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Objective: Previous studies testing the hypothesis that symptoms of anxiety and depression increase blood pressure (BP) levels show inconsistent and limited findings. We examined the association between those symptoms across adult life and BP in late middle age., Methods: Using data from 1683 participants from the MRC NSHD, we investigated associations between affective symptoms at ages 36, 43, 53 and 60-64 years and SBP and DBP at age 60-64. Multivariable linear regression was used to examine the effect on BP of affective symptoms at each age separately and as a categorical cumulative score based on the number of times an individual was classified as a 'case'. Models were adjusted for sex, BMI, educational attainment, socio-economic position, heart rate, lifestyle factors and antihypertensive treatment., Results: In fully adjusted models, we observed lower SBP in study members with case-level symptoms at one to two time-points [-1.83 mmHg; 95% confidence interval (CI) -3.74 to 0.01] and at three to four time-points (-3.93 mmHg; 95% CI -7.19 to -0.68) compared with those never meeting case criteria suggesting a cumulative inverse impact of affective symptoms on SBP across adulthood (P value for trend 0.022). Sex and BMI had a large impact on the estimates while not other confounders. Potential mediators such as heart rate and lifestyle behaviours had a little impact on the association. SBP at age 36 and behavioural changes across adulthood, as additional covariates, had a little impact on the association. A similar but weaker trend was observed for DBP., Conclusion: A cumulative effect of symptoms of anxiety and depression across adulthood results in lower SBP in late middle age that is not explained by lifestyle factors and antihypertensive treatment. Mechanisms by which mood may impact BP should be investigated.

Background: The "nondipping" pattern (NDP) of blood pressure, characterized by the absence of the reduction in blood pressure (BP) that typically takes place during the night time, has been associated with elevated cardiovascular morbidity, including stroke, myocardial infarction, and sudden cardiac-related death. In various cardiovascular diseases, reduced vagal control of cardiac function and elevated lability of cardiac repolarization have been associated with increased risk for ventricular arrhythmia and sudden death. The aim of this study was to assess temporal QT variability, arterial baroreflex sensitivity (BRS), and baroreflex effectiveness index (BEI) in two groups of otherwise healthy subjects, one group consisting of those with a normal BP pattern and the other with a nondipping BP pattern., Methods: Ninety-five healthy subjects underwent 24-h ambulatory BP (AMBP) monitoring. A minimum of 10% reduction in BP during the night relative to daytime levels is considered normal (as found in "dippers"). These individuals were classified as "dippers" (n = 59) and individuals without 10% reduction in BP during night were classified as "nondippers" (n = 36). Electrocardiogram (ECG) readings and beat-to-beat BP were recorded at 1,000 Hz with the subjects at rest in the supine posture for 20 min. BRS, BEI, and QT variability index (QTVI) were calculated., Results: There were no differences between the study groups with respect to age, gender, and average BP. Nondippers showed an increase in QTVI (-1.28 +/- 0.48 in nondippers vs. -1.52 +/- 0.29 in dippers, P < 0.05) and a decrease in BEI (0.34 +/- 0.17 in nondippers vs. 0.43 +/- 0.17 in dippers, P < 0.05), whereas BRS did not differ between the groups., Conclusion: A nondipping BP pattern in healthy subjects is associated with elevated myocardial repolarization lability and impaired baroreflex function, suggesting dysfunction of the autonomic nervous system.

