24-h Ambulatory Systolic Blood Pressure Research Articles

Psychological predictors of the antihypertensive effects of music-guided slow breathing

The possibility that daily sessions of music-guided slow breathing may reduce 24-h ambulatory blood pressure (ABP), and predictors of efficacy were explored in a randomized, placebo-controlled trial with parallel design. Age-matched and sex-matched hypertensive patients were randomized to music-guided slow breathing exercises (4-6 breaths/min; 1: 2 ratio of inspiration: expiration duration) (Intervention; n = 29) or to control groups who were thought to relax while either listening to slow music (Control-M; n = 26) or reading a book (Control-R; n = 31). At baseline and at follow-up visits (1 week and 1, 3 and 6 months), ABP monitoring was performed. At mixed model analysis, intervention was associated with a significant reduction of 24-h (P = 0.001) and night-time (0100-0600 h) (P < 0.0001) systolic ABP. The average reduction of systolic 24-h ABP at 6 months was 4.6 mmHg [confidence limits at 95% 1.93-7.35] and 4.1 mmHg (95% confidence limits 1.59-6.67) vs. Control-M and Control-R groups, respectively, (P < 0.001 for both). Antihypertensive treatment was selected as negative predictor of BP reduction at multivariate stepwise analysis. When antihypertensive treatment was inserted as covariate in a generalized linear model, psychological subscales assessed at baseline by the Mental Health Inventory questionnaire were found to affect systolic blood pressure reduction at 6-month follow-up (general positive affect P < 0.001; emotional ties, P < 0.001; loss of behavioral control, P = 0.035). In particular, a level of general positive affect higher than the 75th percentiles was found to be significantly associated with low treatment efficacy (odds ratio 0.09; 95% confidence limits 0.01-0.93). Daily sessions of voluntary music-guided slow breathing significantly reduce 24-h systolic ABP, and psychological predictors of efficacy can be identified.

Arterial stiffness index based on home (HASI) vs. ambulatory (AASI) blood pressure measurements

Ambulatory arterial stiffness index (AASI) is a novel index derived from the linear relationship between 24-h ambulatory systolic and diastolic blood pressure (BP) measurements. This study investigated whether 'home arterial stiffness index' (HASI) based on self-home BP measurements is similar to AASI. A total of 483 hypertensive subjects underwent 24-h ambulatory and 6-day home BP monitoring. AASI and HASI were defined as one minus the respective regression slope of diastolic on systolic BP. Mean HASI (0.66+/-0.17) was higher than 24-h (0.33+/-0.15) daytime (0.50+/-0.18) and nighttime AASI (0.37+/-0.19, P<0.001 for all comparisons vs. HASI) and was weakly correlated with 24-h (r=0.14, P<0.01) daytime (r=0.14, P<0.01) and nighttime AASI (r=0.09, P=0.05). Compared to 24-h AASI, HASI was less closely associated with age (r=0.46 and 0.10 respectively, P<0.001 for difference), systolic home BP (r=0.30 and 0.09, P<0.001) and pulse pressure (r=0.52 and 0.20, P<0.001), as well as with 24-h ambulatory systolic BP (r=0.21 and 0.05, P<0.05) and pulse pressure (r=0.56 and 0.25, P<0.001). No satisfactory agreement was observed between HASI and 24-h (agreement 63%, kappa 0.02) daytime (agreement 65%, kappa 0.1) or nighttime AASI (agreement 63%, kappa 0.03) in detecting subjects at the top quartile of the respective distributions. HASI appears to be similar but also has important differences from AASI and is less closely associated with markers of arterial stiffness. These data do not support the view that home BP measurements can replace ambulatory monitoring in the assessment of the arterial stiffness index.

Does the ratio of serum aldosterone to plasma renin activity predict the efficacy of diuretics in hypertension? Results of RENALDO

