension in different observational studies, but the association between dietary calcium intake and BP remains unclear. The objective of this study is to investigate the relationship between calcium intake and BP in two large population-based studies.

Design and method:

Calcium intake and BP were evaluated in the Malmö Diet and Cancer (MDC) study (n∼28,000) in Sweden and the UK Biobank (n∼330,000) in the United Kingdom. Calcium intake in the MDC study was determined using a 7-day menu book for recording of meals that varies from day to day (usually lunch and dinner meals) and a 168-item diet questionnaire (“Kosthistoria”), combined with a 45–60 min diet history interview. In the UK Biobank food frequency was assessed using a dietary questionnaire based on a 24-hour dietary recall of the previous day.

Results:

In the MDC study, calcium intake demonstrated an inverse association with systolic (-0.564, 95% CI -0.784/-0.343) and diastolic BP (-0.326, 95% CI -0.444/-0.209) only when the values were not adjusted for total caloric intake. In the UK Biobank, higher calcium intake was associated with lower systolic and diastolic BP when adjusted for caloric intake, but only with diastolic BP when unadjusted for caloric intake. In the MDC, in the subsample of patients with measured serum calcium levels (n=4,095), we observed a positive association between serum calcium level and systolic BP. Upon comparing the association across quartiles of calcium intake, this association was evident only in the three lowest quartiles, while it became negative in the highest quartile.

Conclusions:

Calcium intake from diet tends to be linked with lower BP and appears to mitigate the positive association between serum calcium and BP. Further studies are required to confirm these associations and to explore whether there is an interaction with hormones that regulate calcium distribution in the body.
CLINICAL CHARACTERISTICS OF PATIENTS WITH FIBROMUSCULAR DYSPLASIA WITH AND WITHOUT SPONTANEOUS CERVICAL ARTERY DISSECTION IN THE ARCADIA-POL STUDY
Authors: Sterlinski Ignacy , Talarowska Paulina , Kolodziejczyk-kruk Sylwia , Szwench-pietrasz Elzbieta , Florczak Elzbieta , Kadziela Jacek , Michalowska Ilona , Michalowska Anna , Januszewicz Andrzej , Persu Alexandre , Januszewicz Magdalena
Published: May 2024

Objective:

Fibromuscular dysplasia (FMD) is idiopathic, segmental, non-inflammatory, non-atherosclerotic disease affecting small and medium-sized arteries. FMD causes artery stenosis, although it may also lead to aneurysm, dissection, or arterial tortuosity. The aim of the study was to evaluate clinical characteristics of patients with spontaneous cervical artery dissection (SCeAD) and to assess prevalence of SCeAD among patients with FMD.

Design and method:

The ARCADIA-Pol is an ongoing study, initiated in 2015 at the Department of Hypertension, National Institute of Cardiology in Warsaw, Poland. Patients enrolled in the study met the inclusion criteria: presence or suspicion of FMD and/or radiologically documented episode of spontaneous dissection of any artery. Each patient underwent: clinical and 24h ambulatory blood pressure monitoring, biochemical tests, echocardiography, US Doppler of renal and carotid arteries and whole body angio-CT. We present data of 435 currently enrolled patients.

Results:

Among 435 patients included in the analysis SCeAD was confirmed in 77 subjects, most often in internal carotid arteries (68.8%). Mean age was 43,9 ± 9,6 years, majority of patients were women (64.9%). Hypertension (HT) was present in 59.7% patients, hypercholesterolemia in 44,2%.

Among 77 subjects with SCeAD, the presence of typical FMD changes was confirmed in 35.1% cases. Patients with SCeAD and FMD were older and more often female as compared to those with SCeAD and without FMD. There were no differences in biochemical parameters or target organ damage parameters between SCeAD patients with and without FMD.

Among 281 subjects with FMD, an episode of SCeAD was documented in 9.6% patients. Patients with FMD and SCeAD less often had HT. Women with FMD and SCeAD had more often a history of contraceptive pills use than those without SCeAD. No other differences were found between compared groups.

