Hexane-solubilised reaction centre proteolipid complexes of Rhodopseudomonas sphaeroides.

Reaction centres from Rhodopseudomonas sphaeroides, strain R-26, have been solubilised in hexane by the use of phospholipids and cations. Two procedures have been developed: (I) a two-step technique involving the formation of detergent-free proteoliposomes from detergent solubilised reaction centres and phospholipids and mixing these with hexane in the present of cations; (II) directly sonicating detergent-solubilised reaction centres with phospholipids before mixing with hexane and cations. The yield of the extracted complex varied with the ratios of protein, phospholipid and cations, species of phospholipid, and sonication time. The spectral characteristics of the complex in the organic phase were similar to those of detergent-solubilised reaction centres. The stability of the reaction centres appeared to be dependent on the presence of phospholipid land water in the hexane. The usefulness of the hexane solution as a model membrane system is discussed and its possible future applications are considered.

Reference values for self-recorded blood pressure: a meta-analysis of summary data.

BACKGROUND: The widespread clinical use of self-recorded blood pressure measurement is limited by the lack of generally accepted reference values. The purpose of this study was therefore to perform a meta-analysis of summary data in an attempt to determine an operational threshold for self-recorded blood pressures. STUDIES AND METHODS: Seventeen studies, including a total of 5422 subjects, were reviewed. Eight of these 17 studies included both normotensive and untreated hypertensive subjects, while the other 9 reports included normotensive subjects only. Within each study an operational cutoff point between normotension and hypertension was derived by means of the mean+2 SDs and the 95th percentiles of the self-recorded blood pressure in normotensive subjects. These 2 methods were contrasted with 2 other techniques that have been applied in the literature to calculate (1) the self-recorded pressures equivalent to a conventional pressure of 140 mm Hg systolic and 90 mm Hg diastolic by means of regression analysis and (2) the self-recorded blood pressures at the percentiles corresponding to a conventional pressure of 140/90 mm Hg. The latter 2 methods were applied in untreated subjects not selected on the basis of their blood pressure. RESULTS: With weighting for the number of subjects included in the various studies, the self-recorded blood pressure averaged 115/71 mm Hg in normotensive persons and 119/74 mm Hg in untreated subjects not selected on the basis of their blood pressure. The reference values for self-recorded blood pressures determined by the mean+2 SDs (137/89 mm Hg) or the 95th percentile (135/86 mm Hg) of the distribution in normotensive subjects were concordant within 2/3 mm Hg, whereas the cutoff points derived with the regression and percentile methods were considerably lower, ie, 125/79 and 129/84 mm Hg, respectively. CONCLUSIONS: Until the relationship between self-recorded pressure and the incidence of cardiovascular morbidity and mortality is further clarified by prospective studies, a mean self-recorded blood pressure above 135 mm Hg systolic or 85 mm Hg diastolic may be considered hypertensive.

Subgroup and per-protocol analysis of the randomized European Trial on Isolated Systolic Hypertension in the Elderly.

