Cristina Canali

Changes in Left Ventricular Anatomy and Function in Hypertension and Primary Aldosteronism

We investigated the effects on the heart of hypertension due to the excess of aldosterone and suppression of the renin-angiotensin system caused by primary aldosteronism with M-mode echocardiography and transmitral Doppler flow velocity measurements. We studied 34 consecutive patients with primary aldosteronism and 34 with essential hypertension individually matched for age, gender, race, body mass index, blood pressure values, and duration of hypertension. The groups were similar in age, body mass index, blood pressure, and duration of hypertension. However, lower serum potassium levels (3.5 +/- 0.6 versus 4.1 +/- 0.2 mmol/L, P < .0001) and plasma renin activity (0.53 +/- 0.45 versus 1.82 +/- 1.59 ng Ang I x mL-1 x h-1, P < .0001) and higher plasma aldosterone levels (1107 +/- 774 versus 206 +/- 99 pmol/L, P < .0001), left ventricular wall thickness, and left ventricular mass index (112 +/- 4.7 versus 98 +/- 3.7 g/m2, P = .029) were found in patients with primary aldosteronism compared with those with essential hypertension. Similarly, the PQ interval was longer (173 +/- 20 versus 141 +/- 14 milliseconds, P < .001) in primary aldosteronism than in essential hypertension patients. Significantly more primary aldosteronism than essential hypertension patients had left ventricular hypertrophy or left ventricular concentric remodeling (50% versus 15%, chi 2 = 11.97, P = .007). Both the E wave flow velocity integral (1063 +/- 65 versus 1323 +/- 78, P = .013) and the E/A integral ratio (0.91 +/- 0.05 versus 1.25 +/- 0.08, P < .001) were lower, and atrial contribution to left ventricular filling was higher (53.3 +/- 1.5% versus 45.5 +/- 1.3% P < .001) in patients with primary aldosteronism compared with essential hypertension patients. After 1 year of follow-up, highly significant decreases of left ventricular wall thickness and mass were observed in patients treated with surgical excision of an aldosterone-producing tumor, but not in those with medical therapy. Thus, in patients with primary aldosteronism, the excess aldosterone with suppression of the renin-angiotensin system is associated with both increased left ventricular mass and significant changes of left ventricular diastolic filling. The former changes appear to be reversible on removal of the cause of excessive aldosterone production.

Remodeling of the Left Ventricle in Primary Aldosteronism Due to Conn’s Adenoma

BACKGROUND Since hyperaldosteronism has been experimentally related to myocardial interstitial fibrosis, we investigated the effects of hypertension and excess aldosterone due to aldosterone-producing adenomas (APAs) on the heart. METHODS AND RESULTS In 52 hypertensive individuals, we performed Doppler echocardiography for estimation of left ventricular (LV) wall thickness and dimensions, transmitral LV filling flow velocity indexes, and 24-hour ambulatory blood pressure monitoring. Consecutive patients with APAs (n = 26) and essential hypertension (EH, n = 26) were individually matched for age, sex, race, body mass index, casual blood pressure, and known duration of hypertension. The matched groups were similar for demography, casual and 24-hour blood pressure values and variability, and duration of hypertension but differed for serum potassium, plasma renin activity, and aldosterone levels (all P < .001). A thicker interventricular septum (P = .015) and posterior wall (P = .009) and a higher LV mass index (118 +/- 5 versus 100 +/- 4 g/m2, P = .009) were observed in APA compared with EH patients. Both septum and posterior wall thicknesses had a significant direct relationship with age, plasma aldosterone, and mean blood pressure. The integral of the early diastolic filling wave (Ei) (P = .011) and the ratio Ei/Ai (A wave integral) (P = .038) were lower and the atrial contribution to LV filling was higher (52 +/- 2% versus 46 +/- 2%, P = .038) in APA than in EH patients. The ratio Ei/Ai was significantly (P = .008) inversely related only to age and plasma aldosterone. CONCLUSIONS In APA patients, the excess aldosterone is associated with both increased LV wall thickness and mass and decreased early diastolic LV filling indexes compared with demographically similar EH with superimposable blood pressure values, profile, and variability.

Factors affecting ambulatory blood pressure reproducibility. Results of the HARVEST Trial. Hypertension and Ambulatory Recording Venetia Study.

