Antoinette Pechère-Bertschi

Blood pressure changes after renal denervation at 10 European expert centers

We did a subject-level meta-analysis of the changes (Δ) in blood pressure (BP) observed 3 and 6 months after renal denervation (RDN) at 10 European centers. Recruited patients (n=109; 46.8% women; mean age 58.2 years) had essential hypertension confirmed by ambulatory BP. From baseline to 6 months, treatment score declined slightly from 4.7 to 4.4 drugs per day. Systolic/diastolic BP fell by 17.6/7.1 mm Hg for office BP, and by 5.9/3.5, 6.2/3.4, and 4.4/2.5 mm Hg for 24-h, daytime and nighttime BP (P⩽0.03 for all). In 47 patients with 3- and 6-month ambulatory measurements, systolic BP did not change between these two time points (P⩾0.08). Normalization was a systolic BP of <140 mm Hg on office measurement or <130 mm Hg on 24-h monitoring and improvement was a fall of ⩾10 mm Hg, irrespective of measurement technique. For office BP, at 6 months, normalization, improvement or no decrease occurred in 22.9, 59.6 and 22.9% of patients, respectively; for 24-h BP, these proportions were 14.7, 31.2 and 34.9%, respectively. Higher baseline BP predicted greater BP fall at follow-up; higher baseline serum creatinine was associated with lower probability of improvement of 24-h BP (odds ratio for 20-μmol l−1 increase, 0.60; P=0.05) and higher probability of experiencing no BP decrease (OR, 1.66; P=0.01). In conclusion, BP responses to RDN include regression-to-the-mean and remain to be consolidated in randomized trials based on ambulatory BP monitoring. For now, RDN should remain the last resort in patients in whom all other ways to control BP failed, and it must be cautiously used in patients with renal impairment.

1999–2009 Trends in Prevalence, Unawareness, Treatment and Control of Hypertension in Geneva, Switzerland

Background There are no time trends in prevalence, unawareness, treatment, and control of hypertension in Switzerland. The objective of this study was to analyze these trends and to determine the associated factors. Methods/Findings Population-based study conducted in the Canton of Geneva, Switzerland, between 1999 and 2009. Blood pressure was measured thrice using a standard protocol. Hypertension was defined as mean systolic or diastolic blood pressure ≥140/90 mmHg or self-reported hypertension or anti-hypertensive medication. Unawareness, untreated and uncontrolled hypertension was determined by questionnaires/blood pressure measurements. Yearly age-standardized prevalences and adjusted associations for the 1999–2003 and 2004–2009 survey periods were reported. The 10-year survey included 9,215 participants aged 35 to 74 years. Hypertension remained stable (34.4%). Hypertension unawareness decreased from 35.9% to 17.7% (P<0.001). The decrease in hypertension unawareness was not paralleled by a concomitant absolute increase in hypertension treatment, which remained low (38.2%). A larger proportion of all hypertensive participants were aware but not treated in 2004–2009 (43.7%) compared to 1999–2003 (33.1%). Uncontrolled hypertension improved from 62.2% to 40.6% between 1999 and 2009 (P = 0.02). In 1999–2003 period, factors associated with hypertension unawareness were current smoking (OR = 1.27, 95%CI, 1.02–1.59), male gender (OR = 1.56, 1.27–1.92), hypercholesterolemia (OR = 1.31, 1.20–1.44), and older age (OR 65–74yrs vs 35–49yrs  = 1.56, 1.21–2.02). In 1999–2003 and 2004–2009, obesity and diabetes were negatively associated with hypertension unawareness, high education was associated with untreated hypertension (OR = 1.45, 1.12–1.88 and 1.42, 1.02–1.99, respectively), and male gender with uncontrolled hypertension (OR = 1.49, 1.03–2.17 and 1.65, 1.08–2.50, respectively). Sedentarity was associated with higher risk of hypertension and uncontrolled hypertension in 1999–2003. Conclusions Hypertension prevalence remained stable since 1999 in the canton of Geneva. Although hypertension unawareness substantially decreased, more than half of hypertensive subjects still remained untreated or uncontrolled in 2004–2009. This study identified determinants that should guide interventions aimed at improving hypertension treatment and control.