We hypothesized that the aldosterone: renin ratio (ARR) predicts the antihypertensive response to mineralocorticoid receptor antagonist, spironolactone (SPIRO), when compared with bendroflumethiazide (BFZ). We conducted a randomized, crossover, trial on hypertensive patients with either high ARR (HARR defined as >750 and plasma aldosterone >250 pmol/l) or low ARR (LARR defined as <300 and plasma renin activity <10 ng/ml per h). Each group took SPIRO 50 mg once daily for 12 weeks and BFZ 2.5 mg once daily for 12 weeks in random order separated by 2-week washout. Patients with mean 24-h systolic ambulatory blood pressure (SABP) at least 140 mmHg were included. Primary endpoint was difference in SABP between SPIRO and BFZ in patients with HARR compared with those with LARR. One hundred and eleven patients (60 HARR and 51 LARR) completed the study. SABP at 12 weeks in the HARR group was 129.4 mmHg on SPIRO and 134.4 mmHg on BFZ [difference -5.01; 95% confidence interval (CI) -7.51, -2.52; P < 0.0002]. In the LARR group, SABP was 129.7 mmHg on SPIRO and 133.1 mmHg on BFZ [difference -3.43 (95% CI -6.18, -0.68) P < 0.01]. Difference between groups (HARR vs. LARR) was -1.58 mmHg (95% CI 5.25, -2.08; not significant, P = 0.394). In a secondary analysis of the overall study population of 111 patients, SABP reduction with SPIRO 50 mg was superior to BFZ 2.5 mg [SPIRO -14.8 mmHg, BFZ -10.5 mmHg, difference -4.29 mmHg (95% CI -6.12, -2.46)]. Results were similar for secondary endpoints. Plasma renin activity or aldosterone did not predict blood pressure response to SPIRO. Results were independent of concomitant angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use. The ARR did not predict the blood pressure response to SPIRO. SPIRO 50 mg was significantly more effective than BFZ 2.5 mg in lowering SABP irrespective of baseline ARR, plasma renin activity or aldosterone.

Effects of force-titrated valsartan/hydrochlorothiazide versus amlodipine/hydrochlorothiazide on ambulatory blood pressure in patients with stage 2 hypertension: the EVALUATE study

Previous studies using the combination of angiotensin-receptor blockers and hydrochlorothiazide (HCTZ) have shown superior ambulatory blood pressure (ABP) reduction in study participants with stage 2 hypertension compared with monotherapy. This multicenter, double-blind, parallel group, forced-titration study of individuals with stage 2 hypertension, compared the efficacy of valsartan and amlodipine in combination with HCTZ on ABP reduction. After a 2-week washout period, participants (n=482) with mean office sitting systolic BP >or=160 mmHg and <or=200 mmHg were randomized to receive treatment with either valsartan 160 mg (n=241) or amlodipine 5 mg (n=241), force-titrated to a maximum dose of valsartan/HCTZ 320/25 mg or amlodipine/HCTZ 10/25 mg over 6 weeks and continued through week 10. The primary endpoint was change in mean 24-h ambulatory systolic BP from baseline to week 10. At week 10, changes from baseline in mean office BP were significantly (P<0.0001) decreased by both valsartan/HCTZ (-34.2/-14.2 mmHg) and amlodipine/HCTZ (-34.1/-14.7 mmHg). Changes from baseline in mean 24-h ABP were significantly (P<0.0001) decreased by both valsartan/HCTZ (-21.1/-12.5 mmHg) and amlodipine/HCTZ (-18.1/-9.9 mmHg). However, treatment with valsartan/HCTZ provided significant additional systolic BP (-3.8 mmHg; P=0.0042) and diastolic BP (-2.7 mmHg; P=0.0002) reduction compared with the amlodipine/HCTZ group. The proportion of individuals reaching the office goal BP (<140/80 mmHg) were similar in the valsartan/HCTZ (55.3%) versus amlodipine/HCTZ (54.9%) group, ABP control rates for the recommended ABP goal (<130/80 mmHg) were greater (P=0.0170) in the valsartan/HCTZ group (54.3%) than the amlodipine/HCTZ group (42.7%). Both treatments were well tolerated. On the basis of ABP monitoring but not office measurements, the fixed-dose combination of valsartan/HCTZ is a significantly more effective treatment regimen than amlodipine/HCTZ, with similar tolerability.

Prognostic value of ventricular repolarization prolongation in resistant hypertension: a prospective cohort study