Objective: We assessed the hypothesis that differences in day and night-time systolic blood pressure (SBP) and heart rate (HR) recordings were smaller in obese versus lean children and adolescents, and whether measurements obtained during a school week or during weekends or holidays influenced these nocturnal falls. We also wanted to determine whether the results were influenced by gender., Methods: Ambulatory 24-h BP and HR measurements were performed in 80 subjects, 51 girls and 29 boys. Lean (n = 25) and obese (n = 55) subjects were classified according to body mass index (BMI)-standard deviation (SD) criteria. Forty-eight subjects had their 24-h recordings performed during a school week and 32 during leisure time., Results: The SBP nocturnal dipping response was less pronounced in obese subjects (16.2 +/- 6.3 mmHg) compared with lean controls (21.1 +/- 5.7 mmHg) (P < 0.01) of which the girls constituted most of the difference. HR change between day and night was similar in both groups being approximately 15 b/min. A small but statistical negative correlation was observed between BMI-SD and nocturnal fall in SBP (r = -0.3, P = 0.0065). In all subjects, regardless of BMI-SD, daytime SBP was higher when readings were obtained during a school week (123 +/- 7 mmHg) than during weekends or holidays (119 +/- 7 mmHg) (P = 0.029)., Conclusion: Obese children and adolescents showed smaller nocturnal falls in SBP compared with lean subjects. This pattern may cause increased cardiovascular loading; thus, it may reflect an early sign of high blood pressure development and adds to cardiovascular risk in young obese individuals.

Objectives: Even though most previous studies have shown that central nervous angiotensin II causes sympatho-excitation, there are data suggesting that blockade of the renin-angiotensin system (RAS) could activate the renal sympathetic nerves. The aim of the present study was to investigate overall, cardiac and renal sympathetic nerve activity, before and after intravenous enalaprilat, in healthy normotensive subjects without an activated RAS., Methods: Thirty healthy subjects underwent catheterization of the radial artery, right renal and coronary sinus veins with blood sampling at baseline and 30-40 min after 1.25 or 2.5 mg of intravenous enalaprilat, respectively. Regional and overall sympathetic nervous activity was estimated using isotope dilution, calculating spillovers of norepinephrine., Results: Mean arterial blood pressure decreased by 5% (P < 0.05) after the higher dose and remained unchanged after the lower dose of enalaprilat, whereas renal norepinephrine spillover increased after both doses by 49 and 26% respectively (P < 0.05 for both). Cardiac and total body norepinephrine spillover remained unchanged after both doses of enalaprilat. Pulmonary capillary wedge pressure, which was measured in eight subjects after 2.5 mg enalaprilat, fell by 43% (P < 0.05)., Conclusions: In the absence of, or after a minor, blood pressure fall, intravenous enalaprilat selectively activates the renal nerves in healthy subjects without an activated RAS. Unloading of the low-pressure baroreceptor system and/or a central nervous effect of enalaprilat may be responsible for this differentiated sympathetic nervous response.

The aim of this study was to investigate blood pressure, renal haemodynamics, hormone secretion and the responses to angiotensin II infusion during candesartan cilexetil (candesartan), losartan potassium (losartan) and valsartan treatment in patients with essential hypertension. In this double-blind, randomized, crossover study, 24 patients (mean blood pressure of 163/97 mmHg), received candesartan 16 mg, losartan 50 mg and valsartan 80 mg once daily (o.d.) for 4 weeks after a placebo run-in period. At the end of each period, angiotensin II (0.5, 1.0 and 1.5 ng/min/kg) was infused 24 h after the previous drug administration. Each dose of angiotensin II was infused for 45 min. Before infusion and at the end of each infusion step, blood pressure and renal haemodynamics were assessed and plasma renin activity and plasma concentrations of angiotensin II and aldosterone were measured. During treatment with candesartan, resting mean arterial pressure (mean +/- SEM, 106 +/- 2 mmHg) was significantly decreased compared with treatment with losartan (110 +/- 2 mmHg) and valsartan (109 +/- 2 mmHg). Candesartan inhibited the angiotensin II induced increase in filtration fraction (0.8 +/- 0.4%) significantly more than losartan (1.5 +/- 0.4%) and valsartan (1.6 +/- 0.4%) and reduced the increase in aldosterone secretion (17 +/- 5 pg/ml/) significantly more than losartan (74 +/- 17 pg/ml/) and valsartan (82 +/- 19 pg/ml/). In conclusion, candesartan 16 mg o.d. reduced resting blood pressure significantly more than losartan 50 mg o.d. and valsartan 80 mg o.d. Candesartan almost completely inhibited the exogenous angiotensin II induced renal vasoconstriction, effectively inhibited the increase in filtration fraction and significantly blunted aldosterone secretion compared with losartan and valsartan, indicating a more effective AT1 receptor blockade with candesartan.

Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74g

Adolescent health benefits of different physical activity (PA) intensities, especially of lower intensities, are debated due to challenges in accelerometer data processing and analyses. Using a new accelerometer data processing method and multivariate pattern analysis, this study investigated the association of PA intensities with indicators of cardiovascular and mental health. Adolescents (n = 1,235, mean age 13.6 years, 41% males) were examined for cardiovascular health: body mass index (BMI) z-score, waist circumference (WC), resting heart rate and blood pressure, white blood cell count (WBC), pulse wave velocity (PWV), and answered questionnaires assessing stress and psychosomatic symptoms. Sex, age, and socioeconomic status were confounders. Hip-worn accelerometer data were processed with 10 Hz frequency extended method and a spectrum of 22 PA intensity categories was analyzed for association with health using partial least squares regression. Total explained variances for BMI z-score, WC, resting heart rate, stress, and psychosomatic symptoms were higher (3.3%–8.7%) compared to diastolic blood pressure, WBC, and PWV (0.9%–1.4%). We found positive associations of high-end moderate PA and vigorous PA with cardiovascular and mental health indicators. More sedentary time and lower level of light PA were associated with higher BMI z-score, WC, resting heart rate, diastolic blood pressure, WBC, and PWV, but not with mental health indicators. Very vigorous PA was negatively associated with resting heart rate, stress, and psychosomatic symptoms. In adolescents, PA of varying intensities were generally found to be positively associated with better cardiovascular health, but only higher intensity PA was associated with better mental health. [ABSTRACT FROM AUTHOR]

Objective: Patients with chronic heart failure (CHF) often require higher doses of nitroglycerin (glyceryl trinitrate, GTN) than patients with normal cardiac function to achieve a given haemodynamic goal. Two pathways leading to biotransformation of GTN have been characterized; a high-affinity pathway operative in nanomolar concentration ranges yielding predominantly 1,2-glyceryl dinitrate (1,2-GDN), and a low-affinity pathway operative at higher, micromolar concentrations of GTN associated with a greater proportion of 1,3-GDN formation. We tested the hypothesis that, at a given GTN-induced blood pressure reduction, the CHF group would present with: (i) higher concentrations of GTN; and (ii) decreased ratios of 1,2-GDN/GTN and 1,2-GDN/1,3-GDN compared with healthy subjects (HS). Methods: Twelve patients with CHF (left ventricular ejection fraction 20 ± 5%, NYHA III) and nine HS were investigated during a right cardiac catheterization. GTN was titrated intravenously until mean arterial blood pressure (MAP) was reduced by 15%. Results: At arterial GTN concentrations of 27·2 [10·0–57·8] nmol l−1 in CHF and 2·8 [2·5–3·5] nmol l−1 in HS [median (quartile range), P<0·05 between groups], MAP and mean capillary wedge pressures were reduced similarly in both groups (approx. 15% and 65%, respectively, P = NS between groups). The ratios of 1,2-GDN/GTN and 1,2-GDN/1,3-GDN were lower in CHF (0·86 [0·28–1·58] and 5·8 [5·6–6·3]) compared with HS [1·91 (1·54–2·23) and 7·6 (7·2–10·2), P<0·05], with a negative correlation between the 1,2-GDN/1,3-GDN ratio and the arterial GTN concentrations in the CHF patients ( R = −0·8, P<0·05). Conclusion: Patients with CHF have attenuated GTN responsiveness and decreased relative formation of 1,2-GDN in comparison with HS, indicating an altered biotransformation of GTN. [ABSTRACT FROM AUTHOR]

