Early stratification of patients with chest pain and suspected acute coronary syndrome in the Emergency Department.

AIM: The aim of this study was to investigate the accuracy of a critical pathway in the early stratification and management of patients with chest pain and suspected acute coronary syndrome (ACS) in the Emergency Department (ED). METHODS: An observational study was performed enrolling all patients with non-traumatic chest pain and suspected ACS who presented during a one-year period in the ED, where a critical pathway with five-level risk stratification, based on risk factors, characteristics of pain and ECG, was implemented. Patients were prospectively evaluated for rates of death, unstable angina, myocardial infarction or revascularization procedure occurring during admission or in the 30 days following discharge from the ED. Receiver-Operating Characteristics (ROC) curve was used to measure the accuracy of the stratification method. RESULTS: Overall, 1813 patients were enrolled: 475 patients (26.1%, 95% CI: 24.0-28.1 ) were admitted and 1338 (73.8%, 95% CI: 71.7-75.8) were discharged. Main outcomes occurred in 233 (49.9%, 95% CI: 47.5-52.2) of patients admitted and in 6 (0.4%, 95% CI: 0.06-0.7) of those discharged. The risk stratification system showed a good accuracy with an AUC-ROC curve of 0.90 (95% CI: 0.88-0.93). A total of 1541 (85%) patients were managed according to critical pathway. Adverse events were significantly fewer in patients discharged according to pathway criteria than in those who were not (0.27% vs. 1.37%, difference: 1.1% CI 95%: 0.06-2.1), without significant increase of inappropriate admissions. CONCLUSION: A critical pathway, based on clinical and ECG features, is a safe and accurate tool to stratify and manage the patients with non-traumatic chest pain and suspected ACS in the ED.

Plasma immunoreactive endothelin-1 in primary hyperaldosteronism.

This study evaluated the assessment of plasma endothelin-1 (ET-1) levels in primary aldosteronism and its correlation with other vasoactive hormones such as renin, aldosterone, catecholamines, arginine-vasopressin, and atrial natriuretic peptide. Plasma ET-1 was measured in 12 patients with primary aldosteronism (five adenomas and seven primary hyperplasia) and in 15 normal subjects. No significant differences were found in plasma ET-1 between controls and hypertensive patients both in adenoma and primary adrenal hyperplasia (8.8 + 1.6 pg/mL v 6.2 + 1.4 pg/mL v 6.5 + 1.0 pg/mL, P = NS, respectively). Further, no significant correlations were found among ET-1 and vasoactive hormones. In conclusion, these findings show that there are no differences in ET-1 levels between primary aldosteronism patients and healthy subjects. Circulating ET-1 is not involved in the hypertension in primary aldosteronism.

Spectral characteristics of heart rate and blood pressure variability in primary aldosteronism.

A disturbance of the autonomic cardiovascular function has been postulated in primary aldosteronism as a possible mechanism for hypertension. Using the method of spectral analysis of heart rate and blood pressure variability, the aim of this study was to assess sympathovagal interactions modulating cardiovascular function and baroreflex control in patients with primary aldosteronism. Seventeen patients (7 with adenomas and 10 with idiopathic hyperaldosteronism) and a control group of 11 essential hypertensives (EH) and 10 normotensive subjects were studied. Continuous finger blood pressure was measured using a Finapres device and heart rate was measured using an electrocardiographic monitor. The studies were conducted in each patient for 20 min in the supine position and 10 min during a passive head-up tilt to 60 degrees. The low frequency and the low frequency-to-high frequency ratio of systolic and diastolic blood pressures were significantly higher both in primary aldosteronism and in EH patients compared with normotensives (P < .01). Impaired response to tilt was found in the heart rate and blood pressure variability in primary aldosteronism and EH patients; the increase in low frequency was smaller than in normotensives. Baroreflex gain (assessed by alpha index) was less in primary aldosteronism and EH patients as compared with normotensives. These findings may suggest that volume expansion or sympathetically mediated central translocation of the blood volume, or both, could stimulate the cardiopulmonary receptors and impair the baroreflex gain. Our findings suggest that an enhanced peripheral vascular responsiveness to a normal sympathetic outflow may be involved in the pathogenesis of hypertension in primary aldosteronism.

