Loredano Milani

Heart rate as a predictor of development of sustained hypertension in subjects screened for stage 1 hypertension: the HARVEST Study.

Objective Whether heart rate predicts the development of sustained hypertension in individuals with hypertension is not well known. We carried out a prospective study to investigate whether clinic and ambulatory heart rates assessed at baseline and changes in clinic heart rate during 6 months of follow-up were independent predictors of subsequent blood pressure (BP). Methods The study was conducted in a cohort of 1103 white, stage 1 hypertensive individuals from the HARVEST study, never treated for hypertension and followed-up for an average of 6.4 years. Data were adjusted for baseline BP, age, sex, body fatness, physical activity habits, parental hypertension, duration of hypertension, cigarette smoking, alcohol consumption, and change of body weight from baseline. Results Clinic heart rate and heart rate changes during the first 6 months of follow-up were independent predictors of subsequent systolic blood pressure (SBP) and diastolic blood pressure (DBP) regardless of initial BP and other confounders (all P < 0.01). A significant interaction was found between sex (male) and baseline resting heart rate on final SBP (P = 0.017) and DBP (P < 0.001). The ambulatory heart rate and the heart rate white-coat effect did not add prognostic information to that provided by the clinic heart rate. Patients whose heart rate was persistently elevated during the study had a doubled fully adjusted risk (95% confidence interval 1.4–2.9) of developing sustained hypertension in comparison with subjects with a normal heart rate. Conclusions Baseline clinic heart rate and heart rate changes during the first few months of follow-up are independent predictors of the development of sustained hypertension in young persons screened for stage 1 hypertension.

Effects of nadolol treatment on renal and hepatic hemodynamics and function in cirrhotic patients with portal hypertension

Twelve cirrhotic patients with portal hypertension and esophageal varices were treated with nadolol for 1 month, and the effects on renal and hepatic hemodynamics and function were studied. A significant decrease in cardiac output, portohepatic gradient, and effective hepatic blood flow was found, whereas mean arterial pressure, liver function, effective renal blood flow, glomerular filtration rate, and urinary sodium and potassium excretions were not affected. In seven patients esophageal varices were also reduced. A significant correlation was found between the decrease in portohepatic gradient and that in cardiac output. The percentage of cardiac output distributed to the kidneys was significantly increased after nadolol treatment. In conclusion, nadolol seems to have properties useful for the treatment of portal hypertension in patients with liver cirrhosis.

The Effects of Alcohol Consumption on Ambulatory Blood Pressure and Target Organs in Subjects With Borderline to Mild Hypertension

The objective of this study was to examine the relationship of alcohol consumption to target organ involvement and ambulatory blood pressure (BP) in a population of young borderline to mild hypertensive subjects. Participants were 793 male subjects, aged 18-45 years, from the HARVEST Study. The analysis was performed in three age-matched groups with similar body mass index. Casual and 24-h ambulatory BP monitoring, routine biochemistry, echocardiography, and albumin excretion rate were measured. The men were divided into three groups: 1) nondrinkers, 2) drinkers of < 50 g/day, and 3) drinkers of > or = 50 g/day. Office systolic BP was not significantly different among the three groups, whereas 24-h and daytime BPs increased progressively from the first to the third group (group 1 v 3; P = .01 for 24-h systolic BP and P = .02 for daytime systolic BP). These differences remained significant even after adjusting for smoking. Left ventricular mass index, interventricular septum thickness, and wall thickness increased progressively from group 1 to group 3; this difference also remained significant after adjusting for smoking and 24-h BPs. The albumin excretion rate was much higher in group 3 than in group 1 (P = .003), but when 24-h BP was added to the model the difference was no longer significant. These results indicate that alcohol has a detrimental effect on the heart and the kidney. Alcohols effect on LV wall thickness appears to be direct, whereas its action on albumin excretion rate seems to be mediated mainly by its effect on BP.

How often we need to measure brain natriuretic peptide (BNP) blood levels in patients admitted to the hospital for acute severe heart failure? Role of serial measurements to improve short-term prognostic stratification.

