Elena Berra

Evaluation of Adherence Should Become an Integral Part of Assessment of Patients With Apparently Treatment-Resistant Hypertension.

Since the publication of the first Symplicity studies in 2009 to 2010, renal sympathetic denervation gained acceptance as a novel treatment of drug-resistant hypertension. The latter has been defined as a blood pressure (BP) >140/90 mm Hg, despite appropriate lifestyle measures plus a diuretic and 2 other antihypertensive drugs belonging to different classes at adequate doses.1 According to the US definition, patients with controlled BP on ≥4 antihypertensive drugs are also considered as resistant hypertensives.2 However, a substantial proportion of patients with apparently resistant hypertension are in fact poorly adherents to drug treatment. The highly variable BP response to renal denervation (RDN)3–5 prompted to a more rigorous evaluation of eligible patients, with the goal to exclude false resistant hypertension, because of poor adherence to drug treatment.6–8 In particular, several publications documented a high proportion of low drug adherence in patients with apparently resistant hypertension (23%–66%), using witnessed drug intake9 or plasma/urine drug determinations10–18 (Figure 1). Figure 1. Proportion of poor or nonadherence according to drug monitoring in different cohorts of patients with apparently resistant hypertension. Black indicates total nonadherence, whereas gray indicates partial adherence. Partial adherence was defined as the presence of at least one undetectable drug10–12,14,16–18 or as the presence of fewer medications than prescribed.13,15 Furthermore, RDN studies shed the light on the dynamic character of drug adherence. Inclusion in RDN trials may influence drug adherence in various, unpredictable directions.6 In some patients, close follow-up and massive attention devoted to them may lead to improved adherence to lifestyle measures and drug treatment, particularly in the RDN arm (Hawthorne effect). Other patients may stop their medications after RDN according to their perception that the intervention cured their …

Comparison among Different Screening Tests for Diagnosis of Adolescent Hypertension

The diagnosis of childhood hypertension based upon percentile tables proposed by the international guidelines is complex and often a cause of underdiagnosis, particularly among physicians who have not had specific training in the field of adolescent hypertension. The use of a simple and accurate screening test may improve hypertension diagnosis in adolescents. The aim of our study is to compare the different screening methods currently used in the literature to improve the diagnosis of childhood hypertension. We have conducted a cross-sectional population-based study of 1412 Caucasian adolescents among students of public junior high schools of Turin, Italy. In this population we have defined the hypertensive status with four different screening tests: BPHR, Somus equations, Ardissino, and Kaelber methods. Finally, we compared the diagnostic accuracy of the 4 screening tests with the gold standard. Our analysis identifies in BPHR the test which combines ease of use and diagnostic accuracy.

Renal Artery Stenosis in Patients with Resistant Hypertension: Stent It or Not?

After three large neutral trials in which renal artery revascularization failed to reduce cardiovascular and renal morbidity and mortality, renal artery stenting became a therapeutic taboo. However, this is probably unjustified as these trials have important limitations and excluded patients most likely to benefit from revascularization. In particular, patients with severe hypertension were often excluded and resistant hypertension was either poorly described or not conform to the current definition. Effective pharmacological combination treatment can control blood pressure in most patients with renovascular hypertension. However, it may also induce further renal hypoperfusion and thus accelerate progressive loss of renal tissue. Furthermore, case reports of patients with resistant hypertension showing substantial blood pressure improvement after successful revascularization are published over again. To identify those patients who would definitely respond to renal artery stenting, properly designed randomized clinical trials are definitely needed.