Renal resistive index after captopril test by echo-Doppler in essential hypertension.

In 45 patients with essential hypertension and 15 age-matched normotensive control subjects, the renal resistive index, as an expression of arterial impedance, was determined using Doppler ultrasound. In both kidneys the resistive index was assessed at baseline and after captopril test (50 mg orally). In the moderate and severe hypertensives, compared to mild hypertensives and control subjects, the baseline resistive index was significantly higher (P less than .05). Following captopril, the resistive index increased only in normotensives (P less than .05) and in mild hypertensives (P less than .05). Univariate and multivariate analyses show that the duration and severity of hypertension correlated with an increase of the resistive index both in basal and in dynamic conditions. Thus, the use of the resistive index, as determined by echo-Doppler, could provide useful information for the assessment of renal vascular impedance in essential hypertensive patients. This would help us detect the evolution of hypertensive disease to the higher degrees of severity that are correlated to renal arteriolar damage.

Blood pressure and heart rate in young thalassemia major patients.

The analysis of blood pressure (BP) and heart rate (HR) variability is currently used to investigate the mechanisms responsible for cardiovascular control; therefore, we assessed whether an impairment of 24-h BP and HR profiles and sympathovagal interaction modulating cardiovascular function was present in patients with thalassemia major (TM) in preclinical phase of heart disease. Nine beta-thalassemic patients 18 years old without clinical signs of cardiac failure and 9 age- and sex-matched controls were studied. Twenty-four-hour-ambulatory BP and HR were measured using the SpaceLabs 90207 device. A truncated Fourier series with four harmonics was used to describe the diurnal blood pressure profile. Mean 24-h ambulatory systolic BP, diastolic BP, and mean arterial pressure were significantly lower in TM patients than in normal subjects (P < .05). A significantly higher nighttime HR value was found in TM patients (P < .05). More than 40% of the TM patients did not show a significant diurnal BP and HR rhythm. In TM patients, the overall amplitude of systolic BP, diastolic BP, and HR was significantly lower than in controls (P < .01). The night/day differences of systolic BP, diastolic BP, and HR were significantly lower in TM patients than in normals (P < .01). Furthermore, we performed power spectral analysis on short-term continuous finger BP and HR data in supine position and during passive head-up tilt. Total spectral power of systolic BP was significantly lower in patients than controls (P < .05). Low-frequency (LF) power of systolic BP and diastolic BP and LF/high-frequency (HF) ratio of HR were significantly lower during tilt in TM patients compared to controls (P < .05). High-frequency power of HR was significantly higher in patients than controls (P < .05). The baroreflex gain assessed by alpha-index was the same in supine position but was higher in TM patients during passive tilt (P < .05). An inverse relationship between LF/HF ratio of HR and hemoglobin levels in TM patients was found. Finally, plasma norepinephrine levels were significantly lower in thalassemics (P < .005). In young TM patients in a preclinical stage of heart disease, these findings demonstrated abnormal 24-h BP and HR rhythms and a decreased short-term variability of BP and HR, in particular in the LF range, showing a diminished sympathetic activity.

Impaired baroreflex function and arterial compliance in primary aldosteronism.

