SHAred DEcision making in Pelvic Organ Prolapse (SHADE-POP); Implementation is not as easy as it seems.

OBJECTIVE: Despite the positive effects of decision aids (DAs), implementation remains a significant challenge. The aim of the current study was to determine what barriers clinicians experience using a DA for pelvic organ prolapse (POP). METHODS: This study was conducted with a qualitative descriptive design including in-depth semi-structured interviews according to COREQ-criteria. Participants included clinicians and patients. Grounded theory analysis was used to describe the main themes. RESULTS: A total of 9 clinicians and 4 patients participated. Four major themes (1) opinions about shared decision making (SDM), (2) current practice, (3) experience with the DA, (4) suggestions for improvement and one minor theme (5) experience with the study, emerged. Clinicians were predominantly positive about the DA. CONCLUSION: Despite the positive attitudes of the clinicians in this study, the implementation of a DA is still challenging. The DA is forgotten regularly as improvement of logistics is needed, clinicians assume they already provide good care which might result in a reluctance to change and more engagement of physicians is needed. PRACTICE IMPLICATIONS: Regular contact with clinicians to remind, help and increase engagement and a decrease of the logistic burden is needed to ensure all patients can fully benefit of the DA.

A PUBLIC HEALTH PERSPECTIVE ON THE IMPORTANCE OF PLASMA PHENYLALANINE AND TYROSINE DETERMINATION IN RELATION TO NEWBORN SCREENING AND MONITORING OF TREATMENT IN PHENYLKETONURIA.

Newborn screening of phenylketonuria (PKU) is performed in many countries, including Romania, in addition to screening for congenital hypothyroidism. Patients affected by PKU require frequent measurements of phenylalanine (Phe) level in blood plasma. Such a determination is important not only in early diagnostic, but also in monitoring the treatment of PKU to maintain phenylalaninemia within limits that will not affect the brain. A simple, highly sensitive, accurate and rather inexpensive procedure for the simultaneous determination of Phe and Tyr plasma concentrations was previously described in this journal. The new procedure may be applied in many clinical laboratories, including those with no previous experience in diagnosis of inherited amino acid metabolic disorders. In this way the major public health problems linked to PKU not being detected in the first weeks of life (including the burden of institutionalized children with preventable mental retardation) may be avoided.

Obesity is a strong determinant of hypertensive target organ damage in young-to-middle-age patients.

OBJECTIVE: To examine the impact of overweight and obesity on development of target organ damage in the early stage of hypertension. SUBJECTS: Participants were 727 young-to-middle-age subjects screened for stage 1 hypertension and followed for 8 years. MEASUREMENTS: Ambulatory blood pressure (BP), albumin excretion rate and echocardiographic data were obtained at entry, every 5 years and/or before starting antihypertensive treatment. RESULTS: During the follow-up, hypertension needing treatment was developed by 54.7% of the subjects with normal weight, 66.6% of those with overweight and 73.0% of those with obesity (P<0.001). Kaplan-Meier curves showed that patients with obesity or overweight progressed to sustained hypertension earlier than those with normal weight (P<0.001). At study end, rate of organ damage was 10.7% in the normal weight, 16.4% in the overweight and 30.1% in the obese subjects (P<0.001). In a multivariable logistic regression analysis, overweight (P=0.008) and obesity (P<0.001) were significant predictors of final organ damage. Inclusion of changes in 24-h BP and body mass index, and of baseline organ damage did not virtually modify these associations (P=0.002 and <0.001, respectively). Obesity was a significant predictor of both left ventricular hypertrophy (P<0.001) and microalbuminuria (P=0.015) with an odds ratio (95% confidence interval) of 8.5 (2.7-26.8) and 3.5 (1.3-9.6), respectively. CONCLUSION: These data indicate that in hypertensive subjects obesity has deleterious effects on the cardiovascular system already at an early age. Preventive strategies addressed to achieve weight reduction should be implemented at a very early stage in young people with excess adiposity and high BP.

Phosducin rs12402521 polymorphism predicts development of hypertension in young subjects with overweight or obesity.

