Silvia Totaro

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 is increased in young normotensive subjects with high central blood pressure

Information on high central blood pressure (CBP; HCP) in normotensive subjects (NT) and its relation to target organ damage (TOD) is not well established in young subjects. This study aimed to elucidate determinants of HCP and its relation with TOD. Anthropometrics, lab, brachial, and CBP were obtained on 430 normotensive subjects (NT; 16-24 years, 34% male, 44% Caucasian, 27% type 2 diabetes). HCP was defined as elevated CBP, with normal brachial BP. Subjects with HCP (prevalence, 16%) were more frequently female and African American, and had a higher prevalence of obesity and diabetes, a more adverse metabolic profile, higher levels of inflammation, brachial BP, central pulse pressure, and heart rate compared with NT. HCP also had evidence for TOD with a significant higher carotid intima media thickness, left ventricular mass, augmentation index, pulse wave velocity, and lower brachial distensibility than NT. HCP is related to early cardiac and vascular dysfunction and remain an independent predictor of TOD even after adjusting for cardiovascular risk factors.

Cardiac Organ Damage and Arterial Stiffness in Autonomic Failure: Comparison With Essential Hypertension

Autonomic failure (AF) is characterized by orthostatic hypotension, supine hypertension, and increased blood pressure (BP) variability. AF patients develop cardiac organ damage, similarly to essential hypertension (EH), and have higher arterial stiffness than healthy controls. Determinants of cardiovascular organ damage in AF are not well known: both BP variability and mean BP values may be involved. The aim of the study was to evaluate cardiac organ damage, arterial stiffness, and central hemodynamics in AF, compared with EH subjects with similar 24-hour BP and a group of healthy controls, and to evaluate determinants of target organ damage in patients with AF. Twenty-seven patients with primary AF were studied (mean age, 65.7±11.2 years) using transthoracic echocardiography, carotid-femoral pulse wave velocity, central hemodynamics, and 24-hour ambulatory BP monitoring. They were compared with 27 EH subjects matched for age, sex, and 24-hour mean BP and with 27 healthy controls. AF and EH had similar left ventricular mass (101.6±33.3 versus 97.7±28.1 g/m2, P=0.59) and carotid–femoral pulse wave velocity (9.3±1.8 versus 9.2±3.0 m/s, P=0.93); both parameters were significantly lower in healthy controls (P<0.01). Compared with EH, AF patients had higher augmentation index (31.0±7.6% versus 26.1±9.2%, P=0.04) and central BP values. Nighttime systolic BP and 24-hour systolic BP predicted organ damage, independent of BP variability. AF patients develop hypertensive heart disease and increased arterial stiffness, similar to EH with comparable mean BP values. Twenty-four–hour and nighttime systolic BP were determinants of cardiovascular damage, independent of BP variability.Autonomic failure (AF) is characterized by orthostatic hypotension, supine hypertension, and increased blood pressure (BP) variability. AF patients develop cardiac organ damage, similarly to essential hypertension (EH), and have higher arterial stiffness than healthy controls. Determinants of cardiovascular organ damage in AF are not well known: both BP variability and mean BP values may be involved. The aim of the study was to evaluate cardiac organ damage, arterial stiffness, and central hemodynamics in AF, compared with EH subjects with similar 24-hour BP and a group of healthy controls, and to evaluate determinants of target organ damage in patients with AF. Twenty-seven patients with primary AF were studied (mean age, 65.7±11.2 years) using transthoracic echocardiography, carotid-femoral pulse wave velocity, central hemodynamics, and 24-hour ambulatory BP monitoring. They were compared with 27 EH subjects matched for age, sex, and 24-hour mean BP and with 27 healthy controls. AF and EH had similar left ventricular mass (101.6±33.3 versus 97.7±28.1 g/m2, P =0.59) and carotid–femoral pulse wave velocity (9.3±1.8 versus 9.2±3.0 m/s, P =0.93); both parameters were significantly lower in healthy controls ( P <0.01). Compared with EH, AF patients had higher augmentation index (31.0±7.6% versus 26.1±9.2%, P =0.04) and central BP values. Nighttime systolic BP and 24-hour systolic BP predicted organ damage, independent of BP variability. AF patients develop hypertensive heart disease and increased arterial stiffness, similar to EH with comparable mean BP values. Twenty-four–hour and nighttime systolic BP were determinants of cardiovascular damage, independent of BP variability. # Novelty and Significance {#article-title-49}

