The Association between Urinary Sodium-Potassium Ratio, Kidney Function, and Blood Pressure in a Cohort from the General Population.

INTRODUCTION: Subclinical kidney dysfunction may contribute to salt-sensitive hypertension. We assessed the association between the urinary sodium-potassium ratio (Na/K ratio) and blood pressure (BP) in a general population cohort without diabetes, chronic kidney disease, cardiovascular disease, or treated hypertension. We investigated whether any such association was mediated by the kidney function markers measured glomerular filtration rate (mGFR), urinary albumin-creatinine ratio (ACR), and urinary epidermal growth factor-creatinine ratio (EGF-Cr). METHODS: The Tromsø Study is a population-based study of inhabitants of the municipality of Tromsø, Northern Norway. Participants aged 50-62 years, without diabetes, chronic kidney disease, or cardiovascular disease, were invited to the substudy Renal Iohexol Clearance Survey in Tromsø 6 (RENIS-T6; 2007-09). For the present study, we excluded participants reporting the use of 1 or more antihypertensive agents, leaving 1,311 RENIS-T6 participants for a cross-sectional analysis. We measured office BP, 24-h ambulatory blood pressure (ABP), and mGFR using iohexol clearance. Na/K ratio, ACR, and EGF-Cr were measured in morning urine samples. RESULTS: Urinary Na/K ratio was significantly associated with systolic office BP and ABP independently of cardiovascular risk factors and kidney function markers. A one-standard deviation unit increase in the Na/K ratio was associated with increased systolic ABP by 1.0 (0.3-1.6) mm Hg. Urinary Na/K ratio showed a stronger association with office BP than ABP. EGF-Cr, ACR, and mGFR did not mediate the relationship between urinary Na/K ratio and systolic BP. CONCLUSIONS: In a representative sample of the middle-aged North-European population without diabetes, chronic kidney disease, cardiovascular disease, or treated hypertension, there was a consistent association between urinary Na/K ratio and BP. The association with BP was not mediated through kidney function measures, suggesting a relationship between a diet with high sodium and low potassium and higher BP regardless of kidney function.

Novel biomarkers in patients with uncontrolled hypertension with and without kidney damage.

INTRODUCTION: Estimated glomerular filtration rate (eGFR) and urine albumin/creatinine ratio (ACR) are insensitive biomarkers for early detection of hypertension-mediated organ damage (HMOD). In this nationwide cross-sectional study, we assessed potential biomarkers for early HMOD in healthy persons and patients with hypertension. We hypothesised that plasma levels of biomarkers: (1) are different between healthy controls and patients with hypertension, (2): can classify patients with hypertension according to the degree of hypertension severity. DESIGN AND METHODS: Patients with hypertension prescribed ≥2 antihypertensive agents were selected from a multicentre study. Healthy controls were selected from an ongoing study of living kidney donor candidates. Uncontrolled hypertension was defined as systolic daytime ambulatory blood pressure ≥135 mmHg. Kidney HMOD was defined by ACR > 3.0 mg/mmol or eGFR < 60 mL/min/1.73 m2. Patients with hypertension were categorised into three groups: (1) controlled hypertension; (2) uncontrolled hypertension without kidney HMOD; (3) uncontrolled hypertension with kidney HMOD. Fifteen biomarkers were analysed using a Luminex bead-based immunoassay, and nine fell within the specified analytical range. RESULTS: Plasma levels of Interleukin 1 receptor antagonist (IL-1RA), neutrophil gelatinase-associated lipocalin (NGAL) and uromodulin were significantly different between healthy controls (n = 39) and patients with hypertension (n = 176). In regression models, with controlled hypertension (n = 55) as the reference category, none of the biomarkers were associated with uncontrolled hypertension without (n = 59) and with (n = 62) kidney HMOD. In models adjusted for cardiovascular risk factors and eGFR, osteopontin (OPN) was associated with uncontrolled hypertension without kidney HMOD (odds ratio (OR) 1.77 (1.05-2.98), p = 0.03), and regulated upon activation normal T-cell expressed and secreted (RANTES) with uncontrolled hypertension with kidney HMOD (OR 0.57 (0.34-0.95), p = 0.03). CONCLUSIONS: None of the biomarkers could differentiate our hypertension groups when established risk factors were considered. Plasma OPN may identify patients with uncontrolled hypertension at risk for kidney HMOD.