BACKGROUND Brain natriuretic peptide (BNP) is increasingly used in the management of patients with heart failure (HF). It is still unclear how to use serial BNP measurement in HF. AIM To evaluate the usefulness of three consecutive measurements of BNP in patients (pts) hospitalized for acute HF. METHODS Clinical evaluation, BNP levels and echocardiography were assessed in 150 pts (67% males, age: 69+/-12 years; left ventricular ejection fraction: 34+/-14%) admitted for severe HF (NYHA class III-IV: 146/150). BNP measurements were obtained: at admission (basal, T0), at discharge (T1) and at first ambulatory control (T2), after optimization of medical therapy in those with discharge BNP level >250 pg/mL. End-points were death and hospital readmission during 6-month follow-up. RESULTS According to BNP levels 3 groups of patients were identified: Group 1 (62 pts, 41%), in whom discharge (T1) BNP was high and persisted elevated at T2 despite aggressive medical therapy; at 6-month follow-up 72% died or were hospitalized for HF. Group 2 (36 pts, 24%), in whom discharge (T1) BNP was high but decreased after medical therapy (T2); death and HF-readmission were observed in 8 pts (26%). Group 3 (52 pts, 35%), in whom discharge (T1) BNP levels were <250 pg/mL and persisted below this value at T2; death and HF-hospital readmission were observed in 6 pts (12%). Event rate differences among groups were statistically significant (p<0.001). At Cox-analysis discharge BNP cutoff of 250 pg/mL was the only parameter predictive of a worse outcome. CONCLUSION These data suggest that 3 BNP measurements, at admission, at discharge and few weeks later can allow to identify HF pts whom, despite a further potentiation of medical therapy, will present a worsening or even will die during short-term follow-up.

The NT-proBNP assay identifies very elderly nursing home residents suffering from pre-clinical heart failure.

Little is known about the prevalence of heart failure among very old people, although hospitalisation rates for chronic heart failure are very high. Recently, brain natriuretic peptides have emerged as important diagnostic and prognostic serum markers for congestive heart failure.

Structural Abnormalities and Not Diastolic Dysfunction Are the Earliest Left Ventricular Changes in Hypertension

It has been claimed that diastolic dysfunction is the earliest cardiac abnormality in hypertension, preceding the development of left ventricular (LV) structural abnormalities. To detect early signs of hypertensive cardiac involvement 722 subjects (533 men and 189 women), 18-45 years old, with stage I hypertension, were studied by M-mode and Doppler echocardiography. Blood pressure was measured by 24-h ambulatory monitoring. Ninety-five normotensive individuals of similar age and gender distributions were studied as controls. Significant, though modest, changes of LV mass and geometry were found in the participants in comparison with the normotensive controls. The increment was +10.4 g/m2 for LV mass index, +1.8 mm for LV wall thickness, and +0.032 for relative wall thickness. A slight increase in atrial filling peak velocity was found in the hypertensive subjects at Doppler analysis of transmitral flow, but the ratio of early to atrial velocity of LV diastolic filling did not differ between the two groups. In multiple regression analyses, which included age, body mass index, heart rate, smoking, and physical activity, 24-h mean blood pressure emerged as a significant predictor of LV mass index (men, P = .003; women, P = .04) and wall thickness (men, P = .03; women, P = .004) in the hypertensive subjects, whereas no index of diastolic filling was significantly associated with ambulatory blood pressure in either gender. The present data indicate that changes in LV anatomy are the earliest signs of hypertensive cardiac involvement. Left ventricular filling is affected only marginally in the initial phase of hypertension.

Plasma Brain Natriuretic Peptide Predicts Short-Term Clinical Outcome in Heart Failure Patients With Restrictive Filling Pattern

OBJECTIVE Plasma brain natriuretic peptide (BNP) is an important parameter of severity in congestive heart failure (CHF). We analyzed if BNP might stratify 6-month clinical outcome in outpatients with CHF with restrictive mitral filling pattern. METHODS All subjects with New York Heart Association (NYHA) class II to IV and restrictive filling pattern were enrolled at hospital discharge after an acute decompensation. NYHA class, BNP, and echocardiogram for the evaluation of left ventricular ejection fraction (LVEF) and diastolic function were analyzed. Death and hospital readmission for CHF were the clinical events observed. RESULTS A total of 250 patients (66% were male, mean age 73 years) were enrolled. The mean NYHA class was 2.5 +/- 0.6, LVEF was 38% +/- 15%, and mean deceleration time was 120 +/- 16 ms. The mean BNP was 643 +/- 566 pg/mL. During the 6-month follow-up, 35 patients (14%) died and 106 patients (42.4%) were readmitted for CHF (event group); in 109 patients (43.6%) no events were observed (no-event group). Higher NYHA class (2.7 +/- 0.6 vs 2.4 +/- 0.6, P = .001) and reduced LVEF (34% +/- 13% vs 42% +/- 17%, P = .01) but similar deceleration time (119 +/- 16 ms vs 122 +/- 17 ms, P = not significant) were observed in the event group. A higher level of mean BNP (833 +/- 604 pg/mL vs 397 +/- 396 pg/mL, P = .01) was recorded in the event group. The multivariate Cox analysis confirmed that LVEF (P = .04), NYHA class (P = .02), and plasma BNP (P = .0001) were associated with adverse short-term clinical outcome. CONCLUSION Patients with CHF with a restrictive diastolic pattern had poor short-term clinical outcome. NYHA class and LVEF at discharge might predict cardiovascular events, but plasma BNP proved to be the strongest predictor.