Reasons for not intensifying antihypertensive treatment (RIAT): a primary care antihypertensive intervention study

Objective Hypertension is often poorly controlled, despite its importance and despite the availability of very effective treatments. An under-recognized problem is the failure of consensus guidelines to acknowledge the important difference between efficacy in clinical trials and effectiveness in clinical practice. The present survey was designed to prospectively assess what is the target blood pressure (BP) goal defined by a general practitioner (GP) for an individual patient, and what are the reasons for not modifying an antihypertensive drug regimen, when pre-defined individual BP goals are not achieved. Design Family practice based, open intervention survey. Subjects Participating GPs enrolled 2621 hypertensive patients. At the first visit each physician was required to assess the cardiovascular risk profile of each patient and to define individual BP targets. Interventions Treatment was started with irbesartan alone or in fixed combination with hydrochlorothiazide. Follow-up visits were suggested after 1 month, 2 months and 4 months. Physicians were asked to report BP values under the new treatment regimen and to indicate whether in their opinion pre-defined BP targets set at baseline were achieved or not and whether the antihypertensive regimen was modified or maintained in relation to whether target BP was reached or not. Main outcome measure To provide reasons for not changing the treatment even though BP goals were missed. Results Average target BP values defined by the physicians at baseline were 138 ± 8 mmHg for systolic and 84 ± 5 mmHg for diastolic BP. Among GPs, defined target BP values did not depend on individual risk stratification, but rather depended on baseline BP values. At baseline systolic and diastolic BP averaged 165/97 ± 17/10 mmHg, while at the last visit achieved BP averaged 140/84 ± 14/8 mmHg. There were three main reasons for not intensifying antihypertensive treatment when BP targets were not achieved. These reasons were: (1) the assumption that the time after starting the new drug was too short to appreciate its full effect (44% at first, 14% at last follow-up), (2) that there was a clear improvement or the target BP was almost reached (24% at first, 34% at last follow-up) or (3) that self-measurements were considered satisfactorily (10% at the last visit). Conclusions Failure of physicians to follow guidelines is apparently dependent on the belief that baseline BP dictates the target, that a clear improvement in BP might be sufficient and that the full drug effect may take up to 4 months or more to be attained.

Eligibility for Renal Denervation: Experience at 11 European Expert Centers

Based on the SYMPLICITY studies and CE (Conformité Européenne) certification, renal denervation is currently applied as a novel treatment of resistant hypertension in Europe. However, information on the proportion of patients with resistant hypertension qualifying for renal denervation after a thorough work-up and treatment adjustment remains scarce. The aim of this study was to investigate the proportion of patients eligible for renal denervation and the reasons for noneligibility at 11 expert centers participating in the European Network COordinating Research on renal Denervation in treatment-resistant hypertension (ENCOReD). The analysis included 731 patients. Age averaged 61.6 years, office blood pressure at screening was 177/96 mm Hg, and the number of blood pressure–lowering drugs taken was 4.1. Specialists referred 75.6% of patients. The proportion of patients eligible for renal denervation according to the SYMPLICITY HTN-2 criteria and each center’s criteria was 42.5% (95% confidence interval, 38.0%–47.0%) and 39.7% (36.2%–43.2%), respectively. The main reasons of noneligibility were normalization of blood pressure after treatment adjustment (46.9%), unsuitable renal arterial anatomy (17.0%), and previously undetected secondary causes of hypertension (11.1%). In conclusion, after careful screening and treatment adjustment at hypertension expert centers, only ≈40% of patients referred for renal denervation, mostly by specialists, were eligible for the procedure. The most frequent cause of ineligibility (approximately half of cases) was blood pressure normalization after treatment adjustment by a hypertension specialist. Our findings highlight that hypertension centers with a record in clinical experience and research should remain the gatekeepers before renal denervation is considered.Based on the SYMPLICITY studies and CE (Conformite Europeenne) certification, renal denervation is currently applied as a novel treatment of resistant hypertension in Europe. However, information on the proportion of patients with resistant hypertension qualifying for renal denervation after a thorough work-up and treatment adjustment remains scarce. The aim of this study was to investigate the proportion of patients eligible for renal denervation and the reasons for noneligibility at 11 expert centers participating in the European Network COordinating Research on renal Denervation in treatment-resistant hypertension (ENCOReD). The analysis included 731 patients. Age averaged 61.6 years, office blood pressure at screening was 177/96 mm Hg, and the number of blood pressure–lowering drugs taken was 4.1. Specialists referred 75.6% of patients. The proportion of patients eligible for renal denervation according to the SYMPLICITY HTN-2 criteria and each center’s criteria was 42.5% (95% confidence interval, 38.0%–47.0%) and 39.7% (36.2%–43.2%), respectively. The main reasons of noneligibility were normalization of blood pressure after treatment adjustment (46.9%), unsuitable renal arterial anatomy (17.0%), and previously undetected secondary causes of hypertension (11.1%). In conclusion, after careful screening and treatment adjustment at hypertension expert centers, only ≈40% of patients referred for renal denervation, mostly by specialists, were eligible for the procedure. The most frequent cause of ineligibility (approximately half of cases) was blood pressure normalization after treatment adjustment by a hypertension specialist. Our findings highlight that hypertension centers with a record in clinical experience and research should remain the gatekeepers before renal denervation is considered. # Novelty and Significance {#article-title-32}

