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Journal: Journal of clinical hypertension (Greenwich, Conn.)

19

Digital therapeutics is a new approach to treat hypertension via using software programs such as smartphone apps and/or device algorithms. We develop a HERB system-new interactive smartphone app (HERB Mobile) with web-based patient management console (HERB Console)-to lower blood pressure (BP) based on an algorithm that helps users to promote lifestyle modifications in conjunction with medically validated non-pharmacological interventions. The app can assess the personalities, behavior characteristics, and hypertension determinants of each patient with hypertension to provide adequate guidance. To demonstrate the efficacy of the system, we designed a randomized, controlled, multicenter, open-label trial “HERB-DH1 (HERB digital hypertension 1)” to assess the efficacy of HERB system in patients with essential hypertension. The authors allocate patients to the intervention group (HERB system + standard lifestyle modification) or to the control group (standard lifestyle modification alone). In the intervention group, we provide the HERB Mobile for patients and the HERB Console for their primary physicians for 24 weeks. Both groups are instructed for standard lifestyle modifications based on the current recommendations in the Japanese Society of Hypertension 2019 guideline. The primary outcome is the mean change from baseline to 12 weeks in 24-hour systolic BP measured by ambulatory BP monitoring. We started this study in December of 2019, and the trial results will be expected in early 2021. We believe that this trial enables us to verify the efficacy of the HERB system in patients with essential hypertension.

16

Blood pressure (BP) measurement is the most common procedure performed in clinical practice. Accurate BP measurement is critical if patient care is to be delivered with the highest quality, as stressed in published guidelines. Physician training in BP measurement is often limited to a brief demonstration during medical school without retraining in residency, fellowship, or clinical practice to maintain skills. One hundred fifty-nine students from medical schools in 37 states attending the American Medical Association’s House of Delegates Meeting in June 2015 were assessed on an 11-element skillset on BP measurement. Only one student demonstrated proficiency on all 11 skills. The mean number of elements performed properly was 4.1. The findings suggest that changes in medical school curriculum emphasizing BP measurement are needed for medical students to become, and remain, proficient in BP measurement. Measuring BP correctly should be taught and reinforced throughout medical school, residency, and the entire career of clinicians.

Concepts: Medicine, Education, Physician, Pediatrics, Medical school, Internal medicine, Residency, Medical education

14

The relative efficacy of antihypertensive treatment has been assessed primarily by randomized clinical trials (RCTs). The increasing availability of electronic medical records (EMR) allows results from RCT to be compared to data from actual clinical practice. EMR from TriNetX were used to compare patients starting and adhering to antihypertensive treatment on diuretics, beta blockers, angiotensin II or ACE inhibitors, or calcium channel blockers for at least 36 months. Cardiovascular (CV) events as defined by ICD-10 codes were evaluated for an observation period of three years. Outcomes were assessed with and without propensity score matching for confounding factors. A total of 79 288 patients fulfilled the criteria for first-line therapy and adherence (17.4% diuretics, 25.9% beta blockers, 45.1% inhibitors of the renin-angiotensin system, and 11.6% calcium channel blockers). Differences in demography and comorbidities were consistent with expectations based on treatment guidelines. RAS blockers showed the best BP control (28.7% episodes of uncontrolled BP) and, together with diuretics, the lowest rate of CV events (diuretics, 5.2%; RAS blockers, 5.4%). Beta blockers were associated with the highest rate of uncontrolled BP (45.9%) and a high CV event rate (9.5%). These trends remained after matching the cohorts for confounding factors. EMR show that actual prescribing behavior for first-line treatment of essential hypertension reflects treatment guidelines. Patients taking either RAS blockers or diuretics experienced the lowest CV event rates. Beta blockers, even when adjusted for pre-existing cardiovascular conditions, do not seem to be as protective against CV events as the three other classes.