BACKGROUND: In 1989, the European Working Party on High Blood Pressure in the Elderly started the double-blind, placebo-controlled, Systolic Hypertension in Europe Trial to test the hypothesis that antihypertensive drug treatment would reduce the incidence of fatal and nonfatal stroke in older patients with isolated systolic hypertension. This report addresses whether the benefit of antihypertensive treatment varied according to sex, previous cardiovascular complications, age, initial blood pressure (BP), and smoking or drinking habits in an intention-to-treat analysis and explores whether the morbidity and mortality results were consistent in a per-protocol analysis. METHODS: After stratification for center, sex, and cardiovascular complications, 4695 patients 60 years of age or older with a systolic BP of 160 to 219 mm Hg and diastolic BP less than 95 mm Hg were randomized. Active treatment consisted of nitrendipine (10-40 mg/d), with the possible addition of enalapril maleate (5-20 mg/d) and/or hydrochlorothiazide (12.5-25 mg/d), titrated or combined to reduce the sitting systolic BP by at least 20 mm Hg, to below 150 mm Hg. In the control group, matching placebo tablets were employed similarly. RESULTS: In the intention-to-treat analysis, male sex, previous cardiovascular complications, older age, higher systolic BP, and smoking at randomization were positively and independently correlated with cardiovascular risk. Furthermore, for total (P = .009) and cardiovascular (P = .09) mortality, the benefit of antihypertensive drug treatment weakened with advancing age; for total mortality (P = .05), the benefit increased with higher systolic BP at entry, while for fatal and nonfatal stroke (P = .01), it was most evident in nonsmokers (92.5% of all patients). In the perprotocol analysis, active treatment reduced total mortality by 24% (P = .05), reduced all fatal and nonfatal cardiovascular end points by 32% (P<.001), reduced all strokes by 44% (P = .004), reduced nonfatal strokes by 48% (P = .005), and reduced all cardiac end points, including sudden death, by 26% (P = .05). CONCLUSIONS: In elderly patients with isolated systolic hypertension, stepwise antihypertensive drug treatment, starting with the dihydropyridine calcium channel blocker nitrendipine, improves prognosis. The per-protocol analysis suggested that treating 1000 patients for 5 years would prevent 24 deaths, 54 major cardiovascular end points, 29 strokes, or 25 cardiac end points. The effects of antihypertensive drug treatment on total and cardiovascular mortality may be attenuated in very old patients.

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)

Comparison of the hydrolysis of Zn-PPi2- and the MgPPi2- as substrates and the effect of free cations upon membrane-bound pyrophosphatase of Rhodospirillum rubrum.

The hydrolytic activity of chromatophore membrane-bound pyrophosphatase with Zn-PPi2- as substrate was studied and compared with Mg-PPi2- hydrolysis. The pH profile of Zn-PPi2- hydrolysis is a bell shaped curve with an optimum at 5.25. This behavior is different from the sigmoidal profile obtained for Mg-PPi2- hydrolysis, which has a plateau from pH 6.5 to 9.0. Zn-PPi2- hydrolytic activity is inhibited by 1-butanol and methylene-diphosphate but not by NaF. The enzyme has no activity when free Zn2+ concentration is lower than 7.5 pM (at 0.9-1.2 mM Zn-PPi2-) and therefore free Zn2+ is an essential activator of Zn-PPi2- hydrolytic activity. Free Mg2+, on the contrary, acts as an inhibitor of Zn-PPi2- hydrolysis. The dependence of the reaction rate on the Zn-PPi2- concentration is sigmoidal.

Influence of cholesterol lowering on plasma membrane lipids and cationic transport systems.

BACKGROUND: In order to determine whether alterations in membrane lipids affect transmembrane cationic transport systems in erythrocytes and platelets, cationic fluxes and intracellular cationic concentrations were measured in hypercholesterolaemic patients before and during administration of an inhibitor of 3-hydroxy-3-methlglutaryl coenzyme A reductase. METHODS: After a 1-month run-in placebo period on a lipid-lowering diet the patients were treated, in a double-blind manner, with either placebo (n = 25) or pravastatin (n = 25) for 6 months. Placebo or pravastatin (10 mg during the first month, 20 mg during the second month and 40 mg during the remaining 4 months) was administered once a day in the evening. RESULTS: Compared with the placebo group, the erythrocyte and platelet membrane cholesterol content was reduced in the patients treated with pravastatin. The intra-erythrocyte and intraplatelet Na+ concentration was reduced during pravastatin administration, whereas the activity of the erythrocyte and platelet Na(+)-K+ pump was increased. However, the intra-erythrocyte and intraplatelet K+, Mg2+ and cytosolic Ca2+ concentrations, and water content, as well as the activities of the erythrocyte Na(+)-Li+ countertransporter and Na+,K+ cotransporter, and Na+ and K+ leakage, were not changed during pravastatin treatment. CONCLUSIONS: The present data show that cholesterol lowering in hypercholesterolaemic patients may result in a significant decrease in erythrocyte and platelet membrane cholesterol content. These changes in membrane cholesterol are accompanied by an increase in activity of the Na(+)-K+ pump and a decrease in intra-erythrocyte and intraplatelet Na+ concentrations.