Reference Values and Factors Associated With Renal Resistive Index in a Family-Based Population Study

Increased renal resistive index (RRI) has been recently associated with target organ damage and cardiovascular or renal outcomes in patients with hypertension and diabetes mellitus. However, reference values in the general population and information on familial aggregation are largely lacking. We determined the distribution of RRI, associated factors, and heritability in a population-based study. Families of European ancestry were randomly selected in 3 Swiss cities. Anthropometric parameters and cardiovascular risk factors were assessed. A renal Doppler ultrasound was performed, and RRI was measured in 3 segmental arteries of both kidneys. We used multilevel linear regression analysis to explore the factors associated with RRI, adjusting for center and family relationships. Sex-specific reference values for RRI were generated according to age. Heritability was estimated by variance components using the ASSOC program (SAGE software). Four hundred women (mean age±SD, 44.9±16.7 years) and 326 men (42.1±16.8 years) with normal renal ultrasound had mean RRI of 0.64±0.05 and 0.62±0.05, respectively (P<0.001). In multivariable analyses, RRI was positively associated with female sex, age, systolic blood pressure, and body mass index. We observed an inverse correlation with diastolic blood pressure and heart rate. Age had a nonlinear association with RRI. We found no independent association of RRI with diabetes mellitus, hypertension treatment, smoking, cholesterol levels, or estimated glomerular filtration rate. The adjusted heritability estimate was 42±8% (P<0.001). In a population-based sample with normal renal ultrasound, RRI normal values depend on sex, age, blood pressure, heart rate, and body mass index. The significant heritability of RRI suggests that genes influence this phenotype.

Sinistrin Clearance for Determination of Glomerular Filtration Rate: A Reappraisal of Various Approaches Using a New Analytical Method

Several approaches are available to estimate the glomerular filtration rate (GFR) from the sinistrin clearance. To compare such approaches, GFR was estimated in six healthy volunteers, both after a bolus injection and a bolus dose followed by a 6‐hour infusion. A recently developed high‐performance liquid chromatography method was used for the determination of sinistrin levels, enabling precise measurements in plasma and urine samples with high sensitivity. Blood and urine were sampled up to 6 hours. Four calculation methods for estimating GFR were applied: 1) classical ratio of urinary excretion rate over plasma concentration (UV/P); 2) two‐point (log‐linear regression slope times monocompartmental volume of distribution) after bolus; 3) ratio of dose over area under the curve (D/AUC) after bolus; and 4) ratio of infusion rate over steady‐state concentration during infusion (Rinf/P). The results obtained by fitting a pharmacokinetic model to all the plasma and urine data served as the standard against which the performance of the respective calculation methods were examined. The UV/P method performed poorly on bolus data, mainly by underestimating GFR at late times; on both bolus and infusion data, it suffered from important imprecisions on the urinary volume. The two‐point method appeared applicable only between 2 and 4 hours after the bolus dose. The D/AUC method with extrapolation to infinity was highly reliable when integrating the concentrations up to 3 hours or more after the bolus dose. The Rinf/P method was satisfactory if applied later than 2 to 3 hours after the loading dose. The advantages and drawbacks of each method have to be evaluated in relation to the particular clinical setting in which GFR is to be estimated.

Blood pressure and renal haemodynamic response to salt during the normal menstrual cycle.

The purpose of the present study was to evaluate prospectively blood pressure and the renal haemodynamic response to salt during the normal menstrual cycle. A total of 35 healthy normotensive young women not on oral contraceptives were enrolled; 17 were studied in the follicular phase and 18 in the luteal phase of the menstrual cycle. The women in each group were then randomly allocated to receive a low-sodium (40 mmol/day) or a high-sodium (250 mmol/day) diet for a 7-day period in two consecutive menstrual cycles. At the end of each dietary period, 24 h ambulatory blood pressure, urinary sodium excretion, plasma renin activity, plasma catecholamine levels and renal haemodynamics were measured. Our results show that the blood pressure response to salt is comparable during the luteal and the follicular phases of the normal menstrual cycle and is characterized by a salt-resistant pattern. In the kidney, effective renal plasma flow was significantly greater and the filtration fraction lower (P<0.05) after salt loading in women studied in the luteal phase compared with women investigated in the follicular phase. This study thus demonstrates that the female hormone status does not affect the blood pressure response to sodium in young normotensive women. However, in contrast with systemic haemodynamics, the renal response to salt varies during the normal menstrual cycle, suggesting that female sex hormones play a role (direct or indirect) in the regulation of renal haemodynamics.

