Eugenia Belotti

Inappropriate Left Ventricular Mass in Patients With Primary Aldosteronism

Assessment of appropriateness of left ventricular mass (LVM) for a given workload may better stratify hypertensive patients. Inappropriate LVM may reflect the interaction of genetic and neurohumoral factors other than blood pressure playing a significant role in myocardial growth. Primary aldosteronism (PA) represents a clinical model useful in assessing the effect of aldosterone increase on LVM. The aim of this study was to evaluate the inappropriateness of LVM in patients with PA. In 125 patients with PA (54 females; adrenal hyperplasia in 73 and adenoma in 52 patients) and in 125 age-, sex-, and blood pressure–matched, essential hypertensive patients, echocardiography was performed. The appropriateness of LVM was calculated by the ratio of observed LVM to the predicted value using a reference equation. In all of the subjects plasma renin activity and aldosterone, as well as clinic and 24-hour blood pressure, were measured. The prevalence of inappropriate LVM was greater in patients with traditionally defined left ventricular hypertrophy (70% and 44%, respectively; P=0.02) but also in patients without left ventricular hypertrophy (17% and 9%, respectively; P=0.085). In PA patients, a correlation was observed between the ratio of observed:predicted LVM and the ratio of aldosterone:plasma renin activity levels (r=0.29; P=0.003) or the postinfusion aldosterone concentration (r=0.44; P=0.004; n=42). In conclusion, in patients with PA, the prevalence of inappropriate LVM is increased, even in the absence of traditionally defined left ventricular hypertrophy. The increase in aldosterone levels could contribute to the increase of LV mass exceeding the amount needed to compensate hemodynamic load.

Prognostic role of flow-mediated dilatation of the brachial artery in hypertensive patients.

Background The prognostic role of endothelial dysfunction, as evaluated by flow-mediated vasodilatation of the brachial artery, has been demonstrated in patients at very high risk. We aimed to investigate whether flow-mediated vasodilatation predicts cardiovascular events in uncomplicated hypertensive patients. Methods and results A total of 172 prospectively identified uncomplicated hypertensive patients (age 56 ± 8 years, 41% women, 48 with diabetes mellitus type 2) were studied. At baseline all patients were untreated and underwent baseline standard laboratory examination. A standard echocardiogram was performed for the evaluation of left ventricular anatomy and function and patients with systolic dysfunction or left ventricular wall motion abnormalities were excluded. Endothelial function was measured as flow-mediated vasodilatation of the brachial artery using high-resolution ultrasound. Patients were followed for 95 ± 37 months (range 2–136 months). A first nonfatal or fatal cardiovascular event occurred in 32 patients. The incidence of cardiovascular events was 1.4 and 3.1 per 100 patient-years in patients with a flow-mediated vasodilatation below and above the median value (4.7%), respectively (P < 0.005 by the log-rank test). In Cox analysis, controlling for age, sex, glycemia, cholesterol, smoking, BMI, systolic and diastolic blood pressure at baseline and left ventricular mass index, a low flow-mediated vasodilatation conferred an increased risk of cardiovascular events (odds ratio 2.67, 95% confidence interval 1.17 to 6.1, P = 0.02). Conclusion The presence of endothelial dysfunction, as evaluated by flow-mediated vasodilatation of the brachial artery, identifies hypertensive patients at increased risk of nonfatal and fatal cardiovascular events.

Inappropriate Left Ventricular Mass Changes During Treatment Adversely Affects Cardiovascular Prognosis in Hypertensive Patients

Inappropriate left ventricular mass (LVM; ie, the value of LVM exceeding individual needs to compensate hemodynamic load) predicts the risk of cardiovascular (CV) events, independent of risk factors, either in the presence or in the absence of traditionally defined LV hypertrophy. The relation between changes in appropriateness of LVM during antihypertensive treatment and subsequent prognosis was evaluated in 436 prospectively identified uncomplicated hypertensive subjects, with a baseline and follow-up standard clinical evaluation, laboratory examinations, and echocardiogram (last examination: 6±3 years apart), followed for additional 4.5±2.5 years. The appropriateness of LVM to cardiac workload was calculated by the ratio of observed LVM to the value predicted for individual sex, height, and stroke work at rest. At baseline, low or appropriate LVM (≤128% of predicted) was found in 178 patients, and 258 had inappropriate LVM. A first CV event occurred in 82 patients. Event rate (×100 patient-years) was 3.18 among patients with inappropriate LVM persistence (n=152), 0.97 among patients with inappropriate LVM regression (n=104), 1.87 among patients with inappropriate LVM development (n=75), and 0.81 among patients with persistence of appropriate LVM from baseline to the follow-up (n=105; log-rank test: P=0.0001). Coxs proportional hazard model, considering all of the known CV risk factors, indicated that age, male sex, persistence, or development of inappropriate LVM, in addition to persistence and development of LVH, were independently associated with the occurrence of CV events (P<0.001). The presence of inappropriate LVM during antihypertensive treatment may adversely influence subsequent CV prognosis.