The purpose of this study was to evaluate if changes in vascular properties were related to baroreflex function in patients with primary aldosteronism. Twenty-three patients with primary aldosteronism, 22 essential hypertensive patients and 16 normal controls were studied. Continuous finger blood pressure (BP) was recorded by Portapres device during supine rest and active stand up. Compliance was estimated from the time constant of pressure decay during diastole. Baroreflex sensitivity was calculated by autoregressive cross-spectral analysis of systolic BP and interbeat interval. The result was that baroreflex gain and compliance were lower in primary aldosteronism patients in the supine position (P = 0.002 and P < 0.05 respectively). Aldosterone plasma levels (R2 = 0.31, P = 0.01), age, systolic and diastolic BP, high and low frequency components of diastolic BP variability were independently related to compliance in primary aldosteronism. In conclusion primary aldosteronism is associated with an impaired baroreflex function related in part to a reduced arterial compliance. Despite a reduction of BP values and aldosterone levels, surgical or pharmacological treatment did not significantly change compliance values.

Baroreflex control of heart rate is impaired in pre-eclampsia.

Autonomic nervous dysfunction, such as parasympathetic and sympathetic impairment, has been suggested as possible cause of pre-eclampsia, but the studies are not conclusive. Our purpose was to assess non-invasively if pre-eclampsia is associated with a decreased baroreflex function. Nine women with pre-eclampsia (PE), eight normotensive pregnant women, and seven healthy normotensive non-pregnant women were studied. Continuous finger blood pressure was recorded by a Portapres device in the left lateral recumbent position and active standing. Baroreflex gain was evaluated by cross-spectral analysis of systolic blood pressure and pulse interval. The result was that baroreflex gain at rest was lower in pre-eclamptic women both compared to non-pregnant and healthy pregnant subjects (P<0.05). Moreover, a decrease of the baroreflex sensitivity was present in all pregnant women in the orthostatic position (P<0.05). In conclusion pregnancy per se is associated with a decrease in the baroreflex control of the heart, whereas in pre-eclampsia, the baroreflex sensitivity is impaired further.

Dopaminergic regulation of aldosterone secretion: assessment in different subtypes of primary aldosteronism and in essential hypertension.

The inhibitory effect of dopamine on aldosterone secretion was investigated in patients with different types of primary aldosteronism, six with idiopathic hyperaldosteronism (IHA) and four with dexamethasone-suppressible hyperaldosteronism (DSH), and in 10 patients with essential hypertension. The effects of 10 mg metoclopramide given intravenously, 10 mg bromocriptine given orally and 100 micrograms adrenocorticotrophic hormone given intravenously on plasma aldosterone and renin activities were investigated in all patients. Metoclopramide induced a rise in plasma aldosterone activity only in patients with IHA and not in those with DSH and essential hypertension. After bromocriptine plasma aldosterone concentrations decreased in patients with IHA only, and after adrenocorticotrophic hormone plasma aldosterone concentrations increased in patients with DSH only. Plasma renin activity was unaffected in all cases. These results provide evidence of increased endogenous dopaminergic inhibition of aldosterone secretion in IHA and of a blunted aldosterone response in both DSH and essential hypertension.

Differential Response in Left Ventricular Mass and Arterial Resistive Index following Fosinopril Therapy.

The aim of this study was to assess the differential response in left ventricular mass and resistive index (RI) of renal and carotid arteries in mild to moderate essential hypertensive patients after 1 year of ACE inhibitor therapy. Twenty-six patients (mean age 42.9 +/- 10.9 years) underwent 24-hour ambulatory blood pressure monitoring, echocardiography and renal and carotid echo-Doppler (by measuring RI, as an expression of arterial impedance) after a placebo period and 12 months of fosinopril treatment (20 mg/day). Our study showed a significant decrease in 24-hour BP (p < 0.05), left cardiac mass (p < 0.05) and RI of common carotid and hilum renal arteries (p < 0.05). In contrast, there were no significant reductions in the interlobar renal RI (as an expression of unchanged intrarenal resistance) and in the internal carotid artery RI. While the 24-hour BP decrease was strongly correlated with the left cardiac mass modifications (r = 0.73, p < 0.005), no significant relationship was observed with the renal and carotid artery parameters. In conclusion, the present study demonstrated that long-term treatment with fosinopril produced a differential response in left ventricular mass and arterial RI in patients with mild to moderate essential hypertension. In addition, the arterial impedance modifications of common carotid and hilum renal artery were largely unrelated to the 24-hour BP reduction.

