How to Improve Effectiveness and Adherence to Antihypertensive Drug Therapy: Central Role of Dihydropyridinic Calcium Channel Blockers in Hypertension.

Essential hypertension is a complex clinical condition, characterized by multiple and concomitant abnormal activation of different regulatory and contra-regulatory pathophysiological mechanisms, leading to sustained increase of blood pressure (BP) levels. Asymptomatic rise of BP may, indeed, promote development and progression of hypertension-related organ damage, which in turn, increases the risk of major cardiovascular and cerebrovascular events. A progressive and independent relationship has been demonstrated between high BP levels and increased cardiovascular risk, even in the high-to-normal range. Conversely, evidence from randomized controlled clinical trials have independently shown that lowering BP to the recommended targets reduces individual cardiovascular risk, thus improving event-free survival and reducing the incidence of hypertension-related cardiovascular events. Despite these benefits, overall rates of BP control remain poor, worldwide. Currently available guidelines support a substantial equivalence amongst various antihypertensive drug classes. However, several studies have also reported clinically relevant differences among antihypertensive drugs, in terms of both BP lowering efficacy and tolerability/safety profile. These differences should be taken into account not only when adopting first-line antihypertensive therapy, but also when titrating or modulating combination therapies, with the aim of achieving effective and sustained BP control. This review will briefly describe evidence supporting the use of dihydropyridinic calcium channel blockers for the clinical management of hypertension, with a particular focus on barnidipine. Indeed, this drug has been demonstrated to be effective, safe and well tolerated in lowering BP levels and in reducing hypertension-related organ damage, thus showing a potential key role for improving the clinical management of hypertension.

Impact of cuff positioning on blood pressure measurement accuracy: may a specially designed cuff make a difference?

During blood pressure (BP) measurement, the recommended positioning of the cuff bladder center is directly above the brachial artery. We investigated the relevance of incorrect cuff positioning during (1) auscultatory measurement with an appropriate or improperly small cuff and (2) oscillometric measurement with a wide-range cuff designed to guarantee accurate measurements regardless of position. In subjects with wide BP and arm circumference ranges, (1) auscultatory BP was repeatedly measured with a properly positioned cuff (reference) and, simultaneously, with an identical cuff placed on the other arm in either a correct or an incorrect position (test). The measurements were performed with a properly sized (N=57) or an improperly small cuff (N=33). (2) Auscultatory measurements obtained with a properly positioned and sized cuff were compared with oscillometric measurements obtained with a specially designed wide-range cuff (Omron IntelliWrap) placed on the contralateral arm either in a correct or an incorrect position. Auscultatory BP measures were unaffected by incorrect positioning of a properly sized cuff, whereas with undercuffing, BP was overestimated with the cuff displaced by 90° laterally (systolic/diastolic BP differences: 4.9±4.6/4.0±4.6 mm Hg, P<0.01) or by 180° (3.9±5.4/4.2±5.1 mm Hg, P<0.01) in relation to the correct position. Incorrect placement of the oscillometric cuff had no significant effect on the accuracy of the measurements (difference with correct position <1.5 mm Hg). Incorrect cuff positioning introduces a systematic overestimation of auscultatory BP when the cuff is too small in relation to arm circumference but not when it is correctly sized. No systematic error was observed with oscillometric measurements obtained with a specially designed wide-range cuff.

Diastolic dysfunction in controlled hypertensive patients with mild-moderate obstructive sleep apnea.

BACKGROUND: Hypertension and severe obstructive sleep apnea (OSA) may independently contribute to left ventricular diastolic dysfunction. However, scanty data is available on this issue in hypertensives with mild-moderate OSA. METHODS AND RESULTS: We performed polysomnography, echocardiography and 24h ambulatory blood pressure monitoring in 115 treated essential hypertensives with suspicion of OSA. After exclusion of severe/treated OSA and/or cardiovascular disease patients, mild-moderate OSA (5 ≤ apnoea/hypopnoea index<30 events·h(-1)) was diagnosed in 47.3% of the remaining 91 patients, while 52.7% were free of OSA. Transmitral early (E) and late (A) peak flow velocities were assessed in 69 patients, and mitral annular velocity (E') in 53. Compared to non-OSA, mild-moderate OSA heart rate was higher (p=0.031) while E/A was lower (p<0.001) without differences in 24h mean systolic and diastolic blood pressures (125.36 ± 12.46/76.46 ± 6.97 vs 128.63 ± 11.50/77.70 ± 7.72 mmHg, respectively, NS). Patients with E'< 10 cm/s and E/A<0.8 showed a lower mean SpO2 than subjects with normal diastolic function (p=0.004; p<0.001). In a logistic regression model age, mean SpO2, daytime heart rate and nocturnal diastolic blood pressure fall were associated with altered relaxation pattern, independently from BMI and gender. CONCLUSIONS: In controlled hypertensives mild-moderate OSA may be associated with early diastolic dysfunction, independently from age, gender and mean blood pressure and in the absence of concentric left ventricular hypertrophy. Moreover nocturnal hypoxia may be a key factor in determining early diastolic dysfunction, under the synergic effects of hypertension and mild-moderate OSA.

Clinical relevance of cardiac structure and function abnormalities in patients with Cushing's syndrome before and after cure.