10

Overseas guidelines to manage hypertension recommend selecting different drugs depending on age, but no studies have investigated the relationship between drug selection and age- and sex-related differences, although such information may help to reduce the risk of cardiovascular mortality. The Azilsartan Circadian and Sleep Pressure–the First Study (ACS1) trial was a multicentered, randomized, open-label, two-parallel group study comparing the effects of an angiotensin II receptor blocker (azilsartan) and a calcium channel blocker (amlodipine). The present study is a post hoc analysis of ACS1 to investigate age- and sex-related differences in the antihypertensive effects between azilsartan and amlodipine. Azilsartan significantly reduced diastolic blood pressure in male patients younger than 60 years compared with amlodipine, but amlodipine significantly reduced systolic blood pressure in female patients 60 years and older compared with azilsartan. A randomized controlled trial to evaluate cardiovascular outcomes will demonstrate whether a diastolic blood pressure-lowering effect with azilsartan is significantly effective in male patients younger than 60 years.

Concepts: Hypertension, Blood pressure, Effectiveness, Cardiovascular system, Angiotensin, Renin-angiotensin system, Angiotensin II receptor antagonist, Orthostatic hypotension

9

Several fixed dose combinations (FDCs) of antihypertensive drugs have recently been added to the World Health Organization model list of essential medications. FDCs have advantages in the management of hypertension compared to single drug tablets including improved adherence, greater blood pressure lowering and are associated with reduced cardiovascular complications. FDCs can also reduce ethnic, and age-related variation in blood pressure lowering and have similar or reduced adverse effects relative to single-drug therapy. Best hypertension control practices from the World Health Organization HEARTS program advocates the use of FDC in simple directive treatment protocols. FDC in simple directive protocols was viewed as a key success factor in the control of chronic infections (eg, tuberculosis, HIV). Unfortunately, implementing simple directive protocols with FDC has had substantial opposition from hypertension experts. Hypertension organizations and experts need to familiarize themselves with best practices in hypertension control, their supporting evidence and to become advocates.

8

Elevated serum uric acid is a cardiovascular risk factor in patients with hypertension, even when blood pressure (BP) is well controlled. Xanthine oxidoreductase inhibitors (XORi) reduce serum uric acid levels and have several other potential effects. This multicenter, randomized, open-label study compared the effects of two XORi, topiroxostat and febuxostat, on arterial stiffness, uric acid levels, and BP in hypertensive patients with hyperuricemia. Patients received topiroxostat 40-160 mg/day or febuxostat 10-60 mg/day, titrated to maintain serum uric acid <6 mg/dl, for 24 weeks. The primary endpoint was change in the cardio-ankle vascular index (CAVI) from baseline to 24 weeks. There were no significant changes in CAVI from baseline to 24 weeks (from 9.13 to 9.16 [feboxustat] and 8.98 to 9.01 [topiroxostat]). Compared with baseline, there were significant reductions in serum uric acid (-2.9 and -2.5 mg/dl; both p < 0.001) and morning home systolic BP (-3.6 and -5.1 mm Hg; both p < 0.01) after 24 weeks' treatment with febuxostat and topiroxostat. BP decreased to the greatest extent in the subgroup of patients with uncontrolled blood pressure at baseline. Topiroxostat, but not febuxostat, significantly decreased plasma xanthine oxidoreductase activity versus baseline. The urinary albumin-creatinine ratio (UACR) decreased significantly from baseline to 24 weeks with topiroxostat (-20.8%; p = 0.021), but not febuxostat (-8.8%; p = 0.362). In conclusion, neither topiroxostat nor febuxostat had any significant effects on arterial stiffness over 24 weeks' treatment.

8

Both high sodium and low potassium diets are associated with hypertension, but whether these risk factors are distinct or overlapping has not been thoroughly investigated. The authors evaluated the relationship between dietary sodium, potassium, and high systolic blood pressure among 4716 adolescents aged 12 to 14 years who participated in the National Health and Nutrition Examination Survey from 1999 to 2012. There was no association with blood pressure across most values of sodium or potassium intake. However, participants who reported sodium intake ≥7500 mg/d, potassium <700 mg/d, or sodium-potassium ratio ≥2.5 had increased odds for high systolic blood pressure (≥95th percentile for age, sex, and height). Although the high sodium and low potassium groups did not overlap, 49.2% of these adolescents also had a sodium-potassium ratio ≥2.5. In young adolescents, both excessive sodium and limited potassium are associated with high systolic blood pressure, but the balance between sodium and potassium intake may be more useful in explaining blood pressure in this population.

