Alessandra Bortolazzi

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.

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 Have Increased Risk of Hypertensive Target Organ Damage Compared with Men of Similar Age

BACKGROUND The impact of high blood pressure (BP) on target organs (TO) in premenopausal women is not well known. The purpose of this study was to describe gender differences in TO involvement in a cohort of young-to-middle-aged subjects screened for stage 1 hypertension and followed for 8.2 years. METHODS Participants were 175 women and 451 men with similar age (range 18-45 years). Ambulatory BP at entry was 127.5±12.5/83.7±7.2 mm Hg in women and 131.9±10.3/81.0±7.9 mm Hg in men. Ambulatory BP, albumin excretion rate (AER), and echocardiographic data (n=489) were obtained at entry, every 5 years, and before starting antihypertensive treatment. RESULTS Female gender was an independent predictor of final AER (p=0.01) and left ventricular mass index (LVMI) (p<0.001). At follow-up end, both microalbuminuria (13.7% vs. 6.2%, p=0.002) and left ventricular hypertrophy (LVH) (26.4% vs. 8.8%, p<0.0001) were more common among women than men. In a multivariable Cox analysis, after adjusting for age, lifestyle factors, body mass, ambulatory BP, heart rate, and parental hypertension, female gender was a significant predictor of time to development of microalbuminuria (p=0.002), with a hazard ratio (HR) of 3.06, (95% confidence interval [CI] 1.48-6.34) and of LVH (p=0.004), with an HR of 2.50 (1.33-4.70). Inclusion of systolic and diastolic BP changes over time in the models only marginally affected these associations, with HRs of 3.13 (1.50-6.55) and 3.43 (1.75-6.70), respectively. CONCLUSIONS These data indicate that premenopausal women have an increased risk of hypertensive TO damage (TOD) and raise the question about whether early antihypertensive treatment should be considered in these patients.

Resting Heart Rate as a Predictor of Body Weight Gain in the Early Stage of Hypertension

We did a prospective study to investigate whether clinic heart rate (HR) and 24‐h ambulatory HR were independent predictors of subsequent increase in body weight (BW) in young subjects screened for stage 1 hypertension. The study was conducted in 1,008 subjects from the Hypertension and Ambulatory Recording Venetia Study (HARVEST) followed for an average of 7 years. Ambulatory HR was obtained in 701 subjects. Data were adjusted for lifestyle factors and several confounders. During the follow‐up BW increased by 2.1 ± 7.2 kg in the whole cohort. Both baseline clinic HR (P = 0.007) and 24‐h HR (P = 0.013) were independent predictors of BMI at study end. In addition, changes in HR during the follow‐up either measured in the clinic (P = 0.036) or with 24‐h recording (P = 0.009) were independent associates of final BMI. In a multivariable Cox regression, baseline BMI (P < 0.001), male gender (P < 0.001), systolic blood pressure (BP) (P = 0.01), baseline clinic HR (P = 0.02), and follow‐up changes in clinic HR (P < 0.001) were independent predictors of overweight (Ov) or obesity (Ob) at the end of the follow‐up. Follow‐up changes in ambulatory HR (P = 0.01) were also independent predictors of Ov or Ob. However, when both clinic and ambulatory HRs were included in the same Cox model, only baseline clinic HR and its change during the follow‐up were independent predictors of outcome. In conclusion, baseline clinic HR and HR changes during the follow‐up are independent predictors of BW gain in young persons screened for stage 1 hypertension suggesting that sympathetic nervous system activity may play a role in the development of Ob in hypertension.

Natural History of Hypertension Subtypes in Young and Middle-Age Adults

BACKGROUND The evolution of hypertension (HT) subtypes in young-to-middle-age subjects is unclear. METHODS We did a prospective study in 1,141 participants aged 18-45 years from the HARVEST study screened for stage 1 HT, and 101 nonhypertensive subjects of control during a median follow-up of 72.9 months. RESULTS At baseline, 13.8% of the subjects were classified as having isolated systolic HT (ISH), 24.8% as having isolated diastolic HT (IDH), and 61.4% as having systolic-diastolic HT (SDH). All hypertensive groups developed sustained HT (clinic blood pressure > or =140/90 mm Hg from two consecutive visits occurring at least after > or =6 months of observation) more frequently than nonhypertensive subjects (P < 0.001 for all) with adjusted odds ratio of 5.2 (95%CI 2.9-9.2) among the SDH subjects, 2.6 (95%CI 1.5-4.5) among the IDH subjects, and 2.2 (95%CI 1.2-4.5) among the ISH subjects. When the definition of HT was based on ambulatory blood pressure (mean daytime blood pressure > or =135/85 mm Hg, n = 798), odds ratios were 5.1 (95%CI 3.1-8.2), 5.6 (95%CI 3.2-9.8), and 3.3 (95%CI 1.7-6.3), respectively. In the fully adjusted logistic model, the risk of ambulatory HT was smaller for the ISH than the IDH (P = 0.049) or SDH (P = 0.053) individuals. CONCLUSIONS The present results indicate that young-to-middle-age subjects with ISH have a smaller risk of developing ambulatory HT than either subjects with SDH or IDH. Whether antihypertensive treatment can be postponed for long periods of time in young subjects with mild elevations of clinic systolic BP and low global cardiovascular risk should be examined in further studies.