Statistical evaluation of circadian blood pressure rhythm during isradipine long-term therapy.

In this study, using the two-step truncated Fourier series with four harmonics, we analysed the diurnal blood pressure profile in 13 mild-moderate essential hypertensive patients during isradipine long-term therapy. Circadian parameters such as the amplitudes and phases of the four harmonics and the overall amplitude and phase were obtained from the model. The total duration of the study was 26 weeks. Ambulatory blood pressure was measured at 15-min, intervals using a Takeda TM 2420 device after 2 weeks of placebo and after 6 and 26 weeks of isradipine (5 mg daily) respectively. After 6 and 26 weeks therapy the blood pressure values showed a significant decrease, although the daily blood pressure curves obtained from Fourier analysis showed that the circadian rhythm was not altered by isradipine treatment. Both the night/day differences and the overall amplitude/acrophases were statistically significant at 0.6 and 26 weeks. According the nocturnal blood pressure fall, we found that long-term therapy with isradipine increased the number of patients with nocturnal blood pressure fall and reducing the early morning blood pressure rise. In conclusion, the two-step method Fourier analysis represents a novel and useful statistical approach to evaluate the presence of a significant diurnal blood pressure rhythm and to provide the circadian parameters of the 24-h blood pressure profile during pharmacological therapy.

Twenty-four-hour power spectral analysis by maximum entropy method of blood pressure in primary hyperaldosteronism.

In the present study we estimated the periodic profiles and variance structure of systolic blood pressure, diastolic blood pressure, heart rate and mean arterial pressure by using an autoregressive model of power spectrum, Maximum Entropy Method (MEM) in 8 patients with primary aldosteronism, during long-term therapy with nicardipine slow release. The four blood pressure variables were measured at 30-min intervals, using a noninvasive device (Spacelabs 90202) in 8 hypertensive patients of whom 6 with idiopathic aldosteronism (IHA) and 2 with dexamethasone-suppressible aldosteronism (DSH), before and after 24 weeks of 80 mg nicardipine daily. Blood pressure data were processed by MEM and spectral profiles were obtained. During nicardipine therapy all patients showed a significant decrease of 24-h ambulatory blood pressure values (p < 0.01). Before therapy, spectrum analysis by MEM indicated the presence of high frequency distribution of peaks for SBP, DBP, MAP and HR. The MEM power spectrum showed an increase in amplitude of sharp peaks of systolic, diastolic, MAP and heart rate in all patients after therapy at 24 h corresponding to the circadian rhythm blood pressure. Furthermore, the trend of these variables synchronized themselves in the same period after 24 weeks of nicardipine therapy, with spectral patterns of blood pressure similar to those of normotensive subjects. This chronobiologic approach, by Maximum Entropy Method, may be used as an alternative statistical analysis to search for possible rhythmic behavior of ambulatory blood pressure data before and after pharmacological treatment in secondary hypertensive patients.

Assessment of renal resistance index after captopril test by Doppler in essential and renovascular hypertension.

Ultrasonic duplex scanning has been validated as a noninvasive method to evaluate the kidney arteries and hemodynamic characteristics of renal blood flow in patients with renal artery stenosis. The purpose of our study was to assess the changes in renal vascular impedance in 22 patients with renovascular hypertension, as compared with 45 essential hypertensives and 15 normotensives, by using the Doppler parameter resistance index (RI) before and after a captopril oral test. After the captopril test the delta RI decreased significantly in the stenotic artery (P < 0.05). Univariate analysis showed that PRA values after captopril correlated inversely with the changes of RI only in the stenotic artery (P < 0.05). Thus, our findings suggest that the application of the captopril test to renal echo-Doppler may represent a feasible, noninvasive, and inexpensively useful tool in the screening studies aimed at diagnosing renovascular hypertension.