What is the context? In order to tailor individualised hypertension treatment, a risk assessment for cardiovascular disease (CVD) must be performed. This includes evaluation of established hypertension-mediated organ damage (HMOD), such as the presence of kidney damage and associated risk factors. Today, kidney function is assessed by blood and urine samples. However, today's blood and urine samples are not sensitive enough to capture kidney damage due to hypertension at a stage when prevention may be most effective.What is new? In this study, we evaluated plasma levels of biomarkers related to endothelial and kidney cell pathology, inflammation and fibrosis in healthy patients and patients with hypertension. We hypothesised that plasma levels of biomarkers could differentiate between different degrees of hypertension severity.Healthy controls had lower Interleukin 1 receptor antagonist (IL-1RA) and neutrophil gelatinase-associated lipocalin (NGAL) levels, but higher uromodulin compared to patients with hypertension. Except for osteopontin (OPN), all biomarkers showed significant trends in median biomarker levels across study groups. However, as hypertension severity increased, the median plasma OPN levels also rose. None of the biomarker could consistently differentiate the hypertension severity groups after considering established risk factors. However, OPN may be an early biomarker for kidney damage in hypertension.What is the impact? Biomarkers for early detection of organ damage in hypertension may guide targeted treatment. Plasma OPN may have potential to identify those at risk for hypertensive kidney damage. However, the studied biomarkers lack consistent discrimination across hypertension severity levels.

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.

Associations of urinary orosomucoid, N-acetyl-ß-D-glucosaminidase, and albumin with blood pressure and hypertension after 7 years. The Tromsø Study.

Purpose: Subclinical chronic kidney disease is known to exacerbate hypertension and progression of kidney damage. In order to initiate timely interventions, early biomarkers for this vicious circle are needed. Our aim was to describe the cross-sectional associations of urinary orosomucoid and urinary N-acetyl-ß-D-glucosaminidase (NAG) with blood pressure and the longitudinal associations of urinary orosomucoid and NAG to hypertension after 7 years, and to compare the strength of these associations to the urinary albumin excretion (UAE).Material and methods: The Tromsø Study is a population-based, prospective study of inhabitants of the municipality of Tromsø, Northern Norway. Morning spot urine samples were collected on three consecutive days in the Tromsø 6 survey (2007-2008). We assessed the cross-sectional associations of urinary orosomucoid, NAG and UAE with blood pressure in Tromsø 6. In a cohort of participants attending Tromsø 6 and Tromsø 7 (2015-2016), we studied whether urinary biomarkers were longitudinally associated with hypertension.Results: A total of 7197 participants with a mean age of 63.5 years (SD 9.2), and a mean blood pressure of 141/78 mmHg (SD 23.0/10.6), were included in the study. Orosomucoid and UAE, but not NAG, was significantly associated with systolic and diastolic blood pressure in all the crude and multivariable cross-sectional analyses. Orosomucoid had consistently, although marginally, stronger associations with blood pressure. Incident hypertension at follow-up (Tromsø 7) was consistently significantly associated with urinary orosomucoid, but not urinary NAG or UAE. However, the standardized regression coefficients for orosomucoid were only marginally stronger than the standardized regression coefficients for ACR.Conclusion: In a cohort from the general population urine orosomucoid had a stronger cross-sectional association with blood pressure than UAE. After 7 years, urine orosomucoid showed the strongest association with incident hypertension. There were varying and weak associations between U-NAG, blood pressure and hypertension.