BACKGROUND AND AIMS: The G-protein regulator phosducin has been shown to be associated with stress-dependent blood pressure, but whether obesity is a modulator of the relationship between phosducin and risk of hypertension is unknown. We studied the effect of two phosducin polymorphisms on risk of hypertension in 273 overweight or obese (Ov-Ob) young-to-middle-age participants from the HARVEST and 287 normal weight (NW) participants. METHODS AND RESULTS: Genotyping of phosducin SNPs rs12402521 and rs6672836 was performed by real time PCR. For rs12402521, 64.6% of the participants were homozygous for the G allele, 27.9% heterozygous, and 7.5% homozygous for the A allele. During 7.7 years of follow-up, 339 subjects developed hypertension. In a Cox multivariable model, carriers of the A allele had a 1.28 (95% CI,1.00-1.63, p = 0.046) increased risk of hypertension. However, increased incidence of hypertension associated with A allele (AA + AG, 79% and GG, 59%, p = 0.001) was observed only among Ov-Ob individuals with a hazard ratio of 1.60 (95% CI, 1.13-2.21, p = 0.007) whereas in NW subjects the incidence of hypertension did not differ by genotype (56% in both groups). In the whole cohort, there was a significant interaction of phosducin genotype with body mass index on the risk of hypertension (p = 0.012). For SNP rs6672836 no association was found with incident hypertension. No haplotype effect was detected on the risk of hypertension. CONCLUSION: These data suggest that phosducin rs12402521 polymorphism is an important genetic predictor of obesity-related hypertension. In Ov-Ob carriers of the A allele aggressive nonpharmacological measures should be implemented.

Efficacy and safety of azithromycin 1 g once daily for 3 days in the treatment of community-acquired pneumonia: an open-label randomised comparison with amoxicillin-clavulanate 875/125 mg twice daily for 7 days.

This randomised, open-label, non-inferiority study was designed to demonstrate that a 3-day course of oral azithromycin 1 g once daily was at least as effective as a standard 7-day course of oral amoxicillin-clavulanate 875/125 mg twice daily in the treatment of outpatients with community-acquired pneumonia (Fine class I and II). In total, 267 patients with clinically and radiologically confirmed community-acquired pneumonia were randomly assigned to receive either the azithromycin (n=136) or the amoxicillin-clavulanate (n=131) regimen. At screening, 60/136 (58.8%) and 61/131 (62.9%) respectively had at least one pathogen identified by sputum culture, PCR, or serology. The primary endpoint was the clinical response in the intent-to-treat population at the end of therapy (day 8 to 12). Clinical success rates were 126/136 (92.6%) for azithromycin and 122/131 (93.1%) for amoxicillin-clavulanate (treatment difference: - 0.48%; 95% confidence interval: - 5.66%; 4.69%). Clinical and radiological success rates at follow-up (day 22-26) were consistent with the end of therapy results, no patient reporting clinical relapse. Bacteriological success rates at the end of therapy were 32/35 (91.4%) for azithromycin and 30/33 (90.9%) for amoxicillin-clavulanate (treatment difference: 0.52%; 95% confidence interval - 10.81%; 11.85%). Both treatment regimens were well tolerated: the overall incidence of adverse events was 34/136 (25.0%) for azithromycin and 22/132 (16.7%) for amoxicillin-clavulanate. In both treatment groups, the most commonly reported events were gastrointestinal symptoms. Azithromycin 1g once daily for 3 days is at least as effective as amoxicillin-clavulanate 875/125 mg twice daily for 7 days in the treatment of adult patients with community-acquired pneumonia.

Contaminant-associated disruption of vitamin A and its receptor (retinoic acid receptor alpha) in free-ranging harbour seals (Phoca vitulina).

