bluuebunny/crossref_metadata_2025_split huggingface dataset:
NEUTROPHIL TO LYMPHOCYTE RATIO AND PLATELET TO LYMPHOCYTE RATIO AS ASSESSMENT TOOLS FOR LIPID CONTROL AND CARDIOVASCULAR RISK
Authors: Vintila Ana Maria , Horumba Mihaela , Cimpu Cristiana , Dumitrescu Diana , Miron Paul , Alucai Andreea , Cristea George Gabriel , Vintila Vlad Damian 
Published: April 2021

Objective:
NLR (neutrophil to lymphocyte ratio) and PLR (platelet to lymphocyte ratio) are parameters associated with a higher mortality in patients with atherosclerotic cardiovascular disease (ASCVD). The purpose of our study was to determine if there were any differences in NLR or PLR in very-high risk patients who achieve LDL-cholesterol < 55 mg/dl and those who do not.

Design and method:
We performed a unicentric, retrospective study on hypertensive, diabetic patients admitted to the Internal Medicine and Cardiology Department from 2014 to 2018. Demographics, comorbidities and laboratory test results were recorded including complete blood count, erythrocyte sedimentation rate (ESR) and lipid profile. Data analysis was performed using SPSS version 20.

Results:
A total of 1239 patients were enrolled with a mean age of 71.3 ± 10.1 years and a slight female predominance (59.4% female). Little over half of patients (56.3%) had very-high cardiovascular risk: 54.3% had ASCVD and 4.2% had severe CKD, while all other had high CV risk. There were no significant differences in terms of NLR and PLR between patients at high or very-high CV risk as long as the LDL-cholesterol target was met (3.589 vs. 4.745, p = 0.163; 153.9 vs. 196.5, p = 0.055). However, if LDL-cholesterol targets were not achieved, there were NLR and PLR were higher in patients with very-high CV risk (2.857 vs. 3.940, p < 0.001; 143.5 vs. 174.0, p = 0.001). Both NLR and PLR had a positive correlation with ESR irrespective of high or very-high CV risk (NLR: r = 0.153 p = 0.022 vs. r = 0.264, p < 0.001; PLR: r = 0.214, p = 0.001 vs. r = 0.278, p < 0.001).

Conclusions:
Tighter cholesterol control has a significant role in lowering cardiovascular risk. Our study shows that based on NLR and PLR very-high risk patients who achieve the LDL-cholesterol target of 55 mg/dl have the same risk of CV events as patients who are at high CV risk.
VALIDITY OF FIVE FORMULAS TO ESTIMATE 24-HOUR URINARY SODIUM BY SPOT URINE SAMPLES IN ADULTS LIVING IN NORTHEAST CHINA
Authors: Song Wei , Qian Ni , Guo Ran , Zhang Ying , Jiang Yinong 
Published: April 2021

Objective:
Although several formulas from spot urine have been used to assess 24-hour urinary sodium excretion in order to estimate salt intake, the validity in Chinese adult population is uncertain. The objective was to evaluate the accuracy of five formulas, including INTERSALT without urine potassium, Kawasaki, Tanaka, Uechi simple-mean, and a new formula, by spot urinary to predict 24-hour sodium excretion in adults living in northeast China.

Design and method:
This was a multi-center clinical study, conducted from April 2016 to October 2019. There were 1092 hospitalized patients aged from 18 to 85 years enrolled. Five different formulas were used to predict 24-hour urinary sodium (UNa) excretions by spot morning urinary samples. Actual urinary sodium excretion was measured from 24-hour urine samples. The estimated value is compared with the actual value by examining bias (observed minus predicted UNa), the intraclass correlation coefficients (ICC), and Bland–Altman plots. The differences between actual and estimated sodium excretion across subgroups divided by salt intake were analyzed.