Blood pressure response to renal denervation is correlated with baseline blood pressure variability : A patient-level meta-Analysis

Background: Sympathetic tone is one of the main determinants of blood pressure (BP) variability and treatment-resistant hypertension. The aim of our study was to assess changes in BP variability after renal denervation (RDN). In addition, on an exploratory basis, we investigated whether baseline BP variability predicted the BP changes after RDN. Methods: We analyzed 24-h BP recordings obtained at baseline and 6 months after RDN in 167 treatment-resistant hypertension patients (40% women; age, 56.7 years; mean 24-h BP, 152/90 mmHg) recruited at 11 expert centers. BP variability was assessed by weighted SD [SD over time weighted for the time interval between consecutive readings (SDiw)], average real variability (ARV), coefficient of variation, and variability independent of the mean (VIM). Results: Mean office and 24-h BP fell by 15.4/6.6 and 5.5/3.7 mmHg, respectively (P < 0.001). In multivariable-adjusted analyses, systolic/diastolic SDiw and VIM for 24-h SBP/DBP decreased by 1.18/0.63 mmHg (P ⩽ 0.01) and 0.86/0.42 mmHg (P ⩽ 0.05), respectively, whereas no significant changes in ARV or coefficient of variation occurred. Furthermore, baseline SDiw (P = 0.0006), ARV (P = 0.01), and VIM (P = 0.04) predicted the decrease in 24-h DBP but not 24-h SBP after RDN. Conclusion: RDN was associated with a decrease in BP variability independent of the BP level, suggesting that responders may derive benefits from the reduction in BP variability as well. Furthermore, baseline DBP variability estimates significantly correlated with mean DBP decrease after RDN. If confirmed in younger patients with less arterial damage, in the absence of the confounding effect of drugs and drug adherence, baseline BP variability may prove a good predictor of BP response to RDN.

Alpha-1 antitrypsin deficiency: a novel cause of isolated systolic resistant hypertension?

W e report the case of a young patient with isolated systolic resistant hypertension and alpha-1-antitrypsin (AAT) deficiency and discuss the possible relationship between both entities. A 43-year-old man was referred for resistant hypertension and sympathetic renal denervation. Personal history revealed an unclear history of drug-related anaemia, eosinophilic esophagitis and a left superficial femoral artery stenosis with stenting at 37 years, but no history of smoking, hypercholesterolemia or diabetes. Furthermore, detection of a moderate increase of Alanine Amino Transferase (47 U/l; normal: 10–40U/l) in another hospital led to the diagnosis of MZ AAT deficiency at the heterozygous state, as demonstrated by a decreased AAT plasma level (75 mcg/dl, normal: 95–175) and the presence of a p.Glu366Lys mutation in exon 5 of the SERPINA1 gene [1]. Sitting office blood pressure (BP) was measured at 160/ 50mmHg. Daytime and night-time ambulatory BP were 142/58 and 115/43 mmHg, respectively. BMI was 31.4 kg/m. Clinical examination was otherwise unremarkable. Treatment included seven antihypertensive drugs (olmesartan 40mg, amlodipine 10mg, hydrochlorothiazide 25mg, indapamide 2.5 mg, prazosin 5mg, nebivolol 5mg and lercanidipine 10 mg), rosuvastatin 10mg, clopidogrel 75mg, acetylsalicylic acid 80mg and fluticasone. Glomerular filtration rate, estimated by the Modification of Diet in Renal Disease formula, was 79ml/min per 1.73 m. Urinary metanephrines and 24-h proteinuria were in the normal range. Echocardiography showed a mild concentric left ventricular hypertrophy (left ventricular mass index: 134 g/m) and a slight enlargement of the left atrium (left atrium volume index 36ml/m). Transient liver elastography (Fibroscan; Echosens, Paris, France) was suggestive of the absence of fibrosis (median elasticity of 6.1 kPa with the M probe), but compatible with severe steatosis (stade S3, median Controlled Attenuation Parameter 308 dB/m). Carotid ultrasonography showed bilateral calcifications. Abdominal computed tomography disclosed diffuse aortic calcifications, proximal occlusion of the coeliac trunk and a 50% stenosis of the superior mesenteric artery (Fig. 1). In view of the unexpected finding of resistant systolic hypertension with a very low DBP and diffuse vascular calcifications in a young patient with few cardiovascular risk factors, we measured carotid–femoral pulse wave velocity (Sphygmocor; Atcor Medical, West Ryde, Australia). The latter was estimated at 14.2 m/s, which is higher than 2 SDs of the mean in a multicentric reference population of the same age range (40–49 years) [2] (Fig. 2a). It remained much higher than the expected values when compared with grade 2–3 hypertensive patients from the same cohort (Fig. 2b). In contrast, evaluation of microvascular function using a Canon Cr-Dgi nonmydriatic retinal visualization system combined with a digital camera for the retinal vessels [3,4], and a Handheld Video Capillary Microscope for the sublingual capillaries [5,6] was within the expected range (data not shown). AAT deficiency is an autosomal codominant disorder that results from mutations in the SERPINA1 gene that codes for AAT [7]. This protein, secreted by hepatocytes, protects tissues from enzymes secreted by inflammatory cells, especially neutrophil elastase and proteinase 3 [8]. The cardinal manifestations of AAT deficiency are panacinar emphysema (due to an imbalance between elastase and antielastase enzymes) [9] and chronic liver disease (due to intracellular retention of abnormally folded proteins) [1,10]. AAT deficiency may also be associated with vascular wall alterations. Indeed, elastin is the major component of the elastic lamina that sustains the integrity of the blood vessels and can be degraded by elastase. As AAT breaks down elastase, AAT deficiency could lead to modified elastic properties of vessels [11]. Accordingly, aneurysms or dissections of various localizations have been reported in at least 10 patients with AAT deficiency [12–19] (Table 1). Cymerys et al. [20] reported lower levels of AAT in grade 1 Correspondence