Orthostatic hypotension in a cohort of hypertensive patients referring to a hypertension clinic

The prevalence of orthostatic hypotension (OH) in hypertensive patients ranges from 3 to 26%. Drugs are a common cause of non-neurogenic OH. In the present study, we retrospectively evaluated the medical records of 9242 patients with essential hypertension referred to our Hypertension Unit. We analysed data on supine and standing blood pressure values, age, sex, severity of hypertension and therapeutic associations of drugs, commonly used in the treatment of hypertension. OH was present in 957 patients (10.4%). Drug combinations including α-blockers, centrally acting drugs, non-dihydropyridine calcium-channel blockers and diuretics were associated with OH. These pharmacological associations must be administered with caution, especially in hypertensive patients at high risk of OH (elderly or with severe and uncontrolled hypertension). Angiotensin-receptor blocker (ARB) seems to be not related with OH and may have a potential protective effect on the development of OH.

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-

Efficacy of antihypertensive treatment based on plasma renin activity: An open label observational study

Abstract Background. We investigated the extent of blood pressure (BP) reduction and control (<140/90 mmHg) in patients treated with appropriate or inappropriate drugs according to their plasma renin activity (PRA) level (natriuretic drugs and renin–angiotensin system blockers for low-renin and high-renin hypertension, respectively). Patients and methods. One hundred and seventy Caucasian untreated hypertensive patients (61 females), aged 18–70 years, participated to the study. Patients with secondary hypertension, diabetes or established cardiovascular or renal disease were excluded. The physician prescribed an antihypertensive monotherapy chosen among all drug classes, unaware of patients PRA levels. We compared effect of an inappropriate or appropriate drug, evaluating BP values after a month of treatment. Results. Rate of BP control was not significantly higher in patients treated with an appropriate drug than the others (38% vs 29%, p=0.24). However, in a regression analysis, final diastolic BP (DBP) was lower in subjects treated with an appropriate drug (β=−2.84, p=0.03). Conclusions. The present study does not clearly support the use of PRA in a general population of hypertensive patients to optimize BP control. However, the greater efficacy of a drug appropriate to PRA in reducing DBP may be clinically helpful in young hypertensive patients. Future studies are warranted to evaluate if PRA determination enhances the therapeutic success in patients with predominantly high values of DBP.

Cardiac Organ Damage and Arterial Stiffness in Autonomic Failure

Autonomic failure (AF) is characterized by orthostatic hypotension, supine hypertension, and increased blood pressure (BP) variability. AF patients develop cardiac organ damage, similarly to essential hypertension (EH), and have higher arterial stiffness than healthy controls. Determinants of cardiovascular organ damage in AF are not well known: both BP variability and mean BP values may be involved. The aim of the study was to evaluate cardiac organ damage, arterial stiffness, and central hemodynamics in AF, compared with EH subjects with similar 24-hour BP and a group of healthy controls, and to evaluate determinants of target organ damage in patients with AF. Twenty-seven patients with primary AF were studied (mean age, 65.7±11.2 years) using transthoracic echocardiography, carotid-femoral pulse wave velocity, central hemodynamics, and 24-hour ambulatory BP monitoring. They were compared with 27 EH subjects matched for age, sex, and 24-hour mean BP and with 27 healthy controls. AF and EH had similar left ventricular mass (101.6±33.3 versus 97.7±28.1 g/m2, P=0.59) and carotid–femoral pulse wave velocity (9.3±1.8 versus 9.2±3.0 m/s, P=0.93); both parameters were significantly lower in healthy controls (P<0.01). Compared with EH, AF patients had higher augmentation index (31.0±7.6% versus 26.1±9.2%, P=0.04) and central BP values. Nighttime systolic BP and 24-hour systolic BP predicted organ damage, independent of BP variability. AF patients develop hypertensive heart disease and increased arterial stiffness, similar to EH with comparable mean BP values. Twenty-four–hour and nighttime systolic BP were determinants of cardiovascular damage, independent of BP variability.Autonomic failure (AF) is characterized by orthostatic hypotension, supine hypertension, and increased blood pressure (BP) variability. AF patients develop cardiac organ damage, similarly to essential hypertension (EH), and have higher arterial stiffness than healthy controls. Determinants of cardiovascular organ damage in AF are not well known: both BP variability and mean BP values may be involved. The aim of the study was to evaluate cardiac organ damage, arterial stiffness, and central hemodynamics in AF, compared with EH subjects with similar 24-hour BP and a group of healthy controls, and to evaluate determinants of target organ damage in patients with AF. Twenty-seven patients with primary AF were studied (mean age, 65.7±11.2 years) using transthoracic echocardiography, carotid-femoral pulse wave velocity, central hemodynamics, and 24-hour ambulatory BP monitoring. They were compared with 27 EH subjects matched for age, sex, and 24-hour mean BP and with 27 healthy controls. AF and EH had similar left ventricular mass (101.6±33.3 versus 97.7±28.1 g/m2, P =0.59) and carotid–femoral pulse wave velocity (9.3±1.8 versus 9.2±3.0 m/s, P =0.93); both parameters were significantly lower in healthy controls ( P <0.01). Compared with EH, AF patients had higher augmentation index (31.0±7.6% versus 26.1±9.2%, P =0.04) and central BP values. Nighttime systolic BP and 24-hour systolic BP predicted organ damage, independent of BP variability. AF patients develop hypertensive heart disease and increased arterial stiffness, similar to EH with comparable mean BP values. Twenty-four–hour and nighttime systolic BP were determinants of cardiovascular damage, independent of BP variability. # Novelty and Significance {#article-title-49}

