Accuracy and User Acceptability of 24-hour Ambulatory Blood Pressure Monitoring by a Prototype Cuffless Multi-Sensor Device Compared to a Conventional Oscillometric Device.

OBJECTIVE: 24-hour ambulatory blood pressure monitoring (24ABPM) is state of the art in out-of-office blood pressure (BP) monitoring. Due to discomfort and technical limitations related to cuff-based 24ABPM devices, methods for non-invasive and continuous estimation of BP without the need for a cuff have gained interest. The main aims of the present study were to compare accuracy of a pulse arrival time (PAT) based BP-model and user acceptability of a prototype cuffless multi-sensor device (cuffless device), developed by Aidee Health AS, with a conventional cuff-based oscillometric device (ReferenceBP) during 24ABPM. METHODS: Ninety-five normotensive and hypertensive adults underwent simultaneous 24ABPM with the cuffless device on the chest and a conventional cuff-based oscillometric device on the non-dominant arm. PAT was calculated using the electrocardiogram (ECG) and photoplethysmography (PPG) sensors incorporated in the chest-worn device. The cuffless device recorded continuously, while ReferenceBP measurements were taken every 20 minutes during daytime and every 30 minutes during nighttime. Two-minute PAT-based BP predictions corresponding to the ReferenceBP measurements were compared with ReferenceBP measurements using paired t-tests, bias, and limits of agreement. RESULTS: Mean (SD) of ReferenceBP compared to PAT-based daytime and nighttime systolic BP (SBP) were 129.7 (13.8) mmHg versus 133.6 (20.9) mmHg and 113.1 (16.5) mmHg versus 131.9 (23.4) mmHg. Ninety-five % limits of agreements were [-26.7, 34.6 mmHg] and [-20.9, 58.4 mmHg] for daytime and nighttime SBP respectively. The cuffless device was reported to be significantly more comfortable and less disturbing than the ReferenceBP device during 24ABPM. CONCLUSIONS: In the present study, we demonstrated that a general PAT-based BP model had unsatisfactory agreement with ambulatory BP during 24ABPM, especially during nighttime. If sufficient accuracy can be achieved, cuffless BP devices have promising potential for clinical assessment of BP due to the opportunities provided by continuous BP measurements during real-life conditions and high user acceptability.

What is the context?Hypertension is a major risk factor for cardiovascular and cerebrovascular end-organ damage, morbidity, and mortality world-wide.Accurate measurement of blood pressure is essential for the diagnosis and management of hypertension.What is new?Cuffless blood pressure devices that allow measurement of blood pressure without a pressure cuff is a promising and novel method of blood pressure estimation.The objective of this study is to assess whether pulse arrival time alone can be used to estimate blood pressure accurately during 24-hour ambulatory blood pressure monitoring, using a prototype cuffless device placed on the chest.Our analysis shows that a general model based on pulse arrival time overestimated ambulatory blood pressure, especially during nighttime.User acceptability was higher with the cuffless device compared to a conventional cuff-based oscillometric device during 24-hour ambulatory blood pressure monitoring.What is the impact?This study provides further evidence that accurate blood pressure estimations cannot be achieved by using pulse arrival time alone as a surrogate for blood pressure measurements.

Diabetes og kronisk nyresykdom.

Chronic kidney disease is one of the most serious complications of diabetes. One of the challenges in the follow-up of patients with diabetes is to discover signs of kidney disease. Recent research shows that several drugs have renal protective effects. In this clinical review article we present markers used in the follow-up of patients with diabetes and chronic kidney disease, and new treatment options.

Apparent treatment-resistant hypertension - patient-physician relationship and ethical issues.

BACKGROUND: Poor drug adherence is a major cause of apparent treatment-resistant hypertension. As a consequence, several methods have been developed and attempted implemented in clinical practice to reveal non-adherence and to monitor drug adherence. There are, however, several hitherto unresolved ethical aspects regarding potential methods for drug monitoring in these patients. RESULTS: The most striking challenge is the balance between patient autonomy and the physician's desire for the patient to adhere to the prescribed therapy. Also, methods for monitoring must only be implemented in the treatment of well-informed and consenting patients. Major resources are used on non-adherent patients; how long the physician should encourage continuation of treatment is an important question. CONCLUSIONS: We believe that physicians should reflect and discuss these potential challenges, and that patient education, information and a solid patient-physician relationship are essential for achieving drug adherence. Methods for monitoring adherence represent, however, a useful and often necessary supplement.