Early diagnosis of congestive heart failure: clinical utility of B-type natriuretic peptide testing associated with Doppler echocardiography.

Objective B-type natriuretic peptide (BNP) has emerged as an important diagnostic serum marker of congestive heart failure (CHF). The aim of this study was to evaluate whether BNP measurement associated with echocardiography could effectively stratify patients with new symptoms as part of a cost-effective heart failure programme based on cooperation between hospital cardiologists and primary care physicians. Methods Patients were referred to the cardiology clinic by general practitioners in case of clinical suspect of CHF. All patients underwent clinical examination, transthoracic echocardiography and plasma determination of BNP. Systolic dysfunction was defined as a left ventricular ejection fraction < 45%; diastolic dysfunction was defined as a preserved systolic function with signs of diastolic impairment. Results Three hundred and fifty-seven subjects were examined (50% males, mean age 73 years). BNP concentration was 469 ± 505 pg/ml in the 240 patients diagnosed with CHF, compared with 43 ± 105 pg/ml in the 117 patients without CHF (P = 0.001). CHF patients were grouped into those with diastolic dysfunction (n = 110; BNP 373 ± 335 pg/ml), systolic dysfunction (n = 108; BNP 550 ± 602 pg/ml), and both systolic and diastolic dysfunction (n = 22; BNP 919 ± 604 pg/ml). At receiver operating characteristic analysis, the optimal BNP cut-off level for diagnosing CHF was 80 pg/ml (sensitivity 84%, specificity 91%). According to cost analysis, this cut-off level might provide a cost saving of 31% without affecting diagnostic accuracy. Conclusions In patients referred by general practitioners for suspected CHF, plasma BNP levels might help to stratify subjects into different groups of cardiac dysfunction.

Enhanced Renal Sympathetic Tone in Liver Cirrhosis: Evaluation by Intrarenal Administration of Dihydroergocristine

Mean renal blood flow (MRBF), cortical blood flow (CBF), glomerular filtration rate (GFR), heart rate, arterial blood pressure, Na+ and K+ excretion were determined before and 10 min after intrarenal administration of dihydroergocristine (0.017 mg/kg b.w.) in 13 patients suffering from liver cirrhosis. Cardiac output was also determined in 6 patients. Baseline values of MRBF and CBF were significantly lower in cirrhotics than in the 14 control subjects. Following intrarenal administration of the drug, renal hemodynamic parameters increased significantly, while GFR decreased. Systemic hemodynamic parameters, diuresis, Na+ and K+ excretions were unchanged. These data show that dihydroergocristine has a renal vasodilator effect, probably mediated by alpha-adrenergic blockade. The effect probably is prevalent at the postglomerular site, where the increase in vascular resistance is greatest. The effect of the drug suggests that patients with liver cirrhosis have enhanced renal sympathetic activity which is, at least in part, responsible for the renal vasoconstriction.

Value of prealbumin plasma levels as liver test

To assess the sensitivity, specificity and clinical value of prealbumin as liver test, prealbumin plasma levels were measured in 100 patients with liver disease and in 65 patients without clinical evidence of liver impairment. The sensitivity of prealbuminemia was higher than that of albumin, pseudocholinesterase, apolipoprotein and prothrombin activity. Its specificity was higher than that of pseudocholinesterase and comparable with the specificity of other liver tests. Prealbumin plasma levels were progressively decreasing in patients with liver cirrhosis graded as Childs A, B and C, respectively. In these patients prealbuminemia was correlated with galactose elimination capacity, assumed to be an index of maximal liver functional capacity.