Hypertension - state of the art 2017

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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

Monotherapy with major antihypertensive drug classes and risk of hospital admissions for mood disorders

Major depressive and bipolar disorders predispose to atherosclerosis, and there is accruing data from animal model, epidemiological, and genomic studies that commonly used antihypertensive drugs may have a role in the pathogenesis or course of mood disorders. In this study, we propose to determine whether antihypertensive drugs have an impact on mood disorders through the analysis of patients on monotherapy with different classes of antihypertensive drugs from a large hospital database of 525 046 patients with follow-up for 5 years. There were 144 066 eligible patients fulfilling the inclusion criteria: age 40 to 80 years old at time of antihypertensive prescription and medication exposure >90 days. The burden of comorbidity assessed by Charlson and Elixhauser scores showed an independent linear association with mood disorder diagnosis. The median time to hospital admission with mood disorder was 847 days for the 299 admissions (641 685 person-years of follow-up). Patients on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers had the lowest risk for mood disorder admissions, and compared with this group, those on β-blockers (hazard ratio=2.11; [95% confidence interval, 1.12–3.98]; P=0.02) and calcium antagonists (2.28 [95% confidence interval, 1.13–4.58]; P=0.02) showed higher risk, whereas those on no antihypertensives (1.63 [95% confidence interval, 0.94–2.82]; P=0.08) and thiazide diuretics (1.56 [95% confidence interval, 0.65–3.73]; P=0.32) showed no significant difference. Overall, our exploratory findings suggest possible differential effects of antihypertensive medications on mood that merits further study: calcium antagonists and β-blockers may be associated with increased risk, whereas angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may be associated with a decreased risk of mood disorders

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

Metabolomic profiling identifies novel associations with Electrolyte and Acid-Base Homeostatic patterns.

Electrolytes have a crucial role in maintaining health and their serum levels are homeostatically maintained within a narrow range by multiple pathways involving the kidneys. Here we use metabolomics profiling (592 fasting serum metabolites) to identify molecular markers and pathways associated with serum electrolyte levels in two independent population-based cohorts. We included 1523 adults from TwinsUK not on blood pressure-lowering therapy and without renal impairment to look for metabolites associated with chloride, sodium, potassium and bicarbonate by running linear mixed models adjusting for covariates and multiple comparisons. For each electrolyte, we further performed pathway enrichment analysis (PAGE algorithm). Results were replicated in an independent cohort. Chloride, potassium, bicarbonate and sodium associated with 10, 58, 36 and 17 metabolites respectively (each P < 2.1 × 10-5), mainly lipids. Of all the electrolytes, serum potassium showed the most significant associations with individual fatty acid metabolites and specific enrichment of fatty acid pathways. In contrast, serum sodium and bicarbonate showed associations predominantly with amino-acid related species. In the first study to examine systematically associations between serum electrolytes and small circulating molecules, we identified novel metabolites and metabolic pathways associated with serum electrolyte levels. The role of these metabolic pathways on electrolyte homeostasis merits further studies.Includes MRC, BHF, Wellcome Trust and NIHR

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 (&lt;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

Cardiovascular and renal risk factors and complications associated with COVID-19

The current COVID-19 pandemic, caused by the SARS-CoV-2 virus (Severe Acute Respiratory Syndrome-Coronavirus-2), represents the largest medical challenge in decades. It has exposed unexpected cardiovascular vulnerabilities at all stages of the disease (pre-infection, acute phase and subsequent chronic phase). The major cardiometabolic drivers identified to have epidemiological and mechanistic associations with COVID-19 are abnormal adiposity, dysglycemia, dyslipidemia, and hypertension. Hypertension is of particular interest, because components of the renin-angiotensin system (RAS), which are critically involved in the pathophysiology of hypertension, are also implicated in COVID-19. Specifically ACE2, a multifunctional protein of the RAS, which is part of the protective axis of the RAS, is also the receptor through which SARS-CoV-2 enters host cells causing viral infection. Cardiovascular and cardiometabolic co-morbidities not only predispose to COVID-19, but are complications of SARS-CoV-2 infection. In addition, increasing evidence indicates that acute kidney injury is common in COVID-19, that it occurs early and in temporal association with respiratory failure and is associated with poor prognosis, especially in the presence of cardiovascular risk factors. Here we discuss cardiovascular and kidney disease in the context of COVID-19 and provide recent advances on putative pathophysiological mechanisms linking cardiovascular disease and COVID-19, focusing on the RAS and ACE2 as well as the immune system and inflammation. We provide up-to-date information on the relationship between hypertension, diabetes, and COVID-19 and emphasize the major cardiovascular diseases associated with COVID-19. We also briefly discuss emerging cardiovascular complications associated with long COVID-19, notably postural tachycardia syndrome (POTS)

Vascular dysfunction and increased cardiovascular risk in hypospadias

Aims Hypogonadism is associated with cardiovascular disease. However, the cardiovascular impact of hypogonadism during development is unknown. Using hypospadias as a surrogate of hypogonadism, we investigated whether hypospadias is associated with vascular dysfunction and is a risk factor for cardiovascular disease. Methods and results Our human study spanned molecular mechanistic to epidemiological investigations. Clinical vascular phenotyping was performed in adolescents with hypospadias and controls. Small subcutaneous arteries from penile skin from boys undergoing hypospadias repair and controls were isolated and functional studies were assessed by myography. Vascular smooth muscle cells were used to assess: Rho kinase, reactive oxygen species (ROS), nitric oxide synthase/nitric oxide, and DNA damage. Systemic oxidative stress was assessed in plasma and urine. Hospital episode data compared men with a history of hypospadias vs. controls. In adolescents with hypospadias, systolic blood pressure (P = 0.005), pulse pressure (P = 0.03), and carotid intima-media thickness standard deviation scores (P = 0.01) were increased. Arteries from boys with hypospadias demonstrated increased U46619-induced vasoconstriction (P = 0.009) and reduced acetylcholine-induced endothelium-dependent (P &lt; 0.0001) and sodium nitroprusside-induced endothelium-independent vasorelaxation (P &lt; 0.0001). Men born with hypospadias were at increased risk of arrhythmia [odds ratio (OR) 2.8, 95% confidence interval (CI) 1.4–5.6, P = 0.003]; hypertension (OR 4.2, 95% CI 1.5–11.9, P = 0.04); and heart failure (OR 1.9, 95% CI 1.7–114.3, P = 0.02). Conclusion Hypospadias is associated with vascular dysfunction and predisposes to hypertension and cardiovascular disease in adulthood. Underlying mechanisms involve perturbed Rho kinase- and Nox5/ROS-dependent signalling. Our novel findings delineate molecular mechanisms of vascular injury in hypogonadism, and identify hypospadias as a cardiovascular risk factor in males. Key question Is hypospadias associated with vascular dysfunction? Key finding Boys with hypospadias have evidence of hypercontractility and impaired vasodilation secondary to increased Rho kinase activation and oxidative stress. This leads to raised systolic blood pressure in adolescence and increased risk of admission to hospital for cardiovascular diseases in adulthood. Take-home message Hypospadias is a risk factor for cardiovascular dysfunction in males

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