Results:
The average excretion of sodium was 2958.15 mg/d, which is equivalent to 7.51 g/day of sodium chloride intake. Formulas produced biases for actual urinary sodium were 328.31 mg/d for INTERSALT, 517.56 mg/d for new formula, 897.59 mg/d for Tanaka, 1169.06 mg/d for Uechi, 1971.12 mg/d for Kawasaki. The correlation was positive for all equations, the highest and lowest ICC were 0.37 for new formula and 0.3 for Uechi respectively. There was no significant difference in number of patients which were beyond the mean ± 1.96 standard deviation. The least mean biases in lower salt intake subgroup (UNa no more than 2362.20 mg/d) and middle salt intake subgroup of five equations were 1283.00 mg/d and 74.46 mg/d respectively, which are calculated by INTERSALT. The least mean biases in higher salt intake subgroup (UNa more than 4724.41 mg/d) was 147.62 mg/d for Uechi.

Conclusions:
INTERSALT without urine potassium and new formula may offer a good performance of mean 24-h sodium estimation in lower and middle salt intake subgroups for adults living in Northeast China. The Uechi simple-mean formula performed best in higher salt intake subgroup.
SYSTOLIC INTER-ARM BLOOD PRESSURE DIFFERENCE AND COGNITIVE DECLINE: FINDINGS FROM THE INTERPRESS-IPD COLLABORATION
Authors: Clark Christopher , Boddy Kate , Warren Fiona , Mcdonagh Sinead , Moore Sarah , Aboyans Victor , Cloutier Lyne , McManus Richard , Shore Angela , Taylor Rod , Campbell John 
Published: April 2021

Objective:
Hypertension and dementia are associated with older age and each other. As the populations age, prevalence of dementia will rise, representing substantial costs and care burdens for society. Currently, no interventions halt established cognitive decline, therefore approaches focus on prevention. Systolic inter-arm differences (IAD) in blood pressure (BP) and cognitive decline are associated with cardiovascular disease. We recently published initial evidence for associations of IAD with prospective cognitive decline and now present findings from the INTERPRESS-IPD Collaboration, examining associations of IAD with mild cognitive impairment (MCI) development and dementia.

Design and method:
Individual participant data meta-analyses. We examined time-to-event data for new diagnoses of MCI and dementia, according to IAD status in univariable and multivariable regression models, stratified by study. Multivariable analyses were adjusted for systolic BP, age, sex and highest educational attainment. We also examined changes in Mental State Examination (MSE) scores, with adjustments as above, plus follow-up duration.

Results:
Mean age was 66.2 years, 55% were female, 84% were of White ethnicity and mean systolic IAD was 7.0 mmHg. During 10-year follow-up, 5.9% of 4,635 individuals, from 3 cohorts, had new diagnoses of MCI. In univariable analyses, MCI was associated with systolic IAD >/=5mmHg [Hazard Ratio, 1.34 (95%CI 1.04 to 1.72); p=0.022] and >/= 0mmHg [1.33 (1.03 to 1.73); p = 0.032]. After adjustment, associations with systolic IADs >/ = 5mmHg [1.31 (1.02 to 1.67); p = 0.036] and >/=10mmHg [1.29 (0.99 to 1.68); p = 0.056] remained. There were 95 new diagnoses of dementia during follow-up; no associations were observed between dementia diagnosis and IAD.
MSE scores were recorded for 2,709 participants; 15.5% showed clinically meaningful reductions (>/=5 points) during follow-up. Decreases were associated with IADs >/=5mmHg (p=0.004) and >/=10mmHg (p = 0.006) on univariable analyses. After adjustment, associations with IADs >/=5mmHg remained (p = 0.033); age and educational attainment attenuated the association with IADs >/ = 10mmHg (p = 0.11).