The prognostic value of prolonged ventricular repolarization in patients with resistant hypertension is unknown. The aim of this prospective study was to investigate the usefulness of electrocardiographic QT-interval parameters as predictors of cardiovascular morbidity and mortality. At baseline, 538 resistant hypertensive patients had five QT-interval components measured in standard 12-lead ECGs: maximum QRS, QTpeak, QTend, JT and Tpeak-to-end-interval durations. Primary endpoints were a composite of fatal and nonfatal cardiovascular events, all-cause and cardiovascular mortalities. Multiple Cox regression assessed the associations between QT-interval parameters and subsequent endpoints. After a median follow-up of 4.8 years, 69 (12.8%) patients died, 46 from cardiovascular causes, and 107 (19.9%) fatal or nonfatal cardiovascular events occurred. After adjustment for several traditional risk factors, including 24-h ambulatory systolic blood pressure, an increment of 1 SD (35 ms) in QTcend-interval was associated with hazard ratios of 1.38 (1.15-1.67), 1.51 (1.16-1.98) and 1.30 (1.03-1.64), respectively, for the composite endpoint, cardiovascular mortality and all-cause mortality. Further adjustment for left ventricular hypertrophy attenuated the relative risks, but they remained significant for cardiovascular mortality (1.45, 1.07-1.97) and for the composite endpoint (1.35, 1.11-1.66). After full adjustment, a prolonged QTcend-interval (> or =460 ms) conferred a 1.7-fold (1.1-2.6) higher risk of having a future fatal or nonfatal cardiovascular event. No other QT-interval component added further prognostic information to QTcend-interval duration. Prolonged ventricular repolarization is a risk marker for cardiovascular morbidity and mortality in patients with resistant hypertension, over and beyond traditional cardiovascular risk factors, including ambulatory blood pressure and left ventricular hypertrophy.

The association of a simple blood pressure-independent parameter derived from ambulatory blood pressure variability with short-term mortality

We explored the predictive ability of the blood pressure variability ratio (BPVR), defined as the ratio of 24-h ambulatory systolic blood pressure variability to diastolic variability, and evaluated its predictable relation with blood pressure and the Ambulatory Arterial Stiffness Index (AASI). A total of 3433 consecutive patients were followed up to 16 years for all-cause mortality. Blood pressure variability was expressed by the standard deviation. BPVR, which is the systolic-on-diastolic slope estimated by a known type of symmetric regression ('reduced major axis'), was compared with other expressions of this slope and with AASI using other regression procedures. Time-dependent Cox proportional hazard models, adjusted for demographics, 24-h mean blood pressure, 24-h pulse pressure and dipping were used to assess the association of BPVR and slope-related parameters with all-cause mortality. We found that Pearson's correlation between BPVR and the symmetric slope was 0.957, and between 1-1/BPVR (an AASI-equivalent expression) and the symmetric version of AASI was 0.973. BPVR was entirely independent of mean arterial pressure (r=0.013). Systolic and diastolic ambulatory blood pressure variability was not significantly associated with mortality. Over 16 years, BPVR predicted all-cause mortality [hazard ratio=1.21 (95% CI 1.05-1.40) per 1 s.d. increase]. In time-dependent models, increased BPVR was strongly associated with an 18-month mortality, weakly related to 7 years mortality, showing no effect thereafter. Thus, the ratio between 24-h systolic and diastolic blood pressure variability, readily available from ambulatory monitoring reports, is an easy-to-calculate systolic-on-diastolic slope. It is a blood pressure-independent measure believed to express an arterial property, with prognostic power similar to that of AASI.

Predicting arterial stiffness with ambulatory blood pressure: an 11‐year follow‐up

No prospective data have been published on whether ambulatory blood pressure (BP) works better than casual measurements in predicting arterial stiffness. This study with 11-year follow-up was launched to evaluate the usefulness of ambulatory intra-arterial BP in predicting pulse wave velocity (PWV). Ninety-seven previously healthy men were recruited from a routine physical check-up at baseline. BP was measured with standard cuff and intra-arterial ambulatory methods. Sixty-seven subjects with no antihypertensive medication were enrolled for a visit after a follow-up of 11 years. Arterial stiffness was estimated with PWV derived with impedance cardiography. Ambulatory 24-h systolic blood pressure (SBP) (r = 0.30, P = 0.01), 24-h mean arterial pressure (r = 0.27, P = 0.03), 24-h pulse pressure (r = 0.27, P = 0.03) and daytime SBP (r = 0.26, P = 0.03) were the best BP variables in predicting future PWV. Casual BP values did not bear significant correlations with future PWV. In hierarchical regression analysis, the best predictive value for future PWV was achieved with the model including ambulatory 24-h SBP, smoking (number of cigarettes) and age (adjusted R(2) = 0.26). In conclusion, to our knowledge, this is the only prospective follow-up study to show that ambulatory BP is superior to casual BP measurement in predicting future PWV.