OBJECTIVES: Sustained hypercortisolism impacts cardiac function, and, indeed, cardiac disease is one of the major determinants of mortality in patients with Cushing's syndrome. The aim of this study was to assess the clinical relevance of cardiac structure and function alterations by echocardiography in patients with active Cushing's syndrome and after disease remission. STUDY DESIGN: Seventy-one patients (61 women, 10 men) with Cushing's syndrome and 70 age-, sex- and blood pressure-matched controls were enrolled. Echocardiography was performed in 49 patients with active disease and at several time points after remission in 44 patients (median follow-up 46.4 months), and prevalence of abnormal left ventricular mass measurements and systolic and diastolic functions indices was compared between patients with active disease, after remission and controls. Twenty-two patients were evaluated both before and after remission. RESULTS: Up to 70% of patients with active Cushing's syndrome presented abnormal left ventricular mass parameters; 42% presented concentric hypertrophy and 23% concentric remodelling. Major indices of systolic and diastolic functions, i.e. ejection fraction and E/A ratio, respectively, were normal. Upon remission of hypercortisolism, left ventricular mass parameters ameliorated considerably, although abnormal values were still more frequent than in controls. Both cortisol excess and hypertension contribute to cardiac mass alterations and increase the prevalence of target organ damage. CONCLUSIONS: Cushing's syndrome is associated with an increased risk for abnormalities of cardiac mass, which ameliorates, but does not fully disappear after remission. Systolic and diastolic functions are largely within the normal range in these patients.

Patients with antiphospholipid syndrome display endothelial perturbation.

BACKGROUND: There is strong evidence that antiphospholipid antibodies (aPL) perturb endothelium both in vitro and in experimental animal models. by inducing a vasculopathy and an endothelial pro-inflammatory/coagulant phenotype. However, few contrasting studies raised the issue about the possibility to detect a comparable endothelial perturbation in anti-phospholipid syndrome (APS) patients. The aim of this observational case-control study was to evaluate several parameters of endothelial perturbation in patients with APS and without any other atherosclerosis risk factor. PATIENTS AND METHODS: We investigated plasma levels of soluble adhesion molecules (s-ICAM-1, s-VCAM-1, s-E-selectin), soluble thrombomodulin (sTM), von Willebrand factor (vWF) and tissue plasminogen activator (t-PA) by solid-phase assays in 40 selected APS patients and 40 age- and sex-matched healthy subjects. In addition, we evaluated circulating endothelial cells by flow cytometry and brachial artery flow-mediated vasodilation. Patients and controls were free of conditions known to affect both the biological and the functional endothelial parameters. RESULTS: Plasma levels of sTM, s-E-selectin and s-VCAM-1 did not differ from controls, while a significant increase in s-ICAM-1 (P = 0.029), t-PA (P = 0.003) and vWF titres (P = 0.002) was found. Circulating mature endothelial cells were also significantly higher in patients than in controls (P = 0.05) and decreased during both vitamin K antagonists (P = 0.001) and antiplatelet (P = 0.032) treatments. Mean brachial artery flow-mediated vasodilation responses were significantly impaired compared to healthy subjects (P = 0.0001). CONCLUSIONS: As a whole these findings indicate that APS patients display an endothelial perturbation in the absence of other detectable traditional risk factors for atherosclerosis.

Patterns of QT dispersion in athletic and hypertensive left ventricular hypertrophy.

OBJECTIVE: The objective of this article is to assess whether left ventricular hypertrophy (LVH) due to physical training or of hypertensive patients shows similarities in QT length and QT dispersion. METHODS: A total of 51 subjects were studied: 17 essential hypertensive patients (27.7 +/- 5.6 years), 17 athletes involved in agonistic activity (canoeing) (24.8 +/- 6.1 years), and 17 normotensive healthy subjects as control group (24.8 +/- 3.6 years). The testing protocol consisted of (1) clinic BP measurement, (2) echocardiography, (3) 12-lead electrocardiographic examination (QT max, QTc max, QT min, QTc min, DeltaQT, DeltaQTc). RESULTS: There were no significant differences between the body surface area, height, and age of the three groups. Clinic blood pressure was higher in hypertensives (146.5 +/- 45.2/93.5 +/- 4.9 mmHg) versus athletes (120.9 +/- 10.8/77.1 +/- 6.0 mmHg) and controls (123.5 +/- 4.8/78.8 +/- 2.9 mmHg) by definition. Indexed left ventricular mass (LVM/BSA) was significantly greater in both athletes (148.9 +/- 21.1 g/m2) and hypertensives (117.1 +/- 15.2 g/m2) versus controls (81.1 +/- 14.5 g/m2; P < 0.01), there being no statistical difference among them. LVH (LVMI > 125 g/m2) was observed in all athletes, while the prevalence in hypertensives was 50%. In spite of this large difference in cardiac structure there were no significant differences in QT parameters between athletes and the control group, while hypertensive patients showed a significant increase in QT dispersion versus the two other groups (DeltaQT 82 +/- 2.1, 48 +/- 1.3, 49 +/- 2.3 ms; P < 0.01; DeltaQTc 88 +/- 2.0, 47 +/- 1.4, 54 +/- 2.7; P < 0.01). CONCLUSIONS: LVH induced by physical training activity is not associated with an increase in QT dispersion, whereas pathological increase in LVM secondary to hypertension is accompanied by an increased QT dispersion.