To assess the reproducibility of ambulatory blood pressure, we recorded 24-hour blood pressure twice 3 months apart in 508 hypertensive subjects participating in the HARVEST trial using a noninvasive technique. Blood pressure was measured every 10 minutes during the daytime and 30 minutes during the nighttime. Reproducibility was better for ambulatory than for office blood pressure. It was greater for 24-hour than for daytime blood pressure and lowest for nighttime blood pressure. The reproducibility of blood pressure variability (standard deviation) was poorer than that of the average values. A small but significant decrease in average daytime blood pressure (-0.8/-1.0 mm Hg) and virtually no change in nighttime blood pressure (+0.5/+0.1 mm Hg) were observed at repeat recording. Reducing the sampling rate by 50% caused only a small impairment of the reproducibility indexes of both the average values and variability. Blood pressure reduction was greater during the first and last hours of the recordings, indicating an effect of the hospital environment on the between-monitoring difference. Changes in body weight (-0.7 kg, P = .006, at repeat recording) were related to those of 24-hour diastolic blood pressure (P < .05). In conclusion, patient reaction to medical environment and changes of body weight seem to account for most of the change in 24-hour blood pressure that occurs over a 3-month period.

Interactive Action of the White-Coat Effect and the Blood Pressure Levels on Cardiovascular Complications in Hypertension

PURPOSE This study was undertaken to investigate whether there is a relationship between the white-coat effect and the cardiovascular complications of hypertension. PATIENTS AND METHODS In 1,013 consecutive borderline to severe hypertensive outpatients (889 men) with a mean age (+/-SE) of 33.6 +/- 0.5 years and a mean office blood pressure of 152.3 +/- 0.6/95.5 +/- 0.4 mm Hg, blood pressure was measured by noninvasive 24-hour ambulatory monitoring. Target organ damage was assessed by electrocardiogram, chest X-ray, echocardiography, and ophthalmoscopy. The degree of target organ damage and of left ventricular hypertrophy was assessed in the subjects divided according to the levels of their daytime blood pressure and the extent of their white-coat effect. RESULTS The subjects with a high white-coat effect showed a greater degree of hypertensive complications than those with intermediate or a low white-coat effect. The significant association between the white-coat phenomenon and the hypertensive complications was confirmed by the results of stepwise regression analyses, where sex, age, duration of hypertension, and ambulatory blood pressure were added to the model. A two-way ANOVA showed that both ambulatory blood pressure and the white-coat effect were related to the degree of target organ damage and to left ventricular hypertrophy. Moreover, daytime blood pressure and the white-coat effect showed an interactive effect on hypertensive complications, as the influence of the white-coat effect on end organs increased with increasing levels of ambulatory blood pressure. CONCLUSIONS The present results show that the white-coat effect is related to the degree of hypertensive complications and that this association is stronger in the subject with more severe hypertension.

Ambulatory Blood Pressure Monitoring Editing Criteria* Is Standardization Needed?

The effect of different editing methods on the reproducibility of ambulatory blood pressure and on its correlation with microalbuminuria was studied in a population of 584 stage I hypertensives participating in the Hypertension and Ambulatory Recording Venetia Study (HARVEST) Group. For systolic blood pressure (SBP), a modified version of the Casadei method showed the best reproducibility indices, followed by the original Casadei and the Kennedy methods. The Staessen, SpaceLabs, and A&D methods showed poorer indices, irrespective of whether calculations were made in recordings with more or less than 10% artifactual readings. For diastolic blood pressure (DBP), reproducibility indices did not substantially vary with the various editing procedures except for the Kennedy method, which showed a slightly better performance. Blood pressure variability (standard deviation) showed a better reproducibility with the original and modified versions of the Casadei and the Kennedy procedures than with the other methods, especially in the subjects with percentage of measurement errors greater than 10%. The correlation coefficients between 24-h SBP and albumin excretion rate ranged from 0.128 for the raw data to 0.154 for the data edited according to the Casadei procedures. For DBP, the correlation coefficients were similar except for DBP edited with the Kennedy method, which did not correlate with albumin excretion rate to a statistically significant level. These data suggest that, to make the results of different laboratories comparable, common ambulatory blood pressure editing criteria should be used. The modified version of the Casadei procedure, which is automatic and can be applied to recordings obtained from any device, should be regarded as the method of choice.