Conclusions:
We present the first time-to-event analyses of MCI development with IAD and demonstrate that systolic IADs >/ = 5mmHg and >/ = 10mmHg are associated with MCI onset. If confirmed, these findings could inform individualised treatment decisions to minimise risk of future cognitive decline.
SYSTOLIC BLOOD PRESSURE IS A MAJOR COMPONENT OF THE RISK SCORE FOR NEW PROGRESSION OF CAROTID PLAQUE: THE SUITA STUDY
Authors: Kokubo Yoshihiro , Watanabe Makoto , Higashiyama Aya , Honda-Kohmo Kyoko , Miyamoto Yoshihiro 
Published: April 2021

Objective:
We first showed that the new progression of carotid plaque (Prog-PQ) is a risk factor for cardiovascular disease (CVD), but the Prog-PQ risk score has not been established.

Design and method:
We studied 4,724 Japanese (mean age 59.7 years) without CVD, whose intima-media thickness (IMT) was measured with carotid ultrasonography on both sides of the entire carotid artery areas (April 1994 to August 2001). Carotid plaque was defined as a maximum IMT of the common carotid artery > 1.1 mm. We excluded subjects with carotid plaque at baseline (n = 1,044), lost to follow-up (n = 167), and missing data (n = 2). For 3,511 subjects, the general examination and carotid ultrasonographic follow-ups were performed every two years until March 2016. Cox proportional hazard ratios were analyzed after adjusting for cardiovascular risk factors. We used the area under the receiver operating characteristic curve to evaluate the model's discrimination.

Results:
During 38,454 person-years of follow-up, 1,771 incidences of Prog-PQ were observed. Based on systolic blood pressure (SBP) of less than 120 mmHg, the adjusted hazard ratios of Prog-PQ were 1.18 (1.04–1.33), 1.35 (1.11–1.63), and 1.65 (1.23–2.23) in subjects with SBP = 120–139 mmHg, 140–159 mmHg, and 160 mmHg or more, respectively. We developed a scoring system for each risk factor as follows: 0, 2, 4, 6, 9, and 11 points for age 30's to 80's, respectively; -1 point for women; 0, 1, and 2 points for systolic blood pressure (<120, 120–159, and >  = 160mmHg); 0, 1, 2, and 3 points for total cholesterol (<160, 160–239, 240–279, and > = 280 mg/dL); 2, 0, and -1 points for HDL cholesterol (<35, 35–59, and > = 60 mg/dL); 1 point for overweight or current smoking; and 2 points for diabetes (C-statistic 0.647; 95%CI, 0.629–0.665). Individuals with 2 or 10 points had 27% or 62% observed probability of Prog-PQ in 10 years, respectively.

Conclusions:
We have developed a 10-year risk score for Prog-PQ, that can efficiently predict atherosclerosis in routine clinic/health examinations without carotid ultrasonography.
EFFECTS OF BLOOD PRESSURE-LOWERING ON CANCER RISK: AN INDIVIDUAL PARTICIPANT DATA META-ANALYSIS OF 300,000 PARTICIPANTS
Authors: Copland Emma , Canoy Dexter , Nazarzadeh Milad , Bidel Zeinab , Woodward Mark , Chalmers John , Teo Koon , Pepine Carl , Davis Barry , Kjeldsen Sverre , Sundstrom Johan , Rahimi Kazem 
Published: April 2021

Objective:
Evidence for the effects of pharmaceutical blood pressure (BP)-lowering on cancer risk is inconsistent and based on observational data. We therefore investigated the effect of BP-lowering on the risk of cancer in a large collaborative study.

Design and method:
We included randomised trials participating in the Blood Pressure-Lowering Treatment Trialists’ Collaboration. Placebo-controlled trials, drug class comparison trials and trials comparing more-vs-less intensive BP-lowering that provided individual-level participant data (IPD) on cancer events were pooled. We investigated the effects of BP reduction on cancer risk by conducting one-stage IPD meta-analyses using Cox proportional hazard models, stratified by trial and accounting for competing risks. We also investigated effects stratified by age, gender, body mass index (BMI), smoking and previous antihypertensive use at baseline.