[Color-Doppler ultrasonography and hypertension. Functional assessment of the renal region]. / Eco color Doppler e malattia ipertensiva. Valutazione funzionale del distretto renale.

Color-Doppler US can be used for the morphofunctional assessment of most arterial districts. In hypertension, color-Doppler US can be used to study the renal arteries for both the diagnosis of renovascular hypertension and better physiopathologic assessment of renal arterial blood flow in essential hypertension. To this purpose, we studied renal flow characteristics with the resistive index in both basal conditions and after pharmacologic stimulation with angiotensin-converting enzyme inhibitors. The resistive index was seen to rise in parallel with hypertension severity, as measured by mean arterial pressure; the change was statistically significant (p < 0.05). Values rose step by step from 57.4 (+/- 4.96) in the right renal artery and from 56.6 (+/- 4.18) in the left one in controls, up to 62.2 (+/- 6.6) in the right and 62.3 (+/- 7) in the left renal arteries of severe hypertensives. After pharmacologic stimulation in controls and in mild hypertensives, resistive index values rose significantly (+2.32 +/- 2.1 and +3.5 +/- 5.2, respectively), while in more advanced stages of the disease this index remained unvaried from a statistical point of view (+0.5 +/- 1.7 in moderate and -0.2 +/- 2.1 in severe hypertensives). These data can be explained by reduced capability of renal blood flow autoregulation, as a consequence of a defined vascular damage. In the follow-up of more severe stages of the disease, although pharmacologic treatment had been optimized and mean arterial pressure values reduced (109.08 vs. 118.25 mmHg), even after a prolonged therapeutic wash-out, an abnormal RI response persisted in controls (-1.79 +/- 2.62 vs. -0.94 +/- 1.64), due to persistent arteriolar damage. To date, it is still to be defined if our studies can be applied not only to populations but also to single patients.

Plasma endothelin levels in cirrhotic subjects.

Endothelin-1, a potent vasoconstrictor peptide with 21 amino acid residues, is released by the vascular endothelium. Plasma immunoreactive endothelin levels were measured in 23 patients with cirrhosis and in 20 healthy subjects. Concentrations were significantly lower in patients with non-uraemic cirrhosis than in normal subjects (19.4 +/- 8.9 pmol/l vs. 48.8 +/- 24.8 pmol/l, p less than 0.002). Plasma renin, aldosterone, atrial natriuretic peptide, arginine-vasopressin and catecholamines did not show significant correlations with plasma endothelin-1 levels. Furthermore, there were no significant differences in plasma endothelin levels for etiology of cirrhosis, presence of ascites or varices. These data suggest that low circulating endothelin may be involved in the development or maintenance of systemic vasodilatation in cirrhosis.

Cardiovascular risk factors in adolescence: prevalence and familial aggregation.

BACKGROUND: In the field of primary prevention there is an increasing interest in screening pediatric populations for cardiovascular risk factors. The aim of this study was to determine the overall prevalence of high blood pressure (HBP), obesity, and sedentariness in a population of adolescents. The presence of familial aggregation for these factors was also evaluated. METHODS: The prevalence of HBP, obesity, and low physical activity was determined in 1413 adolescents ages 12-15 years (705 males, 698 females) randomly selected from Turin school children. The prevalence of HBP and obesity in parents was determined. RESULTS: One risk factor was found in 40.9% of females (2.4% HBP, 8.6% obesity, and 29.9% sedentariness) and 39.6% of males (2.8% HBP, 16.4% obesity, and 20.4% sedentariness); the concomitance of two or three risk factors were present, respectively, in 9.9 and 2.7% of females and 10.9 and 1.1% of males with a strong association of obesity and HBP. A significant familial aggregation for obesity was found and no particular relationship was found for BP. CONCLUSION: The ability to identify children developing a single or multiple risk factors is an important contribution to the prevention of serious cardiovascular diseases in adulthood.

Hormonal aspects of the relation of liver cirrhosis to essential hypertension.

