Jean-Paul Degaute

Serial lactate determinations during circulatory shock.

The time course of lactacidemia was studied prospectively in 17 patients during fluid resuscitation for an episode of noncardiogenic shock, in 5 patients after grand mal seizures, and in 5 patients after successful CPR for cardiac arrest. The 9 patients in whom shock was reversed with fluid administration demonstrated a regular decrease in lactate concentrations, which exceeded 5% of the initial value during the first 60 min of treatment. In the other patients who expired despite similar therapy, lactacidemia was not significantly affected. During circulatory shock, repeated lactate determinations represent a more reliable prognostic index than an initial value taken alone. Changes in lactate concentration can provide an early and objective evaluation of the patients response to therapy.

Study on COgnition and Prognosis in the Elderly (SCOPE)

The Study on COgnition and Prognosis in the Elderly (SCOPE) is a multicentre, prospective, randomized, double-blind, parallel-group study designed to compare the effects of candesartan cilexetil and placebo in elderly patients with mild hypertension. The primary objective of the study is to assess the effect of candesartan cilexetil on major cardiovascular events. The secondary objectives of the study are to assess the effect of candesartan cilexetil on cognitive function and on total mortality, cardiovascular mortality, myocardial infarction, stroke, renal function, hospitalization, quality of life and health economics. Male and female patients aged between 70 and 89 years, with a sitting systolic blood pressure (SBP) of 160-179 mmHg and/or diastolic blood pressure (DBP) of 90-99 mmHg, and a Mini-Mental State Examination (MMSE) score of 24 or above, are eligible for the study. The overall target study population is 4000 patients, at least 1000 of whom are also to be assessed for quality of life and health economics data. After an open run-in period lasting 1-3 months, during which patients are assessed for eligibility and those who are already on antihypertensive therapy at enrolment are switched to hydrochlorothiazide 12.5 mg o.d., patients are randomized to receive either candesartan cilexetil 8 mg once daily (o.d.) or matching placebo o.d. At subsequent study visits, if SBP remains >160 mmHg, or has decreased by <10 mmHg since the randomization visit, or DBP is >85 mmHg, study treatment is doubled to candesartan cilexetil 16 mg o.d. or two placebo tablets o.d. Recruitment was completed in January 1999. At that time 4964 patients had been randomized. All randomized patients will be followed for an additional 2 years. If the event rate is lower than anticipated, the follow-up will be prolonged.

Quantitative analysis of the 24-hour blood pressure and heart rate patterns in young men.

To characterize the normal nycterohemeral blood pressure and heart rate profiles and to delineate the relative roles of sleep and circadian rhythmidty, we performed 24-hour ambulatory blood pressure monitoring with simultaneous polygraphic sleep recording in 31 healthy young men investigated in a standardized physical and social environment Electroencephalographic sleep recordings were performed during 4 consecutive nights. Blood pressure and heart rate were measured every 10 minutes for 24 hours starting in the morning preceding the fourth night of recording. Sleep quality was not significantly altered by ambulatory blood pressure monitoring. A best-fit curve based on the periodogram method was used to quantify changes in blood pressure and heart rate over the 24-hour cycle. The typical blood pressure and heart rate patterns were bimodal with a morning acrophase (around 10:00 AM), a small afternoon nadir (around 3:00 PM), an evening acrophase (around 8:00 PM), and a profound nocturnal nadir (around 3:00 AM). The amplitude of the nycterohemeral variations was largest for heart rate, intermediate for diastolic blood pressure, and smallest for systolic blood pressure (respectively, 19.9%, 14.1%, and 10.9% of the 24-hour mean). Before awakening, a significant increase in blood pressure and heart rate was already present Recumbency and sleep accounted for 65-75% of the nocturnal decline in blood pressure, but it explained only 50% of the nocturnal decline in heart rate. Thus, the combined effects of postural changes and the wake-sleep transition are the major factors responsible for the 24-hour rhythm in blood pressure. In contrast, the 24-hour rhythm of heart rate may reflect an endogenous circadian rhythm, amplified by the effect of sleep. We conclude that modulatory factors different from those controlling nycterohemeral changes in blood pressure influence the 24-hour variation in heart rate.

