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The objective of the HOT study, an international, prospective, randomised study is to determine the optimal level of the blood pressure under treatment, in linked with the lowest cardiovascular mortality and morbidity. The target diastolic blood pressure of 80, 85 and 90 mmHg was determined at the randomisation. In order to reach the target blood pressure, a strategy of treatment was determined: the 1st step was felodipine (a long acting dihydropyridine) and the next steps (if the blood pressure reduction is not enough) propose the addition of different therapeutic classes and/or the increase of each drug doses. The available data after 2 years of the patients follow-up allow us to evaluate the incidence of the reported side effects according to the target blood pressure assigned by randomisation and the number of hypertension drugs used to reach these targets. The percentage of patients with at least one side effect at 12 and 24 months of follow-up are respectively: for the target group DBP < or = 90 mmHg: 9.2% versus 6%; for the target group DBP < or = 85 mmHg: 8% versus 4.4%; for the target group DBP < or = 80 mmHg: 7.9% versus 4.9%. The overall tolerability is not influenced by the target diastolic blood pressure but depends on the number of hypertension drugs used. At 24 months, 2.8% of patients are under monotherapy; 7% under bitherapy and 9.8% under tritherapy. The incidence of the side effects decreases after the 1st year, but slower than between the third months and the first year. There is an influence of the region on the incidence of the side effects, the south European countries describing more side effects than France or the north European countries. This seems to be linked with a perception of the side effects more than with a higher rate. In conclusion, these results confirm the possibility to reach a targeted blood pressure using a predetermined strategy without increasing dramatically the incidence of the side effects.

Unlabelled: The objective of the HOT study, an international, prospective, randomised study was to determine the optimal level of the blood pressure under treatment, linked with the lowest cardiovascular mortality and morbidity. The target diastolic blood pressure of 80, 85 and 90 mmHg was determined at the randomisation. In order to reach the target blood pressure, a strategy of treatment was predefined: the 1st step was felodipine (a long acting dihydropyridine) and the next steps (if the blood pressure reduction was not enough) proposed the addition of different therapeutic classes and/or the increase of the doses of each drug. The blood pressure measurements were made, using the oscillometric method (automatic blood pressure measuring device, Hestia). The quality of the blood pressure control observed in the HOT study was verified after 6 months of follow-up ("Quality of the blood pressure control in the clinical practice and in the HOT study", for the French research group of the HOT study. French hypertension meeting, Paris, December 1994). The aim of this second evaluation was to see if the quality of this control was still effective in France and for all countries after 2 years of follow-up. At the inclusion, the mean diastolic blood pressure was 106 +/- 4 mmHg in France (n = 1.574) and 105 +/- 4 mmHg for all countries (n = 18.790). The results at 24 months were the following, according to the target groups: 79.9 for the < or = 80 mmHg target group; 82.1 for the < or = 85 mmHg target and 83.6 for the < or = 90 mmHg target group. The percentages of patients who reached the target blood pressure were respectively 74; 80; 89% for the 3 target groups. The number of antihypertensive treatments needed to reach this blood pressure control slightly increased in the 3 target groups between the first and the second year with a lower rate of monotherapy and a higher rate of bi and tritherapy. But in the 80 mmHg target group (the most strict), the monotherapy was used in more than half of the patients. In comparison with all countries, France had lower number of bi and tritherapies (i.e. in the 85 mmHg target group: 38.4% of bitherapy in France versus 45.6% in all countries)., Conclusion: after 2 years of follow-up, the quality of the blood pressure control is still good. There is a trend toward a slight increase in the number of antihypertensive drugs after the first year in the 3 target groups.

International, prospective, randomized HOT study aims to determine the optimal BP level under treatment in order to reduce at the most the cardiovascular morbidity/mortality. Defined by randomization, the level to obtain is DBP < or = 80, 85, 90 mmHg. The treatment is started by felodipine 5 mg/day then, if necessary, a bitherapy is prescribed and then, if necessary, a tritherapy. 19,193 patients have been included (BP at randomization 170 +/- 15/105 +/- 4 mmHg). After 1 year treatment, it is possible to search for the influence on the clinical tolerance of sex, age, BP goal, geographic area, time and treatment. The percentage of patients with side effects by BP goals and by treatment type are, during the time and in different geographic areas, the following (NE/Northern Europe = Norway, Switzerland, Belgium, Hungary, Sweden, Denmark, Finland, The Netherlands, UK, Germany, Austria; SE/Southern Europe = Italy, Spain, Greece): [table: see text] The target BP and age don't nearly influence the clinical tolerance. The side effects reported by the physicians are more numerous at the treatment start than at longeur terme. That is due to the therapeutic modifications of the physicians or to a better acceptation of the drugs by the patients or to a real disappearance of the side effects. Reported side effects are more frequent in Southern Europe, France than Northern Europe and more frequent among women that men. The incidence of side effects is proportional to the number of prescribed drugs. Time and the number of antihypertensive drugs appear as the most important factors.

