Ettore Ambrosioni

Hypertension in pregnancy is a frequent disorder that includes a spectrum of conditions. We aimed at comparatively evaluating the hemodynamic, echocardiographic and biohumoral profile of a sample of pregnant Caucasian women with different form of pregnancy-related hypertension. We enrolled 39 non-hypertensive pregnant women (NP), 26 with Chronic HBP in pregnancy (CH), 24 with gestational hypertension (G-PIH), and 33 with pre-eclampsia. We recorded and compared blood pressure (BP), echocardiographic parameters, resting plasma renin activity (PRA) and plasma aldosterone (PA), Plasma levels of atrial (ANP) and brain natriuretic peptide (BNP). PE patients had a significantly higher BP than either G-PIH or NP patients. PE patients had also significantly lower cardiac output than NP, G-PIH and CH. In comparison to NP patients, the total peripheral vascular resistance was 61% higher in PE women and 38% higher in CH patients. All echographic parameters were significantly more altered in PE patients when compared with NP, in respect to any other form of hypertension. Either ANP (+35%) and BNP (+40%) were significantly higher in PE patients than in controls. The PRA was reduced in PE and CH patients when compared either with NP (-38 and -35%, respectively) or G-PIH (-47 and -43%, respectively). On the basis of our data, we can conclude that PE is the gestation associated hypertension with the largest anatomical, functional and biohumoral involvement, and so it has to be involved in a more intensive monitoring and evaluation.

Metabolic syndrome is a highly prevalent condition in the Italian population. This study assesses the feasibility and efficacy of a multifactorial approach for primary prevention of cardiovascular disease risk assessment in patients with metabolic syndrome in the daily clinical practice setting. 726 patients were enrolled (males : females = 7 : 3), their ages ranging from 26 to 70 years, with metabolic syndrome and cardiovascular death risk ≥5%, computed by means of the European Systematic COronary Risk Evaluation (SCORE) algorithm. The first phase (3 months) consisted of an improvement in lifestyle and, if necessary, the initial administration of an antihypertensive therapy (valsartan 160 mg/day for patients with blood pressure ≥140/90 mmHg and ≥130/80 mmHg for diabetic patients). During phase 2 (6 months), patients with systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure (DBP) ≥90 mmHg (≥130/80 mmHg for diabetic patients) were administered valsartan 160 mg/day + hydrochlorothiazide 12.5 mg/day combined; those with total cholesterol levels ≥190 mg/dL (≥175 mg/dL for diabetic patients) started treatment with fluvastatin 80 mg prolonged release (XL), as prescribed in the guidelines. A control group was approached with another conventional treatment. After 9 months of monitoring, the SBP dropped by 27 mmHg in the valsartan-treated patients and by 11 mmHg in the control group, while the DBP dropped by 12 mmHg in the former group and 2 mmHg in the latter. Total cholesterolaemia was reduced by 47 mg/dL in patients undergoing fluvastatin and valsartan therapy, by 19 mg/dL in those treated with valsartan only and by 33 mg/dL in those administered another conventional treatment. Relative risk reduction observed after 9 months, compared with the beginning of the study, was almost 48% in the valsartan/valsartan + fluvastatin group, versus 28% observed with the other conventional treatment. The reduction of risk at 60 years of age was an average of 39% at 3 months and 48% at 9 months, compared with the beginning of the study. Therapeutic success was accomplished with 78% of the patients treated with valsartan/valsartan + fluvastatin, compared with 47% of patients in the conventional therapy group. The present study demonstrated that the normalization of the main cardiovascular risk factors in patients with metabolic syndrome may be easily achieved in standard clinical practice settings, by leading an adequate lifestyle and, if necessary, the administration of antihypertensive and/or lipid-lowering monotherapy at the usual doses.