Postchallenge Plasma Glucose and Glycemic Spikes Are Associated with Pulse Pressure in Patients with Impaired Glucose Tolerance and Essential Hypertension

Elevated pulse pressure (PP) is associated with an increased risk of cardiovascular events. We examined whether PP is associated with post-challenge hyperglycemia in Japanese patients with essential hypertension and impaired glucose tolerance (IGT). In a total of 70 untreated essential hypertensive patients (age: 57+/-4 years, mean+/-SD; males=35, females=35), 24-h ambulatory blood pressure (ABP) monitoring, 75 g oral glucose tolerance testing (OGTT), metabolic analysis and echocardiography were performed. Patients were categorized into a high PP group (PP>or=60 mmHg, n=33) or a normal PP group (PP<60 mmHg, n=37). In all patients, 24-h systolic ABP, daytime systolic ABP, nighttime systolic ABP, and nighttime heart rate were significantly higher in the high PP group. Additionally, fasting immunoreactive insulin (F-IRI), homeostasis model assessment (HOMA) index, left ventricular mass index (LVMI) were also elevated in the high PP group. Finally, the high PP group exhibited impaired insulin secretion, increased post-challenge glucose concentrations and greater glucose spikes (PGS) during 75 g OGTT. Of the parameters measured, 24-h PP correlated positively with age, triglyceride, uric acid, F-IRI, HOMA index, 1-h postload glucose and insulin, 2-h postload glucose and insulin, PGS60, PGS120, PGSmax, LVMI, and deceleration time but correlated negatively with HDL-cholesterol and E/A ratio. Multiple regression analysis revealed that PP level was independently predicted by age, LVMI, and PGS120. Our results show that age, LVMI, and PGS120 are significantly associated with high PP in Japanese patients with IGT and essential hypertension.

Stroke Risk in Systolic and Combined Systolic and Diastolic Hypertension Determined Using Ambulatory Blood Pressure: The Ohasama Study

To investigate the risk of stroke in subjects with isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and combined systolic and diastolic hypertension (SDH) in a Japanese general population, we used 24-h ambulatory blood pressure (ABP) and casual-screening blood-pressure (CBP) readings. Subtypes of hypertension were defined based on systolic blood pressure (SBP) >135 mm Hg or diastolic blood pressure (DBP) >80 mm Hg for 24-h ABP, and SBP >140 mm Hg or DBP >90 mm Hg for CBP. We obtained 24-h ABP and CBP data for 1271 (40% male) subjects aged > or =40 years (mean age, 61 years) without a history of symptomatic stroke; their stroke-free survival was then determined. The prognostic significance of each subtype of hypertension was determined by Cox proportional hazard analysis. There were 113 symptomatic strokes during follow-up (mean time, 11 years). Compared with normotension, among the hypertension subtypes determined by 24-h ABP, the adjusted relative hazards (RHs) of stroke were 2.24 for ISH (P = .002) and 2.39 for SDH (P = .0004). The association was less marked among subtypes determined by CBP (RH = 1.40 and P = .13 for ISH; RH = 2.07 and P = .017 for SDH). The IDH group was excluded from the Cox analysis because both the prevalence and the number of events were low in this group. Isolated systolic hypertension, as determined by 24-h ABP measurements, was associated with a high risk of stroke, similar to that found in SDH subjects; this suggests that the prognosis of hypertensive patients would be improved by focusing treatment on 24-h systolic ABP.

Cardiovascular Characteristics in American Youth With Prehypertension

Cardiovascular structure and function in youth with prehypertension have been incompletely investigated. Casual and ambulatory blood pressure (BP) measurement, arterial stiffness, noninvasive hemodynamic profiles, and cardiac structure were studied in a twin cohort of American black and white youth (n = 942; mean age, 17.6 +/- 3.3 years SD). A family history of essential hypertension was used as a proxy to study genetic susceptibility to prehypertension. The occurrence of prehypertension was approximately 12% in the entire sample. Body mass index and waist circumference were significantly greater in prehypertensive subjects than in normotensive subjects. The 24-h ambulatory systolic BP (SBP), 24-h ambulatory diastolic BP (DBP), nighttime ambulatory SBP, and nighttime ambulatory DBP were significantly elevated in prehypertensive subjects compared with normotensive subjects. In whites, prehypertensive subjects compared with normotensive subjects showed increased radial (6.8 +/- 0.1 v 6.2 +/- 0.1 m/sec, P < .001) and foot pulse-wave velocity (PWV) (7.4 +/- 0.1 v 7.0 +/- 0.1 m/sec, P = .001). In whites, the total peripheral resistance index was greater in prehypertensive subjects than in normotensive subjects (P = .005). White prehypertensive subjects had a significantly greater heart rate than white normotensive subjects (69.0 +/- 1.4 v 64.0 +/- 0.6 bpm). In contrast, in blacks, the cardiac index was higher in prehypertensive subjects than in normotensive subjects (3.3 +/- 0.1 v 3.0 +/- 0.1 L/min/m2, P = .004). In blacks and whites, there were no statistical differences in the parameters of left-ventricular structure between normotensive subjects and prehypertensive subjects. Finally, prehypertensive subjects were more likely to have a positive family history of essential hypertension, especially in blacks. Prehypertension compared with normotension exhibited unfavorable cardiovascular phenotypes. Cardiovascular characteristics of prehypertension appear to be race-dependent.

