Glomerular hyperfiltration predicts the development of microalbuminuria in stage 1 hypertension: the HARVEST.

Factors related to the development of microalbuminuria in hypertension are not well known. We did a prospective study to investigate whether glomerular hyperfiltration precedes the development of microalbuminuria in hypertension. We assessed 502 never-treated subjects screened for stage 1 hypertension without microalbuminuria at baseline and followed up for 7.8 years. Creatinine clearance was measured at entry. Urinary albumin and ambulatory blood pressure were measured at entry and during the follow-up until subjects developed sustained hypertension needing antihypertensive treatment. Subjects with hyperfiltration (creatinine clearance >150 ml/min/1.73 m2, top quintile of the distribution) were younger and heavier than the rest of the group and had a greater follow-up increase in urinary albumin than subjects with normal filtration (P<0.001). In multivariable linear regression, creatinine clearance adjusted for confounders was a strong independent predictor of final urinary albumin (P<0.001). In multivariable Cox regression, patients with hyperfiltration had an adjusted hazard ratio for the development of microalbuminuria based on at least one positive measurement of 4.0 (95% confidence interval (CI), 2.1-7.4, P<0.001) and an adjusted hazard ratio for the development of microalbuminuria based on two consecutive positive measurements of 4.4 (95% CI, 2.1-9.2, P<0.001), as compared with patients with normal filtration. Age, female gender, and 24 h systolic blood pressure were other significant predictors of microalbuminuria. In conclusion, stage 1 hypertensive subjects with glomerular hyperfiltration are at increased risk of developing microalbuminuria. Early intervention with medical therapy may be beneficial in these subjects even if their blood pressure falls below normal limits during follow-up.

Early signs of cardiac involvement in hypertension.

BACKGROUND: Whether abnormalities of diastolic function are the earliest cardiac change in hypertension is still a matter for dispute. The aim of this study was to assess whether left ventricular diastolic dysfunction is an early sign of cardiac involvement in hypertension. METHODS: In 578 young patients with stage I hypertension from the Hypertension and Ambulatory Recording Venetia Study (HARVEST) and 101 normotensive control patients echocardiographic Doppler examination and ambulatory blood pressure monitoring were performed. RESULTS: Left ventricular mass, wall thickness, and relative wall thickness, adjusted for confounders, were greater in the hypertensive than in the normotensive patients (all P <.0001). After adjustment for confounders, the A-wave peak velocity was higher in the hypertensive patients (51.5 +/- 11.5 vs 43.4 +/- 8 cm/s, P <.001) as were A-wave velocity time integral (5.6 +/- 1.7 vs 4.6 +/- 1.3 cm, P =.01), total area (16.9 +/- 4.4 vs 15.6 +/- 3.1 cm, P =.04), and E-wave peak velocity (69.9 +/- 15.2 vs 67.5 +/- 13.3 cm/s, P =.03). All indexes of diastolic function were similar in the hypertensive subjects subdivided according to whether they had "white-coat" or sustained hypertension. Among the hypertensive subjects, age and heart rate were the strongest predictors of diastolic indexes, whereas ambulatory blood pressure explained only a marginal part of the E/A ratio, A-wave peak velocity, and the first one third total area ratio (P =.04, P =.02, and P =.05, respectively). Left ventricular mass and wall thickness were not associated with any Doppler index. When a clustering of diastolic indexes (E/A wave ratio, deceleration time, first one third of diastole, and peak E-wave-velocity) was used to identify subjects with diastolic dysfunction, no significant differences in either clinic or ambulatory blood pressure were observed between the group with diastolic dysfunction and the group with normal function. CONCLUSIONS: We conclude that the earliest signs of cardiac involvement in hypertension are left ventricular structural abnormalities. Left ventricular diastolic function is only marginally affected, even when multiple parameters of left ventricular filling are taken into account.

Structural abnormalities and not diastolic dysfunction are the earliest left ventricular changes in hypertension. HARVEST Study Group.

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.

Target-organ damage in stage I hypertensive subjects with white coat and sustained hypertension: results from the HARVEST study.

