The hidden hand of chloride in hypertension

Among the environmental factors that affect blood pressure, dietary sodium chloride has been studied the most, and there is general consensus that increased sodium chloride intake increases blood pressure. There is accruing evidence that chloride may have a role in blood pressure regulation which may perhaps be even more important than that of Na+. Though more than 85 % of Na+ is consumed as sodium chloride, there is evidence that Na+ and Cl− concentrations do not go necessarily hand in hand since they may originate from different sources. Hence, elucidating the role of Cl− as an independent player in blood pressure regulation will have clinical and public health implications in addition to advancing our understanding of electrolyte-mediated blood pressure regulation. In this review, we describe the evidence that support an independent role for Cl− on hypertension and cardiovascular health

Genomics of blood pressure and hypertension: extending the mosaic theory toward stratification

The genetic architecture of blood pressure (BP) now includes more than 30 genes, with rare mutations resulting in inherited forms of hypertension or hypotension, and 1477 common single-nucleotide polymorphisms (SNPs). These signify the heterogeneity of the BP phenotype and support the mosaic theory of hypertension. The majority of monogenic syndromes involve the renin-angiotensin-aldosterone system and the adrenal glucocorticoid pathway, and a smaller fraction are due to rare neuroendocrine tumours of the adrenal glands and the sympathetic and parasympathetic paraganglia. Somatic mutations in genes coding for ion channels (KCNJ5 and CACNA1D) and adenosine triphosphatases (ATP1A1 and ATP2B3) highlight the central role of calcium signalling in autonomous aldosterone production by the adrenal gland. The per-SNP BP effect is small for SNPs according to genome-wide association studies (GWAS), and all of the GWAS-identified BP SNPs explain ∼ 27% of the 30%-50% estimated heritability of BP. Uromodulin is a novel pathway identified by GWAS, and it has now progressed to a genotype-directed clinical trial. The majority of the GWAS-identified BP SNPs show pleiotropic associations, and unravelling those signals and underpinning biological pathways offers potential opportunities for drug repurposing. The GWAS signals are predominantly from Europe-centric studies with other ancestries underrepresented, however, limiting the generalisability of the findings. In this review, we leverage the burgeoning list of polygenic and monogenic variants associated with BP regulation along with phenome-wide studies in the context of the mosaic theory of hypertension, and we explore potential translational aspects that underlie different hypertension subtypes

Does measurement technique explain the mismatch between European head size and WHO charts?

Objective To test whether different measuring techniques produce systematic differences in head size that could explain the large head circumferences found in Northern European children compared with the WHO standard. Design: Cross-sectional observational study. Setting: Scotland, UK. Patients: Study 1: 68 healthy children aged 0.4–18 months from mother and baby groups and a medical students teaching session. Study 2: 81 children aged 0.4 to 25 months from hospital wards and neonatal follow-up clinics. Interventions: Study 1: heads measured with plastic tape using both the WHO tight and UK loose technique. Study 2: heads measured using WHO research technique and a metal measuring tape and compared with routinely acquired measurements. Main outcome measures: Mean difference in head z-scores using WHO standard between the two methods. Results: The tight technique resulted in a mean (95% CI) z-score difference of 0.41 (0.27 to 0.54, p<0.001) in study 1 and 0.44 (0.36 to 0.53, p<0.001) in study 2. However, the mean WHO measurements in the healthy infants still produced a mean z-score that was two-third of a centile space (0.54 SD (0.28 to 0.79) p<0.001) above the 50th centile. Conclusion: The WHO measurement techniques produced significantly lower measures of head size, but average healthy Scottish children still had larger heads than the WHO standard using this method

A tale of two diseases

No abstract available

Diastolic blood pressure J-curve phenomenon in a tertiary-care hypertension clinic