Conclusions:

FMD changes often coexist in patients with SCeAD (35.1%). In FMD patients complication of SCeAD occur relatively often (9.6%), which leads to conclusion that FMD is generalized arteriopathy. It is recommended to perform radiological screening in FMD patients to look for arterial complications in other vascular beds.
THE RELATION OF CIRCULATING VASCULAR BIOMARKERS TO ENDOTHELIAL FUNCTION AND SKIN MICROVASCULAR REACTIVITY IN PATIENTS WITH HYPERTENSION AND DECLINING KIDNEY FUNCTION
Authors: Jekell Andreas , Lundwall Kristina , Kahan Thomas
Published: May 2024

Objective:

Adhesion molecules and glycocalyx (GC) shedding are believed to reflect endothelial dysfunction but few studies have compared circulating vascular biomarkers and measures of peripheral endothelial function and microvascular function in patients with hypertension over a wider range of renal function.

Design and method:

107 patients (58±13 years, 32% women) with hypertension (149±17/87±10 mmHg) and a wide range of renal function (mean eGFR 74, range 130–21 ml/min x 1.73 m2) were included. Skin microvascular function was assessed by laser Doppler fluxmetry and iontophoresis (acetylcholine, ACh, and sodium nitroprusside, SNP); resistance artery endothelial function by the reflection index change (RI%) before and after beta 2-adrenoceptor-agonist stimulation, assessed by pulse wave analysis (SphygmoCor, AtCor Medical); large artery endothelium dependent and independent vasodilatation by post-ischemic flow-mediated vasodilatation (FMD) and glyceryl trinitrate (GTN), respectively. Vascular circulating biomarkers assessed (by ELISA) were GC glycoproteins hyaluronan (HA) and syndecan-1 (syn-1), and the adhesion molecules ICAM-1, VCAM-1, and E-selectin.

Results:

For bivariate significant (p<0.05) correlations multivariate linear regression analyses including age, sex, body mass index, and eGFR, were performed. There were independent inverse relations between syn-1 (β= –0.27, p=0.042) and e-selectin (β= –0.26, p=0.051) to skin microvascular reactivity evaluated by ACh peak flux, while syn-1, and e-selectin were unrelated to SNP peak flux. HA, ICAM-1 and VCAM-1 did not relate to skin microvascular reactivity. Only syn-1 (β= 0.29, p=0.026) related to RI %. No biomarkers were related to FMD or GTN.

Conclusions:

Increased levels of circulating syn-1 and e-selectin reflect skin microvascular dysfunction and endothelial dysfunction of smaller resistance arteries, independently of eGFR. However, none of the circulating vascular biomarkers reflected large artery endothelial function. The lack of relations between the investigated circulating biomarkers and indices of endothelial function suggests that the investigated biomarkers are less suitable to assess large artery endothelial function in hypertensive patients independent of kidney function.
DEFINITION, VALIDATION AND CALIBRATION OF AN OUTCOME-DRIVEN THRESHOLD FOR PULSE PRESSURE AMPLIFICATION
Authors: Huang Qi -FANG , An De -Wei , Aparicio Lucas , Cheng Yi -Bang , Li Yan , Staessen Jan
Published: May 2024

Objective:

Pulse pressure amplification (PPA) is the ratio of brachial-to-aortic pulse pressure and decreases with age and cardiovascular risk factors. In an individual-participant meta-analysis, we aimed to define, calibrate and validate an outcome-driven threshold for PPA in the general population.

Design and method:

Incidence rates and standardized multivariable-adjusted hazard ratios (HRs) of cardiovascular and coronary endpoints associated with PPA, as assessed by the SphygmoCor software, were evaluated in the International Database of Central Arterial Properties for Risk Stratification (n=5608). Model refinement was assessed by the integrated discrimination (IDI) and net reclassification (NRI) improvement.

Results:

Over 4.1 years (median), 255 and 109 participants experienced a cardiovascular or coronary endpoint. In a randomly defined discovery subset of 3945 individuals, the rounded risk-carrying PPA thresholds converged at 1.3. The HRs for cardiovascular and coronary endpoints contrasting PPA <1.3 vs >=1.3 were 1.54 (95% confidence interval: 1.00-2.36) and 2.45 (1.20-5.01), respectively. Models were well calibrated, findings were replicated in the remaining 1663 individuals analyzed as test dataset, and NRI was significant for both endpoints. The HRs associating cardiovascular and coronary endpoints per PPA threshold in individuals <60 vs >=60 years were 3.86 vs 1.19 and 6.21 vs 1.77, respectively. Of the younger high-risk individuals, 1107 (67.7%) were women.