Outcomes in subgroups of hypertensive patients treated with regimens based on valsartan and amlodipine: An analysis of findings from the VALUE trial.

Background In the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial the primary outcome (cardiac morbidity and mortality) did not differ between valsartan and amlodipine-based treatment groups, although systolic blood pressure (SBP) and diastolic blood pressure reductions were significantly more pronounced with amlodipine. Stroke incidence was non-significantly, and myocardial infarction was significantly lower in the amlodipine-based regimen, whereas cardiac failure was non-significantly lower on valsartan. Objectives The study protocol specified additional analyses of the primary endpoint according to: sex; age; race; geographical region; smoking status; type 2 diabetes; total cholesterol; left ventricular hypertrophy; proteinuria; serum creatinine; a history of coronary heart disease; a history of stroke or transient ischemic attack; and a history of peripheral artery disease. Additional subgroups were isolated systolic hypertension and classes of antihypertensive agents used immediately before randomization. Methods The 15 245 hypertensive patients participating in VALUE were divided into subgroups according to baseline characteristics. Treatment by subgroup interaction analyses were carried out by a Cox proportional hazard model. Within each subgroup, treatment effects were assessed by hazard ratios and 95% confidence intervals. Results For cardiac mortality and morbidity, the only significant subgroup by treatment interaction was of sex (P = 0.016), with the hazard ratio indicating a relative excess of cardiac events with valsartan treatment in women but not in men, but SBP differences in favour of amlodipine were distinctly greater in women. No other subgroup showed a significant difference in the composite cardiac outcome between valsartan and amlodipine-based treatments. For secondary endpoints, a sex-related significant interaction was found for heart failure (P < 0.0001), with men but not women having a lower incidence of heart failure with valsartan. Conclusion As in the whole VALUE cohort, in no subgroup of patients were there differences in the incidence of the composite cardiac endpoint with valsartan and amlodipine-based treatments, despite a greater blood pressure decrease in the amlodipine group. The only exception was sex, in which the amlodipine-based regimen was more effective than valsartan in women, but not in men, whereas the valsartan regimen was more effective in preventing cardiac failure in men than in women.

Regression of left ventricular hypertrophy in hypertensive patients treated with indapamide SR 1.5 mg versus enalapril 20 mg: the LIVE study.

Objective To compare the efficacy of indapamide sustained release (SR) 1.5 mg and enalapril 20 mg at reducing left ventricular mass index (LVMI) in hypertensive patients with left ventricular hypertrophy (LVH). Design The LIVE study (left ventricular hypertrophy regression, indapamide versus enalapril) was a 1 year, prospective, randomized, double-blind study. For the first time, a committee validated LVH before inclusion, provided on-going quality control during the study, and performed an end-study reading of all echocardiograms blinded to sequence. Setting European hospitals, general practitioners and cardiologists. Patients Hypertensive patients aged ≥ 20 years with LVH (LVMI in men > 120 g/m2; LVMI in women > 100 g/m2). Data were obtained from 411 of 505 randomized patients. Interventions Indapamide SR 1.5 mg, or enalapril 20 mg, daily for 48 weeks. Main outcome measures LVMI variation in the per-protocol population. Results Indapamide SR 1.5 mg significantly reduced LVMI (−8.4 ± 30.5 g/m2 from baseline; P < 0.001), but enalapril 20 mg did not (−1.9 ± 28.3 g/m2). Indapamide SR 1.5 mg reduced LVMI significantly more than enalapril 20 mg: −6.5 g/m2, P = 0.013 (−4.3 g/m2 when adjusted for baseline values; P = 0.049). Both drugs equally and significantly reduced blood pressures (P < 0.001), without correlation with LVMI changes. Indapamide SR progressively reduced wall thicknesses throughout the 1-year treatment period. In contrast, the effect of enalapril observed at 6 months was not maintained at 12 months. Conclusions Indapamide SR 1.5 mg was significantly more effective than enalapril 20 mg at reducing LVMI in hypertensive patients with LVH.