ABSTRACT Recent evidence suggests a strong relationship between angiotensin 1 (AT1) receptor gene expression and low-density lipoprotein cholesterol (LDL-C) plasma level. This article comparatively evaluates blood pressure-modulating effects and metabolic and haemodynamic actions of an antihypertensive treatment directly interacting (telmisartan) versus non-interacting (bisoprolol) with the AT1 receptor in statin-treated hypercholesterolaemic patients.Sixteen untreated hypertensive hypercholesterolaemic patients (aged 57.4 ± 7 years) were enrolled according to a randomized, single-blind, crossover design with a prospective randomized, open-label, blinded evaluation of the primary endpoint. All of the patients were allocated to treatment with simvastatin 20 mg/day for 2 weeks, and then randomly assigned to treatment with either telmisartan (40-80 mg/day) or bisoprolol (5-10 mg/day) whose daily dose was doubled after 2 weeks if blood pressure control was unsatisfactory. After a cumulative period of 4 weeks, the antihypertensive drugs were withdrawn for a washout period of 2 weeks when the patients were treated with simvastatin alone. They were then allocated to the alternative antihypertensive treatment (bisoprolol or telmisartan) for a cumulative period of 4 additional weeks with a dosage adjustment at week 2. The following were measured in each patient: lying and standing systolic blood pressure (SBP) and diastolic blood pressure (DBP); heart rate; 24-hour SBP and DBP by ambulatory blood pressure measurement; baseline forearm blood flow (FBF); and forearm vascular resistance (FVR), post-ischaemic FBF and FVR, lipid profile and fasting plasma glucose.After 2 weeks of treatment with simvastatin, baseline and post-ischaemic FBF increased (both p < 0.05), while baseline and post-ischaemic FVR decreased (both p < 0.05). Both antihypertensive treatments were associated with a significant reduction in SBP (p < 0.005), DBP (p < 0.05) and mean blood pressure (MBP) [p < 0.05]. Standing DBP and MBP were reduced more in the telmisartan than in the bisoprolol group (p < 0.05). Basal and post-ischaemic FBF were significantly increased (p < 0.05 and p < 0.005, respectively) and basal and post-ischaemic FVR were significantly decreased (both p < 0.005) only in the telmisartan-treated group. LDL-C plasma level significantly improved in both treatment groups (p < 0.05), while plasma triglycerides significantly decreased only in the telmisartan-treated group (p < 0.05).From the result of this preliminary study carried out on a small sample of hypercholesterolaemic hypertensive patients, it appears that the association with telmisartan and simvastatin could exert positive effects on a large quantity of vascular functionality parameters, after just a short treatment. This observation has not been confirmed in bisoprolol-treated patients.Received for publication on 27 February 2008; accepted for publication 15 January 2009.

Hypertension (HTN) and high serum cholesterol (HC) level are often combined in the same subject where they contribute to the overall cardiovascular risk profile. Moreover, HC is associated with an impaired vasodilatory capacity and an overexpression of vascular angiotensin II receptors, which can contribute to the development of HTN. Aim of the present study was to investigate the role of HC, if any, in the development of HTN in the Brisighella Heart Study. 1230 normotensive subjects (SBP/DBP239 mg/dl both after 8 (1980) and 12 (1984) years of follow-up.Moreover, the rate of development of HTN was enhanced in the two older subgroups of subjects (30–59 and >59 years). These data suggest that HC could substantially contribute to the development of HTN and strongly support the wide role of lipid lowering drugs and particulary statins in the primary prevention of cardiovascular disease. (See Table)

Systolic and diastolic dysfunction are quite common among elderly hypertensive patients (pts), but their prevalence respect to different hypertensive left ventricular (LV) geometric patterns is still matter of debate.Aim of the present study was to evaluate LV function respect to the presence of LV hypertrophy (H) and to the different LV geometric patterns in elderly pts with high blood pressure.We studied 134 hypertensive pts more than 65 years aged (M 83, F 51, mean age 70.8 years, range 65–82); they were submitted to clinical and echocardiographic evaluation, assessing blood pressure values, LV diastolic and systolic dimensions, LV mass, LV mass index (LV mass/height2.7), systolic function (ejection fraction, midwall fractional shortening), diastolic function (mitral E/A rate, E wave deceleration time, isovolumetric relaxation time). LVH was defined by a mass index > 51 g/m 2.7; concentric pattern was defined by a relative wall thickness [RWT = (diastolic LV posterior wall thi...

