The role of sacubitril/valsartan in the treatment of chronic heart failure with reduced ejection fraction in hypertensive patients with comorbidities: From clinical trials to real-world settings.

BACKGROUND: Sacubitril/valsartan, the first agent to be approved in a new class of drugs called angiotensin receptor neprilysin inhibitors (ARNIs), has been shown to reduce cardiovascular mortality and morbidity compared to enalapril in outpatient subjects with chronic heart failure (HF) and reduced left ventricular ejection fraction (HFrEF). However, there is little real-world evidence about the efficacy of ARNIs in elderly hypertensive patients with HFrEF and comorbidities. METHODS: In this prospective open-label study, 108 subjects, 54 of them (mean age 78.6 ±â€¯8.2 years, 75.0 % male), with HFrEF (29.8 ±â€¯4.3 %) and New York Heart Association (NYHA) class II-III symptoms were assigned to receive ARNIs twice daily, according to the recommended dosage of 24/26, 49/51, 97/103 mg. Patients were gender- and age-matched with a control arm of patients with HFrEF receiving the optimal standard therapy for HF. The clinic blood pressure (BP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), estimated glomerular filtration rate (eGFR), blood glucose and glycated hemoglobin (HbA1c), uric acid (UA), left ventricular ejection fraction (LVEF) and NYHA class were evaluated at a mean follow-up of 12 months. During the follow-up, the clinical outcomes, including mortality and re-hospitalization for HF, were collected. RESULTS: NYHA class significantly improved in the ARNI arm compared to the control (24.9 vs. 6.4 %, shifting from class III to II, and 55.4 vs. 25.2 %, from class II to I, p < 0.05 for all). A significant improvement in LVEF and eGFR levels was found in the ARNI arm compared to controls (42.4 vs. 34.2 %, 73.8 vs. 61.2 mL/min, respectively; p < 0.001 for all). NT-proBNP, clinic systolic and diastolic BP, blood glucose, HbA1c and UA values were reduced in both treatment arms, but they were lower in the ARNI arm compared controls (3107 vs. 4552 pg/mL, 112.2 vs. 120.4 and 68.8 vs. 75.6 mmHg, 108.4 vs. 112.6 mg/dL, 5.4 vs. 5.9 % and 5.9 vs. 6.4 mg/dL, respectively, p < 0.05). Mortality and re-hospitalization for HF was lower in the ARNI arm than controls (20.1 vs. 33.6 % and 27.7 vs. 46.3 % respectively; p < 0.05 for all). Gender differences were not found in either arm. No patients refused to continue the study, and no side effects to the ARNI treatment were observed. CONCLUSIONS: In elderly patients with HFrEF and comorbidities, ARNI treatment seems effective and safe. The improvement in LVEF and cardiac remodeling, BP, eGFR, serum glucose, UA and HbA1c could be the mechanisms by which ARNIs play their beneficial role on clinical outcomes. However, these results need to be confirmed in studies involving a greater number of subjects, and with a longer follow-up.

Long-term effect of the perindopril/indapamide/amlodipine single-pill combination on left ventricular hypertrophy in outpatient hypertensive subjects.

BACKGROUND: Most antihypertensive drugs used in monotherapy or in combination therapy reduce the left ventricular mass index (LVMI). However, little is known about the effects on LVMI of a triple fixed-dose combination (TFC) therapy, containing in a single pill an angiotensin-converting enzyme inhibitor (ACEI), a diuretic and a calcium channel blocker (CCB). METHODS: In this prospective open-label study, 92 patients with essential hypertension were randomized to treatment with a TFC of perindopril/indapamide/amlodipine at different doses or a triple free combination therapy (FCT) including ACEI/diuretic/CCB. Office blood pressure (BP) measurement, 24 h-ambulatory BP monitoring and echocardiography were performed at baseline and during a 14-month follow-up. The BP variability (BPV) over 24 h was calculated as ± standard deviation of the daytime systolic BP. Differences between office and monitored BP and LVMI were evaluated by ANOVA for repeated measures. RESULTS: A significant BP-lowering effect was observed for both treatments. At follow-up, BPV was reduced in both the treatment groups vs. the baseline (14.0±1.5 vs. 17.0±1.8 and 16.2±2.1 vs. 17.6±2.3, respectively), but it was lower in the TFC vs. the FCT group (14.0±1.5 vs. 16.1±2.2, P < 0.05). LVMI was lower in both the treatment groups, but the change was greater for TFC vs. FCT (-8.3±4.9% vs. -2.0 ±2.1%, P < 0.0001). Left ventricular hypertrophy (LVH) regression was greater in the TFC vs. the FCT group (43.5% vs. 30.4%, P < 0.05). CONCLUSIONS: Independently of BP values achieved, the antihypertensive TFC therapy was more effective than FCT in LVMI reduction and LVH regression, possibly related to drugs' intrinsic properties and to BPV modulation.