Polychlorinated biphenyls (PCBs) have been associated with a number of toxic effects in marine mammals such as endocrine disruption and immunotoxicity that, in turn, are widely thought to have contributed to population level impacts including reproductive failure and outbreaks of disease. In this study, the dietary hormone vitamin A and expression levels of one of its receptors, retinoic acid receptor alpha (RARalpha), were used as biomarkers of PCB-associated health effects in harbour seals. Harbour seal pups (n=24) were live-captured in coastal British Columbia, Canada, and Washington State, USA, and sampled for whole blood (to obtain peripheral blood mononuclear cells, PBMCs) and blood plasma, as well as biopsies of blubber and skin. Concentrations of circulatory vitamin A (retinol) in plasma and stored vitamin A in blubber were negatively associated with blubber PCB concentrations (R=-0.518, p=0.013 and R=-0.645, p=0.009, respectively). However, vitamin A concentrations in skin, an important target tissue, remained constant, which likely reflects a compensatory transfer from blubber to maintain physiological functions. In addition, we characterized the harbour seal RARalpha, and investigated its expression levels as a potential biomarker in seals. RARalpha expression in blubber, but not on PBMCs, was elevated in more contaminated animals (R=0.580, p=0.009). This may represent a direct contaminant-related effect, or, a compensation for the contaminant-related disruption of (circulatory and/or blubber) hormone levels. Since vitamin A is critical to developmental, reproductive and immunological health, our observations of a contaminant-related disruption of its physiology in free-ranging seals may portend population level consequences. Vitamin A concentrations and RARalpha expression levels can therefore represent relevant and sensitive biomarkers of PCB-associated toxic effects in toxicological studies of marine mammals.

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.

Effects of physical exercise on clinic and 24-hour ambulatory blood pressure in young subjects with mild hypertension.

BACKGROUND: The aim of the study was to assess the effect of physical activity on 24-hr ambulatory blood pressure (ABPM) and office blood pressure (BP) in 572 male subjects with borderline to mild hypertension from the HARVEST study. METHODS: Subjects were 18 to 45 years old with diastolic BP of 90-99 mmHg and/or systolic BP of 140-159 mmHg. They never took any anti-hypertensive therapy. All subjects underwent physical examination, office BP measurement and two 24-hr ambulatory BP monitorings performed three months apart. Subjects were classified as non exercisers, group 1 (n=331), mild exercisers, group 2 (n=192) and heavy exercisers, group 3 (n=49). During the three months of follow-up subjects maintained the same physical activity habits. There was no difference in smoking and alcohol consumption between the 3 groups. As the groups differed significantly in age and body mass index data were adjusted for these confounders. RESULTS: At baseline office and ambulatory systolic BP were similar in the 3 groups, while diastolic BP was proportional to the level of physical activity although the difference was significant only between the group of non-exercisers and mild exercisers. Heart rate (HR) was always inversely related to the intensity of exercise. After three months follow-up office systolic BP was similar among the three groups and diastolic BP slightly decreased in the exercisers (group 1 vs group 3 p=0.02, group 2 vs group 3 p=0.04). At ABPM the group of heavy exercisers showed a significant decrease in daytime systolic BP (135.4plus minus0.6 vs 134plus minus0.8 vs 132.2plus minus1.6 mmHg; group 1 vs group 3 p<0.05) and the difference between systolic ambulatory BP at the 3rd month and at baseline, showed an additional significant decrease according to exercise intensity (24-hr systolic BP group 1 vs group 3 p=0.001, group 2 vs group 3 p=0.004; daytime systolic BP group 1 vs group 3 p=0.0009, group 2 vs group 3 p=0.004; night-time systolic BP group 1 vs group 3 p=0.02, group 2 vs group 3 p=0.02). No changes in ambulatory diastolic BP were observed. CONCLUSIONS: In conclusion, physical activity has a positive effect in lowering BP attenuating the risk of hypertension in young subjects with borderline hypertension. The anti-hypertensive effect of physical activity persisted after three months and the group of exercisers had an additional reduction in systolic BP detected by ABPM. To obtain accurate information on chronic levels of arterial pressure over time 24-hr ambulatory BP should be preferred to traditional casual readings.

Efficacy, tolerability and influence on "quality of life" of nifedipine GITS versus amlodipine in elderly patients with mild-moderate hypertension.