Relationship between GFR and Albuminuria in Stage 1 Hypertension

BACKGROUND AND OBJECTIVES Whether glomerular hyperfiltration is implicated in the development of microalbuminuria in hypertension is not well known. This prospective study investigated the relationship between changes in GFR and microalbuminuria in hypertension. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This study assessed 534 stage 1 hypertensive participants from the Hypertension and Ambulatory Recording Venetia Study (n=386 men) without microalbuminuria at baseline, who were recruited from 1990 to 1995 and followed for a median of 8.5 years. Mean age was 33.9±8.6 years and mean BP was 146.6±10.5/94.0±5.0 mmHg. Creatinine clearance and 24-hour urinary albumin were measured at study entry and end. Participants were defined as normofilterers (normo) or hyperfilterers (hyper) according to whether GFR was <150 or ≥150 ml/min per 1.73 m(2), respectively. Participants were divided into four groups based on GFR changes from baseline to follow-up end: normo→normo (n=395), normo→hyper (n=31), hyper→hyper (n=61), and hyper→normo (n=47). RESULTS Microalbuminuria progressively increased across the four groups and was 5.3% in normo→normo, 9.7% in normo→hyper, 16.4% in hyper→hyper, and 36.2% in hyper→normo (P<0.001). This association held true in a multivariable logistic regression in which several confounders, ambulatory BP, and other risk factors were taken into account (P<0.001). In particular, hyperfilterers whose GFR decreased to normal at study end had an adjusted odds ratio of 7.8 (95% confidence interval, 3.3-18.2) for development of microalbuminuria compared with participants with normal GFR throughout the study. CONCLUSIONS These data support the hypothesis for a parabolic association between GFR and urinary albumin in the early stage of hypertension.

Metabolic effects of lisinopril versus hydrochlorothiazide plus amiloride in essential hypertension

Abstract A multicenter, randomized, double-blind, parallel-group trial was conducted to compare the effects of long-term treatment with lisinopril versus hydrochlorothiazide plus amiloride on lipids, glucose, uric acid, and electrolytes in patients with mild to moderate essential hypertension. After 6 months of treatment with hydrochlorothiazide 50 to 100 mg plus amiloride 5 to 10 mg or lisinopril 10 to 20 mg given once daily, the patients receiving the diuretics showed an increase in triglycerides, very-low-density lipoproteins, and apolipoproteins A and B, while the patients receiving lisinopril had only minimal changes in these parameters and an increase in high-density lipoproteins. Serum uric acid levels rose significantly in the group receiving diuretics but did not change in the lisinopril group. The antihypertensive effect was similar for both drug regimens. These data show that the long-acting angiotensin converting enzyme inhibitor lisinopril did not induce any metabolic effects and should be preferred, as a first choice, to antihypertensive drugs such as diuretics, which may cause lipid and uric acid metabolism disorders.

3A.07: NIGHT-TIME HEART RATE IS A LONG-TERM PREDICTOR OF MICROALBUMINURIA IN SUBJECTS SCREENED FOR STAGE 1 HYPERTENSION

Objective: Heart rate (HR) has been found to be associated with target organ damage in hypertension but the predictive capacity of resting HR vs ambulatory HR in longitudinal studies is not well known. We did a prospective study to investigate whether clinic HR and ambulatory HR assessed at baseline were independent predictors of albumin excretion rate (AER) and microalbuminuria (MA) in the early stage of hypertension. Design and method: The study was conducted in a cohort of 621 white stage 1 hypertensive subjects from the HARVEST never treated for hypertension (mean age 33.8 ± 8.4 years, 449 men). Clinic HR was the average of 6 readings. Clinic HR, daytime HR and night-time HR were included separately in linear (for AER) and logistic (for MA) regressions and were adjusted for baseline logAER, age, gender, body mass index, blood pressure, physical activity, smoking, alcohol consumption, and follow-up time. Results: During a median follow-up of 8.5 years AER increased from a median value of 5.7 mg/24 h to 7.2 mg/24 h (p < 0.001 for log-transformed data), and 42 subjects developed MA (AER >  = 30 mg/24 h). In both linear and logistic regressions average night-time HR was an independent predictor of final AER (p = 0.014) and MA (p = 0.007), whereas clinic HR and daytime HR were not associated with these outcomes (p = NS for both). Night-time HR was 62.6 ± 8.3 bpm in the 579 subjects who did not develop MA and was 66.6 ± 7.7 bpm in the 42 subjects who developed MA (p = 0.002). Baseline BMI was another independent predictor of final AER (p = 0.007) and final MA (p = 0.001) and its inclusion into the models slightly attenuated the association of night-time HR with AER (p = 0.029) and MA (p = 0.016). Conclusions: HR is an independent predictor of microalbuminuria in young persons screened for stage 1 hypertension suggesting that the chronic hemodynamic stress related to tachycardia may play a role in the development of renal damage in hypertension. In agreement with previous results, HR measured during sleep seems to be more representative of the overall hemodynamic load on the arteries than HR measured during waking hours or in the doctors office.