Increased total mortality as a function of 24-h pulse pressure dipping.

Elevated pulse pressure (PP) as a difference between systolic and diastolic blood pressure is a significant risk factor of cardiovascular (CV) diseases. The goal of our study was to determine the association between PP and major adverse CV events (MACEs), and all-cause and CV mortality in the different age groups of patients with coronary artery disease (CAD) confirmed by angiography. To the PROGNOSIS study, finally there were included 891 subjects with CAD. An analysis of the receiver operating characteristic was used for predicting PP dipping among the age groups of patients. A COX proportional hazards model was used to examine the association between PP and PP dipping and risk of MACE, revascularization, CV and total mortality after adjusting for sex, diabetes, smoking and low-density lipoprotein cholesterol. The median follow-up period was 8.3 years (interquartile range: 5.3-9.0 years). There were 245 (27%) all-cause deaths including 114 (13%) CV deaths during the follow-up period. MACE occurred in 442 (50%) subjects, but coronary artery interventions (percutaneous coronary intervention or coronary artery bypass grafting) were performed in 578 subjects (65%). A Cox proportional regression analysis confirmed the relationship between PP dipping as well as PP dipping thresholds points and risk of MACE and total mortality only in the group of the oldest subjects. In contrast to younger CAD patients, PP dipping is related to MACE, CV and total mortality in very elderly CAD subjects. Nocturnal PP values tend to be higher than diurnal PP values in the oldest CAD individuals. In conclusion, in contrast to younger CAD patients, PP dipping is related to MACE, CV and total mortality in very elderly CAD subjects. Nocturnal PP values tend to be higher than diurnal PP values in the oldest CAD individuals.

Wavelet transform analysis to assess oscillations in pial artery pulsation at the human cardiac frequency.

Pial artery adjustments to changes in blood pressure (BP) may last only seconds in humans. Using a novel method called near-infrared transillumination backscattering sounding (NIR-T/BSS) that allows for the non-invasive measurement of pial artery pulsation (cc-TQ) in humans, we aimed to assess the relationship between spontaneous oscillations in BP and cc-TQ at frequencies between 0.5 Hz and 5 Hz. We hypothesized that analysis of very short data segments would enable the estimation of changes in the cardiac contribution to the BP vs. cc-TQ relationship during very rapid pial artery adjustments to external stimuli. BP and pial artery oscillations during baseline (70s and 10s signals) and the response to maximal breath-hold apnea were studied in eighteen healthy subjects. The cc-TQ was measured using NIR-T/BSS; cerebral blood flow velocity, the pulsatility index and the resistive index were measured using Doppler ultrasound of the left internal carotid artery; heart rate and beat-to-beat systolic and diastolic blood pressure were recorded using a Finometer; end-tidal CO2 was measured using a medical gas analyzer. Wavelet transform analysis was used to assess the relationship between BP and cc-TQ oscillations. The recordings lasting 10s and representing 10 cycles with a frequency of ~1 Hz provided sufficient accuracy with respect to wavelet coherence and wavelet phase coherence values and yielded similar results to those obtained from approximately 70cycles (70s). A slight but significant decrease in wavelet coherence between augmented BP and cc-TQ oscillations was observed by the end of apnea. Wavelet transform analysis can be used to assess the relationship between BP and cc-TQ oscillations at cardiac frequency using signals intervals as short as 10s. Apnea slightly decreases the contribution of cardiac activity to BP and cc-TQ oscillations.

Early complete donor hematopoietic chimerism in peripheral blood indicates the risk of extensive graft-versus-host disease.

Achievement of complete donor hematopoietic chimerism (CC) is the goal of allogeneic stem cell transplantation (allo-SCT). Persistence of recipient hematopoiesis augments the risk of relapse, which is one of the main reasons for mortality after allo-SCT. Another main reason for morbidity and mortality is severe extensive chronic graft-versus-host disease (cGvHD). We examined chimerism in peripheral blood of 54 allogeneic stem cell recipients using multiplex STR-PCR method and compared it with the timing and severity of cGvHD. In total, 25 patients achieved early CC (by day 100 post transplant) at a median time of 60 days. In total, 21 of them developed extensive cGvHD. In those patients CC uniformly preceded emergence of cGvHD by a mean of 85 days. A total of 26 patients obtained late CC at a median time of 270 days post transplant. Of this group, only eight patients developed extensive disease. Development of cGvHD in those patients preceded achievement of CC in 10 of 13 cases by a mean of 100 days. The difference between early and late CC groups as to the frequency of the extensive cGvHD was statistically significant (P<0.001). Also, there was a significant correlation of the time of CC and time between CC and cGvHD. Additionally, patients with early CC developed significantly more severe cGvHD measured by the need of three-drug treatment to control the disease (P<0.005). It can be concluded that achievement of early complete donor hematopoietic chimerism in peripheral blood is strongly predictive of severe extensive GvHD.

