Purpose of Review
Patients with true resistant hypertension (RH) are characterized by having high sympathetic activity and therefore potentially benefit from treatments such as baroreflex ...amplification (baroreflex activation therapy (BAT) or endovascular baroreflex amplification therapy (EVBA)) or carotid body (CB) modulation. This review aims at providing an up-to-date overview of the available evidence regarding these two therapies.
Recent Findings
In recent years, increasing evidence has confirmed the potential of baroreflex amplification, either electrically (Barostim neo) or mechanically (MobiusHD), to improve blood pressure control on short- and long-term with only few side effects, in patients with RH. Two studies regarding unilateral CB resection did not show a significant change in blood pressure. Only limited studies regarding CB modulation showed promising results for transvenous CB ablation, but not for unilateral CB resection.
Summary
Despite promising results from mostly uncontrolled studies, more evidence regarding the safety and efficacy from ongoing large randomized sham-controlled trials is needed before baroreflex amplification and CB modulation can be implemented in routine clinical practice.
Nonadherence to antihypertensive medication is common, especially in those with apparent treatment-resistant hypertension (true treatment-resistant hypertension requires exclusion of nonadherence), ...and its routine detection is supported by clinical guidelines. Chemical adherence testing is a reliable and valid method to detect adherence, yet methods are unstandardized and are not ubiquitous. This article describes the principles of chemical adherence testing for hypertensive patients and provides a set of recommendations for centers wishing to develop the test. We recommend testing should be done in either of two instances: (1) in those who have resistant hypertension or (2) in those on 2 antihypertensives who have a less than 10 mm Hg drop in systolic blood pressure on addition of the second antihypertensive medication. Furthermore, we recommend that verbal consent is secured before undertaking the test, and the results should be discussed with the patient. Based on medications prescribed in United Kingdom, European Union, and United States, we list top 20 to 24 drugs that cover >95% of hypertension prescriptions which may be included in the testing panel. Information required to identify these medications on mass spectrometry platforms is likewise provided. We discuss issues related to ethics, sample collection, transport, stability, urine versus blood samples, qualitative versus quantitative testing, pharmacokinetics, instrumentation, validation, quality assurance, and gaps in knowledge. We consider how to best present, interpret, and discuss chemical adherence test results with the patient. In summary, this guidance should help clinicians and their laboratories in the development of chemical adherence testing of prescribed antihypertensive drugs.
Carotid baroreflex activation lowers blood pressure and might have potential application for the treatment of resistant hypertension. We did a proof-of-principle trial with a novel endovascular ...baroreceptor amplification device, MobiusHD (Vascular Dynamics, Mountain View, CA, USA), in patients with resistant hypertension.
CALM-FIM_EUR was a prospective, first-in-human, open-label study done at six European centres. Eligible patients were adults with resistant hypertension (office systolic blood pressure ≥160 mm Hg despite taking at least three antihypertensive agents, including a diuretic). MobiusHD devices were implanted unilaterally in the internal carotid artery. The primary endpoint was the incidence of serious adverse events at 6 months. Secondary endpoints included changes in office and 24 h ambulatory blood pressure. This trial is registered with ClinicalTrials.gov, number NCT01911897.
Between December, 2013, and February, 2016, 30 patients were enrolled and underwent successful implantation. Mean age was 52 years (SD 12), 15 patients (50%) were men, and mean antihypertensive use was 4·4 drugs (1·4). Mean office blood pressure was 184/109 mm Hg (18/14) at baseline and was reduced by 24/12 mm Hg (13–34/6–18) at 6 months (p=0·0003 for systolic and p=0·0001 diastolic blood pressure). Mean baseline 24 h ambulatory blood pressure was 166/100 mm Hg (17/14) at baseline and was reduced by 21/12 mm Hg (14–29/7–16) at 6 months (p<0·0001 for systolic and diastolic blood pressure). Five serious adverse events had occurred in four patients (13%) at 6 months: hypotension (n=2), worsening hypertension (n=1), intermittent claudication (n=1) and wound infection (n=1).
In patients with resistant hypertension, endovascular baroreceptor amplification with the MobiusHD device substantially lowered blood pressure with an acceptable safety profile. Randomised, double-blind, sham-controlled trials are warranted to investigate the use of this treatment further.
