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).
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.
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.
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.
Objective
In high-risk patients with left bundle-branch block (LBBB), functional but not perfusion parameters yield incremental prognostic information. The aim of our study was to evaluate the ...prognostic value of gated single photon emission computed tomography (SPECT) in low-intermediate risk LBBB patients.
Methods
One hundred seventy-six subjects underwent stress-rest dual-day protocol 99mTc sestamibi-gated SPECT and were dichotomized in two groups: without LBBB (Group 1,
n
= 86) and with LBBB (Group 2,
n
= 90). Patients were followed for 32 ± 18 months. Cox regression multivariate analysis was used to determine which variable was the best predictor of cardiac event. Event-free survival curves were computed by Kaplan–Meier method.
Results
Myocardial perfusion scintigraphy was abnormal in 32 and 60 patients for Groups 1 and 2, respectively (37 vs. 67 %,
p
< 0.001). In Groups 1 and 2, the mean summed stress score (SSS) was 3.7 ± 5.6 versus 6.7 ± 6.4, while the mean summed difference score (SDS) was 1.6 ± 2.5 versus 2.7 ± 3.3 (both
p
< 0.005); therefore 34 % of patients in Group 1 and 53 % of those in Group 2 presented myocardial ischemia. All functional parameters were significantly different between the two subsets (all
p
< 0.005). Follow-up was completed in 161 patients (92 %); 10 events occurred in Group 1 and 20 in Group 2 (14 vs. 25 %). The event-free survival was significantly higher in patients with normal than in those with abnormal scan (85 vs. 63 %,
p
< 0.005); moreover, the prognosis of patients with LBBB was significantly worse. At multivariate analysis, SDS was found to be the only independent predictor of cardiac events both in all patients and in LBBB population (HR 3.08, and HR 4.99,
p
< 0.05).
Conclusions
This is the first study to assess the prognostic value of gated SPECT in patients with LBBB and low-intermediate cardiac risk. Both perfusion and functional data obtained by gated SPECT are different between patients with and without LBBB. However, SDS is the only predictor of events. Thus, the amount of reversible ischemia at gated SPECT has a discriminative power in stratifying the cardiac risk of LBBB population.
The database of echocardiographic examinations performed during the military screening of 20,946 young men in northeastern Italy was systematically reviewed to assess the frequency, hemodynamic ...characteristics, and aortic sizes of subjects with bicuspid aortic valves (BAVs). One hundred sixty-seven patients with BAVs were identified (0.8%), of whom 80 (48%) were diagnosed de novo during military screening. Aortic insufficiency was the predominant hemodynamic lesion in 110 subjects (66%), mild in 90, and moderate to severe in 20. Patients with BAVs displayed larger aortic sizes than controls at each aortic level, and the degree of dilation was related to the presence but not the severity of aortic insufficiency.
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.
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.
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.
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.
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.
Angiotensin II (Ang II) signaling via type 1 receptor (AT1R) has been extensively characterized, whereas Ang II signaling via type 2 receptors (AT2R), although counteracts actions mediated by AT1R, ...is still not completely understood. Bartter's/Gitelman's patients (BS/GS) have intrinsically blunted AT1R signaling, making them a good model to examine Ang II signaling via AT2R with particular emphasis on mitogen-activated protein kinase phosphatase 1 (MKP-1) that interacts with the Ang II-stimulated ERK pathway of cell signaling.
BS/GS and healthy controls fibroblasts AT1R and AT2R level and the time course of Ang II's effect on MKP-1 levels and ERK1/2 phosphorylation over 1-h time course were assessed by western blot. The time course of Ang II's effect on MKP-1 levels and ERK1/2 phosphorylation alone or in the presence of either PD123319, an AT2R blocker, or Losartan, an AT1R blocker, or in combination was characterized.