The role and interactions of nitric oxide (NO), carbon monoxide (CO), and prostanoids in the pathogenesis of postoperative ileus in rats.

The effects of heme oxygenase (HO) inhibitors, zinc-protoporphyrin-IX (ZnPP-IX), and tin protoporphyrin-IX (SnPP-IX) and their interactions with L-arginine/nitric oxide synthase (NOS) and cyclooxygenase (COX) pathways were investigated in postoperative ileus in rats. Intestinal transit was measured as Evans blue migration after skin incision, laparotomy or laparotomy plus gut evisceration and handling. Laparotomy and small intestinal manipulations increased blood plasma nitrites/nitrates level 1.88-fold. N(omega)-nitro-L-arginine methyl ester, indomethacin, a selective COX-1 blocker (resveratrol) and COX-2 antagonists (nimesulide, DuP-697, NS-398) reversed the additional inhibitory effects of gut manipulation subsequent to laparotomy. In contrast, N-(3-(aminomethyl)benzyl)acetamidine or S-methylisothiourea, highly selective inducible NOS blockers, remained ineffective. ZnPP-IX and SnPP-IX overturned the effects of laparotomy on dye propulsion, but were only partially effective after laparotomy and gut handling attenuating the additional inhibitory influences of gut manipulation, the intestinal transit reaching 89.21%, 92.87%, 53.46%, and 48.56% of respective controls transit. Salutary effects of L-NAME, ZnPP-IX, and SnPP-IX were dose-dependent, L-arginine or hemin (HO substrate) sensitive. Administration of indomethacin and resveratrol subsequent to SnPP-IX reversed the inhibitory effects of laparotomy and manipulation, amounting to 93.91% and 87.43% of controls. On the other hand, L-NAME injected after SnPP-IX abolished the salutary effects of the latter, study dye migration reached 25.18% of control rat. Therefore we demonstrated that nitric oxide, carbon monoxide, and prostanoids play a role in the pathogenesis of postoperative ileus albeit in different mechanisms. Laparotomy stimulated HO activity, whereas gut manipulation led to an excessive constitutive NOS stimulation accompanied by augmented prostanoid synthesis by COX-1. Unaffected synthesis of either NO or CO enables a return of gastrointestinal transit during postoperative period, whereas a pharmacological blockade of two complementary metabolic pathways provides a most effective measure against postoperative ileus development.

Headache in patients with mild to moderate hypertension is generally not associated with simultaneous blood pressure elevation.

OBJECTIVE: Although headache is regarded a symptom of hypertension, its relation to blood pressure, especially in mild and moderate hypertension, is not clear. Thus, the aim of the study was to investigate whether headache in patients with mild to moderate hypertension may be attributed to simultaneous elevations in blood pressure. DESIGN AND METHODS: Ambulatory blood pressure monitoring (ABPM) was performed in patients (mean age 48 +/- 10 years, n = 150, 92 men, 58 women) classified, according to their office blood pressure, as stage 1 -2 hypertensives (JNC VI). Headache periods were recorded in patients' diaries. RESULTS: Headaches were generally not directly associated with blood pressure elevations in the studied group of stage 1-2 hypertensive patients because (i) blood pressure values from headache periods were not significantly higher than those from headache-free periods; (ii) blood pressure values directly preceding the pain were not significantly different from values at the beginning of headache; and (iii) in the vast majority of hypertensives, their maximal blood pressure values were recorded during headache-free periods. Moreover, in some instances, patients who showed maximal ABPM values during headache had relatively high blood pressure, i.e. > or = 180/110 mmHg. CONCLUSIONS: Our results did not support the opinion that headache experienced by stage 1-2 hypertensives was generally caused by simultaneous elevation in blood pressure. The direct mechanisms of headache in hypertension, as well as the relation between increments in blood pressure above 180/110 mmHg and headache, need further investigations.