Vascular Dynamics.
To investigate whether there are sex differences in risk factor management of patients with established coronary heart disease (CHD), and to assess demographic variations of any potential sex ...differences.
Patients with CHD were recruited from Europe, Asia, and the Middle East between 2012-2013. Adherence to guideline-recommended treatment and lifestyle targets was assessed and summarised as a Cardiovascular Health Index Score (CHIS). Age-adjusted regression models were used to estimate odds ratios for women versus men in risk factor management.
10 112 patients (29% women) were included. Compared with men, women were less likely to achieve targets for total cholesterol (OR 0.50, 95% CI 0.43 to 0.59), low-density lipoprotein cholesterol (OR 0.57, 95% CI 0.51 to 0.64), and glucose (OR 0.78, 95% CI 0.70 to 0.87), or to be physically active (OR 0.74, 95% CI 0.68 to 0.81) or non-obese (OR 0.82, 95% CI 0.74 to 0.90). In contrast, women had better control of blood pressure (OR 1.31, 95% CI 1.20 to 1.44) and were more likely to be a non-smoker (OR 1.93, 95% CI 1.67 to 2.22) than men. Overall, women were less likely than men to achieve all treatment targets (OR 0.75, 95% CI 0.60 to 0.93) or obtain an adequate CHIS (OR 0.81, 95% CI 0.73 to 0.91), but no significant differences were found for all lifestyle targets (OR 0.93, 95% CI 0.84 to 1.02). Sex disparities in reaching treatment targets were smaller in Europe than in Asia and the Middle East. Women in Asia were more likely than men to reach lifestyle targets, with opposing results in Europe and the Middle East.
Risk factor management for the secondary prevention of CHD was generally worse in women than in men. The magnitude and direction of the sex differences varied by region.
First in human studies suggest that endovascular baroreflex amplification (EVBA) lowers blood pressure (BP). To explore potential mechanisms for BP reduction, this study examines the effects of EVBA ...on muscle sympathetic nerve activity (MSNA) and baroreceptor sensitivity (BRS).
In a single-center sub-study of the CALM-DIEM study (Controlling And Lowering blood pressure with the MobiusHD-Defining Efficacy Markers), 14 patients with resistant hypertension were treated with EVBA. Microneurography and non-invasive continuous BP measurements were performed at baseline and three months after MobiusHD implantation. The primary outcome was change in MSNA. Secondary outcomes were change in baroreflex sensitivity (BRS), cardiovascular responses to a sympathetic stimulus, BP, heart rate (HR) and heart rate variability (HRV).
The primary endpoint was obtained in 10 of 14 patients enrolled in the sub-study. MSNA burst frequency and burst incidence decreased in 6 of 10 patients: mean change -4.1 bursts/min (95% confidence interval -12.2 to 4.0) and -3.8 bursts/100 heartbeats (-15.2 to 7.7). MSNA spike frequency and spike count decreased in 8 of 10 patients: mean change -2.8 spikes/sec (-7.3 to 1.8) and -3.0 spikes/heartbeat (-6.1 to 0.1). Change in MSNA and BP were not correlated. Office BP decreased by -14/-6 mmHg (-27 to -2/-15 to 3). We observed a trend towards decreased HR (-5 bpm, -10 to 1) and increased total power HRV (623 msec2, 78 to 1168). In contrast, BRS and cardiovascular responses remained unchanged after EVBA.
In this proof-of-principle study, EVBA did not significantly decrease MSNA in patients with resistant hypertension. EVBA did not impair baroreflex function.
Clinical trial registration at NCT02827032.
Most evidence on the relationship between sodium and potassium intake and cardiovascular disease originated from general population studies. This study aimed to evaluate the relation between ...estimated 24-hour sodium and potassium urinary excretion and the risk of recurrent vascular events and mortality in patients with vascular disease.
7561 patients with vascular disease enrolled in the UCC-SMART cohort (1996-2015) were included. Twenty-four hour sodium and potassium urinary excretion were estimated (Kawasaki formulae) from morning urine samples. Cox proportional hazard models with restricted cubic splines were used to evaluate the relation between estimated urinary salt excretion and major adverse cardiovascular events (MACE; including myocardial infarction, stroke, cardiovascular mortality) and all-cause mortality.