OBJECTIVE: The main purpose of this study was to compare efficacy, tolerability and influence on quality of life (QOL) of nifedipine gastrointestinal therapeutic system (NI) 30-60 mg once a day vs amlodipine (AM) 5-10 mg once a day in elderly patients with mild-moderate hypertension. DESIGN: This was a randomized, double-blind, parallel-group, multicenter study. After a 2-week single-blind placebo run-in, patients were randomized to either NI 30 mg or AM 5 mg. Responders continued on the same dosage for 16 additional weeks, while non-responders were titrated to 60 mg NI or 10 mg AM. METHODS: Blood pressure was measured by mercury sphygmomanometer and efficacy equivalence of NI and AM tested by covariance analysis. Diastolic blood pressure (DBP) was the primary efficacy parameter, its baseline value being taken as covariate while centers effect and treatment interaction were included as fixed effects in the analysis model. The secondary efficacy variables systolic blood pressure (SBP) and scores for QOL were analyzed according to the same model. RESULTS: At the end of the study, overall mean DBPs, calculated as least-square means (LSMEANS), in the "by protocol" population were 87.5 mmHg for NI and 86.7 for AM (difference 0.8 mmHg with 90% CI -1.2 to 2.8 mmHg). In the "by intention to treat" (ITT) population LSMEANS were 87.6 mmHg for NI and 86.4 mmHg for AM (difference 1.2 mmHg with 90% CI -0.6 to 3.1 mmHg). SBP LSMEANS in the "by protocol" population were 147.7 mmHg for NI and 147.3 mmHg for AM (difference 0.3 mmHg, with 90% CI -3.7 to 4.3); corresponding values in the "by ITT" population were 148.0 mmHg for NI and 147.2 for AM (difference 0.8 mmHg, with 90% CI -2.8 to 4.6). Mean values for QOL parameters were not significantly different. A total of 173 episodes of adverse events were documented in 54 patients (26 NI and 28 AM), dropouts were 15 (20% of group) on NI and 21 (28%) on AM. CONCLUSIONS: NI 30-60 mg was shown to be as efficacious and safe as AM 5-10 mg in elderly patients with mild-moderate hypertension. QOL improved compared to baseline with no significant difference between the two drugs, thus confirming a positive class effect for calcium antagonists.

Domoic acid: a fascinating marine toxin.

There are indications that toxic algal blooms are increasing because of pollution of coastal waters and worldwide shipping. This mini-review deals with the marine biotoxin domoic acid, also known as amnesic shellfish poison, and its main producing pennate diatom genus Pseudo-nitzschia (Bacillariophyceae). Besides contamination of seafood, these organisms have also been involved in human and marine wildlife mortality. The article aims to give an overview of all biological and environmental factors that should be considered when trying to evaluate a possible increase in toxic blooms of Pseudo-nitzschia spp. Pseudo-nitzschia blooms characteristically occur in a low light regime, at a time when the temperature is falling and at a wide range of salinities. Laboratory studies have shown that the production of domoic acid, a water-soluble amino acid, is related to silicon, phosphorus, nitrogen and trace metal (mainly iron) availability. Domoic acid has no known function in defence or primary metabolism; a role in excretion of excess photosynthetic energy or as a binding ligand for trace metals is suggested. The variability in domoic acid production by different Pseudo-nitzschia spp., or the presence of toxic and non-toxic strains of the same species, cannot be explained. The conclusion is drawn that an increase in toxic blooms of Pseudo-nitzschia spp. might be possible, especially because of the expected increase in nutrient availability from pollution and desert dust. Global warming may have an influence as well by lengthening the growth period for Pseudo-nitzschia, enlarging their global distribution and increasing the dust load through desertification.

Ambulatory blood pressure predicts end-organ damage only in subjects with reproducible recordings. HARVEST Study Investigators. Hypertension and Ambulatory Recording Venetia Study.