[Evaluation of reproducibility of plethysmographic indices according to body posture, choice of forearm and method of measurement]. / Ocena powtarzalnosci wskazników pletyzmograficznych w zaleznosci od pozycji ciala, wyboru badanej konczyny oraz metody pomiaru.

The aim of the study was the analysis of the influence: a) body position (sitting vs. supine), b) choice of the arm (dominant vs. nondominant), c) variant of the method (classic vs. automatic) on plethysmographic indices describing forearm blood flow repeatability (arterial inflow--AI, fast blood flow--FBF, venous outflow VO, venous capacitance--VC). The study group included subjective healthy men, aged from 22 to 60 years. Individuals with body mass index (BMI) > 35 kg/m2 or treated pharmacologically weren't been included into examination. The indices of the forearm blood flow were calculated from the plethysmographic curve using the graphic technique: venous capacitance (VC), arterial inflow (AI), fast blood flow (FBF) and venous outflow (VO). We used relative repeatability coefficient (RRC) and coefficient of variation (CV) for assessing repeatability of obtained parameters. Repeatability of plethysmographic indices was better in supine position than in sitting one. RRC was respectively for supine vs. sitting position for VO: 0.41 vs. 0.68, for VC: 0.42 vs. 0.52 and for AI: 0.57 vs. 0.65. Plethysmographic indices VO, VC, AI were characterised by better repeatability when the exams were performed on the dominant arm. RRC was respectively for dominant vs. nondominant arm for VO: 0.68 vs. 0.71, for VC: 0.52 vs. 0.64 and for AI: 0.65 vs. 0.71. Coefficient of variation of arterial inflow assessed by conventional, automatic and by fast inflow was respectively 20%, 23% and 17%. The long-term repeatability of FBF estimated by RRC was 0.76 whereas CV yielded 17%. The same coefficient of variation was obtained when short-term repeatability was estimated-mean value CV was 17%, after rejection extremal values 11%. In conclusion the best repeatability was obtained when measurements were performed with automatic variant of method, in supine position, on dominant arm.

Nocturnal blood pressure fall on ambulatory monitoring in a large international database. The "Ad Hoc' Working Group.

A wide range of definitions is used to distinguish subjects in whom blood pressure (BP) falls at night (dippers) from their counterparts (nondippers). In an attempt to standardize the definition of nondipping, we determined the nocturnal BP fall and night-day BP ratio by 24-hour ambulatory monitoring in 4765 normotensive and 2555 hypertensive subjects from 10 to 99 years old. In all subjects combined, the systolic/diastolic nocturnal fall and corresponding ratio averaged (+/- SD) -16.7 +/- 11.0/ -13.6 +/- 8.1 mm Hg and 87.2 +/- 8.0%/83.1 +/- 9.6%, respectively. In normotensive subjects, the 95th percentiles were -0.3/-1.1 mm Hg for the nocturnal fall and 99.7%/98.3% for the night-day ratio. Both the fall and ratio showed a curvilinear correlation with age. The smallest fall and largest ratio were observed in older (> or = 70 years) subjects. A higher BP on conventional sphygmomanometry was associated with a larger systolic (partial r = .11) and diastolic (r = .12) nocturnal BP fall. The diastolic (r = .08) but not the systolic night-day ratio increased with higher conventional BP. The nocturnal BP fall was larger and the corresponding night-day ratio smaller in oscillometric (n = 5884) than in auscultatory (n = 1436) recordings, in males (n = 3730) than in females (n = 3590), and in Europe (n = 4556) than in the other continents (n = 2764). The distributions of the nocturnal BP fall and night-day ratio showed considerable overlap among normotensive and hypertensive subjects, but the overlap tended to be larger for the ratio than for the fall. Of all subjects, 3.2% had systolic and diastolic ratios of 100% or more. With adjustments applied for confounders, the probability of being a nondipper increased 2.8 times (95% confidence interval, 2.0-4.0) from 30 to 60 years and 5.7 times (4.4-7.4) from 60 to 80 years. The odds ratios were 1.0 (0.8-1.4) for males versus females. 1.6 (1.2-2.1) for subjects with definite hypertension versus normotensive subjects, 2.4 (1.2-4.7) for Asians (n = 2213, 96% Japanese) versus inhabitants of the other continents, and 2.4 (1.5-3.8) for subjects examined with auscultatory versus oscillometric devices. In conclusion, the mathematical definition of nondipping, ie, having a night-day ratio of 100% or more for systolic and diastolic BPs, closely approximated the 95th percentiles of the night-day ratio in normotensive subjects. The ratio depends less on BP level than the nocturnal BP fall and is therefore to be preferred in the definition of dipping status. Notwithstanding the present findings, the reproducibility of nondipping and its prognostic significance need further clarification.