What is the context? There is a relationship between high blood pressure and cardiovascular and kidney disease. Hypertension is defined as the level of blood pressure at which the benefits of treatment outweigh the risks of treatment. Hypertension is a risk factor for developing kidney disease, and kidney disease is a risk factor for developing hypertension. Today, kidney function is assessed by blood and urine samples (estimated glomerular filtration rate and urinary albumin excretion). However, today's blood and urine samples are not sensitive enough to capture kidney damage due to hypertension at a stage when prevention may be most effective.What is new? In this study, we assessed if urine orosomucoid and N-acetyl-ß-D-glucosaminidase (NAG) are more strongly associated with blood pressure and hypertension than urinary albumin excretion. In the population-based study of residents in Tromsø, Northern Norway, we assessed the relationship between the urine biomarkers and blood pressure, and the development of hypertension after 7 years. In the general population urine orosomucoid had a stronger relationship with blood pressure than urinary albumin excretion. After 7 years, urine orosomucoid had the strongest relationship with the development of hypertension. There were only varying and weak relationships between NAG, blood pressure and hypertension.What is the impact? Orosomucoid showed a stronger relationship with blood pressure and the development of hypertension than urinary albumin excretion. Urine orosomucoid may aid targeted prevention and treatment in hypertension, but further prospective clinical studies are needed to assess if orosomucoid is a clinically useful biomarker in hypertension.

Establishing Serum Reference Ranges for Antihypertensive Drugs.

BACKGROUND: Therapeutic drug monitoring (TDM) involves the measurement of serum drug concentrations to optimize pharmacotherapy. Traditionally, blood pressure measurements alone, and not TDM, have been used to evaluate the antihypertensive drug response. However, approximately 50% of hypertensive patients treated with lifestyle changes and antihypertensive drugs fail to achieve blood pressure control. Serum drug concentration measurements could be useful to select the optimal drugs in adjusted doses and to identify nonadherence. Implementation of TDM in clinical routine for antihypertensive drugs depends on established serum reference ranges. METHODS: Commonly used antihypertensive drugs were identified based on prescription data. The authors performed a review of authoritative literature on reported serum drug concentrations and calculated expected concentrations from previously reported pharmacokinetic parameters with commonly prescribed daily doses. Finally, serum drug concentrations in samples from patients undergoing antihypertensive treatment were measured. RESULTS: Serum reference ranges for 24 frequently used antihypertensive drugs were established based on results from 3 approaches. CONCLUSIONS: Serum drug concentration measurements, interpreted in light of the established reference ranges, together with blood pressure measurements and other clinical data, may help identify nonadherent patients and tailor individual antihypertensive treatment when deviant drug responses appear in line with the concept of personalized medicine.

Renal sympathetic denervation lowers systemic vascular resistance in true treatment-resistant hypertension.

PURPOSE: Renal sympathetic denervation (RDN) is again gaining interest as recent well-designed trials have demonstrated reduced ambulatory blood pressure (BP) after RDN. However, the hemodynamic mechanisms have not been elucidated. We aimed for the first time to investigate the effect of RDN on the "Hallmark of Hypertension" namely increased systemic vascular resistance index (SVRI). MATERIALS AND METHODS: We investigated SVRI change in patients with true treatment-resistant hypertension randomised to RDN (n = 9) or drug adjusted control (n = 9). Treatment-resistant hypertension was defined as office systolic BP ≥ 140 mmHg despite ≥ 3 antihypertensive drugs including a diuretic. True treatment-resistant hypertension was confirmed prior to inclusion with ambulatory daytime systolic BP ≥ 135 mmHg immediately after witnessed intake of antihypertensive drugs. Hemodynamic variables were recorded with thoracic impedance cardiography at baseline and at three and six months follow-up after RDN. This non-invasive method also guided further tailoring of drug treatment in the control group aiming to normalise hemodynamic variables and BP. RESULTS: From three to six months follow-up after RDN, SVRI decreased with a median of -611 dyn*s*m2/cm5 [IQR -949 to -267] (p < 0.01), while supine mean BP decreased with a median of -11 mmHg [IQR -21 to -3] (p = 0.02). In the same period, SVRI in the control group was reduced with -674 dyn*s*m2/cm5 [IQR -1,309 to -340] (p < 0.01), while supine mean BP decreased with -15 mmHg [IQR -29 to -6] (p = 0.01). Thus, hemodynamic variables and BP in the two groups normalised in parallel. CONCLUSION: Our data suggest that in patients with true treatment-resistant hypertension, renal sympathetic denervation lowers BP by reducing systemic vascular resistance of similar size as in the control group with careful individual selection of antihypertensive drugs and dose titration.