The Effects of a New Generation of Nutraceutical Compounds on Lipid Profile and Glycaemia in Subjects with Pre-hypertension.

INTRODUCION: Treatment strategies for patients with pre-hypertension and low-moderate cardiovascular (CV) risk may include nutraceutical compounds (NCs). AIM: To investigate the efficacy and safety of a new-generation of NC in lowering BP values and improving metabolic profile, in a group of hyper-cholesterolemic subjects with pre-hypertension. METHODS: 131 subjects with pre-hypertension (systolic BP 130-139 mmHg and/or diastolic BP 85-89 mmHg) without organ damage and history of CV diseases were enrolled. 66 subjects were treated with a once-daily oral formulation of a NC (red yeast rice, Berberine, Coenzyme Q10, folic acid and chrome) added to diet for 3 months, while 65 patients followed a diet only. Differences in serum total cholesterol (TC), low- and high-density lipoprotein cholesterol (LDLC and HDLC), triglycerides (TG), glycemia, creatine phosphokinase (CPK), aspartate aminotransferase (AST) alanine aminotransferase (ALT) and body mass index (BMI) were evaluated. RESULTS: At the end of treatment, significant reductions of TC, LDLC, TG glucose levels were observed in both treatment groups, while HDLC values increased in the active treatment group only. A greater reduction of TC, LDLC and glycemia was observed in the treatment group. TG levels were not different within the two groups. BP and BMI levels remained unchanged, as well AST, ALT; CPK slightly increased in both groups, but it remained in the normal range. CONCLUSIONS: In patients with pre-hypertension, NC supplementation was safe, well tolerated and effective in improving lipid pattern and glucose levels and in preventing the progression to overt hypertension.

Hypertensive Crisis with Neurological Impairment Mimicking a Guillain-Barrè Syndrome: Searching for a Link.

Guillain-Barré syndrome (GBS) may be complicated by severe hypertension (HT) and in turns severe HT can occur with neurological damage mimicking a GBS, so that underlying causes should be investigated. We describe a case of a 62-year-old woman presented to the emergency department for hypertensive crisis with symmetric flaccid paralysis, hypotonia and hyporeflexia of both upper and lower limbs. Brain computed tomography, magnetic resonance imaging and lumbar puncture were normal. Laboratory investigations revealed severe hypokalemia, renal failure, liver impairment, rabdomyolysis, metabolic alkalosis, and low plasma renin and aldosterone levels. Continuous potassium replacement led to complete clinical resolution. A detailed history revealed chronic intake of 250 g/day black liquorice. Hypokalaemic muscle weakness may simulate a GBS. When serum potassium level falls below 2.5 mmol/l, rhabdomyolysis may occur. In this clinical case, an apparent mineralocorticoid excess syndrome was induced by chronic ingestion of liquorice. This latter contains the glycyrrhetic acid that inhibits the enzyme 11-ß-hydroxysteroid dehydrogenase enzyme type-2 leading an aldosterone-like effect and causing hypertension, hypokalemia, metabolic alkalosis and low renin values. The clinical presentation is similar to that observed in the primary aldosteronism, but in this syndrome plasma aldosterone levels are low rather than elevated as in primary aldosteronism. Liquorice-induced hypertension with severe hypokalemia and rhabdomyolysis is a rare condition and the initial presentation with acute muscle paralysis is still more unusual. Before performing instrumental examinations in middle-aged peoples with hypertension crisis and neurological impairment, a detailed clinical history is mandatory.

Effect of Monacolin K and COQ10 supplementation in hypertensive and hypercholesterolemic subjects with metabolic syndrome.