Concepts: Hypertension, Blood pressure, Aldosterone, Artery, Sodium, Potassium, Orthostatic hypotension, Renin

7

There is an unmet need to prevent cardiovascular disease and chronic kidney disease development and progression worldwide. Losartan, the first angiotensin receptor blocker, was shown to exert significant cardioprotective and renoprotective effects in the LIFE (Losartan Intervention for Endpoint Reduction in Hypertension) and RENAAL (Reduction of Endpoints in NIDDM With the Angiotensin II Antagonist Losartan) trials. Losartan significantly prevented stroke and decreased serum uric acid levels and the rates of new-onset diabetes mellitus and atrial fibrillation. The present review discusses the LIFE (and its subanalyses) and RENAAL trials and the translation of their results to clinical practice. The place of losartan in the current guidelines for hypertension management is also discussed. Losartan still represents an efficacious, safe, and cost-effective therapeutic option in patients with hypertension who have left ventricular hypertrophy. Losartan is a useful antihypertensive agent for stroke prevention and in the management of patients with chronic kidney disease, atrial fibrillation, diabetes mellitus, albuminuria, and hyperuricemia.

6

Hypertension guidelines recommend that blood pressure (BP) should be measured using a monitor that has passed validation testing for accuracy. BP monitors that have not undergone rigorous validation testing can still be cleared by regulatory authorities for marketing and sale. This is the situation for most BP monitors worldwide. Thus, consumers (patients, health professionals, procurement officers, and general public) may unwittingly purchase BP monitors that are non-validated and more likely to be inaccurate. Without prior knowledge of these issues, it is extremely difficult for consumers to distinguish validated from non-validated BP monitors. For the above reasons, the aim of this paper is to provide consumers guidance on how to check whether a BP monitor has been properly validated for accuracy. The process involves making an online search of listings of BP monitors that have been assessed for validation status. Only those monitors that have been properly validated are recommended for BP measurement. There are numerous different online listings of BP monitors, several are country-specific and two are general (international) listings. Because monitors can be marketed using alternative model names in different countries, if a monitor is not found on one listing, it may be worthwhile cross-checking with a different listing. This information is widely relevant to anyone seeking to purchase a home, clinic, or ambulatory BP monitor, including individual consumers for use personally or policy makers and those procuring monitors for use in healthcare systems, and retailers looking to stock only validated BP monitors.

6

Liraglutide is associated with blood pressure reduction in patients with type 2 diabetes. However, it is not known whether this blood pressure reduction can be predicted prior to treatment initiation, and to what extent it correlates with weight loss and with improved glycemic control during follow-up. We analyzed data from a double-blind, placebo-controlled trial, in which 124 insulin-treated patients with type 2 diabetes were randomized to liraglutide or placebo. We evaluated various baseline variables as potential predictors of systolic blood pressure (SBP) reduction, and evaluated whether changes in SBP correlated with weight loss and with improved glycemic control. A greater reduction in SBP among liraglutide-treated patients was predicted by higher baseline values of SBP (P < 0.0001) and diastolic blood pressure (P = 0.012), and by lower baseline values of mean glucose measured by continuous glucose monitoring (CGM; P = 0.044), and serum fasting C-peptide (P = 0.015). The regression coefficients differed significantly between the liraglutide group and the placebo group only for diastolic blood pressure (P = 0.037) and mean CGM (P = 0.021). During the trial period, SBP reduction correlated directly with change in body weight and BMI, but not with change in HbA1c. We conclude that patients with lower mean CGM values at baseline responded to liraglutide with a larger reduction in SBP, and that improved HbA1c during follow-up was not associated with reductions of SBP. Our data suggest that some patients with type 2 diabetes may benefit from liraglutide in terms of weight and SBP reduction.