The increased prostaglandin synthesis that might follow stimulation of the arachidonic acid cascade by angiotensin-converting-enzyme inhibition (ACE-I) has been suggested to underlie the appearance of cough on ACE-I treatment. We investigated whether the prostanoid thromboxane was involved. Nine patients with essential hypertension who had cough after enalapril 20 mg once a day (coughers) were treated, while continuing the enalapril, in a double-blind crossover study with placebo or picotamide, 600 mg twice daily. Picotamide is a platelet antiaggregant that acts through both inhibition of thromboxane synthase and thromboxane-receptor antagonism. Thirteen hypertensive patients with no history of ACE-I-induced cough were also treated with enalapril and served as controls. Cough frequency was measured by a visual analogue scale and by a daily cough diary. 24 h urinary recovery of 11-dehydro-thromboxane-B2 and 6-keto-PGF1 alpha were measured to assess any changes in endoperoxide metabolism during the study periods. 11-dehydro-thromboxane-B2 (TXB2) recovery was significantly reduced by picotamide, which led to the disappearance of cough in eight patients within 72 h. Picotamide urinary recovery data suggested incomplete absorption in the non-responder. At baseline and after rechallenge with enalapril, 11-dehydro-TXB2 excretion was in the same range in the controls and in the coughers, but the latter showed significantly lower excretion of 6-keto-PGF1 alpha, and their ratio of 11-dehydroTXB2 to 6-keto-PGF1 alpha was twice that of the controls (1.40 [95% CI 0.86-1.95] vs 0.61 [0.37-0.84]). A thromboxane antagonist is effective in ACE-I-induced cough. An imbalance between thromboxane and prostacyclin may represent a marker of patients susceptible to ACE-I-induced cough.

ABSTRACT Cardiovascular reactivity to stress may have a pathophysiological role in the development of hypertension. We studied the value of measuring the blood pressure change during standardized mental challenge (mental arithmetic) to prediction of onset of high blood pressure among 80 young patients with borderline hypertension actively followed for 10 years. Patients have been classified as normo- (NR, n.34) or hyperresponders (HR, n.46) in comparison to a control population of 20 normotensive subjects (C). After adjustment for age, resting blood pressure, and body mass index at study entry, larger systolic and diastolic blood pressure responses to mental stress were associated with a higher percentage of 10-year development of high blood pressure. SSP-stressDBP stressAgeSex (%M/F)%HBPNR19.6 ± 4103 ± 3226 ± 683/1722HR29.3 ± 4*,†18.9 ± 3*,†234 ± 573/2745**,††C17.8 ± 311.2 ± 224.1 ± 481/195*p < 0.05**P < 0.01 vs NR†P < 0.05††P < 0.001 vs CThe predictive power was comparable for both systolic and diastolic blood pressure and was not related to baseline blood pressure, baseline or stress heart rate, body mass index and family history of hypertension. These data suggest that subjects at high risk for hypertension might have an exaggerated stress-induced cardiovascular response at younger age.

Echocardiography and carotid ultrasonography, by providing a more accurate assessment of cardiac and vascular damage related to hypertension, may lead to a more precise stratification of the global cardiovascular risk. However, current guidelines do not recommend systematic use of ultrasound examination of heart and large arteries in evaluating the cardiovascular risk in patients with hypertension. To assess the impact of echocardiography and carotid ultrasonography on global risk stratification in hypertensive patients classified as being at low or medium risk according to routine clinical work-up as suggested by current hypertension guidelines. Among 8502 consecutive patients screened at 44 outpatient hypertension hospital clinics in different parts of Italy, 1074 untreated individuals with low-to-medium risk essential hypertension were identified on the basis of the diagnostic routine procedures suggested by 1999 World Health Organization/International Society of Hypertension guidelines: medical history, physical examination and clinic blood pressure measurement; routine blood chemistry and urine analysis; electrocardiogram. The extent of risk for the 1074 individuals was reassessed by adding the results of ultrasound examinations of heart and carotid arteries: left ventricular hypertrophy (defined as left ventricular mass index > 120 g/m(2) in men and > 100 g/m(2) in women), carotid intima-media thickening (defined as diffuse thickening if >or= 0.8 mm), and presence of plaque (defined as focal thickening > 1.3 mm). According to routine classification, 18.7% (n = 201) of the 1074 patients were considered at low risk and 81.3% (n = 873) at medium risk. A marked change in risk stratification was obtained when ultrasound markers of target-organ damage were taken into consideration: the proportion of low-risk patients decreased to 11.1%, and that of medium risk patients to 35.7%, whereas more than 50% of the patients previously classified at low-medium risk were found to be at high absolute risk. According to a multivariate analysis, age, grade of hypertension, male sex, and serum cholesterol concentration were the variables with the greatest impact on risk class change. Ultrasound assessment of the heart and carotid wall helps to obtain a more valid assessment of global cardiovascular risk in hypertensive patients without evidence of target-organ damage after routine examination.