Concerns exist regarding the potential increased cardiovascular risk from lowering diastolic blood pressure (DBP) in hypertensive patients. We analyzed 30-year follow-up data of 10 355 hypertensive patients attending the Glasgow Blood Pressure Clinic. The association between blood pressure during the first 5 years of treatment and cause-specific hospital admissions or mortality was analyzed using multivariable adjusted Cox proportional hazard models. The primary outcome was a composite of cardiovascular admissions and deaths. DBP showed a U-shaped association (nadir, 92 mm Hg) for the primary cardiovascular outcome hazard and a reverse J-shaped association with all-cause mortality (nadir, 86 mm Hg) and noncardiovascular mortality (nadir, 92 mm Hg). The hazard ratio for the primary cardiovascular outcome after adjustment for systolic blood pressure was 1.38 (95% CI, 1.18–1.62) for DBP <80 compared with DBP of 80 to 89.9 mm Hg (referrant), and the subdistribution hazard ratio after accounting for competing risk was 1.33 (1.17–1.51) compared with DBP ≥80 mm Hg. Cause-specific nonfatal outcome analyses showed a reverse J-shaped relationship for myocardial infarction, ischemic heart disease, and heart failure admissions but a U-shaped relationship for stroke admissions. Age-stratified analyses showed DBP had no independent effect on stroke admissions among the older patient subgroup (≥60 years of age), but the younger subgroup showed a clear U-shaped relationship. Intensive blood pressure reduction may lead to unintended consequences of higher healthcare utilization because of increased cardiovascular morbidity, and this merits future prospective studies. Low on-treatment DBP is associated with increased risk of noncardiovascular mortality, the reasons for which are unclear

OPTIMA-BP: empOwering PaTients in MAnaging Blood Pressure – protocol for a randomised parallel group study comparing use of Kvatchii web-based patient education portal as an addition to home blood pressure monitoring

Introduction: Hypertension is the leading modifiable risk factor for cardiovascular disease and is implicated in half of all strokes and myocardial infarctions. One-third of the adults in Scotland have hypertension yet only a quarter of them have their blood pressure (BP) controlled to target (<140/90 mm Hg). Empowering patients to have a better understanding of their condition and becoming actively involved in the monitoring and management of hypertension may lead to improved patient satisfaction, improved BP control and health outcomes and reduction in the use of primary/secondary care hypertension clinics. Methods and analysis: OPTIMA-BP is a randomised parallel group pilot study comparing the use of home BP monitoring accompanied by access to the web-based cardiovascular educational portal (Kvatchii) and home BP monitoring (HBPM) alone in 200 patients with hypertension attending the Glasgow Blood Pressure Clinic, Queen Elizabeth University Hospital, Glasgow. Consented participants will be asked to complete surveys on lifestyle factors, medication adherence, quality of life and hypertension knowledge, understanding and home monitoring. The intervention group will be asked to complete a survey to help evaluate the Kvatchii portal. At 6 and 12 months, the surveys will be repeated via the CASTOR EDC. Both groups will input their HBPM results at 2-month intervals into a CASTOR-EDC survey. OPTIMA-BP will follow-up with participants over 12 months with the study running over 24 months. The primary outcome is HBPM systolic BP area under the curve between baseline and 6 months Ethics and dissemination: OPTIMA-BP was approved by the North of Scotland Research Ethics Committee 2 (22/NS/0095). Current protocol version 1.2 date 6 June 2023. Written informed consent will be provided by all study participants. Study findings will be submitted to international peer-reviewed journals and will be presented at national and international scientific meetings. Trial registration number: ClinicalTrials.gov: NCT05575453. Registered 12 October 2022. https://clinicaltrials.gov/ct2/show/NCT0557545

Prevalence of under and over weight in children with neurodisability, using body composition measures

We aimed to compare rates of under and overweight in children with different neurodevelopmental disorders (NDD) by measuring weight, height/length, arm-to-leg bioelectrical impedance (BIA) and subscapular and triceps skinfolds in 146 children aged 4-16 years attending special schools. Z scores were calculated and skinfolds and lean mass Z scores were further adjusted for height. Underweight was found in 9% (14) children (body mass index (BMI) < 2nd) but only 3% (4) had skinfolds <5th centile. Overweight was much commoner, with 41% (58) children having BMI > 95th and 20% (14) had skinfolds >95th centile. Children with cerebral palsy were very short with low BMI and lean mass, but only 8% (3) had skinfolds <5th centile. The children with Down syndrome were also very short and once adjusted for height, half had skinfolds >95th centile. We conclude that overweight and raised body fat is now common in children with NDD, even when the BMI is low

Assessing machine learning for diagnostic classification of hypertension types identified by ambulatory blood pressure monitoring