The association of liver cirrhosis with arterial essential hypertension has been previously described. The present study extends the previous reports by investigating the hormonal relationships that may occur in patients with established essential hypertension associated to liver cirrhosis. We studied the renin-angiotensin, the adrenergic systems and other vasoactive hormones such as arginine-vasopressin, atrial natriuretic peptide, endothelin and parathyroid hormone in cirrhotic patients with and without essential hypertension. The data suggested that the coincidence of arterial hypertension in cirrhotic patients was characterized by the following findings: a decreased renin-angiotensin activity; a reduced systemic vasodilatation; an increased peripheral pressor effect of vasoactive hormones and an increased effective blood volume.

Noninvasive assessment of spontaneous baroreflex sensitivity in patients with liver cirrhosis.

AIMS/BACKGROUND: An impairment of baroreceptor sensitivity has been found in liver cirrhosis. Noninvasive and spontaneous estimates of baroreflex sensitivity are obtained from beat-to-beat blood pressure and heart rate recordings by means of cross-spectrum analysis and calculation of alpha-index (as a measure of baroreflex gain). The aim of the present study was to investigate the function of the spontaneous baroreflex sensitivity related to clinical Child score in liver cirrhosis. METHODS: The alpha-index was evaluated in 40 cirrhotic patients (18 with and 22 without ascites) and 17 healthy subjects by analysing finger arterial pressure recorded noninvasively with the Portapres device. RESULTS: Baroreflex sensitivity was significantly lower in cirrhotic patients with and without ascites compared with healthy subjects (p<0.01). Furthermore, in patients with ascites the baroreflex gain was significantly related to plasma sodium (p<0.01). A significant inverse relationship was present between baroreflex gain and grade of Child score and the severity of ascites (p<0.01). There were no significant relationships between hormonal parameters (catecholamines, renin, aldosterone, arginine-vasopressin, atrial natriuretic peptide and nitric oxide) and baroreflex gain. No significant differences were found between healthy subjects and cirrhotic patients with respect to systolic and diastolic blood pressure total variability in a supine position, whilst it was lower in cirrhotic patients with ascites in a tilted position (p<0.05). CONCLUSION: Our findings showed that baroreflex sensitivity was significantly impaired in cirrhotic patients when compared with healthy subjects. In addition, there was a significant trend toward lower baroreflex sensitivity values with the grade score of Child class (p<0.01). Spectral analysis of the alpha-index provides viable alternatives to the pharmacological approach for estimation of baroreflex sensitivity and may represent a prognostic tool to identify cirrhotic patients at increased risk of adverse events.

Weighted Fourier analysis of blood pressure curves after lisinopril versus atenolol administration in young hypertensives.

OBJECTIVE: To evaluate and compare the effects of lisinopril versus atenolol administration on the diurnal blood pressure profile and the nocturnal blood pressure fall in young mild-to-moderate essential hypertensives.METHODS: Thirty patients were studied. After a 2-week placebo run-in period, they were single-blind randomly assigned to receive 20 mg lisinopril or 100 mg atenolol. Using a SpaceLabs 90207 device, their ambulatory blood pressure was measured before and after 12 weeks of therapy. The readings were analysed using Fourer series with four harmonics. RESULTS: Lisinopril and atenolol administration significantly decreased office and ambulatory blood pressure values compared with the placebo period. The daily blood pressure curves obtained from Fourier analysis showed that the circadian rhythm was not altered by lisinopril and atenolol administration. From the night:day ratio for the nocturnal blood pressure fall, we found that atenolol administration minimized the average night-time blood pressure dip by increasing the number of non-dippers. In contrast, lisinopril administration did not modify the day-night difference, preserving the nocturnal blood pressure fall. CONCLUSION: Lisinopril and atenolol administration as a first-step treatment of young essential hypertensives produced comparable degrees of diurnal control of arterial pressure. The blood pressure fall at night in patients treated with atenolol was slightly less than that found with lisinopril treatment.