To assess trends in blood pressure (BP) awareness, control, treatment and use of different antihypertensive medications in a cohort of hypertensive patients. This study summarizes the results of a 12-year observation (1984-1996) of a cohort of 940 hypertensive patients from the population of 2329 participants to the Brisighella Heart Study (BHS). Primary outcome measures were the extent of BP control (systolic/diastolic BP < 140/90 mmHg) and prevalence of the use of various antihypertensive medications. From 1984 to 1996 the proportion of patients aware of elevated BP and treated for hypertension rose from 73 to 88% and from 43.8 to 50.3% in men, and from 77 to 87% and from 50 to 56.6% in women (P < 0.001 for all). The rate of BP control increased from 7.5 to 17.4% in men (P < 0.001) and from 7.3 to 18.5% in women (P < 0.001). This occurred with increased use of combination therapy (+0.2 drugs/person) and with a decline in the use of diuretics (-38.2% men and -28% women; P < 0.001) and an increase in use of calcium-channel blockers (CCBs) (24.2% in men and 12.2% in women; P < 0.001) and angiotensin-converting enzyme (ACE) inhibitors (30.7% in men and 30.8% in women; P < 0.001) as first-line drugs. The improved BP control was associated with a lower rate of fatal and non-fatal cardiovascular (CV) events. The results of this observational study confirm that the rate of BP control can be improved in daily clinical practice by increasing the use of drug combinations, as well as by the first-line prescription of ACE inhibitors and CCBs [and probably angiotensin II receptor inhibitors (ARBs)].

A number of patients with chronic heart failure (CHF) have diastolic but not systolic dysfunction. This occurs particularly in the elderly and in hypertension, but the prevalence of diastolic dysfunction in elderly hypertensives without CHF has never been investigated systematically. The Assessment of PRevalence Observational Study of Diastolic Dysfunction (APROS-diadys) project was a cross-sectional observational study on elderly (age >/= 65 years) hypertensives without systolic dysfunction [left ventricular ejection fraction (LVEF) >/= 45%] consecutively attending hospital outpatient clinics in Italy, in order to establish the prevalence of echocardiographic signs of diastolic dysfunction according to various criteria, and to correlate them with a number of demographic and clinical characteristics. Primary criteria for diastolic dysfunction was an E/A ratio (ratio between transmitral peak velocities of E and A waves) < 0.7 or > 1.5 on echocardiographic Doppler examination. Secondary criteria were: E/A < 0.5 and deceleration time (DT) > 280 ms, or isovolumic relaxation time (IVRT) > 105 ms or pulmonary vein (PV) peak systolic/peak diastolic flow (S/D) ratio > 2.5 or PV atrial retrograde flow (PV A) > 35 cm/s. Throughout Italy, 27 447 patients were screened in 107 clinics, with 24 141 excluded according to protocol. Among the remaining 3336 patients, 754 (22.6%) had signs of CHF. After exclusion of 37 protocol violators, 2545 patients (49.0% men, mean age 70.3 years, 95.4% under antihypertensive treatment) were studied ultrasonographically. Diastolic dysfunction (primary criteria) was found in 649 (25.8%) patients. Multiple logistic regression analysis found age, gender, left ventricular mass, systolic and pulse pressures and midwall shortening fraction as significant covariates. Using secondary criteria, the prevalence of diastolic dysfunction was higher (45.6%), mostly because of IVRT > 105 ms or PVA flow > 35 cm/s. CHF and diastolic dysfunction are highly prevalent in elderly hypertensives attending hospital clinics.