INTRODUCTION: Metabolic syndrome (MetS) is a world-wide epidemic disease with an increased risk of morbidity and mortality. Treatment strategies of MetS include pharmacologic and non-pharmacologic interventions and in this respect a relevant role has been shown for nutraceutical compounds (NCs). The aim of this study was to investigate the efficacy and safety of NCs incorporated with diet and lifestyle management versus diet alone, in lowering blood pressure (BP) values and improving lipid and glucose profile, in a group of hypertensives and hyper-cholesterolemic patients with MetS. METHODS: 104 subjects with MetS (mean age 57.4 ±â€¯8.8 years, 51% males) without history of cardio-vascular (CV) diseases were enrolled in the study. 52 subjects were treated with a once-daily oral formulation of a NCs containing red yeast rice and coenzyme Q10 added to their diet for 2 months and were compared with the 52 patients following a diet program. Differences in BP, serum total cholesterol (TC), low- and high-density-lipoprotein cholesterol (LDLC and HDLC), triglycerides (TG) and glucose values were compared by analysis of variance. RESULTS: A significant reduction of BP, TC, TG, LDLC and glucose levels was observed in both treatment groups. However, a greater reduction of systolic BP (-5.2 vs. -3.0 mmHg), diastolic BP (-4.9 vs. 2.9 mmHg), total cholesterol (-17.2%), LDLC (-21.8%), TG (-16.0%) and serum glucose (-3.4%) was observed in the treatment group relative to the control (p < 0.001 for all); HDLC remained unchanged (p = N.S.). Gender difference was not found in either group (p = N.S.). CONCLUSIONS: In patients with MetS, NC supplementation was safe, well tolerated and effective in improving clinic BP, lipid and glucose profile.

The short-term supplementation of monacolin K improves the lipid and metabolic patterns of hypertensive and hypercholesterolemic subjects at low cardiovascular risk.

Background - The clinical hypocholesterolemic effect of nutraceutical compounds (NCs) containing red yeast rice extracts providing a daily dose of 2.5-10 mg of monacolin K is now well established. For this reason, NCs may be a viable alternative to the statin drugs commonly used to lower cholesterol levels. However, in order to avoid some possible statin-like side effects, most NCs available on the market contain low doses of monacolin K, which could reduce their efficacy. The aim of this study was to investigate the efficacy and safety of a NC containing high doses of monacolin K (10 mg) in improving the lipid profile and glucose metabolism when added to the diet versus the diet alone in a group of hypertensive and hyper-cholesterolemic subjects at low cardiovascular risk. Methods - Thirty subjects with grade-1 essential hypertension (mean age 51.5 ± 7.8 years, 62.9% males) were enrolled in the treatment group (NC group). These subjects followed a programmed diet and took one tablet a day of a NC containing red yeast rice, policosanols, resveratrol and chromium picolinate for 1 month and were compared with an equivalent group of subjects that followed only a diet program. Differences in serum total cholesterol (TC), low-density- and high-density-lipoprotein cholesterol (LDLC and HDLC), triglycerides (TG) and blood glucose between groups were compared by analysis of variance. Results - In both groups, a significant reduction of TC, TG and LDLC was observed. In the treatment group from the baseline to the follow-up the reduction of TC (230.93 ± 28.0 vs. 188.63 ± 18.1, p < 0.001) and LDLC (153.10 ± 22.5 vs. 116.54 ± 17.7, p < 0.001) was significantly greater compared to the control group (differences between treatments = 9.19% and 12.29%, respectively); in addition a significant higher reduction in blood glucose (89.1 ± 7.6 vs. 83.7 ± 4.6, p < 0.001) was also observed (differences between treatments = 4.28%). HDLC levels remained unchanged in both groups. Conclusions - In summary, the NC containing high doses of monacolin K appeared to be safe, well tolerated and effective at improving lipid and glucose patterns.

Cost-benefit effectiveness of angiotensin-II receptor blockers in patients with uncomplicated hypertension: A comparative analysis.

OBJECTIVE: The treatment of hypertensive patients (HTs) requires a long-term commitment of compliance for the patient and resources by the healthcare system. This poses an economic dilemma in countries where universal healthcare is standard. The aim of this study was to evaluate the costs/health benefit and effectiveness of treatment with angiotensin-II receptor blockers (ARBs) in uncomplicated essential hypertension. DESIGN AND METHODS: The daily and annual economic commitment for treating patients with ARBs was estimated using pharmacy dispensing records and the BP-lowering effects of candesartan, irbesartan, losartan, olmesartan, telmisartan and valsartan was evaluated retrospectively. In 114 HTs (mean age 59.4±13.5year, 57.5% men), the BP-lowering effect of ARBs as in monotherapy and in fixed-dose combination (FDC) with hydrochlorothiazide at the doses commonly used in the market to reach BP control (i.e. BP <140/90mmHg) was analyzed. The BP lowering-effect was evaluated after an average of 6-month follow-up consulting medical professionals. Analysis of variance for repeated measures was provided. RESULTS: Treatment with candesartan (14.1%) and olmesartan (32,4%) versus other ARBs resulted in a significant decrease in BP as for mono- than for FDC therapy. Our studies suggest that daily (data not shown) and annual costs of olmesartan were higher than candesartan as in mono- (4577.71±1120.55 vs. 894.25±127.75 €) than for FDC therapy (5715.90±459.90 vs. 1580.45±113.15 €). CONCLUSIONS: Treatment: of BP with candesartan appears to be the most favorable option in terms of cost-effectiveness coupled with favorable health outcomes. These data have some limitations, but open the question if candesartan should be preferred to olmesartan in BP management. Further prospective studies comparing ARBs based on their effect on BP control in uncomplicated HTs are needed for validation.