Life style as a blood pressure determinant.

In Belgium, an affluent Western European country, participation in sports, alcohol intake, and living in a working class area were identified as the life style factors with the closest associations with the blood pressure level. Obesity was another important blood pressure correlate. Sodium intake, determined from the 24 h urinary output, and smoking were not associated with blood pressure. Controlled intervention studies have proven that weight reduction, endurance training and alcohol abstinence effectively reduce blood pressure. In the light of these intervention studies, the Belgian findings and the published work highlight the potential of preventive strategies aimed at these major life style factors.

Ambulatory blood pressure monitoring in clinical trials.

Ambulatory blood pressure monitoring is increasingly used in clinical trials. The preliminary threshold values proposed for diagnosing hypertension and adjusting treatment based on ambulatory monitoring cannot yet be widely recommended because they have not been validated in prospective studies. The trough-to-peak or surface ratios may be useful instruments for assessing the duration of action of antihypertensive drugs. Trials with ambulatory monitoring just as clinical experiments based on conventional sphygmomanometry need to be properly controlled, because ambulatory blood pressure measurement is not completely devoid of a placebo effect. Ambulatory compared with conventional blood pressure measurements are characterized by higher reproducibility which makes it possible to reduce sample size in cross-over but not in parallel group trials. Finally, ambulatory monitors used in clinical research should have successfully passed one of the standardized validation protocols.

Ambulatory blood pressure monitoring in clinical trials.

Ambulatory blood pressure monitoring is increasingly being used in clinical trials. Trials with ambulatory monitoring, just like clinical experiments based on conventional sphygmomanometry, need to be controlled properly, because ambulatory blood pressure measurements are not completely devoid of placebo-like effects. The trough: peak ratio might be a useful instrument for assessment of the durations of action of antihypertensive drugs. However, its error term and confidence interval need to be reported and its determination in clinical trials requires further standardization. Ambulatory compared with conventional blood pressure measurements are characterized by a higher reproducibility. This property makes a reduction in sample size possible in cross-over but not in parallel group trials, if instead of the conventional blood pressure the 24 h or daytime blood pressures are compared. Trials focusing on the full course of the blood pressure through the day need a larger sample size than do those just concerning the conventional blood pressure level.

Ambulatory monitoring uncorrected for placebo overestimates long-term antihypertensive action. Systolic Hypertension in Europe (SYST-EUR) Trial Investigators.

This study compares blood pressure (BP) changes during active antihypertensive treatment and placebo as assessed by conventional and ambulatory BP measurement. Older patients (> or = 60 years, n=337) with isolated systolic hypertension by conventional sphygmomanometry at the clinic were randomized to placebo or active treatment consisting of nitrendipine (10 to 40 mg/d), with the possible addition of enalapril (5 to 20 mg/d) and/or hydrochlorothiazide (12.5 to 25 mg/d). At baseline, clinic systolic/diastolic BP averaged 175/86 mm Hg and 24-hour and daytime ambulatory BPs averaged 148/80 and 154/85 mm Hg, respectively. After 13 months (median) of active treatment, clinic BP had dropped by 22.7/7.0 mm Hg and 24-hour and daytime BPs by 10.5/4.5 and 9.7/4.3 mm Hg, respectively (P<.001 for all). However, clinic (9.8/1.6 mm Hg), 24-hour (2.1/1.1 mm Hg), and daytime (2.9/1.0 mm Hg) BPs decreased also during placebo (P<.05, except for daytime diastolic BP); these decreases represented 43%/23%, 20%/24%, and 30%/23% of the corresponding BP fall during active treatment. After subtraction of placebo effects, the net BP reductions during active treatment averaged only 12.9/5.4, 8.3/3.4, and 6.8/3.2 mm Hg for clinic, 24-hour, and daytime BPs, respectively. The effect of active treatment was also subject to diurnal variation (P<.05). Changes during placebo in hourly systolic and diastolic BP means amounted to (median) 21% (range, -1% to 42%) and 25% (-3% to 72%), respectively, of the corresponding changes during active treatment. In conclusion, expressed in millimeters of mercury, the effect of antihypertensive treatment on BP is larger with conventional than with ambulatory measurement. Regardless of whether BP is measured by conventional sphygmomanometry or ambulatory monitoring, a substantial proportion of the long-term BP changes observed during active treatment may be attributed to placebo effects. Thus, ambulatory monitoring uncorrected for placebo or control observations, like conventional sphygmomanometry, overestimates BP responses in clinical trials of long duration.