The epidemiology of the association between hypertension and menopause.

Menopause is a normal aging phenomenon in women and consists of the gradual transition from the reproductive to the non-reproductive phase of life. The median age at the menopause is currently around 50 years. As a result of the increasing life expectancy in the first and second worlds, many women will be postmenopausal for over one-third of their lives. The influence of menopause per se on blood pressure remains uncertain. Recent experimental and epidemiological evidence supports the hypothesis that oestrogen deficiency may induce endothelial and vascular dysfunction and potentiate the age-related increase in systolic pressure, possibly as a consequence of a reduced compliance of the large arteries. However, the latter hypothesis requires further investigation.

Changes in plasma lipids, lipoproteins and apolipoproteins in hypercholesterolaemic patients treated with pravastatin.

Plasma lipids, lipoproteins and apolipoproteins were studied before and during 6 months of pravastatin administration in patients with hypecholesterolaemia. After a 1 month placebo run-in period, the patients were treated double-blind either with placebo (n = 25) or with pravastatin (n = 25) for 6 months. Placebo or pravastatin 10 mg during the first month, 20 mg during the second month and 40 mg during the additional 4 months was administered once daily in the evening. Compared with the placebo group the plasma concentration of total cholesterol and phospholipids, free cholesterol and cholesterol esters as well as the plasma LDL-cholesterol and LDL-phospholipids were decreased during 6 months of pravastation therapy. No changes in plasma VLDL-, HDL-, HDL2-, or HDL3-cholesterol, -phospholipids or -triglycerides were observed in the pravastatin-treated patients. A decrease in the plasma level of apolipoprotein B and of LDL-apo B, but not of VLDL-apo B, was observed during pravastatin therapy; the plasma apolipoprotein AI and AII levels as well as HDL2- and HDL3-apo AI and apo AII levels remained, however, unchanged. Plasma lipoprotein Lp(a) did not change during pravastatin therapy whereas the plasma lecithin cholesterol acyltransferase activity (LCAT) increased. In conclusion, treatment of hypercholesterolaemic patients with pravastatin results in a decrease in the plasma concentration of total and free cholesterol, LDL-cholesterol, apolipoprotein B, LDL-apo B, phospholipids and cholesterol esters and in an increase in plasma LCAT activity. Plasma Lp(a), HDL-cholesterol and triglyceride levels remained, however, unchanged.

Efficacy and safety of pravastatin in hypertensive hypercholesterolaemic patients on antihypertensive drug therapy.

This double-blind, placebo-controlled, six month trial evaluated the efficacy and safety of pravastatin in hypercholesterolaemic, hypertensive patients on antihypertensive treatment, who on a standard lipid-lowering diet maintained a plasma total cholesterol level of at least 250 mg%. Fifty hypertensive patients were randomised to placebo or pravastatin treatment. Once daily dosing consisted of 10 mg pravastatin during the first month, 20 mg during the second month and 40 mg during an additional 4 months or matching placebos. Compared with placebo, pravastatin reduced (P < 0.001) the plasma level of total cholesterol, LDL-cholesterol and phospholipids during the six month study period whereas plasma HDL-cholesterol and triglycerides did not change significantly. These changes in plasma lipids were independent of age and of the nature of the concomitant antihypertensive treatment. No serious side-effects were observed and pravastatin was generally well tolerated. In conclusion, pravastatin 10-40 mg once daily reduced plasma total and LDL-cholesterol in hypercholesterolaemic, hypertensive patients, independent of age and concurrent antihypertensive drug therapy.