Beta-blockers do not impair the cardiovascular benefits of endurance training in hypertensives

Aerobic physical exercise is broadly recommended as a helpful adjunct to obtain blood pressure control in hypertension. Beta-blockade interacts with heart rate, sympathetic tone, maximal workload and local lactate production. In the present randomized-controlled study, we compared the cardiovascular effects of an endurance training programme in elderly hypertensives with or without beta-blockers and developed a first approach to determine a lactate-based training heart rate in presence of beta-blockade. Fifty-two patients (23 with beta-blocker, 29 without beta-blocker) > or =60 years with systolic 24-h ambulatory blood pressure (ABP) > or =140 mm Hg and/or antihypertensive treatment were randomly assigned to sedentary activity or a heart-rate controlled 12-week treadmill exercise programme (lactate 2.0 mmol/l). In the exercise group, the training significantly decreased systolic and diastolic 24-h ABP, blood pressure on exertion (100 W) and increased endothelium-dependent vasodilation (flow-mediated vasodilation, FMD) and physical performance both in the presence and absence of beta-blockade (P<0.05 each). The extent of ABP reduction did not significantly differ in the presence or absence of beta-blockade (Delta systolic ABP 10.6+/-10.5 vs 10.6+/-8.8 mm Hg, Delta diastolic ABP 5.7+/-8.6 vs 5.8+/-4.0 mm Hg). Mean training heart rate was significantly lower in the patients on beta-blockers (97.2+/-7.7 vs 118.3+/-7.5/min, P<0.001). Lactate-based aerobic endurance training evokes comparable cardiovascular benefits in the presence and absence of beta-blockade including a marked improvement of endothelial function. In the present study, target training heart rate with beta-blockers is about 18% lower than without.

Moderate salt restriction effectively lowers blood pressure and degree of salt sensitivity is related to baseline concentration of renin and N-terminal atrial natriuretic peptide in plasma

The effect of salt restriction on blood pressure is under intense debate. We tested the effect of 100 mmol salt reduction on ambulatory blood pressure (ABP) in 46 Swedish individuals, 39 of whom completed the study, using a double-blind, placebo-controlled, cross-over design. Furthermore, we tested whether the basal plasma concentration of renin or N-terminal atrial natriuretic peptide (Nt-proANP) predict the degree of salt sensitivity. Participants received all meals and drinks with a total daily NaCl content of 50 mmol during 8 weeks. In addition, NaCl capsules (100 mmol/day) and corresponding placebo capsules were administered for 4 weeks each in random order. ABP after high-salt intake (150 mmol/day) was compared with ABP after low-salt intake (50 mmol/day). Salt sensitivity was defined as the difference between 24-h systolic ABP at the high-salt versus the low-salt periods. Baseline renin and Nt-proANP were related to salt sensitivity. Lowering of salt intake from 150 to 50 mmol/day induced significant blood pressure reductions (mean reduction, 95% confidence interval) in systolic and diastolic 24-h ABP (5.8, 3.4-8.2 and 2.6, 0.91-4.4 mmHg), daytime ABP (5.5, 2.9-8.1 and 2.3, 0.42-4.1 mmHg) and night-time ABP (6.4, 3.5-9.3 and 3.4, 1.4-5.5 mmHg). Baseline ln(renin) correlated inversely with salt sensitivity (r = -0.50, P = 0.001) whereas baseline ln(Nt-proANP) correlated directly (r = 0.33, P = 0.04). Lowering of salt intake with 100 mmol/day induces clinically relevant ABP reductions. Renin and Nt-proANP, measured with individuals on their habitual diet, could be useful biomarkers to identify individuals with the greatest blood pressure-lowering benefit from reduced salt intake.