The randomised Oslo study of renal denervation vs. Antihypertensive drug adjustments: efficacy and safety through 7 years of follow-up.

PURPOSE: The blood pressure (BP) lowering effect of renal sympathetic denervation (RDN) in treatment-resistant hypertension shows variation amongst the existing randomised studies. The long-term efficacy and safety of RDN require further investigation. For the first time, we report BP changes and safety up to 7 years after RDN, compared to drug adjustment in the randomised Oslo RDN study. MATERIALS AND METHODS: Patients with treatment-resistant hypertension, defined as daytime systolic ambulatory BP ≥135 mmHg after witnessed intake of ≥3 antihypertensive drugs including a diuretic, were randomised to either RDN (n = 9) or drug adjustment (n = 10). The initial primary endpoint was the change in office BP after 6 months. The RDN group had their drugs adjusted after 1 year using the same principles as the Drug Adjustment group. Both groups returned for long-term follow-up after 3 and 7 years. RESULTS: The decrease in office BP and ambulatory BP (ABPM) after 6 months did not persist, but gradually increased in both groups. From 6 months to 7 years follow-up, mean daytime systolic ABPM increased from 142 ± 10 to 145 ± 15 mmHg in the RDN group, and from 133 ± 11 to 137 ± 13 mmHg in the Drug Adjustment group, with the difference between them decreasing. In a mixed factor model, a significantly different variance was found between the groups in daytime systolic ABPM (p = .04) and diastolic ABPM (p = .01) as well as office diastolic BP (p<.01), but not in office systolic BP (p = .18). At long-term follow-up we unveiled no anatomical- or functional renal impairment in either group. CONCLUSIONS: BP changes up to 7 years show a tendency towards a smaller difference in BPs between the RDN and drug adjustment patients. Our data support RDN as a safe procedure, but it remains non-superior to intensive drug adjustment 7 years after the intervention.

Changes in sympathetic nervous system activity after renal denervation: results from the randomised Oslo RDN study.

PURPOSE: Sympathetic nervous system (SNS) over-activity is associated with essential hypertension. Renal sympathetic denervation (RDN) possibly lowers office- and ambulatory blood pressure (BP) in patients with treatment-resistant hypertension (TRH). We aimed to assess the effect of RDN compared to drug adjustment on SNS activity among patients with TRH by measuring plasma catecholamines and heart rate variability (HRV) during stress tests. MATERIALS AND METHODS: Patients with TRH were randomised to RDN (n = 9) or Drug Adjustment (DA) (n = 10). We measured continuous HRV and beat-to-beat-BP using FinaPres® and obtained plasma catecholamines during standardised orthostatic- and cold-pressor stress tests (CPT) before- and six months after randomisation. RESULTS: CPT revealed no differences between groups at baseline in peak adrenaline concentration (69.3 pg/mL in the DA group vs. 70.0 pg/mL in the RDN group, p = 0.38) or adrenaline reactivity (Δ23.1 pg/mL in the DA group vs. Δ29.3 pg/mL in the RDN group, p = 0.40). After six months, adrenaline concentrations were statistically different between groups after one minute (66.9 pg/mL in the DA group vs. 55.3 pg/mL in the RDN group, p = 0.03), and six minutes (62.4 pg/mL in the DA group vs. 50.1 pg/mL in the RDN group, p = 0.03). There was a tendency of reduction in adrenaline reactivity after six months in the RDN group (Δ26.3 pg/mL at baseline vs. Δ12.8 pg/ml after six months, p = 0.08), while it increased in the DA group (Δ13.6 pg/mL at baseline vs. Δ19.9 pg/mL after six months, p = 0.53). We also found a difference in the Low Frequency band at baseline following the CPT (667µs2 in the DA group vs. 1628µs2 in the RDN group, p = 0.03) with a clear tendency of reduction in the RDN group to 743µs2 after six months (p = 0.07), compared to no change in the DA group (1052µs2,p = 0.39). CONCLUSION: Our data suggest that RDN reduces SNS activity after six months. This finding warrants investigation in a larger study. Clinical Trial Number registered at www.clinicaltrials.gov: NCT01673516.