For how many days should blood pressure be measured at home in older patients before steady levels are obtained?

This study investigated the period of time that blood pressure (BP) should be measured at home in older patients in order to obtain steady BP values. Thirty-six men and 38 women (> or =60 years) were recruited at one family practice. At one office visit the family physician measured supine, sitting and standing BPs three times consecutively in each position. During 10 consecutive days, BP was measured at home five times daily. The supine and standing BPs were measured once in the morning and in the evening and the sitting BP once at noon. These home BP values were averaged over the first day (1-day), over the first 3 days (3-day) and all 10 days (10-day) of measurements. In both the supine (-5.1 mm Hg) and sitting (-3.8 mm Hg) positions the 10-day average systolic home BP was significantly lower than the corresponding office BP. The opposite was observed for the 10-day average standing home BP values (+7.3/+3.4 mm Hg). Comparison of the 3-day and 10-day average home BP values showed only a significantly lower 10-day than 3-day systolic BP level in the supine position (-1.1 mm Hg, 95% CI -1.9 to -0.2 mm Hg). Repeated measures ANOVA, showed a small but significant decrease over time only for the supine systolic home BP (-0.29 mm Hg per day, 95% CI -0.49 to -0.08 mm Hg per day). We conclude that in older subjects, 3 days of home measurements may suffice to obtain steady values for the sitting and standing BPs. A longer interval might be required for the supine BP.

Interaction between nonsteroidal anti-inflammatory drug intake and calcium-channel blocker-based antihypertensive treatment in the Syst-Eur trial.

OBJECTIVE: To assess the relationship between chronic intake of nonsteroidal anti-inflammatory drugs (NSAID) and outcome, in particular (gastrointestinal) bleeding and to investigate whether the effect of chronic NSAID intake was similar in untreated and treated elderly hypertensives. METHODS: Eligible patients (> or = 60 years, with systolic blood pressure 160-219 mm Hg and diastolic blood pressure < 95 mm Hg) were randomised to active treatment or placebo. Active treatment consisted of nitrendipine, with the possible addition of enalapril, hydrochlorothiazide, or both, titrated or combined to reduce the sitting systolic blood pressure by at least 20 mm Hg to below 150 mm Hg. Patients never taking NSAIDs (n = 2882) were compared with patients on chronic NSAID intake (n = 861), defined as reporting NSAID intake on at least 50% of the patient forms. RESULTS: There was a tendency towards lower mortality (relative hazard rate (95% confidence interval (CI), 0.77 (0.56-1.06)) and higher incidence of bleeding (1.13 (0.63-2.05) with chronic NSAID intake. Although there was no significant interaction between calcium-channel blocker (CCB)-based treatment and chronic NSAID intake for any of the end points, chronic NSAID intake tended to be associated with a lower incidence of bleeding on active treatment as compared to placebo (P-value of the interaction term = 0.07). CONCLUSION: The effect of chronic NSAID intake on outcome was similar in patients on active treatment based on a dihydropyridine CCB or on placebo. However, chronic NSAID intake might have a less deleterious effect on bleeding on active treatment as compared to placebo.

Systolic Hypertension in Europe (Syst-Eur) trial phase 2: objectives, protocol, and initial progress. Systolic Hypertension in Europe Investigators.