Fixed-Dose Triple Combination of Antihypertensive Drugs Improves Blood Pressure Control: From Clinical Trials to Clinical Practice.

INTRODUCTION: Blood pressure (BP) control is the main clinical goal in the management of hypertensive patients; however, BP in most of these patients remains uncontrolled, despite the widespread availability of antihypertensive drugs as free-combination therapy. This study compared the efficacy of a fixed-dose triple combination (FDTC) of antihypertensive drugs with that of a free combination of three antihypertensives in patients with uncontrolled hypertension. METHODS: Ninety-two patients (mean age 60.8 ± 12.1, 58.0% male) with uncontrolled essential hypertension (office systolic BP ≥ 140 or diastolic BP ≥ 90 mmHg) previously treated with a renin-angiotensin-aldosterone system (RAAS) inhibitor plus hydrochlorothiazide were switched to once-daily FDTC therapy with perindopril/indapamide/amlodipine (5-10/1.25-2.5/5-10 mg). Patients were age- and sex-matched with a control group of hypertensive patients receiving free-combination therapy with three drugs including a RAAS inhibitor, a diuretic, and a calcium channel blocker. Office BP and 24-h ambulatory BP monitoring (ABPM) were evaluated at baseline and after 1 and 4 months. RESULTS: Significant reductions in ambulatory 24-h, daytime, and nighttime systolic BP, and pulse pressure (PP) were found in the FDTC group relative to reductions seen with free-combination therapy, after the first month only of follow-up. Target BP values (mean 24-h ambulatory systolic/diastolic BP < 130/80 mmHg) were reached by more recipients of FDTC than free-combination therapy (64.8% vs. 46.9%, p < 0.05) at month 4 of follow-up, despite reductions in 24-h ABPM values from baseline being similar in both groups at this time point. CONCLUSION: FDTC of perindopril/indapamide/amlodipine was effective at reducing SBP and PP in previously treated patients with uncontrolled hypertension, and well tolerated, providing support for clinicians in choosing a fixed-dose triple combination over the free-combination of a RAAS inhibitor, a diuretic, and a calcium antagonist.

Asymptomatic hyperuricemia is a strong risk factor for resistant hypertension in elderly subjects from general population.

OBJECTIVE: In clinical practice, patient characteristics predicting resistant hypertension (RH) include higher blood pressure levels, left ventricular hypertrophy, older age, obesity, chronic kidney disease and diabetes. On the contrary little is known about the role of serum uric acid (SUA) as a risk factor for RH in subjects from general population. MATERIAL AND METHODS: 580 elderly subjects aged ≥65 years were enrolled in the Risk Of Vascular complications Impact of Genetics in Old people (ROVIGO) study. RH was defined as the failure to maintain blood pressure values below 140mmHg (systolic) and 90mmHg (diastolic) despite therapeutic interventions that include appropriate lifestyle measures plus adherence to treatment with full doses of at least three antihypertensive drugs, including a diuretic. RH was confirmed using 24-h ambulatory blood pressure measurement. Hyperuricemic was defined as the subjects having SUA ≥6.8mg/dl or taking uricosuric drugs. Gender-specific odds ratio (OR) for RH was calculated by logistic regression analysis. RESULTS: The prevalence of RH was 5.7% in the cohort and was higher in women (8.3%) than in men (3.0%, p<0.05). Independent of chronic kidney disease (OR 3.89, 95% confidence interval 1.49-10.1), hyperuricemia predicted resistant hypertension in women (odds ratio 3.11, 95% confidence intervals 1.06-9.1, p=0.03) but not in men. CONCLUSIONS: In elderly women from the general population, an SUA value of ≥6.8mg/dl triples the risk of RH. SUA assessment should be recommended to better define the pattern of risk associated with RH.