Relationship between albumin excretion rate, ambulatory blood pressure and left ventricular hypertrophy in mild hypertension

Objective To study the relationship of urinary albumin excretion to ambulatory blood pressure and other cardiovascular risk factors in borderline to mild hypertension. Patients and methods We studied 779 patients with borderline to mild hypertension (mean±SEM age 33±0.3 years; mean±SEM office blood pressure 146±0.4/94±0.2 mmHg) at 17 hypertension clinics in northeast Italy. Office and 24-h blood pressures were recorded with simultaneous urine collection for albumin measurement. In 510 subjects, left ventricular mass was measured by echocardiography. Results Subjects with overt (>30 mg/24 h) and borderline (16–29 mg/24 h) microalbuminuria had similar 24-h blood pressure levels, higher than those in the subjects without microalbuminuria. In the univariate and multiple regression analyses the albumin excretion rate was closely correlated with 24-h systolic blood pressure and not related to age, body mass index, metabolic parameters, lifestyle factors and degree of left ventricular hypertrophy. Conclusions Borderline values of urinary albumin excretion (16–29 mg/24 h) may be clinically relevant in subjects with borderline to mild hypertension. Renal and cardiac damage do not develop in parallel in the initial phases of hypertension.

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.

24 h rhythm of blood pressure and forearm peripheral resistance in normotensive and hypertensive subjects confined to bed.

Objectives To define whether a diurnal rhythm of peripheral resistance exists in normotensive and hypertensive subjects, has any relationship with that of blood pressure and differs in dipper and non-dipper hypertensives. Design and methods Forty-three subjects (13 normotensives and 30 mild-to-moderate essential hypertensives) confined for 24 h to bed were included. Blood pressure was recorded for 22 h at 15 min intervals, plethysmographic forearm flow was simultaneously measured and forearm resistance calculated. The analysis was performed for the whole 22 h period and for three 4h truncated periods, two of certain wakefulness and one of certain sleep. Results A circadian rhythm of forearm resistance was shown in the normotensives, paralleling that of blood pressure. All the normotensives were dippers, with a nocturnal blood pressure dip (systolic/diastolic) of −4.5/-6.0%. In the hypertensives, the day/night blood pressure trends were not homogeneous: 21 showed higher blood pressure values during waking time, with a trend quite similar to that of the normotensives, whereas the other nine were non-dippers. Resistance was lower during sleep than during waking both in the normotensives and in the dipper hypertensives, whereas in the non-dippers it was higher during sleep. Conclusions A sleep/waking rhythm of peripheral resistance with the highest values during daytime and the lowest during night-time does exist in normotensive as well as in the majority of hypertensive subjects resting continuously in bed, and therefore is largely independent of physical activity. Only in a minority of hypertensive patients are higher values of peripheral resistance present during sleep.

Does Orthostatic Testing Have Any Role in the Evaluation of the Young Subject With Mild Hypertension? An Insight From the HARVEST Study

The aim of the study was to assess the clinical significance of the blood pressure (BP) reaction to standing in 1029 stage I hypertensives. Office BP was measured six times in the supine position and six times after 2 min of standing. All subjects underwent 24-h ambulatory BP monitoring, and measurements of 24-h urinary epinephrine and norepinephrine excretion. Echocardiography was performed in 636 patients. With use of mixture analysis we could single out a population with abnormal diastolic BP response to standing (hyperreactors, n = 95). These subjects had a diastolic BP increase from lying to standing of >11 mm Hg. The other subjects were defined as normoreactors (n = 934). Office systolic BP was similar in the two groups. Diastolic BP was lower (91 +/- 6 mm Hg v 95 +/- 5 mm Hg, P < .0001) and heart rate was higher in the hyperreactors (77 +/- 10 beats/min v 75 +/- 9 beats/min, P = .004). After adjusting for age, gender, and smoking habits the statistical significance did not change. Adjusted 24-h systolic BP (P = .02) and diastolic BP (P = .02) were higher in the hyperreactors than in the normoreactors. Hyperreactors were characterized by higher cardiac index (3.2 +/- 0.8 L/min/m2 v 3.0 +/- 0.7 L/min/m2, P = .008 for adjusted values), lower total peripheral resistance (1420 +/- 330 dyne/sec/cm(-5) v 1600 +/- 380 dyne/sec/cm(-5), P = .003), and higher urinary norepinephrine output (114.9 +/- 80.3 microg/24 h v 90.6 +/- 78.5 microg/24 h, P = .03). Dimensional echocardiographic data and albumin excretion rate did not differ between the two groups. In conclusion, mixture analysis allowed us to identify a population of young mild hypertensives with exaggerated BP response to standing. Hyperreactors were characterized by higher whole-day BP and by a hyperkinetic hemodynamic pattern as a result of increased sympathetic tone.