Management of a Pregnant Woman With Fibromuscular Dysplasia.

A 39-year-old woman of Moroccan origin presented to the Cardiology Department with high blood pressure, with systolic blood pressure repeatedly measured at 170 mm Hg in the office. She was 10 days pregnant. Her treatment included nebivolol 5 mg and barnidipine 10 mg. Her medical history included migraines, an early miscarriage in 2001, and a second pregnancy with delivery at 27 weeks for preeclampsia in December 2014. At post-partum, she had received amlodipine, and then bisoprolol at another hospital. In September 2015, she had consulted at a third hospital for persistent hypertension with moderate to high blood pressure (systolic blood pressure: 170–190 mm Hg). Blood pressure was measured at 170/80 mm Hg in the office. Cardiac test results were normal. The physician concluded that the patient experienced chronic, rather than pregnancy-related hypertension, and replaced bisoprolol 5 mg with nebivolol 5 mg; barnidipine 10 mg was maintained, and the patient was asked to adhere to the therapeutic regimen. Despite mentioning that the hypertension was likely essential, he ordered an etiologic work-up. Renal function was normal (plasma creatinine: 58 μmol/L; estimated glomerular filtration rate: 100 mL/min per 1.73 m2). Urinary analysis revealed a mildly increased proteinuria of one-half gram per 24 hours. Urinary metanephrines were in the normal range, and the renal duplex study suggested a differential diagnosis of right renal artery stenosis and an arterial loop. Dr Micali: I would check the urinary sodium to confirm whether the patient is adhering to the hyposodic diet. This is one approach to check and determine whether the patient is consuming salt or not. Professor Persu: Yes, I think this is a good point, but this patient is not very adherent, and we had instances where we did not succeed in obtaining 24-hour urine samples. Additionally, this was performed in another hospital. I do not have …

High prevalence of cardiac electric abnormalities in patients with phaeochromocytomas.

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[OP.7D.07] INFLUENCE OF RENAL SYMPATHETIC DENERVATION ON BLOOD PRESSURE VARIABILITY: EXPERIENCE AT 11 EUROPEAN EXPERT CENTERS.