Myocardial Ultrasound Tissue Characterization in Patients with Chronic Renal Failure

The objective of this study was to detect ultrastructural changes in myocardium related to collagen content by ultrasound tissue characterization in patients with chronic kidney disease (CKD) and in uncomplicated hypertensive control subjects. In 25 hemodialysis (HD) patients, in 25 patients with moderate to severe chronic renal failure (CRF), and in 10 patients with essential hypertension (EH) and normal renal function matched for age, BP, and left ventricular mass index, left ventricular anatomy and function were evaluated by conventional echocardiography, and integrated backscatter signal (IBS) was analyzed by acoustic densitometry. IBS mean reflectivity increased from 48% in patients with EH to 56% in patients with CRF to 62% in HD patients (ANOVA P < 0.01). IBS mean cyclic variation was progressively increased from 4.35 +/- 1.2 dB in HD patients to 5.27 +/- 0.90 in patients with CRF to 6.50 +/- 1.6 dB in patients with EH (ANOVA P < 0.01). At multivariate analysis, IBS mean reflectivity was positively related to age and serum creatinine (beta 0.351, P = 0.036; and beta = 0.408, P = 0.016, respectively). IBS mean cyclic variation was inversely related to age and serum creatinine (beta = -0.274, P = 0.025; and beta = -0.262, P = 0.025, respectively) and positively related to left ventricular midwall fractional shortening and transmitral E/A ratio (beta = 0.269, P < 0.05; and beta = 0.314, P < 0.001, respectively). The data support the hypothesis that interstitial collagen deposition may appear early in the course of CKD and suggest that acoustic densitometry may represent a useful tool for the assessment of myocardial tissue changes in patients with CKD.

Pulse wave velocity and cardiovascular risk stratification in a general population: the Vobarno study.

Background Hypertension guidelines underline the importance of quantification of total cardiovascular risk; an extensive evaluation of target organ damage (TOD) may increase the number of patients classified at high-added cardiovascular risk. Objective To assess the effect of the evaluation of different forms of TOD, in addition to ‘routine’ workup, on cardiovascular risk stratification in a general population sample in Northern Italy. Methods In 385 patients (age 57 ± 10 years, 44% men, 64% hypertensives, 32% treated), left ventricular and carotid artery structure and carotid–femoral pulse wave velocity (PWV) were measured. All patients underwent laboratory examinations. Patients were divided into risk categories according to European Society of Hypertension/European Society of Cardiology guidelines before and after TOD evaluation. Results After routine workup, patients were classified as follows: 6% at average cardiovascular risk, 35% at low cardiovascular risk, 25% at moderate cardiovascular risk, 33% at high cardiovascular risk and 1% at very high cardiovascular risk. The proportion of patients at low or moderate cardiovascular risk reclassified at high cardiovascular risk were 5, 14, 30 and 14% after echocardiography, measurement of albuminuria and estimated glomerular filtration rate, carotid ultrasound and PWV, respectively (χ2 P < 0.001 for all vs. routine). Assessment of PWV in addition to echocardiography led to an increase of the proportion of patients at high risk (from 5 to 15%, P < 0.001), as for PWV in addition to albuminuria, estimated glomerular filtration rate or both (from 14 to 31%, P < 0.01), but did not affect risk stratification in addition to carotid ultrasound (from 30 to 34%, P = NS). Conclusion Our data suggest that measurement of PWV may significantly change cardiovascular risk stratification in addition to echocardiography and to detection of albuminuria and/or of a reduction of estimated glomerular filtration rate, but not after carotid ultrasound. Our results confirm that evaluation of different forms of TOD is useful for a more accurate assessment of global cardiovascular risk.