Background: The physiological determinants of left ventricular mass (LVM) measured by cardiac magnetic resonance (CMR) imaging are not well defined as prior investigators have studied either adults or adolescents in isolation or have not strictly excluded hypertension or accounted for the effects of exercise habits, haemodynamic, demographic, or body shape characteristics. Methods: Ninety-seven healthy volunteers (11–81 years, 51 males) underwent CMR. All parameters [unstandardized and adjusted for body surface area (BSA)] were analysed according to gender and by adolescence versus adulthood (adolescents <20 years, adults ≥20 years). The influence of haemodynamic factors, exercise and demographic factors on LVM were determined with multivariate linear regression. Results: Left ventricular mass rose during adolescence and declined in adulthood. LVM and LVMBSA were higher in males both in adults (LVM: 188 ± 22 versus 140 ± 21 g, P<0.001; LVMBSA: 94 ± 11 versus 80 ± 11 g m-2, P<0.001) and in adolescents when adjusted for BSA (LVM: 128 ± 29 versus 107 ± 20 g, P = 0.063; LVMBSA: 82 ± 8 versus 71 ± 10 g m-2, P = 0.025). In adults, systolic blood pressure (SBP) and self-reported physical activity increased while meridional and circumferential wall stress were constant with age. Multivariate regression analysis revealed age, gender and BSA as the major determinants of LVM (global R² = 0.68). Conclusions: Normal LVM shows variation over a broad age range in both genders with a rise in adolescence and subsequent decline with increasing age in adulthood despite an increase in SBP and physical activity. BSA, age and gender were found to be major contributors to the variation in LVM in healthy adults, while haemodynamic factors, exercise and wall stress were not. [ABSTRACT FROM AUTHOR]

Spontaneous baroreflex sensitivity (BRS), the reflex heart rate modulation in response to blood pressure changes (predominantly an index of cardiac vagal activity) and temporal QT variability (an index of myocardial repolarization) have been demonstrated to convey important prognostic information. The information about reproducibility of BRS and temporal QT variability is limited and there is lack of information regarding patients with cardiovascular diseases. We investigated reproducibility of spontaneous BRS using the sequence technique and temporal QT variability index (QTVI) in terms of intra-, interexaminer and within-subject variability in end-stage renal disease patients (ESRD, n=17, age 55±14 years) and healthy subjects (HS, n=29, age 32±12 years,P<0.01). ECG and blood pressure (Portapres) were recorded on two separate days and BRS and QTVI were evaluated by two independent examiners. The mean heart rate was similar in ESRD patients in comparison to healthy controls, whereas the mean arterial pressure was 13 % higher in ESRD patients (P<0.01). Spontaneous BRS was 62% lower (P<0.01) and QTVI was 41% higher in ESRD patients (P<0.01) compared to healthy subjects, respectively. Coefficient of variation (CV) of within-subject reproducibility of BRS and QTVI measurements was moderate (BRS: 33 % for ESRD, 27% for HS; QTVI: 40% for ESRD, 18% for HS). The 95% limit of within-subject reproducibility of BRS measurements was 3.8ms/mm Hg for ESRD patients and 8.1ms/mm Hg for healthy subjects; whereas the 95% limit of reproducibility of within-subject reproducibility of QTVI measurements was 0.73 for ESRD patients and 0.55 for healthy subjects. Concordance correlation coefficients of within-subject variability of BRS and QTVI were between 0.74 and 0.83 in both groups. CV of intra- and inter-examiner reproducibility of BRS and QTVI measurements in both groups ranged between 1 and 11%. In conclusion, the intra- and inter-examiner reproducibility/agreement of BRS and QTVI were high, whereas the within-subject reproducibility of these two methods was moderate, in both ESRD patients and healthy subjects. Thus, small differences in BRS and QTVI in longitudinal/interventional studies should be interpreted with caution. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate blood pressure, renal haemodynamics, hormone secretion and the responses to angiotensin II infusion during candesartan cilexetil (candesartan), losartan potassium (losartan) and valsartan treatment in patients with essential hypertension. In this double-blind, randomized, crossover study, 24 patients (mean blood pressure of 163/97 mmHg), received candesartan 16 mg, losartan 50 mg and valsartan 80 mg once daily (o.d.) for 4 weeks after a placebo run-in period. At the end of each period, angiotensin II (0.5, 1.0 and 1.5 ng/min/kg) was infused 24 h after the previous drug administration. Each dose of angiotensin II was infused for 45 min. Before infusion and at the end of each infusion step, blood pressure and renal haemodynamics were assessed and plasma renin activity and plasma concentrations of angiotensin II and aldosterone were measured. During treatment with candesartan, resting mean arterial pressure (mean ± SEM, 106 ± 2 mmHg) was significantly decreased compared with treatment with losartan (110 ± 2 mmHg) and valsartan (109 ± 2 mmHg). Candesartan inhibited the angiotensin II induced increase in filtration fraction (0.8 ± 0.4%) significantly more than losartan (1.5 ± 0.4%) and valsartan (1.6 ± 0.4%) and reduced the increase in aldosterone secretion (17 ± 5 pg/ml/) significantly more than losartan (74 ± 17 pg/ml/) and valsartan (82 ± 19 pg/ml/). In conclusion, candesartan 16 mg o.d. reduced resting blood pressure significantly more than losartan 50 mg o.d. and valsartan 80 mg o.d. Candesartan almost completely inhibited the exogenous angiotensin II induced renal vasoconstriction, effectively inhibited the increase in filtration fraction and significantly blunted aldosterone secretion compared with losartan and valsartan, indicating a more effective AT[sub 1] receptor blockade with candesartan. [ABSTRACT FROM AUTHOR]