Ambulatory blood pressure in normotensive and hypertensive subjects: Results from an international database

Objective To delineate more precisely an operational threshold for making clinical decisions based on ambulatory blood pressure (ABP) measurement by studying the ABP in subjects who were diagnosed as either normotensive or hypertensive by conventional blood pressure (CBP) measurement. Subjects: Twenty-four research groups recruited 7069 subjects. Of these, 4577 were normotensive (CBP 140/90 mmHg), 719 were borderline hypertensive (systolic CBP 141–159 mmHg or diastolic CBP 91–94 mmHg) and 1773 were definitely hypertensive. Of the subjects in the last of these categories, 1324 had systolic hypertension (systolic CBP 21 60 mmHg) and 131 0 had diastolic hypertension (diastolic CBP 295 mmHg). Combined systolic and diastolic hypertension was present in 861 subjects. Hypertension had been diagnosed from the mean of two to nine (median two) CBP measurements obtained at one to three (median two) visits. Results The 95th centiles of the ABP distributions in the normotensive subjects were (systolic and diastolic, respectively) 133 and 82 mmHg for 24-h ABP, 140 and 88mmHg for daytime ABP and 125 and 76mmHg for night-time ABP, respectively. Of the subjects with systolic hypertension, 24% had 24-h systolic ABP 4 33 mmHg. Similarly, 30% of those with diastolic hypertension had 24-h diastolic ABP 432 mmHg. The probability that hypertensive subjects had 24-h ABP below these thresholds tended to increase with age and was two- to fourfold greater if the CBP of the subject had been measured at only one visit and if fewer than three CBP measurements had been averaged for establishing the diagnosis of hypertension. By contrast, for each 1 O-mmHg increment in systolic CBP, this probability decreased by 54% for 24-h systolic ABP and by 26% for 24-h diastolic ABP, and for each 5-mmHg increment in diastolic CBP it decreased by 6 and 9%, respectively. In comparison with 24-h ABP, the overlap in the daytime and night-time ABP between normotensive and hypertensive subjects was of similar magnitude and was influenced by the same factors. Conclusions The ABP distributions of the normotensive subjects included in the present international database were not materially different from those in previous reports in the literature. One-fifth to more than one-third of hypertensive subjects had an ABP which was below the 95th centile of the ABP of normotensive subjects, but this proportion decreased if the hypertensive subjects had shown a higher CBP upon repeated measurement. The prognostic implications of elevated CBP in the presence of normal ABP remain to be determined.

Short report: Ambulatory blood pressure in normotensive compared with hypertensive subjects

Objective: To delineate more precisely an operational threshold for making clinical decisions based on ambulatory blood pressure (ABP) measurement by studying the ABP in subjects who were diagnosed as either normotensive or hypertensive by conventional blood pressure (CBP) measurement. Subjects: Twenty-four research groups recruited 7069 subjects. Of these, 4577 were normotensive (CBP ≥140/90mmHg), 719 were borderline hypertensive (systolic CBP 141–159mmHg or diastolic CBP 91–94mmHg) and 1773 were definitely hypertensive. Of the subjects in the last of these categories, 1324 had systolic hypertension (systolic CBP ≤160 mmHg) and 1310 had diastolic hypertension (diastolic CBP ≤95 mmHg). Hypertension had been diagnosed from the mean of two to nine (median two) CBP measurements obtained at one to three (median two) visits. Results: The 95th centiles of the 24-h ABP distributions in the normotensive subjects were (systolic and diastolic, respectively) 133 and 82 mmHg. Of the subjects with systolic hypertension, 24% had 24-h systolic ABP <133 mmHg. Similarly, 30% of those with diastolic hypertension had 24-h diastolic ABP <82 mmHg. The probability that hypertensive subjects had 24-h ABP below these thresholds tended to increase with age and was two- to fourfold greater if the CBP of the subject had been measured at only one visit and if fewer than three CBP measurements had been averaged for establishing the diagnosis of hypertension. By contrast, for each 10-mmHg increment in systolic CBP, this probability decreased by 54% for 24-h systolic ABP and by 26% for 24-h diastolic ABP, and for each 5-mmHg increment in diastolic CBP it decreased by 6 and 9%, respectively. Conclusions: The ABP distributions of the normotensive subjects included in the present international database were not materially different from those in previous reports in the literature. One-fifth to more than one-third of hypertensive subjects had an ABP which was below the 95th centile of the ABP of normotensive subjects, but this proportion decreased if the hypertensive subjects had shown a higher CBP upon repeated measurement. The prognostic implications of elevated CBP in the presence of normal ABP remain to be determined.