Effect of antihypertensive treatment on circulating endothelial progenitor cells in patients with mild essential hypertension

Abstract It has been reported that the number of circulating endothelial progenitor cells (EPCs) reflects the endogenous vascular repair ability, with the EPCs pool declining in the presence of cardiovascular risk factors. However, their relationship with hypertension and the effects of anti-hypertensive treatment remain unclear. We randomized 29 patients with mild essential hypertension to receive barnidipine up to 20 mg or hydrochlorothiazide (HCT) up to 25 mg. Circulating EPCs were isolated from peripheral blood at baseline and after 3 and 6 months of treatment. Mononuclear cells were cultured with endothelial basal medium supplemented with EGM SingleQuots. EPCs were identified by positive double staining for both FITC-labeled Ulex europaeus agglutinin I and Dil-labeled acethylated low-density lipoprotein. After 3 and 6 months of treatment, systolic and diastolic blood pressure (BP) were significantly reduced. No difference was observed between drugs. An increase in the number of EPCs was observed after 3 and 6 months of anti-hypertensive treatment (p < 0.05). Barnidipine significantly increased EPCs after 3 and 6 months of treatment, whereas no effect was observed with HCT. No statistically significant correlation was observed between EPCs and clinical BP values. Our data suggest that antihypertensive treatment may increase the number of EPCs. However, we observed a different effect of barnidipine and HCT on EPCs, suggesting that, beyond its BP lowering effect, barnidipine may elicit additional beneficial properties, related to a healthier vasculature.

Effects of barnidipine in comparison with hydrochlorothiazide on endothelial function, as assessed by flow mediated vasodilatation in hypertensive patients.

Abstract Background. In hypertensive patients, endothelial dysfunction is associated with an increased incidence of cardiovascular events. Calcium-channel antagonists can reverse impaired endothelium-dependent vasodilation in different vascular districts, while conflicting results are found in the brachial artery. Aim. To investigate the effect of barnidipine in comparison with hydrochlorothiazide on endothelial function of hypertensives, as assessed by flow-mediated vasodilation (FMD) of the brachial artery. Methods. Patients with mild to moderate hypertension (age range 26–67 years) were randomized to receive barnidipine or hydrochlorothiazide. A thorough clinical examination, including blood pressure (BP) measurement, was performed at randomization as well as after 6, 12 and 24 weeks. FMD and 24-h BP monitoring was performed at randomization, after 12 and 24 weeks. Results. After 12 and 24 weeks of treatment, a significant reduction in clinic BP was observed in both groups. Furthermore, a significant reduction in 24-h SBP and DBP was observed in patients receiving barnidipine but not in those receiving diuretic. The percentage change in FMD was different between the two groups of patients treated with barnidipine (at 12 weeks +1.2 ± 2.2%, p = 0.023 and at 24 weeks +1.25 ± 3.15%, p = 0.16 from baseline) or with hydrochlorothiazide (at 12 weeks −1.0 ± 3.0. p = 0.09 and at 24 weeks −1.78 ± 2.9%, p = 0.015 from baseline). A significant difference in FMD changes between the two groups was confirmed by analysis of covariance (p = 0.031). Conclusions. In presence of a similar clinic BP reduction, an improvement of endothelial function was observed during treatment with barnidipine but not with hydrochlorothiazide, suggesting that the barnidipine may exert a favourable effect on endothelial dysfunction in hypertensive patients.

Coronary Flow Reserve and Small Artery Remodelling in Hypertensive Patients Re-Analysis of Data and Review of the Literature

Objective: To evaluate the relationship between subcutaneous small arteries structure and coronary flow reserve in patients with essential hypertension.Methods: Eighteen patients with mild to moderate essential hypertension and normal epicardial coronary arteries were included in the study and underwent a biopsy of the subcutaneous fat from the gluteal region. Subcutaneous small arteries were dissected and mounted on a micromyograph. The media thickness, the normalized internal diameter and the media: lumen ratio were then calculated. Measurement of coronary flow velocity in the left anterior descending artery before and during maximal pharmacological vasodilatation was performed by transesophageal Doppler echocardiography.Results: Mean and peak coronary flow reserve (CFR) as well as minimum coronary resistance were significantly correlated to both media: lumen ratio and normalized internal diameter of subcutaneous small arteries. Those patients with a mean CFR (mCFR) of <2.69 (i.e. 1 SD below the mean of values in our normal reference subjects) had a greater media: lumen ratio and a smaller internal diameter compared with those with a mCFR of ≥2.69. Similarly, patients with a media: lumen ratio of ≥0.109 had a smaller mCFR compared with those with a media: lumen ratio of <0.109.Conclusions: These results are in keeping with the hypothesis of a generalized remodelling of small arteries, that may also be responsible for a reduced coronary vasodilator capacity even in patients with mild to moderate essential hypertension.