Michele Covella

Echocardiographic aortic root dilatation in hypertensive patients: a systematic review and meta-analysis.

Objective: The risk of thoracic aortic dissection is strictly related to the diameter of the ascending aorta. Arterial hypertension represents a major risk factor for the development of aortic dissection and is thought to be directly involved in the pathogenesis of aortic aneurysms. Recent studies have suggested a high prevalence of aortic root enlargement in the hypertensive population, but evidence of a direct link between blood pressure values and size of the aortic root has been inconclusive so far. The aim of the current study was to evaluate prevalence of aortic root dilatation (ARD) in the hypertensive population and to assess the correlates of this condition. Methods: Medical literature was reviewed to identify articles assessing prevalence of echocardiographic ARD in hypertensive patients. Results: A total of eight studies including 10 791 hypertensive patients were considered. Prevalence of ARD in the pooled population was 9.1% with a marked difference between men and women (12.7 vs. 4.5%; odds ratio 3.15; 95% confidence interval 2.68–3.71). Hypertensive patients with ARD and those with normal aortic root size had similar office blood pressure values, but the former were older and had a significantly higher left-ventricular mass (0.52 SDs, 95% confidence interval 0.41–0.63). Conclusion: ARD is a common phenotype in hypertensive patients, with men showing a markedly higher susceptibility, but office blood pressure values do not appear to be directly associated with aortic root diameter.

Arterial stiffness: from physiology to clinical implications.

Current European guidelines for the management of arterial hypertension introduce the assessment of arterial stiffness by pulse wave velocity (PWV) as an index of hypertension-related cardiovascular target organ damage. An increase in arterial stiffness is related to haemodynamic modifications at the level of the aorta, leading to a rise in cardiac afterload, a reduction in coronary perfusion and an overstretch of the aortic walls. An increasing number of studies have demonstrated the accuracy of PWV as an independent predictor of cardiovascular events and cardiovascular mortality in patients with different co-morbidities and cardiovascular risk. Many strategies have demonstrated their efficacy in preventing arterial stiffening; therapy of arterial hypertension is the mainstay in the management of patients with increased PWV and altered pulse wave reflection. Literature has clearly shown the specific efficacy of drugs interfering with the renin-angiotensin-aldosterone system and calcium-channel blockers in the control of central haemodynamics, particularly when compared with β-blockers (β-adrenoceptor antagonists). The same action has not yet been demonstrated on PWV. Further studies are needed to assess the real relative efficacy of different drug classes on the management of arterial stiffness and the clinical and prognostic relevance of these therapies.

Adherence to antihypertensive therapy and therapeutic dosage of antihypertensive drugs

Adherence to antihypertensive therapy is critical to achieving adequate blood pressure control. About half of hypertensive patients do not take their drugs as directed and the physicians often underestimate this issue. Non-adherence has important public health economic implications (numbers of visits, diagnostic procedures, prescribed drugs) and, moreover, it results in increased morbidity and mortality rates. Poor adherence can have several patients and therapy related causes. Currently, multiple different direct and indirect methods to measure therapeutic adherence are available, but, in clinical practice, there is no cost-effective and simple one. Therapeutic drug monitoring (TDM), characterized by drug (or metabolites) concentration measurement in body fluids (blood or urine), is a cost-effective direct method to assess therapeutic adherence. Despite some limitations, TDM may decrease health costs, by reducing the number of visits and by identifying those patients who would undergo unnecessary invasive procedures. Moreover, TDM can be a new alternative method to identify patients with true resistant hypertension, improving the achievement of blood pressure control In this minor revision, we would assess poor therapeutic adherence in hypertensive population, analyzing the different direct and direct available methods, with emphasis on TDM.

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.