An epidemiological approach to ambulatory blood pressure monitoring:the Belgian Population Study.

BACKGROUND: In order to determine reference values for ambulatory blood pressure, a random population sample of 1057 persons, 20-88 years old, was investigated in a geographically defined area of Belgium. This article is the final report on the cross-sectional phase of this population survey. METHODS:Twenty-four-hour ambulatory pressure was recorded at 20 min intervals from 0800 to 2200 h and at 45 min intervals from 2200 to 0800 h. Conventional blood pressure was measured by trained nurses at the participants' homes and also in a subgroup of 532 persons at a locally organized clinic. A conventional blood pressure exceeding 140 mmHg systolic or 90 mmHg diastolic and the taking of antihypertensive drugs were the criteria used to distinguish between normotensive and hypertensive persons. RESULTS: In the 1057 patients, of whom 328 were hypertensive, 24 h, daytime (2200 to 0800 h) and night-time (0000 to 0600 h) pressures averaged 119/71, 125/77 and 108/62 mmHg, respectively. Compared with daytime values, blood pressures at home were 3.5/1.5 mmHg lower in 729 normotensive people but 11.6/4.5 mmHg higher in 328 hypertensive patients. In the normotensive subgroup the 95th percentiles of the 24 h, daytime and night-time pressures were 129/80, 137/88 and 121/72 mmHg, respectively. These boundaries were not materially altered when we considered only the 275 participants who had been normotensive both at home and at the clinic (127/79, 135/87 and 118/72 mmHg, respectively). When, in addition to the Belgian data, other reports on large cohorts were also analysed, the transition from normotension to hypertension on ambulatory measurement was likely to be within the ranges of 130-135/80-85, 135-140/85-90 and 120-125/70-75 mmHg for 24 h, daytime and night-time pressures, respectively. CONCLUSION: In comparison with other population surveys and with the earlier interim reports on the Belgian study, the present analysis produced remarkably consistent results with respect to the distributions of the ambulatory measurements. The working definitions of normality based on the 95th percentiles of the ambulatory measurements in the normotensive participants in the present survey and various other studies need further validation in terms of the incidence of cardiovascular complications. For this purpose, the Belgian participants as well as other cohorts are being prospectively followed.

Treatment of hypertensive patients according to the conventional or ambulatory pressure: a progress report on the APTH trial. APTH Investigators. Ambulatory Blood Pressure and Treatment of Hypertension.