Long-term effects of low-dose 17β-estradiol plus dydrogesterone on 24-h ambulatory blood pressure in healthy postmenopausal women: A 1-year, randomized, prospective study

The aim of the present 12-month, randomized, prospective controlled study was to investigate the long-term effects of low-dose oral hormone replacement therapy (HRT) on 24-h blood pressure in healthy, normotensive postmenopausal women. A total of 80 postmenopausal women received either 1 mg micronized 17β-estradiol daily, sequentially combined with 10 mg dydrogesterone for 14 days of each 28-day cycle (n = 44), or no treatment (n = 36). Ambulatory blood pressure was recorded for a 24-h period at baseline and after 12 months. After 12 months, mean 24-h systolic ambulatory blood pressure fell significantly in the HRT group (−5.4 mmHg; p < 0.01). The difference between the values in the HRT and control groups after 12 months was significant (p < 0.01). Mean 24-h heart rate also fell significantly with HRT (−4.9 beats/min; p < 0.05), and the value was significantly lower than in the control group (p < 0.05). Mean daytime systolic blood pressure fell significantly in the HRT group (−6.6 mmHg; p < 0.001), and the value was significantly lower than in the control group (p < 0.05). There were no significant changes in blood pressure in the control group. In conclusion, sequential low-dose oral HRT with 17β-estradiol/dydrogesterone caused a significant decrease in 24-h and daytime systolic ambulatory blood pressure in normotensive postmenopausal women.

COMPARATIVE EVALUATION OF ENALAPRIL AND DILTIAZEM EFFICACY IN MENOPAUSAL WOMEN WITH ARTERIAL HYPERTENSION

Aim. To compare enalapril (E) and diltiazem (D) efficacy in menopausal women with arterial hypertension (AH) using three methods of blood pressure (BP) measurement. Material and methods. There was a cross-over randomised study with E and D included 22 menopausal women with AH. E was given at a daily dose of 5-20 mg and D – at a daily dose of 180-360 mg. At baseline and at the end of each treatment period ambulatory blood pressure monitoring (ABPM) was carried out. Self blood pressure measurement (SBPM) was performed during all study period. To assess a steadiness of antihypertensive effect we calculated smoothness index and trough-to-peak ratio based on ABPM data. Results. Ambulatory 24-h systolic BP and diastolic BP were decreased in the E group (-15.2/-9.6 mm Hg) and in the D group (-10.9/-6.0 mm Hg). E demonstrated a greater antihypertensive effect on SBPM results in the evening. Values of smoothness index on E treatment were slightly higher than on D treatment (0.86±0.15/0.64±0.13 vs 0.67±0.17/0.62±0.15). Trough-to-peak ratio was inconclusive in this study. Conclusions. Results of the study have shown some advantages of antihypertensive therapy with E compared with these of D in slow release formulation (both drugs at a single daily dose) in menopausal women. A sustained antihypertensive effect without negative influence on circadian BP profile allows to consider E as one of perspective agents for the AH treatment in this type of patients.

Ambulatory blood pressure variability and brachial-ankle pulse wave velocity in untreated hypertensive patients.

Blood pressure (BP) variability is estimated as the standard deviation of 24-h ambulatory BP. The present study was performed to determine the effect of the mean 24-h ambulatory BP values and standard deviations on arterial wall stiffness assessed by brachial-ankle pulse wave velocity (baPWV). Brachial-ankle pulse wave velocity, carotid intima-media thickness (IMT), urinary albumin excretion (UAE) and 24-h ambulatory BP were measured before the start of antihypertensive therapy in 203 newly diagnosed hypertensive patients (53.3+/-0.7 years old; clinic systolic/diastolic BP: 154+/-1/98+/-1 mm Hg), and univariate and multivariate regression analyses of these clinical and biological parameters were performed. Univariate regression analyses revealed a significant association between mean baPWV values and the standard deviations of ambulatory systolic/diastolic BP. Mean ambulatory systolic/diastolic BP values were also associated with UAE, and the standard deviations of ambulatory systolic BP were associated with maximum carotid IMT. Quintile analyses showed that patients with a mean 24-h ambulatory mean BP value and standard deviation below 110 and 20 mm Hg, respectively, had the lowest baPWV. Moreover, the multivariate regression analyses confirmed a significant correlation between baPWV and the standard deviation of 24-h ambulatory systolic BP. In conclusion, untreated hypertensive patients with a higher 24-h ambulatory systolic BP variability had stiffer arterial walls. Ambulatory systolic BP variability may be involved in stiffening of the arteries of hypertensive patients.