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.

Cardiac Organ Damage and Arterial Stiffness in Autonomic FailureNovelty and Significance

Autonomic failure (AF) is characterized by orthostatic hypotension, supine hypertension, and increased blood pressure (BP) variability. AF patients develop cardiac organ damage, similarly to essential hypertension (EH), and have higher arterial stiffness than healthy controls. Determinants of cardiovascular organ damage in AF are not well known: both BP variability and mean BP values may be involved. The aim of the study was to evaluate cardiac organ damage, arterial stiffness, and central hemodynamics in AF, compared with EH subjects with similar 24-hour BP and a group of healthy controls, and to evaluate determinants of target organ damage in patients with AF. Twenty-seven patients with primary AF were studied (mean age, 65.7±11.2 years) using transthoracic echocardiography, carotid-femoral pulse wave velocity, central hemodynamics, and 24-hour ambulatory BP monitoring. They were compared with 27 EH subjects matched for age, sex, and 24-hour mean BP and with 27 healthy controls. AF and EH had similar left ventricular mass (101.6±33.3 versus 97.7±28.1 g/m2, P=0.59) and carotid–femoral pulse wave velocity (9.3±1.8 versus 9.2±3.0 m/s, P=0.93); both parameters were significantly lower in healthy controls (P<0.01). Compared with EH, AF patients had higher augmentation index (31.0±7.6% versus 26.1±9.2%, P=0.04) and central BP values. Nighttime systolic BP and 24-hour systolic BP predicted organ damage, independent of BP variability. AF patients develop hypertensive heart disease and increased arterial stiffness, similar to EH with comparable mean BP values. Twenty-four–hour and nighttime systolic BP were determinants of cardiovascular damage, independent of BP variability.Autonomic failure (AF) is characterized by orthostatic hypotension, supine hypertension, and increased blood pressure (BP) variability. AF patients develop cardiac organ damage, similarly to essential hypertension (EH), and have higher arterial stiffness than healthy controls. Determinants of cardiovascular organ damage in AF are not well known: both BP variability and mean BP values may be involved. The aim of the study was to evaluate cardiac organ damage, arterial stiffness, and central hemodynamics in AF, compared with EH subjects with similar 24-hour BP and a group of healthy controls, and to evaluate determinants of target organ damage in patients with AF. Twenty-seven patients with primary AF were studied (mean age, 65.7±11.2 years) using transthoracic echocardiography, carotid-femoral pulse wave velocity, central hemodynamics, and 24-hour ambulatory BP monitoring. They were compared with 27 EH subjects matched for age, sex, and 24-hour mean BP and with 27 healthy controls. AF and EH had similar left ventricular mass (101.6±33.3 versus 97.7±28.1 g/m2, P =0.59) and carotid–femoral pulse wave velocity (9.3±1.8 versus 9.2±3.0 m/s, P =0.93); both parameters were significantly lower in healthy controls ( P <0.01). Compared with EH, AF patients had higher augmentation index (31.0±7.6% versus 26.1±9.2%, P =0.04) and central BP values. Nighttime systolic BP and 24-hour systolic BP predicted organ damage, independent of BP variability. AF patients develop hypertensive heart disease and increased arterial stiffness, similar to EH with comparable mean BP values. Twenty-four–hour and nighttime systolic BP were determinants of cardiovascular damage, independent of BP variability. # Novelty and Significance {#article-title-49}