Results:
This analysis included 300,098 participants (42% women) from 39 trials. At baseline, the mean age of participants was 66 (standard deviation [SD] = 9), mean BMI was 28 (SD = 5), 18% were current smokers and 75% were previously on BP-lowering medication. Over a median duration of 4 years, 16,748 participants were diagnosed with cancer, and 4347 cancer deaths were reported. The hazard ratio (HR) per 5mmHg reduction in systolic BP was 1.03 (95% confidence interval [CI] 0.99–1.07) for any cancer and 1.05 (95% CI 0.98–1.12) for cancer death. We found heterogeneity in the effects of BP-lowering across age, gender, BMI and smoking groups for any cancer and cancer death, and across groups defined by previous antihypertensive use for any cancer. However, there was no evidence that BP-lowering significantly increased the risk of developing cancer in specific patient subgroups. We found no evidence for trends in increasing or decreasing risk over time for either outcome (P for trend: any cancer = 0.98, cancer death = 0.99).

Conclusions:
This large-scale IPD meta-analysis found no evidence that BP-lowering had an important effect on cancer risk. Although we found that BP-lowering effects differed across several patient characteristics, there was no evidence for trend in cancer risk over time. We plan to further investigate the effects of BP-lowering on site-specific cancers (breast, colorectal, kidney, lung, prostate and skin) and present these results at the meeting.
SOMATIC MUTATIONS IN ADRENALS FROM PATIENTS WITH PRIMARY ALDOSTERONISM NOT CURED AFTER ADRENALECTOMY SUGGEST COMMON PATHOGENIC MECHANISMS BETWEEN UNILATERAL AND BILATERAL DISEASE
Authors: Hacini Inès , De Sousa Kelly , Boulkroun Sheerazed , Meatchi Tchao , Amar Laurence , Zennaro Maria-Christina , Fernandes-Rosa Fabio Luiz 
Published: April 2021

Objective:
Primary aldosteronism (PA) is the most common form of secondary and curable hypertension, with a prevalence of 5% in primary care and 10% in referred patients. Different germline and somatic mutations are found in aldosterone producing adenoma (APA) and familial forms of the disease, while the causes of bilateral adrenal hyperplasia (BAH) remain largely unknown. Adrenalectomy is the recommended treatment for patients with aldosterone-producing adenoma (APA); however, 6% of patients are not cured and show persistent PA after surgery suggesting BAH. The objective of this study was to analyze clinical data of patients with APA without biochemical success after adrenalectomy and the histological and genetic characteristics of their adrenal glands.

Design and method:
Clinical data from 16 PA patients undergoing adrenalectomy between 2008 and 2018 without biochemical success were compared to those from 39 PA patients with hormonal cure after surgery. Histological, morphological and genetic characterization of the adrenals was carried out by CYP11B2 and CYP11B1 immunostaining and by CYP11B2 guided next generation sequencing on formalin-fixed paraffin-embedded APA tissues.

Results:
Patients with absent hormonal cure displayed longer duration of arterial hypertension before PA diagnosis and lower index of lateralization of aldosterone production on adrenal vein sampling. In 14 patients, APA expressing CYP11B2 were identified. No difference in histological and morphological characteristics was observed between patients with our without hormonal cure. Somatic mutations in APA driver genes were identified in 13 out of 14 CYP11B2 positive APA. Mutations in the CACNA1D gene were the most frequent genetic abnormality and associated with smaller nodules. The mutational status of APA in patients without hormonal cure was not associated with differences in CYP11B1 or CYP11B2 expression.