Adherence to medication and drug monitoring in apparent treatment-resistant hypertension.

Poor drug adherence is one of the main reasons for the failure to achieve treatment targets in hypertensive patients. In patients who receive pharmacological treatment, assessment of drug adherence is of the utmost importance. The aim of this review is to present an update of the methods available to reveal and monitor non-adherence in patients with apparent treatment-resistant hypertension. Methods for monitoring adherence are divided into indirect and direct methods. The indirect methods are mainly based on self-reported adherence and can easily be manipulated by the patient. Directly observed therapy and therapeutic drug monitoring are examples of direct methods. There are limitations and advantages to all of the methods, and because of the patient's ability to manipulate the outcome of indirect methods, direct methods should be preferred. Therapeutic drug monitoring and directly observed therapy with subsequent ambulatory blood pressure measurement are considered to be reliable methods and should be used more in the routine assessment of patients with apparent treatment-resistant hypertension.

Tertiary work-up of apparent treatment-resistant hypertension.

OBJECTIVE: Treatment-resistant hypertension (TRH) has regained attention with development of new methods for treatment. However, the prevalence of TRH varies considerably from primary to secondary and tertiary care. We aimed to assess the prevalence of true TRH in a population of patients with apparent TRH in a university hospital setting of tertiary work-up and also investigate reasons for poor BP control and evaluate how work-up can be performed in general practice and secondary care. METHODS: In this cohort study, we characterize a study population from Oslo Renal Denervation (RDN) Study. Patients (n = 83) were referred for RDN from secondary care. All patients underwent thorough medical investigation and 24-h ambulatory blood pressure measurements (24ABPM) after directly observed therapy (DOT). We then assessed reasons for lack of BP control. RESULTS: Fifty-three of 83 patients did not have true TRH. Main reasons for non-TRH were poor drug adherence (32%), secondary hypertension (30%) and white coat hypertension (15%). Forty-seven percent achieved blood pressure control after DOT with subsequent 24ABPM. There were otherwise no statistically significant differences in patient characteristics between the true TRH and the non-TRH group. CONCLUSION: Despite being a highly selected cohort referred for tertiary work-up of apparent TRH, BP control was achieved or secondary causes were identified in almost two thirds of the patients. Thorough investigation according to guidelines and DOT with subsequent 24ABPM is needed in work-up of apparent TRH.

[Medication adherence and monitoring of antihypertensive treatment]. / Medikamentetterlevelse og monitorering av antihypertensiv behandling.

Lack of adherence to medication may be the explanation for unsatisfactory drug efficacy and is often misinterpreted as resistance to treatment. When encountering patients with persistent high blood pressure despite antihypertensive treatment, it is therefore important to discover whether they are actually taking their medication. This article aims to provide an updated overview of methods of revealing and monitoring medication adherence. The article is based on non-systematic literature searches in PubMed and on the senior authors' own clinical experience.

Medical Measures in Hypertensives Considered Resistant.

BACKGROUND: Patients with resistant hypertension are the group of hypertensive patients with the highest cardiovascular risk. METHODS: All rules and guidelines for treatment of hypertension should be followed strictly to obtain blood pressure (BP) control in resistant hypertension. The mainstay of treatment of hypertension, also for resistant hypertension, is pharmacological treatment, which should be tailored to each patient's specific phenotype. Therefore, it is pivotal to assess nonadherence to pharmacological treatment as this remains the most challenging problem to investigate and manage in the setting of resistant hypertension. RESULTS: Once adherence has been confirmed, patients must be thoroughly worked-up for secondary causes of hypertension. Until such possible specific causes have been clarified, the diagnosis is apparent treatment-resistant hypertension (TRH). Surprisingly few patients remain with true TRH when the various secondary causes and adherence problems have been detected and resolved. Refractory hypertension is a term used to characterize the treatment resistance in hypertensive patients using ≥5 antihypertensive drugs. All pressor mechanisms may then need blockage before their BPs are reasonably controlled. CONCLUSIONS: Patients with resistant hypertension need careful and sustained follow-up and review of their medications and dosages at each term since medication adherence is a very dynamic process.

Cardiovascular Outcomes in Hypertension-Treated Patients With Peripheral Artery Disease: The VALUE Trial.