Appropriateness of Referral to a European Society of Hypertension Center of Excellence

In the European health care system, the general practitioner is a patient’s primary medical contact and point of referral to specialist care. Although current guidelines strongly recommend the pharmacologic treatment of hypertension in patients, adequate blood pressure (BP) control is achieved in only <30% of patients. To improve the care of the hypertensive patient, the ‘‘Hypertension Specialist’’ was introduced by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC 7). Referral to a specialist is recommended for patients with resistant hypertension, severely complicated hypertension, and if a secondary form of hypertension is suspected. The aim of our study was to determine the appropriateness, in terms of efficiency and effectiveness, of referrals to specialized centers by general practitioners. We reviewed the computer-stored data of 9874 Caucasian hypertensive patients (aged 3–101 years, 4794 men, 5080 women) consecutively referred by general practitioners to our hypertension clinic from 1989 to 2008. The first visit and the 5 follow-up visits were considered for each patient to assess and compare the patient’s management by the general practitioner and the specialist. BP values were classified and resistant hypertension was defined according to 2007 European Society of Hypertension (ESH) ⁄ European Society of Cardiology (ESC) guidelines. Both pediatric hypertension and patients with comorbidities were included in the study. We subdivided the analysis into 3 different periods (1989–1994, 1995–2001, and 2002–2008), chosen on the basis of the publication years of the main hypertension guidelines. The time spent by doctors and patients for inappropriate referral was calculated. Means and standard deviations for descriptive variables and proportions for categoric variables were calculated. One-way analysis of variance (continuous variables) and chi-square test (categorical variables) were used to analyze data. The mean age was significantly increased between the first and the last periods but the body mass index was unchanged. With regards to lifestyle, a significant decrease in smoking was observed with time although a lack of physical activity persisted. BP values (161 ⁄ 99– 150 ⁄ 90 mm Hg, P<.0001) and the average number of antihypertensive drugs taken at the baseline visit (1.32 in the first period and 1.18 in the last, P<.0001) decreased with time. At the baseline visit, 16% of referred patients had controlled BP at the baseline visit and this significantly increased over the 3 periods (5.8% and 23.8% in the first and last periods, respectively) (Table I). Regarding pharmacologic treatment, in the last period only 57.6% of patients were already treated with one drug when referred to our unit, compared with 74.7% in the first period. Overall, 51.63% of patients met at least one of the criteria for referral, with a higher percentage during the mid-period but with a marked reduction over the last period (41.54%). Of patients who were incorrectly referred, 40% were untreated, 31% were taking monotherapy, and only 29% took >1 antihypertensive drug. The most common reasons for referral were complicated hypertension and comorbidities, followed by resistant hypertension. The referral process has impli-

Mechanism of Progressive Heart Failure and Significance of Pulmonary Hypertension in Obstructive Hypertrophic CardiomyopathyCLINICAL PERSPECTIVE

Background— There are limited data on the prevalence, pathophysiology, and management implications of pulmonary hypertension in patients with obstructive hypertrophic cardiomyopathy and advanced heart failure. Methods and Results— To assess the clinical significance of measured cardiopulmonary hemodynamics in hypertrophic cardiomyopathy patients with heart failure, we retrospectively assessed right heart catheterization data in 162 consecutive patients with outflow tract gradients (median [interquartile range], 90 mm Hg [70–110 mm Hg]), 59±11 years old, and 49% men, predominately New York Heart Association class III/IV status. Pulmonary hypertension (mean pulmonary artery pressure, ≥25 mm Hg) was present in 82 patients (51%), including 29 (18%) regarded as moderate-severe (mean pulmonary artery pressure, ≥35 mm Hg) and 28 (34%) also had increased pulmonary vascular resistance >3.0 WU. The pulmonary artery wedge pressure was ⩽15 mm Hg in 54%, indicating that left atrial hypertension was absent in a majority of patients. Notably, 9 patients (11%) met hemodynamic criteria for precapillary pulmonary hypertension (mean pulmonary artery pressure, ≥25 mm Hg; pulmonary vascular resistance, >3.0 WU; pulmonary artery wedge pressure, ⩽15 mm Hg). Over a median follow-up of 327 days (90–743 days) after surgical myectomy (or alcohol septal ablation), 92% and 95% of patients with or without preoperative pulmonary hypertension, respectively, were asymptomatic or mildly symptomatic. One postoperative death occurred in a 59-year-old woman with acute respiratory failure and mean pulmonary artery pressure of 65 mm Hg. Conclusions— Pulmonary hypertension was common in obstructive hypertrophic cardiomyopathy patients with advanced heart failure. Although possibly a contributor to preoperative heart failure, pulmonary hypertension did not significantly influence clinical and surgical outcome. Notably, a novel patient subgroup was identified with resting invasive hemodynamics consistent with pulmonary vascular disease.