Conclusions:
In conclusion, 93% of adrenals from patients with absent hormonal cure showed CYP11B2 expressing adenomas carrying somatic mutations, confirming the diagnosis of APA. However, these patients were diagnosed later and exhibited lower lateralization index of aldosterone production, suggesting asymmetric aldosterone production in the context of BAH. Somatic mutations in adrenal glands from those patients indicate common mechanisms underlying BAH and APA.
BLOOD PRESSURE EFFECTS OVER TIME OF BIPOLAR RADIOFREQUENCY RENAL DENERVATION IN UNTREATED HYPERTENSION
Authors: Weber Michael , Kirtane Ajay , Weir Matthew , Leon Martin 
Published: April 2021

Objective:
It is believed that interruption of the renal nerves which lie in close proximity to the renal arteries, will effectively reduce blood pressure. As a first step, this study measured the blood pressure effects of ablating these nerves using radiofrequency energy produced by a bipolar catheter positioned into each renal artery in untreated hypertensive patients.

Design and method:
REINFORCE was a randomized, sham-controlled multicenter trial. Patients with office systolic blood pressure (SBP) of 150–180 mmHg and average 24-hour ambulatory SBP of 135–170 mmHg after medication washout underwent bipolar radiofrequency renal denervation or a sham procedure. The planned outcome was 8-week change in 24-hour ambulatory SBP. Enrollment was terminated for apparent futility before a sufficient sample for powered efficacy comparisons was enrolled, although patient observation continued. Safety assessments included all-cause death, renal failure, severe hypotension/syncope, hypertensive crisis, and renal artery stenosis.

Results:
Baseline 24-hour BP was 148.3 ± 10.9/85.7 ± 9.1 mmHg for the denervation group (N = 34, age 58.5 ± 10.1 years, 47% female) and 149.1 ± 7.2/86.4 ± 9.8 mmHg for the control group (N = 17, age 58.2 ± 9.8 years, 24% female). At 8 weeks, mean 24-hour SBP reductions for the renal denervation and control groups were 5.3 mmHg (95%CI -8.8, -1.8) and -8.5 mmHg (95%CI -13.3, -3.8), respectively (difference 3.3 [95%CI -2.8, 9.3]; p = .30). Antihypertensive medications could then be added. By 6 months, decreases in SBP were greater for the denervation group, yielding between-group differences of -7.2 (95%CI -15.2, 0.8; p = .08), -9.7 (95%CI -17.7, -1.7; p = .02), and -11.4 (95%CI -19.2, -3.7; p < .01) for 24-hour, daytime ambulatory, and office measurements, respectively. Control rates (office SBP < 140) were higher in the denervation group both at 6 months (52% vs. 12%, p < 0.01) and 12 months (42% vs. 13%, p = 0.048). Medication use was similar in both groups. By 12 months, one denervation patient had a hypertensive urgency and one experienced progression of renal artery stenosis.

Conclusions:
The antihypertensive effects of renal denervation can be delayed for weeks following the procedure, but then appear to be sustained for at least 12 months.
PATIROMER VS PLACEBO TO ENABLE SPIRONOLACTONE IN PATIENTS WITH RESISTANT HYPERTENSION AND CKD: ANALYSIS ACCORDING TO PATIENT SEX (AMBER TRIAL)
Authors: Williams Bryan , White William B. , Mayo Martha R. , Warren Suzette , Arthur Susan , Ackourey Gail , Rossignol Patrick , Agarwal Rajiv 
Published: April 2021

Objective:
Spironolactone (SPIRO) effectively reduces BP in patients (pts) with resistant hypertension (RHTN), but hyperkalaemia (HK) may limit its use in pts with advanced CKD. In AMBER, patiromer (PAT) enabled more persistent SPIRO use in pts with RHTN and eGFR 25– < = 45 mL/min/1.73 m2. As biological differences between men and women may contribute to variations in drug response, we evaluated the AMBER results by sex in a prespecified analysis.