OBJECTIVE: To determine whether the prediction of target-organ damage varies according to the reproducibility of 24 h blood pressure. SETTING: Seventeen hypertension clinics in northeast Italy. MAIN OUTCOME MEASURES: Correlations of left ventricular mass index and albumin excretion rate with 24 h and office blood pressures in relation to tertiles of ambulatory blood pressure reproducibility. PATIENTS AND METHODS: In 716 consecutive, stage I, hypertensives enrolled in the Hypertension and Ambulatory Recording Venetia Study (HARVEST), ambulatory blood pressure monitoring was performed twice, 3 months apart In all subjects, the albumin excretion rate was measured by radioimmunoassay, and in 567, the left ventricular mass index was assessed by echocardiography. RESULTS: The subjects were divided into tertiles of ambulatory blood pressure consistency (between-monitoring differences, regardless of the sign). In the tertile of subjects with good reproducibility, correlation coefficients of systolic and diastolic ambulatory blood pressure with left ventricular mass and urinary albumin excretion were significant and higher than those of office blood pressure. In contrast, in the two tertiles with poorer reproducibility, the coefficients were barely or not significant for both pressures. The advantage of ambulatory blood pressure over office blood pressure in predicting target-organ damage was no longer present for systolic blood pressure differences greater than 3.8 mmHg and diastolic blood pressure differences greater than 3.1 mmHg. CONCLUSIONS: These data indicate that ambulatory blood pressure is a better predictor of left ventricular mass and urinary albumin excretion than office blood pressure, but only in subjects with good pressure reproducibility. Therefore, the assessment of hypertensive patients should be based on duplicate blood pressure monitorings. Recordings with 24 h systolic and diastolic blood pressure differences greater than 4 and 3 mmHg, respectively, should be considered with caution.

An independent relationship between plasma leptin and heart rate in untreated patients with essential hypertension.

OBJECTIVE: To test the hypothesis that hemodynamic measurements in patients with essential hypertension are related independently to plasma leptin levels. PATIENTS AND METHODS: We measured plasma leptin, insulin, office and ambulatory blood pressure and heart rate in 60 men with untreated mild hypertension. RESULTS: Plasma leptin correlated significantly with body mass index (r = 0.43, P = 0.001), 24 h heart rate (r = 0.35, P = 0.006) and 24 h diastolic blood pressure (r = 0.27, P = 0.04) but not with age (r = 0.03; P = 0.85) or 24 h systolic blood pressure (r = -0.08, P = 0.56). Plasma leptin levels adjusted for body mass index correlated significantly with 24 h heart rate (r = 0.36, P = 0.005) but not with 24 h diastolic blood pressure (r = 0.19, P = 0.15). We divided the patient population into tertiles of body mass index-adjusted plasma leptin levels. Age, plasma insulin, blood pressure, smoking status and physical activity habits were similar across the adjusted leptin tertiles. Patients from the third tertile of adjusted plasma leptin distribution (those with leptin levels higher than would be expected on the basis of body mass index) had significantly faster ambulatory heart rates than subjects from both the first and the second tertiles. The difference in heart rate across the three tertiles was most pronounced for the night-time values. CONCLUSIONS: In patients with essential hypertension, heart rate is faster in those patients with higher plasma leptin levels. This relationship is independent of age, body mass index, insulin levels, blood pressure level, smoking status and physical activity.

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.

Tolerability and efficacy of fosinopril and hydrochlorothiazide compared with amiloride and hydrochlorothiazide in patients with mild to moderate hypertension.

This 6-month multicentre, randomised, double-blind, parallel group clinical trial compared the tolerability and antihypertensive efficacy of a once-daily combination of fosinopril 20mg/hydrochlorothiazide 12.5mg (FOS/HCTZ) with a combination of amiloride 5mg/hydrochlorothiazide 50mg (AMI/HCTZ) in 217 patients with mild to moderate essential hypertension. Adverse events related to hypotension or to specifically targeted clinical laboratory values were observed infrequently with FOS/HCTZ compared with AMI/HCTZ: with FOS/HCTZ, only 4 of 104 patients (3.9%) experienced such events, compared with 16 of 113 (14.1%) in the AMI/HCTZ group (p < 0.001). While statistically significant differences were found between the two treatment groups for changes from baseline in serum potassium, cholesterol, triglyceride and glucose values, the metabolic profile was uniformly unfavourable towards the AMI/HCTZ group; for example, reductions in potassium and elevations in cholesterol, triglyceride and glucose were more pronounced with the AMI/HCTZ group than with the FOS/HCTZ group. Both antihypertensive regimens produced statistically significant reductions from baseline in seated diastolic blood pressure that were equivalent at most points of measurement during double-blind treatment. Therapeutic response rates were high (>/=95%) and were similar for both regimens throughout the study. Because the relative risk for adverse events was markedly less over the long term with FOS/HCTZ than with AMI/HCTZ, the combination of fosinopril and hydrochlorothiazide may offer significant tolerability advantages over amiloride plus hydrochlorothiazide for such patients.

