Fabrizio Pegoraro

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.

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.

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.

Regular physical activity prevents development of left ventricular hypertrophy in hypertension

AIMS The longitudinal relationship between aerobic exercise and left ventricular (LV) mass in hypertension is not well known. We did a prospective study to investigate the long-term effect of regular physical activity on development of LV hypertrophy (LVH) in a cohort of young subjects screened for Stage 1 hypertension. METHODS AND RESULTS We assessed 454 subjects whose physical activity status was consistent during the follow-up. Echocardiographic LV mass was measured at entry, every 5 years, and/or at the time of hypertension development before starting treatment. LVH was defined as an LV mass >/=50 g/m(2.7) in men and >/=47 g/m(2.7) in women. During a median follow-up of 8.3 years, 32 subjects developed LVH (sedentary, 10.3%; active, 1.7%, P = 0.000). In a logistic regression, physically active groups combined (n = 173) were less likely to develop LVH than sedentary group with a crude OR = 0.15 (CI, 0.05-0.52). After controlling for sex, age, family history for hypertension, hypertension duration, body mass, blood pressure, baseline LV mass, lifestyle factors, and follow-up length, the OR was 0.24 (CI, 0.07-0.85). Blood pressure declined over time in physically active subjects (-5.1 +/- 17.0/-0.5 +/- 10.2 mmHg) and slightly increased in their sedentary peers (0.0 +/- 15.3/0.9 +/- 9.7 mmHg, adjusted P vs. active = 0.04/0.06). Inclusion of changes in blood pressure over time into the logistic model slightly decreased the strength of the association between physical activity status and LVH development (OR = 0.25, CI, 0.07-0.87). CONCLUSION Regular physical activity prevents the development of LVH in young stage 1 hypertensive subjects. This effect is independent from the reduction in blood pressure caused by exercise.

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.

PREMENOPAUSAL WOMEN ARE AT HIGHER RISK OF HYPERTENSIVE COMPLICATIONS THAN MEN: PP.35.455

Objective: Little is known about whether hypertension has a different impact on target organs in young to middle-age women compared to men. The purpose of this study was to describe sex-specific differences in target organ involvement in a cohort of never treated hypertensive subjects followed for a median of 7 years. Design and Methods: Participants were 626 adults (451 men) aged 18 to 45 years screened for stage 1 hypertension. Ambulatory blood pressure (BP) at entry was 127.5 ± 12.5/83.7 ± 8.2 mmHg in women and 131.9 ± 10.3/81.0 ± 7.9 mmHg in men. Patients were seen every six months for BP and global risk assessment until they needed drug therapy according to current guidelines. Ambulatory BP, albuminuria, and echocardiographic data (n = 470) were obtained at entry, every 5 years, and/or before starting treatment. Data were adjusted for age, body mass, BP, physical activity, parental hypertension, smoking, coffee and alcohol use. Results: Female gender was a significant predictor of urinary albumin (p = 0.002) and left ventricular mass indexed to height (LVMI,p = 0.002) at final assessment. At follow-up end, microalbuminuria was more common among women than men (13.7% versus 6.2%, adjusted p = 0.001) as was left ventricular hypertrophy (LVH, 26.4% versus 8.8%, p < 0.0001). These differences remained significant also when adjusted for baseline urinary albumin or LVMI. In a multivariable Cox analysis, female gender was a significant predictor of time to development of microalbuminuria (p = 0.002) with a HR(95%CL) of 2.6(1.4–4.7), and of LVH (p = 0.01) with a HR of 2.1(1.2–3.8). After inclusion of BP changes over time in the models, HRs were 3.2(1.7–5.9) and 2.7(1–5–5.1), respectively. When baseline urinary albumin or LVMI were taken into account, the associations remained highly significant with HRs of 2.7(1.4–5.1) and 2.5(1.3–4.6), respectively. Conclusions: These data show that in young-to-middle-age hypertensive subjects the risk of target organ damage is much greater among women than men irrespective of the BP changes over time. This raises the question about whether early antihypertensive treatment should be considered for premenopausal women.