Gender differences in association between uric acid and all-cause mortality in patients with chronic heart failure.

BACKGROUND: Elevated serum uric acid (SUA) is associated with poor prognosis in patients with cardiovascular disease, yet it is still not decided whether the role of SUA is causal or only reflects an underlying disease. The purpose of the study was to investigate if SUA was an independent predictor of 5-year all-cause mortality in a propensity score matched cohort of chronic heart failure (HF) outpatients. Furthermore, to assess whether gender or renal function modified the effect of SUA. METHODS: Patients (n = 4684) from the Norwegian Heart Failure Registry with baseline SUA were included in the study. Individuals in the highest gender-specific SUA quartile were propensity score matched 1:1 with patients in the lowest three SUA quartiles. The propensity score matching procedure created 928 pairs of patients (73.4% males, mean age 71.4 ± 11.5 years) with comparable baseline characteristics. Kaplan Meier and Cox regression analyses were used to investigate the independent effect of SUA on all-cause mortality. RESULTS: SUA in the highest quartile was an independent predictor of all-cause mortality in HF outpatients (hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.03-1.37, p-value 0.021). Gender was found to interact the relationship between SUA and all-cause mortality (p-value for interaction 0.007). High SUA was an independent predictor of all-cause mortality in women (HR 1.65, 95% CI 1.24-2.20, p-value 0.001), but not in men (HR 1.06, 95% CI 0.89-1.25, p-value 0.527). Renal function did not influence the relationship between SUA and all-cause mortality (p-value for interaction 0.539). CONCLUSIONS: High SUA was independently associated with inferior 5-year survival in Norwegian HF outpatients. The finding was modified by gender and high SUA was only an independent predictor of 5-year all-cause mortality in women, not in men.

Directly observed therapy prior to ambulatory blood pressure measurement (DOT-HTN) in uncontrolled hypertensive patients - Effect on blood pressure, safety and patient perception.

Aims: Non-adherence to medication is a key challenge in treatment of hypertensive patients. Directly Observed Therapy prior to ambulatory blood pressure measurement (DOT-HTN) is relatively new in hypertension research and knowledge about its use and patients' perception of such control is warranted. We aimed to investigate DOT-HTN in relation to blood pressure control, procedural safety and patients' perception. Methods and results: Twenty patients with uncontrolled hypertension (daytime systolic ambulatory blood pressure measurement (ABPM) ≥135 mm Hg) were randomized to intervention with DOT-HTN and a visual analogue scale (VAS) assessment if they found DOT-HTN problematic (10 cm = very problematic), or to standard ABPM. They were followed for 2-4 weeks. There were no differences in baseline characteristics. Despite no difference in daytime systolic ABPM (p = 0.67) two patients were suggested to be non-adherent after DOT-HTN with reductions in daytime systolic ABPM of 18 and 22 mm Hg, respectively. No post DOT-HTN adverse reactions were reported. VAS assessment indicated that the patients had no problem being controlled (VAS median 0.30 cm (0.0-2.6)), however interesting comments and observed behaviour questioned the reliability of the patient-reported VAS in 38% of patients. Conclusions: Two of eight patients seemed to be non-adherent after DOT-HTN. Descriptive findings suggested reluctance towards control with DOT-HTN not captured by the VAS assessment. No DOT-related medical adverse-effects were reported.

Renal fibromuscular dysplasia and hypertension. / Renal fibromuskulær dysplasi og hypertensjon.

Fibromuscular dysplasia affects the muscles of small and medium-sized arteries. The aetiology of the condition is unknown; it is most frequently seen in middle-aged women, but can affect both sexes at any age. Hypertension is the most common clinical manifestation when the renal arteries are affected. The diagnosis is made based on clinical suspicion and specific angiographic findings. The treatment is aimed at normalisation of blood pressure with the aid of drugs or through revacularisation.

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.

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.

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.

[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.

High screening blood pressure at young age predicts future masked hypertension: A 17 year follow-up study.

