Paolo Mormino

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.

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.

Relation between physical training and ambulatory blood pressure in stage I hypertensive subjects. Results of the HARVEST Trial. Hypertension and Ambulatory Recording Venetia Study.

BACKGROUND This study was undertaken to assess whether ambulatory blood pressure (BP) in a population of stage I hypertensive individuals was lower in the subjects performing regular exercise training. METHODS AND RESULTS The study was carried out in 796 young hypertensive patients (592 men) who had never been treated who took part in the HARVEST trial. The diagnosis of stage I hypertension was made on the basis of six office BP measurements. Subjects underwent noninvasive 24-hour ambulatory BP monitoring, 24-hour urine collection for catecholamine assessment, and echocardiography (n = 457). They were classified as exercisers if they reported at least one session of aerobic sports per week and as nonexercisers if they did not engage regularly in sports activities. Age (P < .0001), body mass index (P = .002), 24-hour heart rate (P < .0001), alcohol intake (P = .02), smoking (P = .02), and norepinephrine output (P = .04) were lower in the active (n = 153) than the inactive (n = 439) men. Physically active men exhibited a lower 24-hour and daytime diastolic BP than the inactive men, while there were no group differences in office BP or in nighttime diastolic BP and in ambulatory systolic BP. The between-group ambulatory diastolic BP difference remained statistically significant after adjustment for age, body mass index, alcohol intake, and smoking (P < .0001). Of the nonexercisers, 46.2% were confirmed hypertensives, compared with only 26.8% of the exercisers (P < .0001), on the basis of daytime diastolic BP. Echocardiographic left ventricular dimensional and functional indexes were similar in the two groups of men. Similar findings were shown by the 16 women who engaged in aerobic sports. CONCLUSIONS These data suggest that participation in aerobic sports may attenuate the risk of hypertension in young subjects whose office BP is in the stage I hypertensive range at office measurement.

Independent predictors of isolated clinic ('white-coat') hypertension.

Background Hypertension guidelines recommend 24 h ambulatory blood pressure (ABP) monitoring in hypertensive subjects with suspected isolated clinic hypertension (ICH). However, the pre-test probability of ICH based on the distribution of its independent predictors has not yet been estimated in hypertensive subjects with mildly elevated blood pressure. Objective To ascertain the independent predictors of ICH in mildly hypertensive subjects. Methods In the setting of the HARVEST-PIUMA collaboration, we studied 1564 subjects with hypertension stage I. At entry, all subjects were untreated and all underwent ABP monitoring and echocardiography. Diabetes, hypertension grade > I, renal failure or previous cardiovascular morbid events were exclusion criteria. Clinic BP was 143/92 mmHg (SD 9/5) and 24 h ABP was 128/81 mmHg (SD 10/8). Results Prevalence of ICH (daytime ABP < 130 mmHg systolic and 80 mmHg diastolic) was 10.4%. In a multivariate logistic regression analysis, sex (P = 0.002), smoking (P = 0.038) and clinic diastolic BP (P = 0.0002) were the sole independent predictors of ICH according to the following equation:Y = 2.6438 + 0.5128 × sex (0 = men; 1 = women) + 0.4543 × current smoking (0 = yes; 1 = no) − 0.0531 × clinic diastolic BP (mmHg) and P (probability of ICH) = exp(Y)/[1 + (exp(Y)]. Left ventricular (LV) mass at echocardiography was a further independent predictor (P = 0.002) of ICH according to the following equation:Y = 3.4343 + 0.4603 × sex + 0.5989 × current smoking − 0.0482 × clinic diastolic BP − 0.0312 × LV mass [g/height (m)2.7]. LV mass was greater (P < 0.01) in the group with ambulatory hypertension [42.3 g/height (m)2.7] than in that with ICH [39.2 g/height (m)2.7] and not dissimilar between the ICH group and a control group of 370 healthy normotensive subjects [38.1 g/height (m)2.7]. Conclusions In untreated subjects with stage I hypertension, ICH is most frequent among women, non-smokers and subjects with low clinic BP and smaller LV mass. These findings allow identification of subjects with indication to ABP monitoring because of suspected ICH.

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.

Evaluation of Hypertension and Related Target Organ Damage by Average Day-time Blood Pressure

Aim of the present study was to verify whether average blood pressure continuously recorded throughout the day correlates with the degree of target organ damage more closely than casual pressure in hypertensive patients. The study was conducted in 102 subjects with borderline, moderate and severe hypertension. Our results confirm a closer relationship between cardiovascular complications and recorder blood pressure than casual pressure possibly because the latter less perfectly reflects the patients usual pressures which are generally lower. However our results further demonstrate that blood pressure variability also contributes to the degree of target organ damage since for equal average day-time pressures a greater severity of cardiovascular complications was observed in patients with the highest blood pressure variability and the highest peaks of pressure. These findings should be carefully considered when evaluating the effect of antihypertensive drugs.

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.

G-Protein β3-Subunit Gene 825T Allele and Hypertension: A Longitudinal Study in Young Grade I Hypertensives

Introduction Essential hypertension affects approximately 25% of individuals in Western societies, with an increased prevalence in older subjects. It has long been recognized that a significant part of the susceptibility for hypertension is inherited. However, unlike monogenic disorders, hypertension develops on the genetic background of multiple gene alterations in concert with environmental factors, eg, nutrition and physical activity. The hunt for hypertension susceptibility genes is nourished from different aspects. One goal is easily understood: if a causative mutation or polymorphism is found, there exists, at least theoretically, the possibility to modify the activity of the gene product through existing or novel drugs. Moreover, since hypertension is not a disorder per se but a major risk factor for stroke, left ventricular hypertrophy, myocardial, and renal insufficiency, genetic testing could identify individuals at highest risk in order to provide them with optimized medical care to prevent the aforementioned sequels. Finally, one could envisage a scenario in which certain genotypes may be used to guide antihypertensive therapy in terms of drug class and dosage.Abstract—The 825T allele of the GNB3 gene has been associated with essential hypertension and obesity in cross-sectional studies. We have therefore planned a longitudinal cohort study to assess whether the GNB3 825T allele is predictive of blood pressure increase in young subjects with grade I hypertension. We genotyped at the GNB3 825 locus 461 participants of the Hypertension and Ambulatory Recording Venetia Study (HARVEST) study (age, 18 to 45 years) at low cardiovascular risk, according to 1999 ISH/WHO criteria. The study end point was eligibility for antihypertensive medication, that is, progression to grade II hypertension during the first year of observation or office systolic blood pressure ≥150 mm Hg and/or office diastolic blood pressure ≥95 mm Hg in two later consecutive visits during follow-up. At baseline, there was no statistically significant difference among genotypes with respect to body mass index, blood pressure, and heart rate. During follow-up (mean, 4.7 years), 113 (51.1%) patients with CC genotype and 145 (60.4%) patients with TT/TC genotype reached the end point. According to survival analysis, the patients carrying the 825T allele had an increased risk of reaching the blood pressure end point (CI, 1.108 to 1.843; P =0.006). In young patients with grade I hypertension, the 825T allele is associated with increased risk of progression to more severe hypertension requiring antihypertensive therapy. The GNB3 825T allele may be considered a genetic marker of predisposition for 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.

Ambulatory blood pressure predicts end-organ damage only in subjects with reproducible recordings

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 presssure differences greater than 4 and 3 mmHg, respectively, should be considered with caution.