Copeptin Is Associated with Kidney Length, Renal Function, and Prevalence of Simple Cysts in a Population-Based Study

Arginine vasopressin (AVP) has a key role in osmoregulation by facilitating water transport in the collecting duct. Recent evidence suggests that AVP may have additional effects on renal function and favor cyst growth in polycystic kidney disease. Whether AVP also affects kidney structure in the general population is unknown. We analyzed the association of copeptin, an established surrogate for AVP, with parameters of renal function and morphology in a multicentric population-based cohort. Participants from families of European ancestry were randomly selected in three Swiss cities. We used linear multilevel regression analysis to explore the association of copeptin with renal function parameters as well as kidney length and the presence of simple renal cysts assessed by ultrasound examination. Copeptin levels were log-transformed. The 529 women and 481 men had median copeptin levels of 3.0 and 5.2 pmol/L, respectively (P<0.001). In multivariable analyses, the copeptin level was associated inversely with eGFR (β=-2.1; 95% confidence interval [95% CI], -3.3 to -0.8; P=0.002) and kidney length (β=-1.2; 95% CI, -1.9 to -0.4; P=0.003) but positively with 24-hour urinary albumin excretion (β=0.11; 95% CI, 0.01 to 0.20; P=0.03) and urine osmolality (β=0.08; 95% CI, 0.05 to 0.10; P<0.001). A positive association was found between the copeptin level and the presence of renal cysts (odds ratio, 1.6; 95% CI, 1.1 to 2.4; P=0.02). These results suggest that AVP has a pleiotropic role in renal function and may favor the development of simple renal cysts.

Inactive Matrix Gla-Protein Is Associated With Arterial Stiffness in an Adult Population–Based Study

Increased pulse wave velocity (PWV) is a marker of aortic stiffness and an independent predictor of mortality. Matrix Gla-protein (MGP) is a vascular calcification inhibitor that needs vitamin K to be activated. Inactive MGP, known as desphospho-uncarboxylated MGP (dp-ucMGP), can be measured in plasma and has been associated with various cardiovascular markers, cardiovascular outcomes, and mortality. In this study, we hypothesized that high levels of dp-ucMGP are associated with increased PWV. We recruited participants via a multicenter family-based cross-sectional study in Switzerland. Dp-ucMGP was quantified in plasma by sandwich ELISA. Aortic PWV was determined by applanation tonometry using carotid and femoral pulse waveforms. Multiple regression analysis was performed to estimate associations between PWV and dp-ucMGP adjusting for age, renal function, and other cardiovascular risk factors. We included 1001 participants in our analyses (475 men and 526 women). Mean values were 7.87±2.10 m/s for PWV and 0.43±0.20 nmol/L for dp-ucMGP. PWV was positively associated with dp-ucMGP both before and after adjustment for sex, age, body mass index, height, systolic and diastolic blood pressure (BP), heart rate, renal function, low- and high-density lipoprotein, glucose, smoking status, diabetes mellitus, BP and cholesterol lowering drugs, and history of cardiovascular disease (P⩽0.01). In conclusion, high levels of dp-ucMGP are independently and positively associated with arterial stiffness after adjustment for common cardiovascular risk factors, renal function, and age. Experimental studies are needed to determine whether vitamin K supplementation slows arterial stiffening by increasing MGP carboxylation.

Blood pressure measurements are unreliable to diagnose hypertension in primary care

Objectives: To evaluate the accuracy of blood pressure (BP) measurements performed by primary care physicians (PCPs), and to assess whether it improves following a short theoretical training. Methods: Observational study in 26 primary care practices in Geneva, Switzerland. The PCPs were asked to measure BP on 10 volunteers, within the usual context of their practice. Two trained research assistants repeated the measures immediately after the PCPs. The PCPs were then randomized to receive detailed training documentation on standardized BP measurement (group I: 14 doctors) or information about high BP (group II: 12 doctors). Measures were repeated a few weeks later. We computed accuracy and diagnostic categorization of high BP comparing the PCPs’ measurements to the average value of four measurements by the research assistants (gold standard). T-tests were used to compare measurements between the two educational groups, both at baseline and following exposure to the educational material. Results: BP measurements were performed on 257 volunteers at baseline and 251 after training. At baseline, the mean BP difference between PCPs and the gold standard were 23.0 mmHg (21.3–24.6) for systolic and 15.3 mmHg (14.3–16.3) for DBP. Following training, the mean difference remained high [group I: 22.3 mmHg (20.4–24.2) and 14.4 mmHg (12.6–16.2); group II: 25.3 mmHg (22.7–27.9) and 17.0 mmHg (15.3–18.7)]. As a result, 24–32% volunteers were misdiagnosed as having systolic hypertension and 15–21% as having diastolic hypertension. Conclusion: Though widely used in the assessment of hypertension in ambulatory settings, in-office BP measurements are highly inaccurate, even following training.