Renal Sympathetic Denervation in a Previously Stented Renal Artery

To the Editor: Despite the development of numerous antihypertensive medications and the use of multidrug therapy, about 5% to 20% of all hypertensive patients are resistant to medical therapy. Sympathetic overdrive is responsible for the development and maintenance of resistant hypertension (RH). In the kidney, efferent sympathetic activity promotes Na re-absorption and renin release, while afferent nerves stimulate central sympathetic outflow and produce vasoconstriction. The physiological basis of renal sympathetic denervation (RDN) is the suppression of the hyperadrenergic state by the interruption of the renal sympathetic nerve fibers. Two trials—Symplicity HTN-1 and Symplicity HTN-2—have demonstrated the efficacy and the safety of RDN in patients with RH. In these trials, patients with renal artery stenosis or stent were excluded; therefore, there are few data about RDN in these patients. Moreover, a meta-analysis did not find an improvement in blood pressure (BP) in patients with renal artery stenosis treated with renal artery stenting. Therefore, a double mechanism maintains hypertension: renovascular and sympathetic tone. In the following, we report the case of a patient with RH treated by RDN after renal artery stenting. A 54-year-old man was admitted to our unit for resistant hypertension (office BP 220/120 mm Hg) despite treatment with 5 antihypertensive agents. During secondary hypertension evaluation, angiography demonstrated a high-grade right renal artery stenosis, which was treated with angioplasty and stenting. Office BP values after angioplasty were 140/90 mm Hg during the first month, but BP returned close to baseline after 3 months. Remarkably, there was no restenosis on results of Doppler imaging. The patient subsequently underwent radiofrequency ablation of both renal arteries using Medtronic’s Symplicity Catheter System (Medtronic, Inc, Minneapolis, MN). Because of the presence of a right renal artery stent, ablation on this side was performed only at the distal segment of the renal artery, distal to the stent. The distance between the stent and the first point of renal ablation was 25 mm. The procedure was completed without complications. After 1 month, office BP decreased from 175/120 mm Hg to 140/90 mm Hg and mean 24-hour ambulatory BP from 164/98 mm Hg to 130/81 mm Hg. Medical therapy remained unchanged. No renal artery stenoses were shown on Doppler ultrasound examination at 1 month (Figure 1 and Figure 2). Johansson’s and Miyajima’s clinical studies underlined the relevance not only of the renin-angiotensin system but also of adrenergic overactivity in renovascular hypertension. Johansson and Elam compared arterial plasma renin activity (PRA), angiotensin II (ATII), norepinephrine (NE) spillover, and musclesympathetic-nerve activity (MSNA) between hypertensive patients with renal artery stenosis and healthy patients. Not only were PRA and ATII higher in the first group but NE spillover and MSNA were also increased. Likewise, Miyajima and colleagues observed that in some patients who underwent renal artery balloon angioplasty, sympathetic tone remained higher than in normotensive patients. Therefore, in renovascular hypertension, elevated BP is caused by renin-angiotensin system and sympathetic overactivity. This could explain why in some patients, BP is uncontrolled after renal artery balloon angioplasty. To our knowledge, this is the second case of RDN in a formerly stented renal artery. As in Ziegler’s case, also in our patient, BP values decreased significantly after RDN, whereas this happened transiently after renal artery angioplasty and doi: 10.1111/jch.12251 FIGURE 1. Catheter for renal denervation inside the renal artery beyond the stent.