Objective: Sympathetic tone is one of the main determinants of blood pressure (BP) variability. The aim of our study was to assess the changes in BP variability after renal sympathetic denervation (RDN) in resistant hypertensive patients, and, conversely, to look for the predictive value of baseline BP variability on mean BP changes after RDN. Design and method: Twenty-four hour BP measurements were analyzed in 167 resistant hypertensive patients recruited at 11 expert centers within the European Network Coordinating research on Renal Denervation (ENCOReD) (mean age 56.7 years; 40 % women; mean baseline office BP: 172/98 mmHg; 24-h ambulatory BP: 152/90 mmHg), both at baseline and after RDN. Blood pressure variability was assessed by the weighted standard deviation (SDw), average real variability (ARV), coefficient of variation (CV) and variability independent of the mean (VIM) of 24-h ambulatory BP. Results: After an average follow up of 6.7 months, mean office and 24-h ambulatory BP fell by 15.4/6.6 mmHg and 5.5/3.7 mmHg respectively (P < 0.0001 for both). Whereas no significant changes in ARV or CV were observed, SDw and VIM for 24-h systolic BP decreased by −1.29 mmHg (95%CI: −2.17 to −0.42; P < 0.01) and −1.11 mmHg (95%CI: −1.92 to −0.30; P < 0.01), respectively. Decrease in these systolic BP variability estimates remained significant in multivariable-adjusted analyses and was paralleled by similar changes for 24-h diastolic BP. Finally, baseline SDw (P = 0.0006), ARV (P = 0.012) and VIM (P = 0.04) were significantly correlated with mean changes in diastolic - but not systolic - BP after RDN. Conclusions: Renal denervation was associated with a significant decrease in BP variability independent of the mean, which in the long term may decrease cardiovascular risk. Furthermore, baseline BP variability was predictive of diastolic BP changes after RDN. These results are consistent with the known influence of sympathetic nervous system on BP variability and peripheral vascular resistances. Our findings need confirmation in randomized controlled studies testing second-generation RDN catheters, preferably including younger patients with higher sympathetic tone and less advanced vascular damage.

[OP.LB01.04] HIGH PREVALENCE OF CARDIAC ELECTRIC ABNORMALITIES IN PATIENTS WITH PHEOCHROMOCYTOMAS AND SECRETING PARAGANGLIOMAS.

Objective: Pheochromocytomas and paragangliomas (PPGLs) are catecholamine-producing tumours of chromaffin cells of the adrenal medulla and extra-adrenal paraganglia. Besides hypertension, they can be at the origin of a wide range of cardiovascular manifestations, including cardiac electric abnormalities such as long QT interval, ventricular tachycardia and torsades de pointe. However, knowledge about PPGL-related arrhythmias is scarce and mostly derived from case reports. The aim of our study was to evaluate the prevalence, nature and reversibility of cardiac electric changes and arrhythmias in patients with PPGLs. Design and method: We retrospectively reviewed the medical records of patients diagnosed with PPGLs at the Cliniques Universitaires Saint-Luc (Brussels) from 1995 to 2015. All patients with secreting PPGLs in whom an electrocardiogram (ECG) was available at the time of diagnosis were eligible. Results: Forty-five patients with secreting PPGLs were identified. The mean age at diagnosis was 48 years (12-72), 40% of patients (n = 18) were males and location of the tumour was adrenal in 87% of cases (n = 39). An ECG was available in 31 patients at the time of diagnosis. Of these, 77% (n = 24) presented at least one electric abnormality. While a positive Sokolow index was found in only 3 patients, non-specific ST-abnormalities were documented in 14 patients (45%), a T-wave inversion in at least two precordial leads in 9 (29%) and a predominant U- wave in 7 patients (23%). Finally, two patients had severe bradycardia (<50 bpm) and extremely long QTc (>600 ms), two patients presented with polymorphic ventricular tachycardia related to a long QT interval at diagnosis that never recurred after surgery, and one patient was diagnosed with paroxystic atrial fibrillation, which resolved after tumour removal. Conclusions: We report a high prevalence (77%) of cardiac electric abnormalities in a retrospective monocentric series of PPGLs. While our findings need confirmation in larger, prospective cohorts, they strongly suggest that cardiac electric abnormalities are an underrecognized, frequent complication of catecholamine excess in patients with PPGLs, and should be an integral part of the work-up and management of these patients.