Jean-Michel Mallion

Lipid Peroxidation Is Not Increased in Patients With Untreated Mild-to-Moderate Hypertension

Abstract—In contrast with the huge amount of experimental data available, only few and somewhat unconvincing clinical studies support the hypothesis that oxidative stress is involved in the early stages of essential hypertension in humans. Isoprostanes are chemically stable lipid peroxidation products of arachidonic acid, the quantification of which provides a novel approach to the assessment of oxidative stress in vivo. The main objective of this study was to quantify the urinary levels of 15-F2t-IsoP in the early stages of essential hypertension, using gas chromatography/mass spectrometry, by comparing 30 patients with never-treated mild-to-moderate hypertension with 30 gender- and age-paired healthy controls. Urinary 15-F2t-IsoP levels were not significantly different in hypertensive patients (69±36 pmol/mmol creatinine) compared with controls (75±34 pmol/mmol creatinine, 95% confidence intervals on differences: −23 to 13). No significant correlation was found between basal urinary 15-F2t-IsoP levels and age, low-density lipoprotein cholesterol, glucose, clinical pulse pressure, carotid intima-media thickness, left ventricular mass index, or aortic pulse wave velocity. In conclusion, this study shows that lipid peroxidation is not increased in never-treated mild-to-moderate hypertension. This suggests that oxidative stress is not implicated in the pathogenesis of human essential hypertension, at least in the early stages.

Comparison of angiotensin-converting enzyme inhibitors and calcium antagonists in the treatment of mild to moderate systemic hypertension, according to baseline ambulatory blood pressure level

This study was aimed at determining whether baseline ambulatory blood pressure (BP) levels influence the efficacy of angiotensin-converting enzyme inhibitors and calcium antagonists in the same manner. Accordingly, the ambulatory BP recordings of 236 mild to moderate hypertensive patients who had previously entered a clinical trial and had received either a calcium antagonist (n = 121) or an angiotensin-converting enzyme inhibitor (n = 115) were reviewed. The inclusion criterion was a clinic diastolic BP between 95 and 115 mm Hg at the end of the placebo period. Patients were classified according to the difference between their observed and predicted ambulatory BP (the latter assessed by regressing the observed ambulatory BP on the clinic BP). Reduction in ambulatory systolic and diastolic BP seemed to be greater (p less than 0.0001, p = 0.01) in patients receiving an angiotensin-converting enzyme inhibitor than in those who were given a calcium antagonist. However, analysis of variance showed (1) there was a significant interaction (F = 6.37 p = 0.01) between the pharmacologic class and the baseline systolic ambulatory BP; and (2) the difference in diastolic ambulatory BP reduction between both classes was no longer significant when adjusted for baseline diastolic ambulatory BP. In patients with higher than predicted ambulatory BP levels, angiotensin-converting enzyme inhibitors and calcium antagonists had roughly a similar effect (reduction in systolic BP, 9 +/- 8% vs 7 +/- 6%, p = not significant; reduction in diastolic BP, 11 +/- 8% vs 8 +/- 6%, p = not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular hypertrophy and arterial hypertrophy.

In the most recent WHO recommendations of 1996 it was reiterated that the classification of HT still remains based on the actual BP figures but also on the importance of target organ lesions. Thus the study of cardiac and vascular function and in particular the presence of hypertrophy or remodeling is of importance. A limited number of studies have examined the prevalence, the association and the correlation between modifications and remodeling in the heart and in the vasculature. It is important to distinguish compliance vessels such as the carotid from resistance vessels such as the radial. For compliance vessels the prevalence of cardiac and vascular hypertrophy are nearly identical being around 5% for normotensive subjects and around 12% for hypertensive subjects. This prevalence of thickening in the intima-media is more evident in subjects with left ventricular hypertrophy (LVH). The left ventricular geometric pattern is also an element to take into account. The presence of concentric remodeling of the left ventricle without LVH has already been associated with an increase in intima-media thickness (IMT). When there is an LVH this IMT is similar in severity to the LVH and in particular concentric. For resistance vessels such as the radial artery the number of studies is limited but a significant correlation between left ventricular mean wall thickness and common carotid artery distensibility and compliance has been found. There is also a significant correlation between the radial median lumen ratio and the relative wall thickness but this correlation disappears when age and systolic BP are taken into account. Thus for this type of vessel it is too early to conclude the elements contributing to structural changes. The determinant factors for these structural changes in the heart and the carotid arteries associated with hypertension are certainly multiple be they haemodynamic, hormonal or genetic. The observation establishing an association between anomalies at cardiac and vascular level may have undoubted diagnostic, prognostic and therapeutic implications which are all intimately related and which require refinement and confirmation.