Unlabelled: Relationships between baroreflex sensitivity (BRS) and arterial distensibility are evaluated by continuous measurement of blood pressure (Finapres) and carotid-femoral pulse wave velocity measurement (PWV); 73 subjects are recruited on WHO criteria (age: 48 +/- 13). An ambulatory measurement of BP is also performed to evaluate the mean BP 24 level. The BRS is evaluated at rest during 20 min of acquisition data in a lying position, using a dedicated software [(automatic detection by of BP sequences were 3 or more systolic BP and RR interval increased of 1 mmHg for SBP and 4 ms for RR (PS+/RR+) or decreased (PS-/RR-)]. The BRS is the slope of the regression line between SBP and RR interval of each sequences (if correlation coefficient > 0.95)., Results: resting BP: SBP/DBP = 170 +/- 12 mmHg. HR 72 +/- 15 batt/min, PWV = 10.8 +/- 3.2 m/s. Mean BRS is 8.2 +/- 3.8 for PS+/RR+ and 8.7 +/- 3.8 ms/mmHg PS-/RR-. The coefficient of correlation (Pearson) between PWV and BRS is -0.59* for PS+/RR+ and -0.41* for PS-/RR- (*: p < 0.01). In multivariate analyses, these relations were statistically independent of age and BP for the sequences PS+/RR+ but not for the sequences PS-/RR- suggesting a predominant vagal alteration in hypertensive subjects associated with the alteration of carotido-femoral pulse wave velocity.

Unlabelled: The objective is to study the relation between left ventricular (LV) effect (index of LV mass (LVMI) and index of inotropic state) and arterial compliance determined but the proximal aortic pressure waveform and by the carotid femoral pulse wave velocity., Material: 72 untreated hypertensives; systolic blood pressure (SBP) 170 +/- 18 mmHg/diastolic blood pressure (DBP); heart rate: 69 +/- 9 batt/min; age: 48 +/- 13 years; duration of hypertension 4.6 +/- 4.8 years; sex ratio 49 M/23 F., Objective: Proximal aortic pressure waveform (carotid artery) was studied by applanation tonometry. We derived the index of amplification (AI = Pmax-Pinflex)/PP, %), pulse pressure (PP), the maximum rate of rise of pressure (dpdt, mmHg.s-1). Echocardiography was used to define the index of LV mass (VLMI), end systolic volume (ESV), end systolic stress (ESS), myocardial contractile force (ESS/ESV), inotropic state (SBP/ESV). Carotid-femoral pulse wave velocity was determined by mechanogram (PWW m/s)., Results: 1. Relationship of physiological changes of AI and SDA to age, height, PP, DBP, PWV, and LVMI were observed in table I (r-Pearson cor. coefficient, * < p 0.05; **: p < 0.001). [table: see text] In stepwise regression analysis, even allowing for BP, age, and height, there was no relationship between LVMI and the index of aortic amplification (AI). 2. In the subjects with LVH (LVMI > 110 g/m2) we found a bimodal distribution of the AI which defines two groups in agreement with the Murgo Classification. [table: see text] In type B, where AI is weaker, the indices of aortic rigidity are reduced, there is an increased ESS and a paradoxal fall in LV performances., Conclusion: Analysis of proximal aortic pressure waveform don't allow to predict index of LV mass. These results suggest that in the sphere of LV aortic compiling the reduction of LV function contributes to modification of the BP waveform with diminution of dpdt and the index of amplification.