The main objective of the Ambulatory Blood Pressure and Treatment of Hypertension (APTH) trial is to test the hypothesis that antihypertensive treatment based on ambulatory monitoring may be more beneficial than treatment guided by conventional sphygmomanometry. After a 2-month run-in period on single-blind placebo, hypertensive patients were randomized to two groups, one in which the target pressure was a sitting diastolic pressure from 80 through 89 mm Hg on conventional sphygmomanometry (conventional blood pressure [CBP] group), and one in which a daytime (from 10 to 20 h) diastolic pressure from 80 through 89 mm Hg had to be achieved (ambulatory blood pressure [ABP] group). After randomization all patients were started on lisinopril 10 mg/day. One month later lisinopril could be continued at 10 or 20 mg/day or discontinued depending on the attained blood pressure level. This article is an interim report on 207 patients followed for two months into the trial. At one month lisinopril was discontinued more frequently in the ABP than the CBP group (24 vs 9 patients, p = 0.004). Nevertheless at two months, blood pressure control was not significantly different in the two treatment groups. The baseline-adjusted differences in systolic pressure between the two treatment arms of the trial (ABP-CBP group) were +2.7 mm Hg (95% confidence interval [CI]): -2.9, +8.3) for the conventional pressure, +0.4 mm Hg (CI: -4.3, +5.1) for the 24 h pressure, -0.1 mm Hg (CI: -5.1, +4.8) for the daytime pressure and -0.7 mm Hg (CI: -6.7, +5.4) for the night-time pressure. The corresponding differences in diastolic pressure were -1.3 mm Hg (CI: -4, +1.4), +0.1 mm Hg (CI: -3, +3.1), -1.1 mmgH (CI: -4.4, +2.1) and +0.3 mm Hg (CI: -3.7, +4.3), respectively. Thus, the present findings do not refute the APTH research hypothesis. In terms of blood pressure control and the number of patients remaining on antihypertensive drugs, treatment based on ambulatory recordings may be preferable to treatment guided by conventional sphygmomanometry.

The trough-to-peak ratio as an instrument to evaluate antihypertensive drugs. The APTH Investigators. Ambulatory Blood Pressure and Treatment of Hypertension Trial.

The U.S. Food and Drug Administration designed the trough-to-peak ratio as an instrument for the evaluation of long-acting antihypertensive drugs, but the ratios are usually reported without accounting for interindividual variability. This study investigated how the trough-to-peak ratio would be affected by interindividual and intraindividual variability and by smoothing of the diurnal blood pressure profiles. The ambulatory blood pressure was recorded on placebo in 143 hypertensive patients (diastolic pressure on conventional measurement > 95 mm Hg). After 2 months, the recordings were repeated on 10 mg (n = 66) or 20 mg (n = 77) lisinopril given once daily between 7 and 11 PM. The baseline-adjusted trough-to-peak ratios were determined from diurnal blood pressure profiles with 1-hour precision. Lisinopril reduced (+/- SD) the 24-hour pressure by 16 +/- 17 mm Hg for systolic and 10 +/- 10 mm Hg for diastolic (P < .001). According to the usual approach, disregarding interindividual variability, the trough-to-peak ratio was 0.72 for systolic pressure and 0.67 for diastolic pressure. In the 143 patients the ratios were not normally distributed. They were the same on both lisinopril doses. When interindividual variability was accounted for, the median trough-to-peak ratio was 0.34 (P5 to P95 interval, -0.46 to 0.87) for systolic pressure and 0.26 (-0.44 to 0.84) for diastolic pressure. In 66 patients examined twice on 10 mg lisinopril at a median interval of 32 days, the trough-to-peak ratios were characterized by large intraindividual variability.(ABSTRACT TRUNCATED AT 250 WORDS)

Trough-to-peak versus surface ratio in the assessment of antihypertensive agents. APTH Investigators. Ambulatory Blood Pressure and Treatment of Hypertension.

This study investigated whether the 'surface ratio', a novel index to characterize long-acting antihypertensive agents, would provide a more reproducible estimate of the duration of the antihypertensive effect than the more commonly used trough-to-peak ratio. In 66 hypertensive patients (diastolic pressure on conventional measurement > 95 mmHg), the ambulatory blood pressure was measured on a placebo at baseline and 2 months later, while the patients took 10 mg lisinopril once a day between 7 p.m. and 11 p.m. Diurnal treatment effect curves were obtained by subtracting the blood pressure at baseline from the corresponding value at 2 months for all time intervals considered in the analysis. In order to calculate the surface ratio, the area under the treatment effect curve was divided by the product of the maximal blood pressure lowering effect and the dosing interval (24 h). Reproducibility of the trough-to-peak and surface ratios was investigated by the Bland and Altman techniques. At 2 months, lisinopril reduced (+/- standard deviation) the 24 h pressure by 13 +/- 16 mmHg systolic and by 8 +/- 8 mmHg diastolic (p < 0.001). According to the usual approach, disregarding inter-individual variability, the trough-to-peak ratio was 0.7 for systolic and diastolic pressure. When in individual patients diurnal treatment effects curves with a 1 h resolution were investigated, the median trough-to-peak ratio was 0.30 for systolic pressure (5th-95th percentile interval [PI]: -0.51, 0.82) and 0.28 for diastolic pressure (PI: -0.37, 0.78); the corresponding values for the surface ratio were 0.33 (PI: 0.03, 0.58) and 0.30 (PI: -0.01, 0.55). In the same manner, the trough-to-peak ratios and surface ratios became larger when the individual blood pressure profiles were progressively smoothed by substituting 1 h averages by 2 h moving averages, 2 h averages, 3 h moving averages or by 3 h averages. The distributions of the trough-to-peak ratios and surface ratios were non-normal in 37 of 40 instances (p < 0.001, Shapiro-Wilk's test). Consistency was higher (p < 0.001) for the surface than for the trough-to-peak ratios. The within-subject reproducibility of the surface ratios tended to be superior to that of the corresponding trough-to-peak ratios. In conclusion, the surface ratio provides an index of the duration of action of antihypertensive agents. Moreover, in the present patients, the surface ratio tended to be characterized by a higher within-subject reproducibility than the trough-to-peak ratio.