Design and method:
AMBER was a randomised, double-blind, placebo (PBO)-controlled RCT in adults with eGFR 25– < = 45 mL/min/1.73 m2 and uncontrolled RHTN (unattended systolic automated office blood pressure [AOBP]) 135–160 mm Hg, despite taking > = 3 antihypertensives. Pts were assigned (1:1) to receive PBO or PAT, and SPIRO 25 mg QD, to start along with their baseline (BL) BP medications. Dose titrations were permitted after 1 week for PAT/PBO and after 3 weeks for SPIRO. The primary endpoint (between-group difference at Wk 12 in % of pts on SPIRO) was assessed in prespecified subgroups by sex.

Results:
Of 295 pts randomised, there were 153 (51.9%) men and 142 (48.1%) women with BL mean (SD) systolic AOBP of 144.6 (6.7) mmHg and 143.5 (6.8) mmHg and serum K+ of 4.77 (0.37) mmol/L and 4.65 (0.35) mmol/L, respectively. More pts treated with PAT than PBO remained on SPIRO at Wk 12 in both subgroups (between treatment difference of 19.3% [P = 0.0035] for men and 19.7% [P = 0.0065] for women with P = 0.80 for interaction between subgroups) (Figure). LS Mean (SE) cumulative SPIRO dose was higher with PAT than PBO, by 449 (180) mg in men and 326 (178) mg in women. Similar reductions in AOBP were observed in both subgroups at 12 weeks (P < 0.0001). Adverse events occurred in 52% (PBO) and 53% (PAT) of men and 55% (PBO) and 59% (PAT) of women. One PBO (woman) and 3 PAT pts (2 men, 1 woman) had serum Mg 0.49 to < 0.58 mmol/L; none had serum Mg < 0.49 mmol/L.

Conclusions:
SPIRO reduced AOBP in pts with advanced CKD and RHTN and PAT enabled more of these pts to continue treatment with SPIRO, regardless of sex.
LACK OF FUNDING AND LONG-TERM JOB SECURITY THREATENS TO HAVE PROFOUND EFFECTS ON CARDIOVASCULAR RESEARCHER RETENTION IN AUSTRALIA
Authors: Marques Francine , Climie Rachel , Wu Jason , Calkin Anna , Chapman Niamh , Colafella Katrina , Picone Dean , Viola Helena , Murphy Andrew , Nelson Mark , Nichols Stephen , Hool Livia , Figtree Gemma 
Published: April 2021

Objective:
Cardiovascular disease is the leading cause of death in Australia, yet funding has stagnated in recent years, resulting in economic challenges within the cardiovascular research sector. Here we investigated the challenges faced by cardiovascular researchers in Australia as an initiative of the Emerging Leaders Committee of the Australian Cardiovascular Alliance (ACvA).

Design and method:
We developed a questionnaire, which was distributed via email and social media to ACvA members, Australian cardiovascular societies, councils, universities and research institutes for 6 months during April-November 2019.

Results:
There were 548 completed responses (out of 703, 80%). The respondents primary career stage was group leader or laboratory head (40%) followed by post-doctoral (33%), most were females (53%), and 31% reported career interruptions, especially parental leave. Only 23% had permanent (ongoing) employment. Eighty one percent of full-time workers said they regularly work more than 40 hours per week, and 85% were not compensated for overtime work. Sixty eight percent said they have considered leaving the cardiovascular research sector. If their position could not be funded in the next few years, 43% would consider leaving Australia to work in cardiovascular research overseas, and only 9% said they would not leave the sector. Greater job security (76%) and government investment in cardiovascular research (71%) were highlighted as the main strategies for retaining cardiovascular researchers in the sector in Australia. Compared to male cardiovascular researchers, women were less likely to be a laboratory head, hold secure funding or have confidence in a long-term career path as cardiovascular researcher, and were more likely to consider leaving the sector (all P < 0.05).

Conclusions:
Our survey suggests that the current lack of funding in cardiovascular research, combined with a lack of long-term job security, threatens to have profound effects on cardiovascular researcher retention in Australia, especially for women. Strategies to increase retention and address the issues highlighted by our survey are urgently needed.