BACKGROUND: Systolic blood pressure (BP) is a key predictor of cardiovascular events, but patients with peripheral artery disease (PAD) are rarely included in hypertension trials. The VALUE trial (Valsartan Antihypertensive Long-Term Use Evaluation) investigated the long-term effects of valsartan- or amlodipine-based treatments on cardiovascular outcomes in patients with hypertension with a high cardiovascular risk. The aim of this subanalysis was to clarify the relationship between achieved BP on treatment and cardiovascular outcomes in patients with hypertension with PAD. METHODS: Patients were followed for 4 to 6 years, and BP was measured regularly. The primary end point was time to the first major adverse cardiovascular event, including myocardial infarction, stroke, cardiovascular death, and heart failure requiring hospitalization. Statistical analyses were performed using Cox regression, adjusting for various baseline covariates. RESULTS: Of the 13 803 participants, 1898 (13.8%) had PAD. During a median follow-up of 4.5 years, patients with PAD had a 23% increased risk of major adverse cardiovascular events compared with patients without PAD. Patients with an achieved systolic BP <130 mm Hg and 130 to 139 mm Hg, compared with those with systolic BP ≥140 mm Hg, were associated with a decreased risk of a major adverse cardiovascular event (hazard ratio, 0.65 [95% CI, 0.43-0.97]; P=0.037; 0.85 [95% CI, 0.74-0.97]; P=0.016, respectively). Additionally, systolic BP <130 mm Hg was associated with a decreased risk of cardiovascular death (hazard ratio, 0.33 [95% CI, 0.12-0.92]; P=0.034). The incidence of the primary outcome did not differ between antihypertensive treatment regimens (P=0.365). CONCLUSIONS: Our results indicate that more intensive BP control is associated with a reduction in cardiovascular morbidity and mortality in patients with hypertensive PAD.

Effect of Drug Monitoring on Adherence and Blood Pressure: A Multicenter Randomized Clinical Trial.

BACKGROUND: Drug concentration in blood or urine is an acknowledged method to detect non-adherence. Observational studies suggest that informing patients about low or absent serum drug levels improves blood pressure (BP). We performed a multicenter randomized clinical trial to test the hypothesis that therapeutic drug monitoring (TDM) could improve drug adherence and BP in patients with uncontrolled hypertension and reduced adherence to antihypertensive drugs. METHODS: Patients were ≥18 years on stable treatment with at least two antihypertensive agents. We planned to randomize 80 non-adherent patients with a systolic daytime ambulatory BP (ABPM) ≥135 mmHg to TDM-intervention or not. The control group and the study-personnel who measured BP remained uninformed about serum drug measurements throughout. All patients and physicians were blinded for BPs. Lifestyle advice and detailed information on disease process and importance of BP treatment were given to both groups. RESULTS: From 2017 to 2022, we randomized 46 diagnosed non-adherent from a total of 606 patients with uncontrolled hypertension. The TDM-group had a 6.7 (±14.5) mmHg reduction from 147.9 (±10.3) to 141.1 (±14.1) mmHg, and the control group experienced a 7.3 (±13.2) mmHg reduction from 147.1 (±9.2) to 139.1 (±17.4) mmHg, p=0.9 between groups. Adherence improved in both groups, 73% in the TDM group and 59% in the control group became adherent at three months, p=0.51. CONCLUSIONS: In our prospective multicenter clinical trial of uncontrolled and non-adherent hypertensive patients, we found no additional effect of therapeutic drug monitoring (TDM) on blood pressure and drug adherence compared with standard care.

Accuracy of non-invasive cuffless blood pressure in the intensive care unit: Promises and challenges.