Conclusions:

Over and beyond common risk factors, low PPA defined as a brachial-to-central PP ratio of <1.3 is a forerunner of cardiovascular and coronary complications, in particular in women younger than 60 years. Our study supports pulse wave analysis for risk stratification.
PREDICTIVITY OF ESTIMATED PULSE WAVE VELOCITY FOR FATAL AND NONFATAL OUTCOMES IN RURAL POPULATION
Authors: Domislovic Marija , Baric Mirta Abramovic , Matijevic Vesna , Bosnic Zvonimir , Brzic Ivan , Capak Krunoslav , Prelevic Vladimir , Radunovic Danilo , Jelakovic Ana , Josipovic Josipa , Jelakovic Bojan
Published: May 2024

Objective:

Our study assesses the predictive value of arterial stiffness measured by estimated pulse wave velocity (ePWV) for fatal and nonfatal outcomes in general rural adult population.

Design and method:

This was a prospective observational study (1175 adult subjects) from the ENAH rural project in Croatia. Subjects were followed up for an average of 11.3 (8.3-13.65) years. Mortality data were collected from the National Institute for Public Health, and data for morbidity from the medical records of local physicians. ePWV was calculated using a validated equation.

Results:

In total, there were 264 deaths (22.5%), and 171 (14.5%) subjects experienced one of the non-fatal outcomes (myocardial infarction, atrial fibrilation, heart failure, stroke, TIA, dialysis). Kaplan Meier analysis (KMa) showed that survival is lower in group with ePWV>10m/s compared with group with ePWV<10m/s (HR=12.8, 95%CI 9.9-16.6, p<0.001) (Figure 1A). Similarly, KMa showed that survival to non-fatal outcome is lower in group with ePWV>10m/s compared to group with ePWV<10m/s (HR=1.50, 95%CI 1.0-2.1, p=0.008), Figure 1B. In the multivariate analysis of predictors for fatal outcome, male gender and ePWV maintained statistical significance in predicting increased risk for death (HR 1.75, 95%CI 1.18-2.61, p=0.006 and HR 1.81, 95%CI 1.08-3.04, p=0.030, respectively). In the multivariate analysis, significance was not confirmed for any predictor for non-fatal outcomes, however, in the multivariate analysis for composite fatal and non-fatal outcome results showed that men were exposed to a greater risk compared to women (HR=1.54; 95%CI 1.14-2.08, p=0.006), and ePWV showed to be a risk factor (HR=1.94, 95%CI 1.50-2.51, p<0.001).

Conclusions:

ePWV was found to be significant independent predictor for cardiovascular deaths and composite fatal and non-fatal outcomes suggesting that this simple and reliable measure of arterials stiffness could be recommended for clinical work at least in remote rural areas where measurements of arterial stiffness is not feasible.
RISK FACTORS FOR CHRONIC HYPERTENSION 5 YEARS AFTER A PREGNANCY COMPLICATED BY PREECLAMPSIA: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Voskamp Lotte , Rousian Melek , Koerts Joni J , Steegers-theunissen Regine Pm , Danser Ah Jan , Verdonk Koen
Published: May 2024

Objective:

Around 30% of women with preeclampsia develop chronic hypertension, a well-known risk factor for cardiovascular diseases, within ten years after pregnancy. This systematic review aimed to summarize risk factors associated with chronic hypertension during a 5-year follow-up period after pregnancies complicated by preeclampsia.

Design and method:

Embase, Medline, Web of Science, Cochrane Central and Google Scholar were searched with terms “preeclampsia” and “hypertension” or “cardiovascular risk” up to October 27, 2023. Observational studies published in English reporting prevalence of chronic hypertension (defined as blood pressure >140 />90 mmHg or prescription of antihypertensive drugs) after 5 years for distinct characteristics of women with preeclampsia were eligible for inclusion. Two researchers independently screened titles and abstracts and evaluated full text articles for inclusion. Study quality and risk of bias were assessed using the ErasmusAGE score. Where possible, a meta-analysis was conducted.