Controversy remains on whether white coat hypertension is a benign clinical condition or carries an increased risk of target-organ damage. Nine hundred forty-two stage I hypertensive subjects enrolled in the HARVEST trial underwent 24-hour ambulatory blood pressure monitoring and urine collection for albumin measurement. Reliable echocardiographic data were obtained in 722 subjects. White coat hypertensive subjects were defined on the basis of three different partition values: mean daytime blood pressure <130/90 mm Hg, <135/85 mm Hg, or <140/90 mm Hg. Ninety-five normotensive subjects with similar age and sex distribution were studied as controls. With all threshold levels, left ventricular mass index and wall thicknesses were greater in the sustained hypertensive subjects than in the white coat hypertensive subjects, also when these differences were adjusted for blood pressure readings taken in the office. Relative wall thickness was similar in the two hypertensive groups. All echocardiographic dimensional data were greater in the white coat hypertensive subjects than in the normotensive subjects. Urinary albumin and the prevalence of microalbuminuria were also greater in the sustained hypertensive subjects than in the white coat hypertensive subjects. No significant differences in urinary albumin were found between the white coat hypertensive and the normotensive subjects. These results show that within a population of subjects with stage I hypertension, subjects with white coat hypertension have a smaller degree of hypertensive complications than those with sustained hypertension, irrespective of their blood pressure levels taken in the office. However, in comparison with normotensive subjects, white coat hypertensive subjects seem to be at greater risk. Cardiac involvement seems to precede glomerular damage in the early stage of hypertension.

Target organ damage and ambulatory blood pressure in stage I hypertension. The Hypertension and Ambulatory Recording Venetia Study.

According to recent international guidelines the decision on whether to treat young subjects during the early phase of hypertension should be based not only on their office blood pressure but also on their ambulatory blood pressure and whether target organ damage has occurred. Few data on the prevalence of hypertensive complications in young subjects with mild hypertension are available. In the Hypertension and Ambulatory Recording Venetia Study (HARVEST), a multicenter trial conducted in northeast Italy, the percentage of young borderline-to-mild hypertensive subjects with echocardiographic left ventricular hypertrophy was 4.5% and the percentage with concentric remodeling was 4%. Clear differences in cardiac size and geometric adjustment to ambulatory systolic pressure between the two sexes were found. The impact of blood pressure on the walls of the left ventricle and on the left ventricular mass was remarkable in women but weak in men. The assessment of left ventricular systolic function confirmed that many young mild hypertensive subjects have an increased ejective performance. The left ventricular contractility evaluated by midwall measurement was, however, found to be depressed in 9.2% of the HARVEST participants. Their left ventricular diastolic function was similar to that of 50 normotensive controls. The prevalence of microalbuminuria [albumin excretion rate (AER) > 30 mg/24 h) was 6.1%, only slightly higher than that found by other authors among normotensive subjects and much lower than that observed among patients with more severe hypertension. For our stage I hypertensives, however, the AER was correlated to the 24 h blood pressure with high statistical significance, whereas we found no relationship between the AER and left ventricular mass index either for all of the subjects taken together or for the men and women considered separately. The results suggest that renal and cardiac involvement do not occur in parallel during the initial phase of hypertension.

Relationship of plasma renin activity with caffeine intake and physical training in mild hypertensive men. HARVEST Study Group.

UNLABELLED: To study the relationship between plasma renin activity (PRA) and coffee consumption, cigarette smoking, alcohol intake and physical activity habits. SETTING: The multicentre HARVEST trial, involving 17 Hospital Centres in Northeast Italy. SUBJECTS: 351 borderline to mild hypertensive men (mean age +/- SEM 22.7 +/- 0.47 years), never treated for hypertension. INTERVENTIONS: Office and 24-hour blood pressure measurement, supine and standing PRA levels, and urinary catecholamines output. MAIN OUTCOME MEASURES: PRA levels according to coffee intake and physical activity status. RESULTS: Coffee intake showed a major effect on PRA. Supine PRA levels were 40% higher in the subjects abstaining from coffee (n = 94) than in the coffee drinkers and was similar in the moderate (n = 223) and heavy (n = 34) drinkers. A weaker negative association was found between coffee use and PRA on standing. Office and whole-day blood pressure and heart rate, and urinary catecholamines did not differ according to coffee intake. Supine PRA was lower in the subjects performing regular physical activity than in the inactive subjects. Office and whole-day diastolic blood pressure and heart rate, and urinary norepinephrine were lower in the active than in the sedentary men. No relationship was found between PRA measured either in the supine or the upright posture and tobacco or alcohol use. In a multiple linear regression model supine PRA was negatively correlated with age, coffee consumption and physical activity habits. CONCLUSIONS: Chronic coffee intake and physical training showed an inverse relationship with PRA in mild hypertensive men, while tobacco and alcohol use were unrelated to PRA.

Prevalence and clinical correlates of microalbuminuria in stage I hypertension. Results from the Hypertension and Ambulatory Recording Venetia Study (HARVEST Study).