Maternal Preeclampsia Predicts Elevated Blood Pressure in 12-Year-Old Children: Evaluation by Ambulatory Blood Pressure Monitoring

Ambulatory blood pressure (ABP) monitoring offers a reliable method for determining blood pressure (BP) in children. The aim of this cohort study was to examine whether maternal preeclampsia is associated with elevated BP in an offspring. The study population consisted of 57 children born to preeclamptic mothers (PRE) and their 57 age- and sex-matched control subjects born to normotensive mothers (non-PRE). We examined the 24-h ABP at 12 y of age in the PRE and non-PRE children. Within the two groups, the association of anthropometric measures, plasma catecholamine (epinephrine [E], norepinephrine [NE]) concentrations, and ABP was examined. The PRE children had significantly higher mean 24-h systolic and diastolic ABPs than the non-PRE children. The same was true for the mean daytime and nighttime systolic and diastolic ABPs. The PRE boys had higher 24-h systolic ABP than the PRE girls. In the PRE children, high plasma E concentration and being born small for gestational age (SGA) predicted high systolic 24-h ABP in logistic regression analysis. In the non-PRE children, high current body mass index (BMI) and high plasma E concentration was associated with high systolic 24-h ABP. In conclusion, systolic and diastolic ABP values were elevated in the PRE children. High plasma E concentration and being born SGA were associated with high systolic 24-h ABP in the PRE children. Presumably maternal preeclampsia affects offspring via several mechanisms, including genetic ones and metabolic consequences of restricted intrauterine growth.

CYP3A5 genotype is associated with elevated blood pressure

The present study aimed to determine whether a polymorphism in CYP3A5, encoding the major CYP3A enzyme in the human kidney, is associated with blood pressure in Caucasians. A homogenous group of 115 young, white male students with normal or mildly elevated, but untreated blood pressure was included. Blood pressure was recorded by ambulatory 24-h blood pressure-monitoring and compared between individuals with high (*1/*3) and low CYP3A5 expression (*3/*3). Moreover, genotype-dependent differences in parameters associated with the renin-angiotensin-aldosterone system were evaluated. Twenty-four hour diastolic blood pressure values were not significantly different between the two groups. However, individuals with the CYP3A5*3/*3 genotype had significantly higher 24-h ambulatory systolic blood pressure values compared to subjects with the CYP3A5*1/*3 genotype (129+/-10 versus 124+/-9, P < 0.05). There was no association of CYP3A5 genotype with angiotensin II plasma concentrations, renal plasma flow, glomerular filtration rate, urinary sodium excretion and parameters determined by echocardiography, but the *3/*3 group had significantly lower serum aldosterone concentrations compared to the individuals with the *1/*3 genotype (101+/-29 versus 117+/-29 pg/ml, P < 0.05). These data, as generated with a homogenous population of young Caucasians, indicate that the CYP3A5 genotype affects blood pressure in humans possibly by genotype-dependent differences in renal, CYP3A5-mediated metabolism of cortisol and/or aldosterone. We interpret the lower serum aldosterone concentration in the genotype group with the elevated systolic blood pressure as a counter-regulatory mechanism to attenuate the increased blood pressure associated with the CYP3A5*3/*3 genotype.

Beneficial Effects of Adding Spironolactone to Recommended Antihypertensive Treatment in Diabetic Nephropathy

The objective of this study was to evaluate the safety and short-term effect of adding spironolactone to conventional antihypertensive treatment including diuretics and maximally recommended doses of an ACE inhibitor or an angiotensin II receptor blocker (ARB) on albuminuria and blood pressure in type 2 diabetic patients with nephropathy. Twenty-one type 2 diabetic patients with nephropathy were enrolled in a randomized, double-masked, cross-over study. Patients were treated in random order with spironolactone 25 mg once daily and matched placebo for 8 weeks, respectively, in addition to ongoing antihypertensive treatment including diuretics and maximally recommended doses of an ACE inhibitor and/or an ARB. At the end of each treatment period, albuminuria, 24-h ambulatory blood pressure (ABP), and glomerular filtration rate (GFR) were determined. During the addition of placebo, values were as follows: albuminuria (geometric mean [range]) 1,566 [655-7,762] mg/24 h, ABP (mean +/- SE) 138 +/- 3/71 +/- 1 mmHg, and GFR (mean +/- SE) 74 +/- 6 ml/min per 1.73 m2. During the addition of spironolactone, albuminuria was reduced by 33% (95% CI 25-41) (P < 0.001), fractional clearance of albumin by 40% (24-53) (P < 0.001), and 24-h ABP by 6 mmHg (2-10) for systolic and 4 mmHg (2-6) for diastolic (P < 0.001 for both). The change in albuminuria did not correlate with the change in systolic 24-h ABP (r = 0.19, P = 0.42) or diastolic 24-h ABP (r = 0.01, P = 0.96). Spironolactone treatment induced an insignificant reversible reduction in GFR of 3 ml/min per 1.73 m2 (-0.3 to 6) (P = 0.08). One patient was excluded from the study due to hyperkalemia. Otherwise treatment was well tolerated. Our study suggests that spironolactone safely adds to the reno- and cardiovascular protective benefits of treatment with maximally recommended doses of ACE inhibitor and ARB by reducing albuminuria and blood pressure in type 2 diabetic patients with nephropathy.