OBJECTIVE: Approximately 10-20% of the general population have masked hypertension. However, how best to identify affected individuals is uncertain, and what predicts future masked hypertension is largely unknown. This study aimed to identify longitudinal predictors of masked hypertension. METHODS: A long-term follow-up study of 100 healthy young men who had normal (n = 28) or high (n = 72) screening blood pressure (BP) at the compulsory military draft was carried out. They were examined in a detailed and highly standardized way for cardiovascular risk markers at baseline and at follow-up after a mean of 17.4 years. RESULTS: At follow-up, 40% had masked hypertension. Participants with high screening BP had a 4.8 times higher likelihood of having masked hypertension at follow-up compared to men with low screening BP (odds ratio 4.8, 95% confidence interval 1.7-13.5, p = 0.003). Furthermore, only 25% of the men with masked hypertension had high normal office BP at follow-up, and the remaining 75% would, according to guidelines, not be recommended ambulatory BP measurements, and thus go undiagnosed. CONCLUSION: Our data suggest that high screening BP at a young age is an important predictor of future masked hypertension in young men, and that BP measurement according to guidelines is insufficient to uncover masked hypertension.

[Renal sympathetic denervation in treatment-resistant hypertension]. / Renal sympatisk denervering ved terapiresistent hypertensjon.

BACKGROUND: Renal denervation (RDN) has been introduced as a potential new treatment for patients with treatment-resistant hypertension, defined as a blood pressure above 140/90 mm Hg despite treatment with at least three antihypertensive drugs. We present an overview of this type of treatment, describe the method and discuss its possible future uses. METHOD: The review is based on a discretionary selection of relevant articles from our archive, our own experience and a literature search in PubMed. RESULTS: The use of RDN for treatment-resistant hypertension is based on a single randomised study with a total of 104 patients, in which the intervention group experienced a fall in blood pressure of 32/12 mm Hg, while blood pressure in the control group remained unchanged. More than 16,000 patients, particularly in Germany, have been treated on this basis. In the USA, data from a larger randomised study (n = 530) that includes sham surgery are awaited before any decision is made on whether to approve the method for use. INTERPRETATION: Before RDN can become recommended treatment in Norway, more evidence is required that the method lowers blood pressure, and that this reduces morbidity and mortality.

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.

Nonadherence by Serum Drug Analyses in Resistant Hypertension: 7-Year Follow-Up of Patients Considered Adherent by Directly Observed Therapy.

Background Measurement of serum concentrations of drugs is a novelty found useful in detecting poor drug adherence in patients taking ≥2 antihypertensive agents. Regarding patients with treatment-resistant hypertension, we previously based our assessment on directly observed therapy. The present study aimed to investigate whether serum drug measurements in patients with resistant hypertension offer additional information regarding drug adherence, beyond that of initial assessment with directly observed therapy. Methods and Results Nineteen patients assumed to have true treatment-resistant hypertension and adherence to antihypertensive drugs based on directly observed therapy were investigated repeatedly through 7 years. Serum concentrations of antihypertensive drugs were measured by ultra-high-performance liquid chromatography-tandem mass spectrometry from blood samples taken at baseline, 6-month, 3-year, and 7-year visits. Cytochrome P450 polymorphisms, self-reported adherence and beliefs about medicine were performed as supplement investigations. Seven patients (37%) were redefined as nonadherent based on their serum concentrations during follow-up. All patients reported high adherence to medications. Nonadherent patients expressed lower necessity and higher concerns regarding intake of antihypertensive medication (P=0.003). Cytochrome P450 polymorphisms affecting metabolism of antihypertensive drugs were found in 16 patients (84%), 21% were poor metabolizers, and none were ultra-rapid metabolizers. Six of 7 patients redefined as nonadherent had cytochrome P450 polymorphisms, however, not explaining the low serum drug concentrations measured in these patients. Conclusions Our data suggest that repeated measurements of serum concentrations of antihypertensive drugs revealed nonadherence in one-third of patients previously evaluated as adherent and treatment resistant by directly observed therapy, thereby improving the accuracy of adherence evaluation. Registration URL: https://www.clinicaltrials.gov; unique identifier: NCT01673516.