Background: Inaccurate blood pressure classification results in inappropriate treatment. We tested if machine learning (ML), using routine clinical data, can serve as a reliable alternative to Ambulatory Blood Pressure Monitoring (ABPM) in classifying blood pressure status. Methods: This study employed a multi-centre approach involving three derivation cohorts from Glasgow, Gdańsk, and Birmingham, and a fourth independent evaluation cohort. ML models were trained using office BP, ABPM, and clinical, laboratory, and demographic data, collected from patients referred for hypertension assessment. Seven ML algorithms were trained to classify patients into five groups: Normal/Target, Hypertension-Masked, Normal/Target-White-Coat, Hypertension-White-Coat, and Hypertension. The 10-year cardiovascular outcomes and 27-year all-cause mortality risks were calculated for the ML-derived groups using the Cox proportional hazards model. Results: Overall XGBoost showed the highest AUROC of 0.85-0.88 across derivation cohorts, Glasgow (n=923; 43% females; age 50.7±16.3 years), Gdańsk (n=709; 46% females; age 54.4±13 years), and Birmingham (n=1,222; 56% females; age 55.7±14 years). But accuracy (0·57-0·72) and F1 scores (0·57-0·69) were low across the three patient cohorts. The evaluation cohort (n=6213, 51% females; age 51.2±10.8 years) indicated elevated 10-year risks of composite cardiovascular events in the Normal/Target-White-Coat and Hypertension-White-Coat groups, with heightened 27-year all-cause mortality observed in all groups except Hypertension-Masked, compared to the Normal/Target group. Conclusions: Machine learning has limited potential in accurate blood pressure classification when ABPM is unavailable. Larger studies including diverse patient groups and different resource settings are warranted

Survey and evaluation of hypertension machine learning research

Background: Machine learning (ML) is pervasive in all fields of research, from automating tasks to complex decision‐making. However, applications in different specialities are variable and generally limited. Like other conditions, the number of studies employing ML in hypertension research is growing rapidly. In this study, we aimed to survey hypertension research using ML, evaluate the reporting quality, and identify barriers to ML's potential to transform hypertension care. Methods and Results: The Harmonious Understanding of Machine Learning Analytics Network survey questionnaire was applied to 63 hypertension‐related ML research articles published between January 2019 and September 2021. The most common research topics were blood pressure prediction (38%), hypertension (22%), cardiovascular outcomes (6%), blood pressure variability (5%), treatment response (5%), and real‐time blood pressure estimation (5%). The reporting quality of the articles was variable. Only 46% of articles described the study population or derivation cohort. Most articles (81%) reported at least 1 performance measure, but only 40% presented any measures of calibration. Compliance with ethics, patient privacy, and data security regulations were mentioned in 30 (48%) of the articles. Only 14% used geographically or temporally distinct validation data sets. Algorithmic bias was not addressed in any of the articles, with only 6 of them acknowledging risk of bias. Conclusions: Recent ML research on hypertension is limited to exploratory research and has significant shortcomings in reporting quality, model validation, and algorithmic bias. Our analysis identifies areas for improvement that will help pave the way for the realization of the potential of ML in hypertension and facilitate its adoption

Integrating new approaches to atrial fibrillation management: the 6th AFNET/EHRA Consensus Conference.

There are major challenges ahead for clinicians treating patients with atrial fibrillation (AF). The population with AF is expected to expand considerably and yet, apart from anticoagulation, therapies used in AF have not been shown to consistently impact on mortality or reduce adverse cardiovascular events. New approaches to AF management, including the use of novel technologies and structured, integrated care, have the potential to enhance clinical phenotyping or result in better treatment selection and stratified therapy. Here, we report the outcomes of the 6th Consensus Conference of the Atrial Fibrillation Network (AFNET) and the European Heart Rhythm Association (EHRA), held at the European Society of Cardiology Heart House in Sophia Antipolis, France, 17-19 January 2017. Sixty-two global specialists in AF and 13 industry partners met to develop innovative solutions based on new approaches to screening and diagnosis, enhancing integration of AF care, developing clinical pathways for treating complex patients, improving stroke prevention strategies, and better patient selection for heart rate and rhythm control. Ultimately, these approaches can lead to better outcomes for patients with AF