Stroke has a high prevalence in Italy, and is the third cause of death worldwide. Hypertension is the most important risk factor contributing to the risk of stroke. The aims of this study were to assess the risk of stroke in a large cohort of hypertensive patients, and to determine the percentage with controlled blood pressure, to establish the contribution of this factor to the risk of stroke. The study involved general practitioners to make it representative of clinical practice. They were asked to recruit 10 consecutive hypertensive patients, treated and untreated. Data collection included a full medical history and a physical examination. The 10-year absolute risk of stroke was calculated by an algorithm derived, with some modification, from the Framingham study. Most untreated hypertensive patients were grade 1 or 2. In treated hypertensive patients, controlled blood pressure values occurred in 18.4%, the percentage being less in patients with left ventricular hypertrophy and diabetes. In diabetic hypertensive patients the more stringent blood pressure control recommended by the guidelines was achieved in only 3.0% of cases. The average 10-year stroke risk was 17%, a greater risk being more common in elderly patients, diabetic individuals and in those with left ventricular hypertrophy. Current antihypertensive treatment achieved blood pressure control in a limited fraction of hypertensive patients seen by general practitioners. The risk of stroke in hypertensive patients is by no means negligible, which emphasizes the need for more attention to be paid to the prevention of this disease.

The effects of long-term treatment with differing dosages of captopril and hydrochlorothiazide in combination were evaluated in 22 hypertensive patients. There was no significant difference in antihypertensive efficacy between captopril 25 mg twice a day in combination with hydrochlorothiazide 25 mg once or twice daily and captopril 50 mg twice a day in the same combination. About 75% of patients achieved normotension. Once daily therapy with captopril 50 mg and hydrochlorothiazide 25 mg was effective in only 25% of patients. Long-term treatment (11 months) with captopril and hydrochlorothiazide did not cause any of the metabolic effects usually observed during diuretic administration. Intracellular (lymphocytic) Na+ was significantly reduced and intracellular K+ significantly increased by captopril and hydrochlorothiazide, and this led to the normalization of the intracellular Na+:K+ ratio, which is abnormally high in essential hypertension. Our data suggest that the association of low doses of captopril and hydrochlorothiazide is highly effective, well tolerated, prevents the metabolic side effects of diuretics, and has favorable effects on intracellular ionic composition.

This article reviews the data from literature regarding cell sodium and potassium content in young subjects at risk of developing essential hypertension (subjects with family history of hypertension or with borderline hypertension). The studies performed with red blood cells have produced conflicting results: approximately one-half of these studies have found an increase in intracellular Na+ in subjects with family history of hypertension (genetic normotensives) whereas the other studies found no difference. The reasons for these discrepancies are discussed. Studies with leukocytes gave more univocal results and the majority of these studies found an increase in intracellular Na+ in many genetic normotensives. These observations emphasize that it is possible to find a high intracellular Na+ in subjects with normal blood pressure. Longitudinal studies are need to clarify whether subjects with high Na+ are those who will develop hypertension. The data from our studies suggest that subjects with high Na+, even if they are normotensive, exhibit an exaggerated pressor response to mental and physical activities and that a reduction in dietary salt content produces a parallel decrease in intracellular sodium and in pressor reactivity. The data on borderline hypertension are even more scarce than those on genetic normotensives and the different classification criteria produce results which are frequently not comparable. Our studies showed that in borderline subjects not only intracellular Na+ can be increased, but also intracellular K+.(ABSTRACT TRUNCATED AT 250 WORDS)

Forty-four young subjects with borderline hypertension underwent a 5-year follow-up. At the first examination their intralymphocytic Na+ (Nai) was measured before and after 1 month of a low-salt diet. Blood pressure and heart rate were recorded at rest (baseline), during mental arithmetic, and after the test (recovery). After 5 years, no subject with normal Nai developed hypertension, and, furthermore, subjects with normal Nai had no increase in blood pressure values. Thirty-one percent of subjects with high Nai developed hypertension. Subjects developing hypertension were characterized by a high pressor response to mental stress and by an increase in recovery diastolic blood pressure in comparison with baseline diastolic blood pressure. Sixty percent of the subjects whose recovery diastolic blood pressure was at least 6% higher than baseline developed hypertension. Eighty percent of subjects whose Nai was not reduced after the diet became hypertensive. Nai and diastolic blood pressure were unrelated at the first examination; however, a significant correlation was found between Nai recorded at first examination and diastolic blood pressure recorded after 5 years. It is concluded that Nai is a good predictor of future blood pressure in borderline subjects and that subjects with normal Nai have a very low risk of developing high blood pressure.