Mood Disorders in Uncontrolled Hypertension Despite Multiple Anti-Hypertensive Medications: Searching for a Link.

INTRODUCTION: Resistant hypertension is a clinical condition in which blood pressure (BP) control is not achieved under a pharmacological therapy including a diuretic and at least two additional antihypertensive drug classes. AIM: To discuss an unusual presentation of uncontrolled hypertension despite multiple anti-hypertensive medications. METHODS AND RESULTS: A 46-year-old woman presented with resistant hypertension (HT) and with a long history of polydipsia, polyuria, weight loss and psychiatric symptoms (sudden onset of personality disorder with free anxiety, negativism and asthenia) unsuccessfully treated with antidepressant drugs. Tests for secondary HT showed a marked increase of serum renin and aldosterone both in clinostatic (342 pg/ml and 907 pmol/l, respectively) and orthostatic posture (351 pg/ml and 2845 pmol/l, respectively), hypokalemia (2.9 mmol/l) and macroalbuminuria (431 mg/day). Diagnostic examinations also revealed a focal stenosis of approximately 70 % of the proximal right renal artery with post-stenotic dilation. After percutaneous balloon angioplasty and stent implantation, BP was normalized with 5 mg/day amlodipine and psychiatric symptoms suddenly disappeared. CONCLUSIONS: Psychopathological symptoms are rare at the onset of hyperaldosteronism, and their aetiology is not well defined. A proper diagnostic and therapeutic process is mandatory in order to get the recommended therapeutic targets in short-midterm improving long-term prognosis. We also suggest not considering depressed or treat with antidepressant agents a young hypertensive subject with uncontrolled hypertension despite multiple anti-hypertensive medications without having ruled out a secondary form of hypertension.

Nutraceuticals for Serum Lipid and Blood Pressure Control in Hypertensive and Hypercholesterolemic Subjects at Low Cardiovascular Risk.

INTRODUCTION: Primary cardiovascular (CV) prevention may be achieved by lifestyle/nutrition changes, although a relevant role is now emerging for specific, functional foods and nutraceutical compounds (NCs). The aim of this study was to investigate the efficacy and safety of NCs in lowering blood pressure (BP) and improving lipid profile, when added to diet and lifestyle management versus diet alone in a group of patients with hypertension (HT) and hypercholesterolemia (HCh) with low CV risk. METHODS: Sixty-six patients with HT and HCh with grade 1 essential HT (mean age 56.0 ± 4.6 years) without history of CV diseases or organ damage were analyzed. These subjects were started on one tablet of an NC-containing red yeast rice, policosanol, berberine, folic acid and coenzyme Q10 once daily for 6 months and were age and gender matched with subjects following a diet program. Differences in clinic BP, 24-h ambulatory BP (24 h-ABPM), serum total cholesterol, low-density and high-density lipoprotein cholesterol (LDL-C and HDL-C) and triglyceride values were compared by analysis of variance. RESULTS: In the treatment group, a significant reduction of systolic 24 h-ABPM (141.6 ± 6.4 vs. 136.2 ± 4.8 mmHg; p < 0.05) and pulse pressure 24 h-ABPM (52.6 ± 7.2 vs. 47.3 ± 5.4 mmHg; p < 0.05) was found at the end of follow-up. A reduction of total cholesterol (-19.2%), LDL-C (-17.4%) and triglycerides (-16.3%) was observed (p < 0.001 for all); HDL-C remained unchanged. No difference was found in the control group. CONCLUSIONS: The tested NCs was found to be safe, well tolerated and effective in reducing mean 24-h systolic and 24-h pulse pressure and in improving lipid pattern.

The ROVIGO study (risk of vascular complications: impact of genetics in old people): protocol, study design, and preliminary results of the initial survey : cardiovascular epidemiology in the elderly.