The sympathetic nervous system seems to be a non hemodynamic factor involved in the development of hypertension and in left ventricular hypertrophy determinism. The aim of this study was to estimate the myocardial norepinephrine content in essential hypertensive patients, using a reliable radio-iodinated marker of norepinephrine: the 123I-meta-iodobenzylguanidine (123I-meta-iodobenzylguanidine). Eight male and female hypertensive patients with left ventricular hypertrophy and average age of 52 +/- 9 years underwent a resting, ambulatory and effort blood pressure measure. Echocardiographic parameters allowed measure of left ventricular mass index (according to Devereux, and we considered left ventricular hypertrophy as left ventricular mass index greater than 120g/m2. Plasma norepinephrine is measured at rest. Cardiac and mediastinal radioactivity is detected 4 h after a 4mCi i.v. injection of 123I-meta-iodobenzylguanidine and meta-iodobenzylguanidine myocardial uptake is definite as the cardiac/mediastinal ratio (N:1.78 +/- 0.19). Meta-iodobenzylguanidine-myocardial uptake average value of hypertensive patients was 1.89 +/- 0.19 (1.63 to 2.25) without statistical difference to control subjects. We found a significative correlation between meta-iodobenzylguanidine myocardial uptake and effort systolic blood pressure variation in one hand, and with heart rate increase with effort in the other hand. There is no correlation between meta-iodobenzylguanidine-myocardial uptake and left ventricular mass index or ambulatory blood pressure. In hypertensive patients with left ventricular hypertrophy, meta-iodobenzylguanidine myocardial uptake is normal or high, in agreement with experimental data in SHRs, model of human essential hypertension. Therefore myocardial scintigraphy with 123I-meta-iodobenzylguanidine can appreciate cardiac norepinephrine content in humans.

The high incidence of cardiovascular morbidity and mortality in hypertensive patients with left ventricular hypertrophy shows the great interest in understanding the pathophysiology of this process. Many reports suggest the role of catecholamines in generating left ventricular hypertrophy. The aim of this study is to evaluate the effect of labetalol on myocardial norepinephrine content in hypertensive subjects with left ventricular hypertrophy by using an isotopic norepinephrine marker, the 123I-meta-iodobenzylguanidine (123I-MIBG). Eight male and female hypertensive patients with left ventricular hypertrophy were investigated after a 30 day placebo period. Resting, ambulatory and effort blood pressure was measured. Echocardiographic parameters allowed measure of left ventricular mass index according to Devereux. And we considered left ventricular hypertrophy as left ventricular mass index greater than 120 g/m2. Cardiac and mediastinal radioactivity is detected 4 h after a 4 mCi i.v. injection of 123I-MIBG and MIBG myocardial uptake is definite as the cardiac/mediastinal ratio (N : 1.78 +/- 0.19). All subjects received at the beginning of the study (D0) 2 tablets of labetalol 200 mg, increased to 4 tablets if diastolic blood pressure during follow-up remained above 95 mmHg. Patients again underwent these explorations after 3 months of treatment (D90). Labetalol decreases in considerable manner MIBG myocardial uptake as it has been shown that it decreases tissular norepinephrine content in experimental studies. Therefore, MIBG myocardial uptake seems to be a reliable tool in evaluating drugs effect on cardiac sympathetic nervous system.

The results of several studies, mostly without controls, have suggested that betablockers, administered at progressively increasing doses, may be beneficial in cardiac failure. Based on this hypothesis, betablockers with a peripheral vasodilator effect, such as Nebivolol, could be particularly valuable in this indication. A preliminary study of its tolerance, haemodynamic and neurohormonal effects was carried out with a noninvasive methodology in 12 patients with cardiac failure in sinus rhythm, 8 men and 4 women (average age 53 +/- 12 years), all of whom had Class III or IV symptoms according to the NYHA Classification. The protocol had 2 phases: the first was an open phase during which Nebivolol was administered at a dose of 1 mg/day for 48 hours then 2.5 mg/day for 72 h. In the second phase, the patients were randomly separated into 2 groups, one to receive placebo and the other 2.5 mg for one week then 5 mg of Nebivolol for the 5 remaining weeks. The heart rate decreased significantly from 70 +/- 3 to 63 +/- 4 beats/min (p < 0.01) with Nebivolol 1 mg/day without further slowing at the 2.5 mg dosage. During the randomised phase, the heart rate remained stable in the Nebivolol group but increased to its initial value in the group given placebo. No aggravation of symptoms was observed in the Nebivolol group. No significant changes in cardiac output, parameters of cardiac loading or contractility could be demonstrated after 6 weeks' treatment. During submaximal exercise testing, plasma concentrations of catecholamines and atrial natriuretic factor tended to be higher with Nebivolol than with placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Although there has never been a consensus about the presentation and analysis of the results of ambulatory blood pressure recordings, it is important to define the stages and useful means both for studying individual and groups of recordings (therapeutic trials): individual recordings: edition of results, 24 hour display, quantification of the blood pressure over predefined periods, comparison with reference values; therapeutic trials: verification of the quality of the recordings (consecutive hours without measurements, artefacts), preparation of the results for analysis (grouped in hourly mean values), search for confusing factors and non-adherence to the protocol, analysis of efficacy over 24 hours and predefined periods, partial studies (non-responders, normalisation of blood pressure with respect to reference values, control of efficacy over more than 24 hours...). All these stages must be predefined in the study protocol.