Hypertension and high serum cholesterol levels are two of the most relevant risk factors for cardiovascular diseases. A combined increase in both risk factors has been reported in a significant proportion of patients with coronary artery disease. Statins are the most widely used drugs to treat hypercholesterolemia, and they interact with blood pressure control in different populations of hypertensive patients. A significant reduction in blood pressure associated with the use of statins has been described in patients with untreated hypertension and in patients treated with antihypertensive drugs, particularly angiotensin converting enzyme inhibitors and calcium channel blockers. The effect of statins on blood pressure control has also been reported in diabetic patients. The mechanisms responsible for the hypotensive effect seem to be largely independent of the effect of statins on lipid profile, and are probably related to their interaction with endothelial function or angiotensin II receptors. The capacity of statins to improve blood pressure control could be a useful consideration for an integrated approach to better prevention of cardiovascular diseases.

The standard mercury sphygmomanometer (SMS) and two automatic blood pressure recording devices, Dinamap 845 (D) and Sentron (S), were compared by means of a randomized 3-period cross-over experiment. Both devices recorded diastolic BP lower than SMS, on average and for most individual patients. Systolic BP was similar for SMS and S, and slightly lower for D, with variations for individual patients. A second study failed to detect effects of the physician's presence when BP was measured, whereas the difference between D and SMS was substantially confirmed.

We evaluated the antiarrhythmic efficacy and the minimal effective concentrations of propafenone and its metabolite 5-hydroxy-propafenone during a) acute intravenous infusion (1.5 mg/kg in bolus followed by 45 minutes infusion), b) an acute oral single-dose test (450 mg), and c) 14-day chronic therapy (300 mg tid) followed by a washout. Oxidative metabolism was assessed by a debrisoquine oral test in every patient. Eleven patients with stable ventricular premature beats (VPBs) greater than or equal to 300/hr and Lown class greater than or equal to 3 completed the study. The main results emphasized a certain discrepancy between the clinical effect of the acute intravenous infusion (efficacy in 5 out of 11 patients) and of the acute oral test and chronic therapy (efficacy in 11/11), with a time lag of the ECG changes during the acute intravenous infusion. The minimal effective concentrations were lower after acute oral administration compared with chronic treatment both for propafenone (200 +/- 189 ng/ml vs. 492 +/- 530 ng/ml; p less than 0.05) and for 5-hydroxy-propafenone (82 +/- 40 ng/ml vs. 149 +/- 80 ng/ml; p less than 0.02). A linear correlation was demonstrated between drug/metabolite ratios of propafenone and debrisoquine, either after acute oral (r = 0.91) or after chronic administration (r = 0.84). The pharmacokinetics of propafenone was nonlinear and showed wide interindividual variations.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of the present study was to separately investigate the effects of two different dosages of captopril on pressor, vascular and humoral response to acute extracellular volume expansion in patients with borderline hypertension (BHT). Thirty-five patients were randomly allocated in two groups undergoing acute saline infusion (0.40 ml/min/kg for 45 min and 0.15 ml/min/kg for 75 min)before and after a 7-day period of treatment with either placebo or captopril at the dose of 12.5 (LD-CAP) or 50 mg (HD-CAP) twice a day. At baseline the effects of LD-CAP were limited to an increase in PRA and to a decrease in plasma aldosterone whereas HD-CAP decreased systolic and diastolic blood pressure (SBP, DBP), forearm vascular resistance (FVR) and increased venous distensibility (VV(30)) as well. After saline loading patients treated with HD-CAP showed an increase in SBP, DBP not observed in patients allocated to LD-CAP. Urinary sodium excretion in response to NaCl loading was selectively enhanced by LD-CAP (+25%) whereas HD-CAP did not (+6.3%). The present data suggest that low-doses of ACE-inhibitors acting through a selective blockade of RAA not associated with hemodynamic changes can enhance the natriuretic response to acute volume expansion in borderline hypertensives.