BACKGROUND: The epidemiology of cardiovascular risk (CV) in the elderly is far from being defined, and the reasons why some subjects retain a healthy body while growing old while others are affected by different diseases or die prematurely are still unknown. AIMS: To compare the CV risk pattern in two elderly cohorts living in North-East Italy. MATERIALS AND METHODS: The Risk Of Vascular complications: Impact of Genetics in Old people (ROVIGO) study is a population-based study including 580 unrelated elderly subjects representative of general population living in Rovigo in the Veneto region. They were compared to a cohort of 580 age-gender-matched unrelated subjects from the CArdiovascular STudy in the Elderly (CASTEL) living in the same region in Castelfranco Veneto and Chioggia. RESULTS: Blood pressure (BP), heart rate (HR), low-density-lipoprotein cholesterol, and prevalence of coronary heart disease, heart failure and chronic pulmonary disease were lower in the ROVIGO than in the CASTEL cohort, while high-density-lipoprotein cholesterol and the prevalence of diabetes were higher in the former than in the latter. In the ROVIGO cohort, diabetes, left ventricular hypertrophy, coronary and cerebrovascular diseases were more represented in men. In the CASTEL cohort, systolic BP was higher in women. In both cohorts, the lipid pattern was less favourable and HR higher in women, chronic pulmonary disease more represented in men. CONCLUSIONS: People living in Rovigo were at lower CV risk than those in Castelfranco Veneto and Chioggia, mainly due to lower BP values, better lipid pattern and lower prevalence of CV and pulmonary disease.

Hyperhomocysteinemia is an independent predictor of sub-clinical carotid vascular damage in subjects with grade-1 hypertension.

Although the role of homocysteinemia (Hcy) as a coronary risk factor (RF) has been scaled down, hyper-Hcy and carotid vascular damage (CVD) are still considered as RFs for cerebrovascular events. In 276 grade-1 hypertensives (160 men and 116 women aged 59.6 ± 15.0 years) without known cardiovascular disease and having hyper-Hcy (≥15 µM/L), subclinical CVD was evaluated by ultrasonographic carotid-wall intima media thickness (IMT). Hcy was divided into quartiles and C667→T polymorphism codifying for methylenetetrahydrofolate reductase (MTHFR) was determined. According to the genotype, subjects were divided into CC (wild), CT (heterozygote) and TT (homozygous mutation). Differences between continuous variables were evaluated by analysis of variance, while gender specific odds ratio (OR) and 95 % confidence intervals (CI) of CVD (IMT >0.9 mm or plaque) were calculated by multivariate logistic regression analysis. Blood pressure (BP) values were not different across the quartiles of Hcy. In 46.4 % of cases, sub-clinical CVD was found, with a prevalence increasingly distributed in the quartiles of Hcy (31.9, 42, 52.2, 59.4 %, p < 0.001). Prevalence of TT allele of the MTHFR genotype was also significantly distributed in the quartiles of Hcy (13.6, 12.3, 23.5 and 50.6 %, p < 0.0001), whereas no relationship was found between genotype and CVD. The last quartile of Hcy predicted CVD (OR 1.32, CI 1.12-2.2, p = 0.02) independent of age (OR 1.23, CI 1.002-1.56, p = 0.0001), systolic BP (OR 1.52, CI 1.24-2.10), diabetes (OR 2.11, CI 1:32-2.88, p = 0.01) and smoking (OR 1.45, CI 1.14-1.98, p = 0.04). Adding gender did not modify the model. In hypertensives, Hcy values >36.5 µM/L independently predict CVD and in those who are also diabetic and smokers, Hcy assessment without MTHFR genotype should be recommended to obtain a better stratification of global cerebrovascular risk.

Anti-hypertensive treatment in pheochromocytoma and paraganglioma: current management and therapeutic features.

Pheochromocytoma (PH) and paraganglioma (PG) are neuroendocrine neoplasms arising from chromaffin cells of the adrenal medulla and the sympathetic ganglia, respectively. Although are unusual cause of hypertension (HT) accounting for at most 0.1-0.2 % of cases, they may lead to severe and potentially lethal hypertensive crisis due to the effects of the released catecholamines. However, both PH and PG may be asymptomatic as ~30 % of subjects are normotensive or have orthostatic hypotension and in these cases the 24 h ambulatory blood pressure (BP) monitoring is an important toll to diagnose and treat HT. HT treatment may be difficult when PH or PG occurs in pregnancy or in the elderly subjects and in these cases a multidisciplinary team is required. When surgical excision is mandatory the perioperative management requires the administration of selective α1-adrenergic blocking agents (i.e., doxazosin, prazosin or terazosin) followed by a ß-adrenergic blockade (i.e., propranolol, atenolol). This latter should never be started first because blockade of vasodilatory peripheral ß-adrenergic receptors with unopposed α-adrenergic receptor stimulation can lead to a further elevation of BP. Although labetalol is traditionally considered the ideal agent due to its α- and ß-adrenergic antagonism, experimental studies do not support its use in this clinical setting. As second regimen, the administration of vasodilators as calcium channel blockers (i.e., nicardipine, nifedipine) may be required to control BP. Oral and sublingual short-acting nifedipine are potentially dangerous in patients with hypertensive emergencies and are not recommend. The latest evidences into the diagnosis and treatment of hypertensive crisis due to PH and PG are reviewed here.