Objective: Continuous non-invasive cuffless blood pressure (BP) monitoring may reduce adverse outcomes in hospitalized patients if accuracy is approved. We aimed to investigate accuracy of two different BP prediction models in critically ill intensive care unit (ICU) patients, using a prototype cuffless BP device based on electrocardiogram and photoplethysmography signals. We compared a pulse arrival time (PAT)-based BP model (generalized PAT-based model) derived from a general population cohort to more complex and individualized models (complex individualized models) utilizing other features of the BP sensor signals. Methods: Patients admitted to an ICU with indication of invasive BP monitoring were included. The first half of each patient's data was used to train a subject-specific machine learning model (complex individualized models). The second half was used to estimate BP and test accuracy of both the generalized PAT-based model and the complex individualized models. A total of 7,327 measurements of 15 s epochs were included in pairwise comparisons across 25 patients. Results: The generalized PAT-based model achieved a mean absolute error (SD of errors) of 7.6 (7.2) mmHg, 3.3 (3.1) mmHg and 4.6 (4.4) mmHg for systolic BP, diastolic BP and mean arterial pressure (MAP) respectively. Corresponding results for the complex individualized model were 6.5 (6.7) mmHg, 3.1 (3.0) mmHg and 4.0 (4.0) mmHg. Percentage of absolute errors within 10 mmHg for the generalized model were 77.6, 96.2, and 89.6% for systolic BP, diastolic BP and MAP, respectively. Corresponding results for the individualized model were 83.8, 96.2, and 94.2%. Accuracy was significantly improved when comparing the complex individualized models to the generalized PAT-based model in systolic BP and MAP, but not diastolic BP. Conclusion: A generalized PAT-based model, developed from a different population was not able to accurately track BP changes in critically ill ICU patients. Individually fitted models utilizing other cuffless BP sensor signals significantly improved accuracy, indicating that cuffless BP can be measured non-invasively, but the challenge toward generalizable models remains for future research to resolve.

Middle-Aged and Older Patients With Left Ventricular Hypertrophy: Higher Mortality With Drug Treated Systolic Blood Pressure Below 130 mm Hg.

BACKGROUND: Approximately 40% of people with hypertension have left ventricular hypertrophy (LVH) detected by ECG or echocardiography. Because patients with LVH have poor myocardial microcirculation, they may be too sensitive to lowering systolic blood pressure (SBP) too much due to a lack of myocardial perfusion pressure. We aimed to investigate whether the average achieved SBP <130 mm Hg may cause harm in patients with LVH in the Valsartan Antihypertensive Long-Term Use Evaluation trial (VALUE). METHODS: Of the 15 245 VALUE participants, we identified 13 803 patients without cardiovascular events during the first 6 months after randomization. Of these, 2458 patients had electrocardiographic LVH (ECG-LVH). Cox analyses adjusted for age, gender, and baseline variables compared cardiac and all-cause mortality and other prespecified end points for patients who achieved average SBP 130 to 139 mm Hg (No-LVH group n=4863; ECG-LVH group n=929) and <130 mm Hg (No-LVH group n=2107; ECG-LVH group n=305). Reference groups were patients who achieved average SBP ≥140 mm Hg following the first excluded 6 months (No-LVH group n=4375; ECG-LVH group n=1224). RESULTS: The No-LVH group achieving average SBP <130 mm Hg had a significantly lower incidence of several cardiovascular end points. The ECG-LVH group achieving average SBP <130 mm Hg had higher cardiac mortality (hazard ratio, 1.98 [95% CIs, 1.06-3.70]; P=0.032) and all-cause mortality (hazard ratio, 1.74 [95% CIs, 1.17-2.60]; P=0.007), and SBP <130 mm Hg was not associated with a reduction in any end point. CONCLUSIONS: Our findings may be seen as a signal that caution is warranted when treating middle-aged and older patients with electrocardiographic or echocardiographic LVH to SBP <130 mm Hg.

Blood Pressure Response and Pulse Arrival Time During Exercise Testing in Well-Trained Individuals.

Introduction: There is a lack of data describing the blood pressure response (BPR) in well-trained individuals. In addition, continuous bio-signal measurements are increasingly investigated to overcome the limitations of intermittent cuff-based BP measurements during exercise testing. Thus, the present study aimed to assess the BPR in well-trained individuals during a cycle ergometer test with a particular focus on the systolic BP (SBP) and to investigate pulse arrival time (PAT) as a continuous surrogate for SBP during exercise testing. Materials and Methods: Eighteen well-trained male cyclists were included (32.4 ± 9.4 years; maximal oxygen uptake 63 ± 10 ml/min/kg) and performed a stepwise lactate threshold test with 5-minute stages, followed by a continuous test to voluntary exhaustion with 1-min increments when cycling on an ergometer. BP was measured with a standard automated exercise BP cuff. PAT was measured continuously with a non-invasive physiological measurements device (IsenseU) and metabolic consumption was measured continuously during both tests. Results: At lactate threshold (281 ± 56 W) and maximal intensity test (403 ± 61 W), SBP increased from resting values of 136 ± 9 mmHg to maximal values of 219 ± 21 mmHg and 231 ± 18 mmHg, respectively. Linear within-participant regression lines between PAT and SBP showed a mean r 2 of 0.81 ± 17. Conclusion: In the present study focusing on the BPR in well-trained individuals, we observed a more exaggerated systolic BPR than in comparable recent studies. Future research should follow up on these findings to clarify the clinical implications of the high BPR in well-trained individuals. In addition, PAT showed strong intra-individual associations, indicating potential use as a surrogate SBP measurement during exercise testing.