Myocardial Homing of Nonmobilized Peripheral‐Blood CD34+ Cells After Intracoronary Injection

Granulocyte– colony‐stimulating factor administered for autologous hematopoietic stem cell isolation from blood may favor restenosis in patients implanted after acute myocardial infarction (AMI). We therefore tested the isolation of peripheral‐blood CD34+ cells without mobilization in six patients with AMI. After large‐volume cytapheresis and positive CD34+ cell selection, 3.6 to 27.6 million CD34+ cells were obtained. We performed intra‐coronary implantation of these cells and recorded no restenosis or arrhythmia. We used positron emission tomography (PET) to assess myocardial‐labeled CD34+ cell homing, which accounted for 5.5% of injected cells 1 hour after implantation. In conclusion, large amounts of CD34+ cells, in the range reported in previous studies, can be obtained from nonmobilized peripheral blood. PET with [18F]‐fluorodeoxyglucose cell labeling is an efficient imaging method for homing assessment.

A study of the dynamic interactions between sleep EEG and heart rate variability in healthy young men

OBJECTIVE We investigated the interactions between heart rate variability and sleep electroencephalogram power spectra. METHODS Heart rate and sleep electroencephalogram signals were recorded in 8 healthy young men. Spectral analysis was applied to electrocardiogram and electroencephalogram recordings. Spectral components of RR intervals were studied across sleep stages. The cross-spectrum maximum was determined as well as coherencies, gains and phase shifts between normalized high frequency of RR intervals and all electroencephalographic frequency bands, calculated over the first 3 NREM-REM cycles. RESULTS RR intervals increased from awake to NREM and decreased during REM. Normalized low frequency decreased from awake to NREM and increased during REM while normalized high frequency evolved conversely. Low to high frequency ratio developed in opposition to RR intervals. Coherencies between normalized high frequency and power spectra were high for all bands. The gain was highest for delta band. Phase shift between normalized high frequency and delta differed from zero and modifications in normalized high frequency preceded changes in delta by 41+/-14 degrees. CONCLUSIONS Our study demonstrates that: (1) all electroencephalographic power bands are linked to normalized high frequency; (2) modifications in cardiac vagal activity show predominantly parallel changes and precede changes in delta band by a phase shift corresponding to a lead of 12+/-5 min.

Validity of pulse pressure and augmentation index as surrogate measures of arterial stiffness during beta-adrenergic stimulation.

Objective Increased arterial stiffness is a determinant of cardiovascular mortality. Pulse wave velocity (PWV) is a direct measure of arterial stiffness. Aortic augmentation index (AI) and pulse pressure (PP) are surrogate measures of arterial stiffness. Both PWV, AI and PP increase with cardiovascular risk factors. The aim of this study was to test the validity of AI and PP as surrogate measures of arterial stiffness compared with PWV, during beta-adrenergic stimulation with Isoprenaline (Iso). Design and methods A total of 41 healthy volunteers entered a randomized, double-blind, placebo-controlled, cross-over study. In random order, subjects were given intravenous infusion in equal volume of Iso 8 μg/kg per min (dissolved in glucose 5%) and placebo (glucose 5%). A wash-out period of 25 min was observed between the infusions. Measurements included blood pressure (BP), heart rate (HR), PWV, and AI. PWV were determined using complior (Complior, Artech-Medical, Paris, France). AI and aortic PP were obtained from pulse wave analysis of radial applanation tonometry, using transfer function (SphygmoCor Windows software). Results Baseline AI increased (P < 0.05) with aging, a lower height and a larger diastolic BP (DBP). Iso increased (P < 0.0001) HR, brachial SBP, brachial and aortic PP as compared with placebo. In contrast, Iso decreased (P < 0.05) AI, brachial DBP, peripheral PWV, but not aortic PWV. Decrease of AI induced by Iso was not related to PWV. In stepwise multiple regression changes in HR, brachial SBP and DBP were independent determinants of AI response to Iso (r = 0.78, P < 0.0001). Conclusions Our findings show that AI and PP fail as surrogate measures of arterial stiffness during beta-adrenergic stimulation.