Examines the role of nitric oxide (NO) and endothelin in the genesis of sympathetic nervous activation following experimental subarachnoid hemorrhage. Use of spectral analysis of blood pressure rhythms; Infusion of the NO donor sodium nitroprusside; Reduction of the mid-frequency oscillations in blood pressure.

Objective: The demonstration of the effectiveness of endothelin antagonists and nitric oxide donors in managing vasospasm following subarachnoid hemorrhage is encouraging. Whether such drugs can modify the sympathoexcitation that accompanies this condition remains unknown and was the basis for the present report. Methods: Subarachnoid hemorrhage was induced in conscious rats by injecting blood via a catheter placed along the surface of the brain and directed towards the circle of Willis. We combined measurements of arterial plasma catecholamines with the spectral analysis of blood pressure variability in order to examine sympathetic nervous activation following subarachnoid hemorrhage. Experiments were performed in untreated animals and in rats following pretreatment with either bosentan or sodium nitroprusside. Results: Indicative of a pronounced sympathoexcitation, the 0.2–0.6 Hz frequency components of blood pressure were markedly elevated following subarachnoid hemorrhage (2.5±0.5 vs. 8.9±2.6 mmHg2, P<0.01). Parallel changes in plasma norepinephrine concentration were observed (1.0±0.2 vs. 2.4±0.4 nmol/l, P<0.01). The subarachnoid injection of saline did not modify blood pressure variability or plasma norepinephrine concentrations. Pretreatment with either bosentan or sodium nitroprusside completely prevented the subarachnoid hemorrhage induced sympathoexcitation. Conclusions: Experimental subarachnoid hemorrhage is associated with a pronounced activation of the sympathetic nervous system. It would appear that this sympathoexcitation has its roots ensconced in either the release of endothelin or an impairment in nitric oxide mediated vasodilation. [ABSTRACT FROM PUBLISHER]

Examines the relationship between salt and blood pressure in hypertensive patients on chronic angiotensin converting enzyme inhibition. Measurement of intracellular erythrocyte sodium and potassium content by flame photomometry; Measurement of the increase in the intracellular sodium concentration; Determination of the rate of active sodium efflux; Performance of blood pressure registration.