[PP.01.15] ACCURACY OF HOME BLOOD PRESSURE MONITORING IN ARTERIAL HYPERTENSION DIAGNOSIS

Objective: The arterial hypertension diagnosis is based on office blood pressure measurement, and current guidelines suggest the use of out-of-office blood pressure measurement techniques in specific cases, as suspected white-coat or masked hypertension. Home Blood Pressure Monitoring (HBPM) is recommended as a complementary method to Ambulatory Blood Pressure Monitoring (ABPM). However usually HBPM is only used for implementing blood pressure control in treated patients. We tried to identify the accuracy between HBPM and ABPM in untreated patients. (We tried to identify HBPM accuracy between to ABPM in untreated patients.) Design and method: We enrolled 83 consecutive untreated patients who performed ABPM in our Hypertension Unit and completed a short HBPM schedule (two measurements, twice daily, for four days) between November 2011 and June 2015. Patients were instructed about HBPM in accord to current hypertension guidelines and they used validated automated arm devices. We compared the accuracy between the two techniques and the HBPM ability to identify arterial hypertension in comparison with ABPM. Results: Pearsons correlation coefficient between HBPM 4-day average and day-time ABPM values was 0.59 for systolic blood pressure (SBP) and 0.77 for diastolic blood pressure (DBP). Bland-Altman analysis revealed a mean difference of -5.68 mmHg, SD 8.82 mmHg for SBP, and -4.64, SD 6.33 mmHg for DBP. ROC curves described AUC for SBP of 0.75 and for DBP of 0.877. The ABPM identify as hypertensive 54 subjects on 83 (65.1%), the HBPM 29 subjects (34.9%), p-value 0.01609. Conclusions: HBPM has a moderate correlation and a moderate accuracy in the identification of arterial hypertension compared with ABPM. Although HBPM is recommended as alternative method respect to ABPM, in untreated patients it is not reliable for arterial hypertension diagnosis and probably it is not able to identify specific hypertension patterns, in contrast with current guidelines.

[PP.23.13] ANALYSIS OF ELIGIBILITY CRITERIA FOR RENAL SYMPATHETIC DENERVATION

Objective: Resistant hypertension (RH) is a rare condition that affects approximately 10% of hypertensive population, its defined as blood pressure (BP) > 140/90 mmHg despite three full doses antihypertensive drugs including a diuretic. True RH is confirmed when pseudo-hypertension, secondary hypertension or poor adherence are excluded. Percutaneous radio-frequency catheter-based renal sympathetic denervation (DRN) is one of the most used invasive treatments for these patients. The goal of the study is to assess the percentage of eligibility to DRN and analyze the exclusion criteria in a group of resistant hypertensive patients. Design and method: We retrospectively analyzed data of 35 patients (63% female) referred to our Hypertension Unit between June 2011 and June 2014. We considered eligible for DRN subjects with office systolic blood pressure > = 160 mmHg and patients with severe hypertension treated with fewer drugs for poly-intolerances/allergies. Secondary hypertension form and white coat hypertension were excluded. Patients with confirmed true resistant hypertension underwent CT angiography in order to check the renal anatomic criteria of eligibility to the DRN. Results: 35 caucasian patients (63% female) referred to our Hypertension Unit between June 2011 and June 2014 for DRN assessment. At the first evaluation median systolic and diastolic office BP were 179 ± 25 mmHg and 105 ± 20 mmHg; six month later, after appropriate changes in lifestyle and drug therapy, systolic/diastolic office BP was reduced of 18/8 mmHg (p < 0.05). In the most of cases, patients had to BP control with introduction of antialdosteronic (35%). In our sample, 27 patients were considered unsuitable for the DRN for many reason: blood pressure control with optimization of drug therapy (52%), evidence of white coat effect (22%), secondary hypertension (22%), lack of true resistant hypertension (18%), absence of consent to the procedure (29%). Conclusions: A carreful patients selection in Specialistic Center is necessary before DRN; indeed frequently a good BP control is obtained with appropriate drug therapy changes and exclusion of secondary forms.

Evaluation of a short home blood pressure measurement in an outpatient population of hypertensives

ABSTRACT Current guidelines suggest the use of home blood pressure monitoring (HBPM) as a method complementary to ambulatory blood pressure monitoring (ABPM) for the identification of arterial hypertension. A cross-sectional study was conducted to evaluate the accuracy of a short HBPM schedule compared with ABPM, and to evaluate to what extent HBPM can replace ABPM. A total of 310 patients who performed ABPM in our hypertension clinic were enrolled between November 2011 and June 2015. They performed a 4-day HBPM schedule, with two readings in the morning and two readings at night. Results showed a moderate correlation between HBPM and ABPM (r = 0.59 for systolic blood pressure (SBP) and r = 0.72 for diastolic blood pressure (DBP)) and moderate diagnostic agreement (area under curve: 0.791 for SBP and 0.857 for DBP). No significant difference was found between first-day average and those of days 2–4. Diagnostic agreement between the two techniques was moderate, supporting the notion that HBPM cannot replace ABPM in the general population. However, we identified two HBPM thresholds, 123/75 and 144/87 mm Hg, through which subjects who may not require further ABPM can be identified.