The objective of the present study was to examine the association between albumin excretion rate (AER) and office and ambulatory blood pressures (BP), and other recognized cardiovascular risk factors in stage I hypertension. The study was carried out in 870 never-treated 18- to 45-year-old hypertensives (628 men, 242 women). Office and ambulatory BP, 24-h urinary collection for AER assessment, and echocardiographic left ventricular mass (n = 587) were obtained. AER was similar in men and women (12.3 v 12.5 mg/24 h) and was unrelated to age and body mass index. In 85.2% of the subjects, AER was < 16 mg/24 h, in 8.3% it was between 16 and 29 mg/24 h (borderline microalbuminuria), and in 6.1% it was >or= 30 mg/24 h (overt microalbuminuria). Office systolic BP was not different in the three groups, whereas 24-h systolic BP was higher in the subjects with microalbuminuria than in those with normal AER (P < .0001) and was similar in the two microalbuminuric groups. Office and 24-h diastolic BPs were higher in the subjects with overt microalbuminuria than in those with normal AER. Left ventricular mass was correlated to systolic (P < .0001) and diastolic (P = .01) 24-h BP, but was unrelated to AER. Family history for hypertension, smoking, coffee and alcohol intake, and physical activity habits did not influence AER. In a logistic regression analysis, 24-h systolic BP emerged as the only determinant of microalbuminuria (P < .0001). In conclusion, these results indicate that borderline levels of microalbuminuria may also be clinically relevant in stage I hypertension. Overweight and lifestyle factors do not appear to influence AER in these patients. Finally, the lack of correlation between AER and left ventricular mass suggests that renal and cardiac involvement do not occur in a parallel fashion in the initial phase of hypertension.

[Isolated ACTH deficiency: description of a clinical case]. / Deficit isolato di ACTH: descrizione di un caso clinico.

A 34-year man was admitted to the hospital with symptoms of hypoglycemia. The endocrine investigations indicated adrenocortical insufficiency secondary to isolated ACTH deficiency: low ACTH and cortisol plasma levels, significant increase of cortisol following prolonged stimulation with depot tetracosactrin, normal secretory reserve of other anterior pituitary hormones. The absence of ACTH-response after corticotropin releasing hormone and insulin tolerance tests suggested a primary impairment of corticotropin cells.

[A computerized support system for the ambulatory treatment of patients with arterial hypertension]. / Un sistema computerizzato di supporto al trattamento ambulatoriale del paziente con ipertensione arteriosa ("AGAPE").

AGAPE (Computer-based Outpatients' Clinic Programme) is a programme for IBM-compatible microcomputers realised by physicians for the management of hypertensive patients. The programme is planned to make the operators' work complete and expeditious while, at the same time, respecting the standard formulation of the clinical approach to the patient. The collection, organisation, recording and communication of data are handled on line by the programme under the operator's control. Special attention has been given to the control of the quality of the data collected as well as to their easy use for clinical, research and statistical purposes. This programme was used for 52 months in a hypertension clinic where physicians and nurses work jointly. Up to April 1989, 1924 new patient visits and 10,639 control visits together with 3,375 groups of lab tests were inserted. The mean training time for new operators was 3.2 hours; the mean data insertion time was 12.5 minutes for the first visit, 3 minutes for the subsequent visits and 2.5 minutes for lab tests. The drop-outs, evaluated at one-year follow-up on each 250 patients before and after the introduction of the computerized system, were 84/250 and 64/250 respectively (p less than 0.05), with a trend to wards the better control of hypertension (diastolic blood pressure less than 90 mmHg, 128/250 vs 143/250, n.s.).

[Therapeutic action of Piroxicam administered rectally in rheumatic diseases. Controlled double-blind study]. / Attività terapeutica del Piroxicam per via rettale nelle malattie reumatiche. Studio controllato in doppio cieco.

In a 15 day double-blind clinical trial 39 patients affected with rheumatic disease have been enrolled to evaluate the therapeutic effect of rectal administration of Piroxicam, in comparison with Indomethacin. At the end of the study, 20 patients had been treated with Piroxicam and 19 with Indomethacin. Nine patients in the Indomethacin group and one in the Piroxicam group dropped-out. Both drugs safety resulted good in the patients who completed the study, whereas 5 out of 10 dropped-out patients stopped the trial in consequence of severe side-effects of Indomethacin. Piroxicam induced a very good improvement in 76% of the patients, moderate in 19% and no improvement in 5%; Indomethacin induced a very good improvement in 75% of the patients, moderate in 15% and no improvement in 10%. No significative modifications resulted from the control of the laboratory blood tests. Piroxicam (30 mg/die) showed a therapeutic activity similar to Indomethacin (100 mg/die). The rectal administration of Piroxicam can be then considered a very good alternative to the oral one, particularly in the patients in which oral use of NSAID is counter-indicated.