Gender differences in the relationship between left ventricular size and ambulatory blood pressure in borderline hypertension. The HARVEST Study.

AIM: To assess whether the are gender differences in cardiac adaptation to raised blood pressure levels in young subjects with borderline to mild hypertension. METHODS AND RESULTS: In 499 18-45-year-old stage I hypertensive subjects (377 men and 122 women) with a mean age of 33 +/- 9 years and office blood pressure of 146 +/- 11/ 94 +/- 6 mmHg, ambulatory blood pressure monitoring in duplicate, echocardiography and 24-h urinary catecholamines measurement were performed. RESULTS: The whole group was divided into quartiles of increasing daytime blood pressure and differences in left ventricular echocardiographic data were analysed in the two sexes separately. In men no left ventricular parameter differed across the quartiles, while in women left ventricular mass, posterior wall thickness and interventricular septum thickness showed a clear tendency to increase with increasing levels of systolic blood pressure. In multiple regression analysis, daytime systolic blood pressure explained only a small fraction of the variance in left ventricular parameters in men, while in women daytime systolic blood pressure was a main determinant of left ventricular mass and posterior wall and septal thicknesses. Body weight explained most of the variance in all dimensional parameters in men. In women weight was an important predictor of left ventricular mass and diameter, but was unrelated to left ventricular posterior wall and septal thicknesses. CONCLUSIONS: Daytime systolic blood pressure is the most important predictor of left ventricular mass and geometry in pre-menopausal women with stage I hypertension, while in men left ventricular dimensional indices are chiefly explained by body weight.

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.

24-hour blood pressure control by once-daily administration of irbesartan assessed by ambulatory blood pressure monitoring. Irbesartan Multicenter Investigators' Group.

OBJECTIVES: To compare 24 h ambulatory blood pressure and trough office blood pressure lowerings after 8 weeks of therapy with 75 mg irbesartan once a day, 150 mg irbesartan once a day , and 75 mg irbesartan twice a day versus placebo; and to assess safety and tolerability of irbesartan therapy. DESIGN: Multicenter, double-blind, randomized, placebo-controlled trial. SETTING: Sixteen centers in Italy. PATIENTS: Caucasian patients (n = 215) aged > or = 18 years with seated diastolic blood pressure 95-110 mmHg and ambulatory diastolic blood pressure (ADBP) > or = 85 mmHg. PRIMARY OUTCOME: Mean 24 h ADBP after 8 weeks of irbesartan therapy. RESULTS: Mean changes (value before treatment minus value after treatment) in ADBP for placebo, 75 mg irbesartan once a day, 150 mg irbesartan once a day, and 75 mg irbesartan twice a day were -0.2, -5.4, -7.2, and -7.2 mmHg, respectively; respective changes in ambulatory systolic blood pressure were +1.6, -8.3, -10.5, and -9.7 mmHg. All irbesartan regimens reduced trough office seated diastolic blood pressure and seated systolic blood pressure after 2 and 8 weeks of treatment (all P < 0.01, versus placebo except for seated systolic blood pressure in patients in the 75 mg irbesartan once a day group). Trough: peak ratios were > or = 55% with 150 mg irbesartan once a day. Percentages of patients whose blood pressures were normalized with 150 mg irbesartan once a day (45%) and 75 mg irbesartan twice a day (47%) were greater than those with placebo (14%, P < 0.01) and with 75 mg irbesartan once a day (19%, NS, versus placebo). Adverse events with irbesartan were similar to those with placebo. CONCLUSIONS: All irbesartan regimens significantly reduced mean 24 h ADBP and ambulatory systolic blood pressure, and were well tolerated. Administration of 150 mg irbesartan once a day provided significant reduction of blood pressure for 24 h, equivalent to that obtained with the same daily dose divided into two separate administrations.

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 (> or = 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 factor 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.