Results:

Thirty-three studies were included, involving 230939 patients and reporting 30 risk factors. Studies were of cohort (n=25) and case-control (n=8) design, with a median quality score of 6/10. Preeclampsia in a subsequent pregnancy was strongly associated with chronic hypertension (11 studies, N=139900). A meta-analysis of 5 studies (N=569) showed no association between early-onset preeclampsia <34 weeks of gestation and chronic hypertension (RR 1.90, 95%CI 0.76-4.74). Other factors associated with chronic hypertension were maternal age, body mass index, preconceptional blood pressure, severe preeclampsia defined as blood pressure >160/>110 mmHg or proteinuria >5g/24 hours, HELLP syndrome before 29 weeks of gestation, higher left ventricular mass index 8 months postpartum and a family history of preeclampsia. No associations with preterm birth, birthweight or laboratory parameters describing liver and renal function were observed. Notably, eclampsia showed a negative association with chronic hypertension.

Conclusions:

Preeclampsia in a subsequent pregnancy was the most consistently reported risk factor for chronic hypertension beyond 5 years after pregnancy. Early-onset of preeclampsia and preterm birth are not associated with chronic hypertension within this 5-year period. Maternal body mass index and blood pressure are key factors to include in a postpartum risk assessment for chronic hypertension after preeclampsia.
MEDIATION BY ANTIHYPERTENSIVE DRUG ADHERENCE IN THE IMPACT OF AMBULATORY BLOOD PRESSURE MONITORING ON THE CARDIOVASCULAR OUTCOMES IN THE NEWLY TREATED HYPERTENSION PATIENT
Authors: Shin Jinho , Kim Kwang-IL , Kim Hack-Lyoung , Ihm Sang Hyun
Published: May 2024

Objective:

Non-adherence has been a growing challenge for breakthrough in the improvement of hypertension control. As the standard method for out of office BP measurement, we reported that ambulatory BP monitoring (ABPM) is also associated with improved antihypertensive drug adherence and improved CV outcome. But the magnitude of the contribution of improved adherence by ABPM on the better CV outcomes is uncertain.

Design and method:

In the database of The Korean National Health Insurance System, 27357 newly prescribed hypertension patients performed ABPM before the prescription were propensity score matched with the randomly selected 118594 newly prescribed patients without ABPM during 2008.1∼2009.12. Among them, 25312 patients without history of cardiovascular diseases were followed. Primary composite end points were any event of ischemic stroke, intracranial hemorrhage, and acute myocardial infarction. Secondary composite end points were any event of the primary composite end points, and admission for heart failure. Proportion mediated (PM) by good adherence was calculated by using the equation for non-linear outcome model, i.e., PM = natural direct effect (NDE) x [natural indirect effect (NIE)-1]/(NDE x NIE-1).

Results:

Age of the subject was 49.7+/-12.4 years and the proportion of the female was 41.1%. Median follow-up duration was 8.58 years. Adjusting the covariate and the adherence as the mediator, the hazard ratio of ABPM was 0.65 (95% CI:0.58, 0.74), p <0.0001) and 0.72 (95% CI: 0.66, 0.79, p <0.0001) for the primary and the secondary composite outcomes, respectively. In the mediation analysis, PNDE was 0.71 (95% CI: 0.64, 0.79) and TNIE was 0.95 (95% CI: 0.88, 1.02). PM was calculated as 11.1% (p <0.0001). When considering the interaction term of ABPM∗adherence in the log linear model, PNDE was 0.76 (95% CI: 0.64, 0.91) and TNIE was 0.93 (95% CI: 0.93, 0.83). PM was calculated as 19.1% (p < 0.0001).

Conclusions:

ABPM before antihypertensive drug prescription could have a good impact on both the drug adherence and CV prognosis. The contribution of good drug adherence to the overall impact of ABPM on improved cardiovascular outcomes is minor.