Effect of low-dose positive inotropic drugs on human internal mammary artery flow.

BACKGROUNDnDobutamine (a beta-receptor agonist), enoximone (a type III selective phosphodiesterase inhibitor), and epinephrine (an alpha- and beta-mimetic) frequently are used in the perioperative management of patients undergoing coronary artery bypass grafting.nnnMETHODSnWe performed a double-blind clinical study to compare the effects on internal mammary artery free flow of low doses of these three positive inotropic drugs. Thirty patients in whom the left internal mammary artery was used for coronary artery bypass grafting were randomized into three groups. Internal mammary artery free flow and hemodynamic measurements were evaluated before and 10 minutes after the intravenous infusion of dobutamine (3 microg x kg(-1) x min(-1)), enoximone (200 microg/kg), or epinephrine (0.05 microg x kg(-1) x min(-1)).nnnRESULTSnA significant increase in free flow occurred only in the dobutamine group (33 +/- 7.5 and 42.2 +/- 7.9 mL/min before and after drug infusion, respectively; p = 0.013). Comparison of the increase in flow between the groups, however, showed no difference. These drugs, at doses designed to produce a positive inotropic effect, caused little increase in the free flow of the internal mammary artery.nnnCONCLUSIONSnThe use of dobutamine, enoximone, and epinephrine as low-dose positive inotropic treatments in the perioperative and postoperative periods of coronary artery bypass grafting should depend on their positive inotropic effects rather than their vasodilative effects on the arterial grafts.

Use of Ambulatory Blood Pressure Monitoring in the Management of Antihypertensive Therapy

SummaryThe recent development of ambulatory blood pressure (ABP) monitoring techniques has improved recording of blood pressure in therapeutic trials and in the clinical setting. The application of ABP differs according to which of these 2 applications is being considered.In therapeutic trials, a placebo control is required. The large quantity of precise data acquired with ABP monitoring allows the study of a limited number of patients; it also allows individual study of patients with a ‘white coat’ response (i.e. elevated blood pressure in response to examination by the clinician). Analysis of data from ABP monitoring may include the following: comparison of mean blood pressure values over 24 hours, daytime or night-time, or over any other selected time period; 24-hour blood pressure profiles, or analysis hour-by-hour, giving true chronotherapy, and providing data regarding the wearing-off of a drug effect or loss of therapeutic control; analysis of blood pressure at particular times, such as on waking; or specific examination of nonresponders.In individual patients, ABP monitoring should be reserved for specific indications. It can be used before initiation of treatment to confirm the necessity for treatment, especially in the context of hypertension at rest or the ‘white coat’ effect. With established treatment, ABP monitoring can be used in patients with resistant hypertension, in severe hypertension to examine loss of blood pressure control over time or inversion of the day/night cycle, and in patients with a specific illness, e.g. diabetes, in order to obtain the lowest blood pressure readings possible.Examination of these factors assists clinicians to accurately decide upon the timing and frequency of antihypertensive therapy.

P-602: Lipid peroxydation is not increased in never treated hypertension

To compare the levels of urinary isoprostanes (UIP), a marker of lipid peroxydation expressing the degree of oxidative stress, in hypertensive and normotensive patients. Thirty mild to moderate never treated hypertensive patients (HT) (clinical SBP 140 mmHg and/or DBP 90 mmHg) (age 53 12 years, sex ratio 1) (Mean clinic BP 152/95 mmHg, duration of HT 41 59 months) were included. Three of the 30 patients (10%) had white coat hypertension. Thirty control subjects were matched for age and sex. All the subjects had an ambulatory BP recording over 24 hours, a carotid intima-media thickness measurement by ultrasound, an echocardiography, a measurement of the carotid to femoral pulse wave velocity (PWV), and a determination of glucose concentration, serum lipids and urinary isoprostanes. The two groups were similar apart for BP, by definition, and the PWV which was greater in the HT group (10.4 2.2 vs 9.1 2.2 m/s, p 0.05). The levels of UIP were no different between the groups (69 36 in HT vs 75 34 pmol/mmol of creatinine in control subjects). No correlation was found between the levels of UIP and the BP and cardiovascular parameters. Many experimental studies have shown the importance of the effect of oxidative stress on vascular remodelling and the rise in BP. In our study, lipid peroxydation as evaluated by the level of UIP is not increased in humans with never treated mild to moderate essential HT. These results can be partly explained by the relatively short duration and the moderate levels of HT in our population.