Blood pressure altering method affects correlation with pulse arrival time.

OBJECTIVE: Pulse arrival time (PAT) is a potential main feature in cuff-less blood pressure (BP) monitoring. However, the precise relationship between BP parameters and PAT under varying conditions lacks a complete understanding. We hypothesize that simple test protocols fail to demonstrate the complex relationship between PAT and both SBP and DBP. Therefore, this study aimed to investigate the correlation between PAT and BP during two exercise modalities with differing BP responses using an unobtrusive wearable device. METHODS: Seventy-five subjects, of which 43.7% had a prior diagnosis of hypertension, participated in an isometric and dynamic exercise test also including seated periods of rest prior to, in between and after. PAT was measured using a prototype wearable chest belt with a one-channel electrocardiogram and a photo-plethysmography sensor. Reference BP was measured auscultatory. RESULTS: Mean individual correlation between PAT and SBP was -0.82 ± 0.14 in the full protocol, -0.79 ± 0.27 during isometric exercise and -0.77 ± 0.19 during dynamic exercise. Corresponding correlation between PAT and DBP was 0.25 ± 0.35, -0.74 ± 0.23 and 0.39 ± 0.41. CONCLUSION: The results confirm PAT as a potential main feature to track changes in SBP. The relationship between DBP and PAT varied between exercise modalities, with the sign of the correlation changing from negative to positive between type of exercise modality. Thus, we hypothesize that simple test protocols fail to demonstrate the complex relationship between PAT and BP with emphasis on DBP.

Detection of Nonadherence to Antihypertensive Treatment by Measurements of Serum Drug Concentrations.

[Figure: see text].

Which Target Blood Pressure in Year 2018? Evidence from Recent Clinical Trials.

The Systolic Blood Pressure Intervention Trial (SPRINT) suggested a favourable effect of lowering blood pressure to < 120/80 mmHg in high-risk hypertensive patients; however, new American guidelines in 2017 have not followed SPRINT but lowered its recommended treatment target to < 130/80 mmHg. We aimed to review the latest research from large randomised controlled trials and observational analyses in order to investigate the evidence for new treatment targets. We assessed recent data from the Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD) study, the International Verapamil-Trandolapril Study (INVEST), the Telmisartan, Ramipril or Both in Patients at High Risk for Vascular Events trial (ONTARGET)/the Telmisartan Randomised AssessmenNt Study in aCE iNtolerant participants with cardiovascular Disease (TRANSCEND) study and The Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study. These studies confirm a positive effect on cardiovascular protection with blood pressure lowering treatment to between 120-140 mmHg in patients with and without diabetes, but no additional effect of lowering blood pressure to < 120 mmHg; possibly too aggressive treatment may increase both cardiovascular morbidity and mortality. Thus, a target blood pressure < 130/80 mmHg appears appropriate in most high-risk hypertensive patients. Additionally, early and sustained BP control below this target is required for optimal cardiovascular protection.

A Case for Less Intensive Blood Pressure Control: It Matters to Achieve Target Blood Pressure Early and Sustained Below 140/90mmHg.

Although high blood pressure (BP) is the leading risk factors for cardiovascular (CV) disease, the optimal BP treatment target in order to reduce CV risk is unclear in the aftermath of the SPRINT study. The aim of this review is to assess large, randomized, and controlled trials on BP targets, as well as review selected observational analyses from other large randomized BP trials in order to evaluate the benefit of intense vs. standard BP control. None of the studies, except SPRINT, favored intense BP treatment. Some of the studies suggested favorable effects of lowering treatment target in patients with diabetes or high risk of stroke. In SPRINT, a new BP measurement method was introduced, and the results must be interpreted in light of this. The results of the observational analyses indicated the best preventive effect when achieving early and sustained BP control rather than low targets. In conclusion, today's guidelines' recommended treatment target of <140/90mmHg seems sufficient for most patients. Early and sustained BP control should be the main focus.