After a median follow-up of 7.4 years (interquartile range: 4.1-11.0), the relations between estimated 24-hour sodium urinary excretion and outcomes were J-shaped with nadirs of 4.59 gram/day for recurrent MACE and 4.97 gram/day for all-cause mortality. The relation between sodium-to-potassium excretion ratio and outcomes were also J-shaped with nadirs of 2.71 for recurrent MACE and 2.60 for all-cause mortality. Higher potassium urinary excretion was related to an increased risk of both recurrent MACE (HR 1.25 per gram potassium excretion per day; 95%CI 1.13-1.39) and all cause-mortality (HR 1.13 per gram potassium excretion per day; 95%CI 1.03-1.25).
In patients with established vascular disease, lower and higher sodium intake were associated with higher risk of recurrent MACE and all-cause mortality. Higher estimated 24-hour potassium urinary excretion was associated with a higher risk of recurrent MACE and all-cause mortality.
Abstract Background and aims Pseudoxanthoma elasticum (PXE) is a monogenetic disorder with progressive calcifications of the skin, the Bruch's membrane in the eyes and the arterial wall. Vascular ...disease is considered to be very prevalent, but the whole-body distribution of arterial calcifications in PXE is unknown. We aimed to systematically investigate arterial calcifications in PXE. Methods We included 104 PXE patients from the Dutch PXE cohort and 93 hospital controls. All subjects underwent full-body low-dose CT scans without contrast. To investigate the prevalence and severity of arterial calcification per arterial location, CT scans were scored using a reproducible semi-quantitative scale with four calcification categories (interobserver kappa 0.54–0.99). Results PXE patients (38/104 males) were 54 ± 13 years and controls (45/93 males) 54 ± 16 years old. Arterial calcifications were significantly more common in PXE patients in the intracranial internal carotid artery (75% vs. 44%), the arteries of the arms (20% vs. 3%), the femoral-popliteal arteries (74% vs. 44%) and the subpopliteal arteries (84% vs. 38%). In these arteries, calcification scores also indicated more severe calcification. No significant differences in prevalence of arterial calcification were observed in other arterial beds such as the coronary arteries (45% vs. 43%, p = 0.776), the carotid arteries (52% vs 46%, p = 0.476) and the abdominal aorta (71% vs. 63%, p = 0.287). Analyses using patients younger than 55 years only, showed similar differences in prevalence of arterial calcifications between PXE patients and controls, with most pronounced calcifications in the arteries of the lower legs (67% vs. 8%). Similar patterns were observed in those without concomitant diabetes or renal dysfunction. Conclusions In PXE, a vascular phenotype can be identified with a distribution of arterial calcifications that is clearly distinct from hospital controls and involves arterial calcifications in the legs, the intracranial internal carotid artery and the arteries of the arms.
To assess the effect of the bisphosphonate etidronate on choroidal neovascular (CNV) activity in patients with pseudoxanthoma elasticum (PXE).
This is an ancillary study in a single center, ...randomized, double-blind placebo-controlled trial (RCT) in which 74 patients with PXE were assigned to either one-year etidronate or placebo treatment. Spectral domain optical coherence tomography (SD-OCT) imaging and color fundus photography were performed every three months for one year and were systematically assessed on signs of CNV activity.
In the etidronate group, 11 (30%) of the patients had CNV activity at baseline, compared to 25 (67%) of the patients in the placebo group (P = 0.005). The proportion of eyes with CNV activity during the study ranged from 18-33% in the etidronate group and 42-56% in the placebo group and no significant difference in improvement or worsening of CNV activity was found (P = 0.168). Using a generalized mixed model for repeated measures, there was a protective effect of etidronate in crude analysis (RR 0.86, 95% CI 0.75-0.98) that disappeared when adjusting for baseline CNV activity (RR 0.97, 95% CI 0.84-1.13).
In this post-hoc RCT analysis we did not observe a protecting or deteriorating effect of etidronate on CNV activity in patients with PXE after adjustment for baseline CNV.
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