While hair cortisol is proposed as a biomarker for chronic stress and a possible mediator linking chronic stress and cardiovascular risk in adults, studies in adolescents are scarce. We explored the associations between self-perceived stress, hair cortisol (HairF) and cortisone (HairE), and cardiometabolic risk markers in adolescents. Further, we examined whether association between self-perceived stress and HairF may depend on the use of the coping strategies "shift-persist". Participants were 7th grade pupils recruited to the STudy of Adolescence Resilience and Stress (STARS) and data from the baseline examinations were used. Adolescents (n = 1553, 26 % boys, M age =13.6, SD = 0.4) completed questionnaires assessing perceived stress and coping strategies "shift-persist", provided hair sample, and examined for cardiometabolic risk factors including waist circumference (WC), body mass index (BMI) z-score, blood pressure, and white blood cell counts (WBC). HairF and HairE were analysed using liquid chromatography with tandem mass spectrometry. We conducted descriptive analyses (Student's t-test, Wilcoxon Signed Ranks test, Chi-square test) and linear regression analyses. Perceived stress was not associated with HairF, neither had the use of coping strategies "shift-persist" any influence on this association. Both HairF and HairE were positively associated with BMI z-score (beta coefficients (β): 0.178 (p < 0.001) and 0.119 (p < 0.001) for boys; 0.123 (p < 0.001) and 0.089 (p < 0.01) for girls) and WC (β: 0.089 (p > 0.05) and 0.098 (p < 0.05) for boys; 0.103 (p < 0.01) and 0.076 (p < 0.05) for girls). Perceived stress was also positively associated with BMI z-score and WC. Perceived stress, but not HairF, remained associated with WC in boys (β = 0.200, p < 0.001) in the models with HairF and perceived stress presented simultaneously. Modest association between HairE and WBC was found in boys (β = 0.149, p < 0.01). The study supports the association between chronic stress and overweight/obesity in adolescents. Hair cortisol and self-perceived stress capture different aspects of how chronic stress is related to overweight/obesity in adolescents. • Hair glucocorticoids are associated with higher BMI and waist circumference in adolescents. • Hair cortisol & perceived stress capture different aspects of how chronic stress is related to higher BMI & WC. • Perceived stress did not reflect chronic activation of the HPA, neither had coping strategies influence on the association. [ABSTRACT FROM AUTHOR]

Abstract: Background: We have used a novel ultra high-frequency (55MHz) ultrasound technique to non-invasively measure the radial arterial vessel wall and separate the intima–media (IMT) complex into measurements of intima and media thickness (IT and MT). Since no previous study has measured IT and MT separately in individuals with prehypertension and hypertension, the aim of the current study was to measure IT and MT thickness of the radial arteries among individuals with prehypertension, hypertension and healthy subjects. Methods and results: Individuals with prehypertension (n =32), hypertension (n =34) and healthy subjects (n =29) underwent ultra high-resolution ultrasound of the radial artery. Individuals with prehypertension showed a 14% increase in IT compared to healthy subjects (0.083±0.020mm versus 0.073±0.015mm; p <0.05), whereas no difference was seen in MT. Individuals with hypertension showed a 12% increase of in IT compared to healthy subjects (0.082±0.018mm versus 0.073±0.015mm, p <0.05), whereas no differences were seen regarding MT. Prehypertensive and hypertensive individuals did not differ regarding IT and MT. Conclusion: Both prehypertension and hypertension are associated with thickening of the intimal layer of the radial artery. The present data indicates that intima thickening appears early during the development of hypertension even when blood pressure is only slightly elevated. [Copyright &y& Elsevier]