Recurrent syncope in a hypertensive subject with vascular cognitive impairment and permanent pacemaker.

Syncope following permanent pacemaker (PM) implantation is a nightmare for electrophysiologists. We describe a case of daily recurrent syncope in an 84-year-old man having a dual-chamber pacemaker implanted for complete atrio-ventricular block occurred 4 years before the admission to our department. He had a history of arterial hypertension, parossistic atrial fibrillation, chronic obstructive pulmonary disease, stage-III chronic renal failure, mild vascular cognitive impairment and glaucoma. The initial work-up including electrocardiogram (ECG), repeated PM interrogations, Holter electrocardiogram, blood pressure measurement in orthostatic position, complete blood count, serum glycaemia, electrolytes and thyroid function tests showed normal findings. Syncope occurred in lying position and during 90° left clockwise neck rotation and was associated to pallor, sweating, tonic-clonic seizures and transient self-limited loss of consciousness lasting a few seconds. Electroencephalogram was normal. During continuous ECG monitoring, the right rotation of the head determined a ventricular asystolic pause lasting 9 seconds associated with loss of consciousness. Restoration of sinus rhythm was observed after bringing back the head in axis. The PM interrogation, performed during pacing failure, recorded low impedance of bipolar ventricular lead, suggesting a damage in lead insulation. It is likely that lead movements during clockwise neck rotation produced an intermittent short circuit that prevented sufficient energy delivery to the myocardium with a consequence of sudden loss of capture.

Antihypertensive Treatment in the Elderly and Very Elderly: Always "the Lower, the Better?".

Arterial hypertension (HT) is age dependent and, with the prolongation of life expectancy, affects more and more elderly people. In the elderly, HT is a risk factor for organ damage and cardiovascular (CV) events. Both pharmacologic and nonpharmacologic reduction of blood pressure (BP) is associated with a corresponding decrease in systolic-diastolic or isolated systolic HT. Clinical trials have shown that BP lowering is associated with a decrease in stroke and other CV events. Therefore, BP reduction per se appears more important than a particular class of antihypertensive drugs. The benefit of antihypertensive treatment has been confirmed up to the age of 80 years, remaining unclear in the octogenarians. The benefit in lowering diastolic BP between 80 and 90 mmHg is well established, while that of lowering systolic BP below 140 mmHg requires further confirmations.

Renal scintigraphy predicts global cardiovascular risk in hypertensive subjects with normal serum creatinine levels.

BACKGROUND. This cross-sectional study investigates the role of renal scintigraphy on cardiovascular (CV) risk stratification in normoalbuminuric, non-diabetic hypertensive subjects (HTs) free from CV disease and renal dysfunction. METHODS. In 200 HTs aged 55-75 years, glomerular filtration rate (GFR) was measured by technetium-99m-diethylene triamine pentacetic acid clearance during renal scintigraphy. Stage III chronic kidney disease (CKD) was defined as GFR < 60 ml/min/1.73 m(2). For comparing the impact of different methods for CKD diagnosis on CV risk stratification, CKD was also considered as GFR estimated by the Modification of Diet in Renal Disease (MDRD) equation and Cockcroft-Gault's formula. Target organ damage (TOD) was assessed by echocardiography and carotid ultrasonography. Gender-specific odds ratio (OR) with 95% confidence intervals for CKD were derived from a multiple stepwise logistic regression analysis. Global CV risk was stratified according to routine examinations, TOD and CKD. RESULTS. In 38% of cases, an unknown stage III CKD was found. Independent of age, CKD was predicted by history of hypertension (OR = 1.69, p = 0.0001), albuminuria (OR = 1.25, p = 0.0001), smoking (OR = 1.85, p = 0.028) and pulse pressure (OR = 1.21, p = 0.019) in men only. Men had an increased risk of CKD (OR = 2.62, p = 0.002) in comparison with women. Prevalence of TOD was significantly higher only in HTs having CKD diagnosed by renal scintigraphy; TOD and CKD assessment added to classic risk factors modified the CV risk stratification from low-moderate to high and very high. CONCLUSIONS. Renal scintigraphy is an important aid in risk stratification and should be performed in HTs aged >55 years. Pulse pressure was the main blood pressure component that predicted the risk of stage III CKD.

Neurophysiological correlates of post-hypnotic alexia: a controlled study with Stroop test.