Increased urinary C-peptide and albumin excretion in juvenile borderline hypertensives.

The study was designed to evaluate the urinary excretion of C-peptide and albumin, and urinary N-acetyl-beta-D-glucosaminidase (NAG) activity in juvenile borderline hypertensives. The second aim was to examine the relationship between these variables and ambulatory blood pressure level and variability. The study group consisted of 21 non-obese males consecutively chosen from patients with borderline hypertension, defined by sphygmanometer readings, examined in our outpatient clinic. All subjects collected separately their day-time and night-time urines during the period of ambulatory blood pressure monitoring. In 16 patients, who were considered to have "sustained" borderline hypertension, both 24-h urinary C-peptide excretion and 24-h UAE were significantly increased in comparison to those of the controls, while NAG activity did not differ significantly between the two groups. UAE was significantly lower at night than during the day in both borderline hypertensives and controls. Twenty-four-hour UAE in borderline hypertensives correlated significantly with the ambulatory blood pressure variability, but not with the average blood pressure level. These results suggest that the 24-h insulin secretion rate estimated by means of urinary C-peptide excretion is significantly increased in "sustained" borderline hypertensives. Elevated UAE in juvenile borderline hypertensives can be explained by a possible direct effect of systemic blood pressure variability on albuminuria.

[Circadian rhythm of blood pressure and heart rate in hypertension with type 2 diabetes mellitus]. / Rytm dobowy cisnienia tetniczego i tetna w nadcisnieniu tetniczym i curkzycy typu 2.

Hypertension is an important risk factor for cardiovascular complications of diabetes. Most of the studies performed in diabetics so far, however, have dealt with the assessment of blood pressure by traditional sphygmomanometry. In order to investigate the circadian pattern of blood pressure and heart rate in patients with different categories of glucose tolerance, we performed ambulatory blood pressure monitoring in 28 obese hypertensives without clinical nephropathy divided in two groups. Group A consisted of 14 hypertensive males with type 2 diabetes mellitus (mean age 49.7 +/- 7.1 years, mean duration of diabetes 4.0 +/- 2.9 years); group B consisted of 14 hypertensive males with normal glucose tolerance according to National Diabetes Data Group (mean age 47.2 +/- 7.1 years). There was no significant difference in casual blood pressure (151.4/104.8 in group A versus 148.5/104.2 mmHg in group B). Ambulatory blood pressure monitoring revealed significantly higher systolic blood pressure in group A during the day (162.2 +/- 12.1 vs 152.1 +/- 9.0 mmHg in group B, P < 0.05) and at night (141.0 +/- 13.2 vs 125.5 +/- 12.5 mmHg in group B, P < 0.005). That suggests that casual readings underestimate systolic blood pressure as a predictor for macrovascular events in type 2 diabetics. The decline in nocturnal heart rate was significantly lower in group A (11.2 +/- 5.2 min-1) in comparison to group B (16.9 +/- 7.0 min-1; P < 0.05) suggesting reduced parasympathetic tone at night in diabetic patients. We conclude that type 2 diabetes has significant influence on systolic blood pressure and heart rate 24-h profiles even in patients without diabetic nephropathy.