AT1R and AT2R levels did not differ between BS/GS and healthy controls. Ang II induced ERK1/2 phosphorylation in BS/GS fibroblasts, but peak ERK1/2 phosphorylation declined more rapidly than that in control and BS/GS fibroblasts also exhibited increased MKP-1 levels at 30-min incubation. PD123319, an AT2R blocker in BS/GS fibroblasts, abolished the increased MKP-1 and ERK1/2 phosphorylation time course became same as that for control. Losartan, an AT1R blocker, alone altered the time course of control fibroblast MKP-1 to mimic the increase seen in BS/GS fibroblasts, whereas ERK1/2 declined concomitantly. Treatment with Losartan and PD123319 in controls reduced MKP-1 and elevated ERK1/2 phosphorylation to the level observed in BS/GS patients treated with PD123319.
ERK1/2 phosphorylation time course found in BS/GS fibroblasts tracked changes in MKP-1 levels and incubation with an AT2R blocker, PD123319, abrogated those responses. Losartan, an AT1R blocker, reproduced these changes in healthy controls, whereas the presence of both AT1R and AT2R inhibitors in controls abolished these changes. These data strongly suggest that MKP-1 is a major effector in altering ERK1/2 phosphorylation status. Moreover, the results provide insight into the blunted responses in BS/GS reported for Ang II short-term and long-term effects, the mechanisms responsible, and thereby yield additional support for the role of AT2R signaling in the proposed effects of Ang II AT1R blockers beyond AT1R blockade.
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 ≥140/90 mm Hg from two consecutive visits occurring at least after ≥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 ≥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.
ACE and ACE2 produce angiotensin II (Ang II), a vasopressor that induces cardiovascular remodeling, and Ang 1-7, a vasodilator with an antiremodeling effect. While Ang 1-7 has antiarrhythmic ...properties, at higher concentration it may induce ventricular tachycardia and sudden death. ACE2, therefore, may play an essential role in blood pressure homeostasis, in the long-term complications of hypertension (cardiovascular remodeling), and in the induction of cardiac electric abnormalities. This study evaluated the levels of ACE2 and Ang 1-7 in Bartter's/Gitelman's patients (BS/GS) who have elevated Ang II and endogenous blockade of Ang II type 1 receptor signaling compared with healthy subjects (C) and essential hypertensives (EH). BS/ GS patients were also considered because of their predisposition to cardiac arrhythmias, which has yet to be completely clarified.
Mononuclear cell ACE2 and Ang 1-7 were evaluated using western blot.
One-way ANOVA showed that ACE2 and Ang 1-7 levels were significantly different between the three groups (p=0.0074 and p=0.0001, respectively). Post-hoc analysis (Tukey's HSD) showed that both ACE2 (1.59+/-0.63) and Ang1-7 (2.26+/-1.18) were significantly elevated in BS/GS compared with either C (0.98+/-0.45; p=0.008; 1.12+/-0.48, p=0.002, respectively) or EH (1.06+/-0.24; p=0.043; 0.72+/-0.28; p=0.0001, respectively). ACE2 and Ang 1-7 directly correlated only in BS/GS (r=0.91, p<0.0003).
The elevated ACE2 and Ang 1-7 in BS/ GS patients mirror those in hypertensives and are in line with the clinical, hemodynamic and pathophysiological characteristics of BS/GS, likely contributing to them. In consideration of the clinical picture of these syndromes, the opposite of hypertension, the results of this study further strengthen the importance of the ACE2/Ang 1-7 system in the regulation of vascular tone and cardiovascular biology.
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.
To ascertain the independent predictors of ICH in mildly hypertensive subjects.
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).
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 x sex (0 = men; 1 = women) + 0.4543 x current smoking (0 = yes; 1 = no) - 0.0531 x 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 x sex + 0.5989 x current smoking - 0.0482 x clinic diastolic BP - 0.0312 x 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.
In untreated subjects with stage I hypertension, ICH is most frequent among women, nonsmokers 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.
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.
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