To clarify whether hypnotically-induced alexia was able to reduce the Stroop effect due to color/word interference, 12 volunteers (6 with high and 6 with low hypnotizability according to Stanford Hypnotic Susceptibility Scale Form C) underwent a Stroop test consisting of measuring, both in basal conditions and during post-hypnotic alexia, the reaction times (RT) at appearance of a colored word indicating a color. In basal conditions, RT were greater in case of incongruence. In highly hypnotizable participants, the interference was less pronounced during post-hypnotic alexia (-34%, p = 0.03). During alexia, late positive complexamplitude was also greater for congruent than incongruent conditions (p < 0.03), and cardiovascular response to stress was less pronounced as well. In participants showing low hypnotizability, no reduction of Stroop effect was detected during post-hypnotic alexia. Posthypnotic alexia is therefore a real and measurable phenomenon, capable of reducing the color-word interference and the haemodynamic effects of the Stroop test.

Comparison of methods for determination of glomerular filtration rate in hypertensive subjects with normal serum creatinine.

BACKGROUND: Glomerular filtration rate (GFR) measured through technetium-99m diethyl triamine penta-acetic acid (Tc(99m)DTPA) renal scintigraphy (rsGFR) was compared with that estimated (eGFR) from 24-h creatinine clearance (CrCl) and, using both the Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) formulas, in a population of hypertensive subjects (HTs) with normal serum creatinine (SCr) levels. PATIENTS AND METHODS: In 200 normoalbuminuric (<30 mg/24 h) HTs 55-75 years old, without diabetes and history of coronary and cerebrovascular diseases, Pearson's correlation assess the relationship between rsGFR and eGFR. The Bland-Altman method was used to assess the agreement between rsGFR and eGFR, separately in subjects with low (<60 ml/min/1.73 m(2)) and normal (≥60 ml/min/1.73 m(2)) rsGFR. The span between -1.96 and +1.96 standard deviations of mean difference (bias) was calculated and used for this purpose. RESULTS: In 76 subjects, an unknown low renal function was found by Tc(99m)DTPA renal scintigraphy. In subjects with normal rsGFR the Bland-Altman analysis showed that the smallest span between rsGFR and eGFR was evident for ClCr values (26.0 ml/min/1.73 m(2)), whereas higher values were detected with the CG and MDRD formulas (41.0 and 40.4 ml/min/1.73 m(2), respectively). The same results were observed for low rsGFR, where a smaller span was found for ClCr (21.2 ml/min/1.73 m(2)), whereas CG and MDRD methods gave greater results (30.4 and 31.8 ml/min/1.73 m(2) respectively); no differences were found between genders. The degree of agreement for eGFR estimated with the CG and MDRD formulas was wider than that derived from ClCr, reflecting a greater between-methods variability and a considerable discrepancy of rsGFR values in the former than in the latter. CONCLUSIONS: In HTs with normal SCr values, Tc(99m)DTPA renal scintigraphy discovered un known renal organ damage in 38% of cases. If this methodology is not available, ClCr measurement should be preferred to estimate GFR whereas CG and MDRD formulas are of limited efficacy.

Chronic obstructive pulmonary disease and cardiovascular mortality in elderly subjects from general population.

AIMS: To ascertain whether chronic obstructive pulmonary disease (COPD) is an independent risk factor for cardiovascular (CV) mortality in the elderly subjects from general population. METHODS: 3282 subjects of the Northern Italy aged > or =65 years were followed up for 12 years in the frame of the CArdiovascular STtudy in the ELderly. Multivariate stepwise proportional hazard Cox regression was therefore used to identify the prognostic role of COPD on CV mortality in hypertensive (HT) and normotensive (NT) subjects. The hazard ratio (HR) of COPD with 95% confidence interval (CI) for mortality was adjusted for confounders in both genders. RESULTS: COPD resulted to be an independent predictor of CV mortality (HR 1.34, CI 1.13-1.61) in HT but not in NT subjects. This was evident both in men (HR 1.44, 1.25-1.95) and women (HR 1.32, CI 1.14-1.53); pulse pressure (PP) was directly related and anti-hypertensive therapy inversely related to risk of CV mortality, an association that was greater in subjects with than without COPD. CONCLUSION: COPD should be included in the computation of global risk in HT subjects. PP is the main BP component in increasing CV risk in subjects with COPD. Controlled trials should be performed to evaluate the pressor targets to be reached in HT subjects with COPD, with the aim of decreasing their CV risk.