Effects of amlodipine and fosinopril on heart rate variability and left ventricular mass in mild-to-moderate essential hypertension

The differences between long-acting dihydropyridines and angiotensin-converting enzyme inhibitors with regard to their long-term effects on 24-h heart rate variability (HRV) and left ventricular (LV) mass are less clear in mild-to-moderate essential hypertension. We studied the long-term effects of amlodipine and fosinopril on 24-h HRV and LV mass in mild-to-moderate essential hypertension. In this study, 27 patients with never treated mild-to-moderate essential hypertension were randomised to receive either amlodipine or fosinopril once daily as monotherapy. At baseline and at the end of the third and sixth months, each of the patients underwent 24-h HRV and ambulatory systolic (SBP) and diastolic (DBP) blood pressure analysis. LV mass index was calculated from echocardiographic examination at baseline and at the end of the sixth month. In amlodipine group (n = 14), 24-h SBP/DBP (mmHg) decreased from 144 +/- 8/94 +/- 4 to 128 +/- 6/83 +/- 3 at the end of the third month and to 125 +/- 5/81 +/- 2 at the end of the sixth month (p < 0.0001). In fosinopril group (n = 13), the respective changes were 143 +/- 9/97 +/- 7, 132 +/- 6/87 +/- 5 and 127 +/- 6/82 +/- 3 (p < 0.0001). At the end of the sixth month, LV mass index (g/m(2)) decreased from 122 +/- 26 to 105 +/- 21 in amlodipine group (p < 0.0001) and from 118 +/- 23 to 101 +/- 14 in fosinopril group (p < 0.0001). There were no significant changes in HRV parameters in both the groups. It was concluded that both drugs caused significant decrease in SBP and DBP, and LV mass in patients with mild-to-moderate essential hypertension did not have significant long-term effects of either amlodipine or fosinopril on 24-h HRV parameters reflecting sympathetic or parasympathetic activity in these patients.

The combination of vitamin C and grape-seed polyphenols increases blood pressure: a randomized, double-blind, placebo-controlled trial

There is growing evidence that oxidative stress contributes to the pathogenesis of hypertension and endothelial dysfunction. Thus, dietary antioxidants may beneficially influence blood pressure (BP) and endothelial function by reducing oxidative stress. To determine if vitamin C and polyphenols, alone or in combination, can lower BP, improve endothelial function and reduce oxidative stress in hypertensive individuals. A total of 69 treated hypertensive individuals with a mean 24-h ambulatory systolic blood pressure > or = 125 mmHg participated in a randomized, double-blind, placebo-controlled, factorial trial. Following a 3-week washout, participants received 500 mg/day vitamin C, 1000 mg/day grape-seed polyphenols, both vitamin C and polyphenols, or neither for 6 weeks. At baseline and post-intervention, 24-h ambulatory BP, ultrasound-assessed endothelium-dependent and -independent vasodilation of the brachial artery, and markers of oxidative damage, (plasma and urinary F2-isoprostanes, oxidized low-density lipoproteins and plasma tocopherols), were measured. A significant interaction between grape-seed and vitamin C treatments for effects on BP was observed. Vitamin C alone reduced systolic BP versus placebo (-1.8 +/- 0.8 mmHg, P = 0.03), while polyphenols did not (-1.3 +/- 0.8 mmHg, P = 0.12). However, treatment with the combination of vitamin C and polyphenols increased systolic BP (4.8 +/- 0.9 mmHg versus placebo; 6.6 +/- 0.8 mmHg versus vitamin C; 6.1 +/- 0.9 mmHg versus polyphenols mmHg, each P < 0.0001) and diastolic BP (2.7 +/- 0.6 mmHg, P < 0.0001 versus placebo; 1.5 +/- 0.6 mmHg, P = 0.016 versus vitamin C; 3.2 +/- 0.7 mmHg, P < 0.0001 versus polyphenols). Endothelium-dependent and -independent vasodilation, and markers of oxidative damage were not significantly altered. Although the mechanism remains to be elucidated, these results suggest caution for hypertensive subjects taking supplements containing combinations of vitamin C and polyphenols.