The Systolic Hypertension in Europe (Syst-Eur) trial proved that blood pressure (BP) lowering therapy starting with nitrendipine reduces the risk of cardiovascular complications in older (> or = 60 years) patients with isolated systolic hypertension (systolic BP > or = 160 mm Hg and diastolic BP < 95 mm Hg). After the completion of the Syst-Eur trial on 14 February 1997, 3506 consenting patients (93.0% of those eligible) were enrolled in phase 2 of the Syst-Eur trial. This open follow-up study aims to confirm the safety of long-term antihypertensive therapy based on a dihydropyridine. To lower the sitting systolic BP below 150 mm Hg (target BP), the first-line agent nitrendipine (10-40 mg/day) may be associated with enalapril (5-20 mg/day), hydrochlorothiazide (12.5-25 mg/day), both add-on study drugs, or if required any other antihypertensive agent. On 1 November 1998, 3248 patients were still being followed, 86 patients had proceeded to non-supervised follow-up, and 43 had died. The median follow-up in Syst-Eur 2 was 14.3 months. At the last available visit, systolic/diastolic BP in the patients formerly randomised to placebo (n = 1682) or active treatment (n = 1824), had decreased by 13.2/5.2 mm Hg and by 4.6/1.6 mm Hg, respectively, so that the between-group BP difference was 1.7 mm Hg systolic (95% Ci: 0.8 to 2.6 mm Hg; P < 0.001) and 0.9 mm Hg diastolic (95% Cl: 0.4 to 1.5 mm mm Hg; P < 0.001). At the beginning of Syst-Eur 2, the goal BP was reached by 25.4% and 50.6% of the former placebo and active-treatment groups; at the last visit these proportions were 55.9% and 63.1%, respectively. At that moment, 45.9% of the patients were on monotherapy with nitrendipine, 29.3% took nitrendipine in combination with other study drugs. Until the end of 2001, BP control of the Syst-Eur 2 patients will be further improved. Cardiovascular complications and adverse events, such as cancer or gastro-intestinal bleeding, will be monitored and validated by blinded experts.

Determination of the physicochemical constants and spectrophotometric characteristics of the metallochromic Zincon and its potential use in biological systems.

In this work we report a detailed characterization of the metallochromic Zincon. Zincon forms complexes with Zn2+ and Cu2+, producing change in colour; the complexes with Fe2+, Mn2+ and Ca2+ cause the bleaching of the Zincon solutions. Mg2+ does not interact with Zincon nor does it change its spectral characteristics. The presence of Ca2+ and Mg2+ does not interfere with the spectral characteristics of the Zn-Zincon complex. The Kd, Ks and delta epsilon values for the complexes were determined. The delta epsilon values were very high, making this spectrophotometric method very sensitive. The complex Zn-Zincon is fully reversible; however, the complex Cu-Zincon is only partially reversible. The free Zincon, and the complexes Zn-Zincon and Cu-Zincon, does not partition into organic solvents, does not permeate liposome membrane, and neither does it interact with biological membranes. All these characteristics make the metallochromic Zincon useful in biological systems.

Antihypertensive therapy in older patients with isolated systolic hypertension: the Syst-Eur experience in general practice

Background and objective. This interim report from the Syst-Eur trial investigated the level of blood pressure control achieved during the double-blind period in patients followed in general practices. Methods. In the Syst-Eur trial elderly patients (60 years or older) with isolated systolic hypertension were randomized to either active or placebo treatment. Active treatment consisted of nitrendipine combined with enalapril and/or hydrochlorothiazide to reduce systolic pressure to Results. This analysis was restricted to patients of general practitioners who had been followed for at least 12 months. The placebo (N = 204) and active treatment (N = 217) groups had similar characteristics at randomization. At one year, the difference in sitting pressure between the two treatment groups was 10 mmHg systolic and 4 mmHg diastolic. Fewer patients remained on monotherapy in the placebo than in the active treatment group and on placebo the second and third line medications were started earlier. Nitrendipine tablets were discontinued in 10 patients on placebo and in 21 patients assigned to active treatment (P Conclusions. A significant blood pressure reduction can be achieved and maintained in older patients with isolated systolic hypertension followed by general practitioners. Whether this blood pressure reduction results in a clinically meaningful decrease of cardiovascular complications is under investigation. Keywords. Antihypertensive treatment, general practice, isolated systolic hypertension, randomized clinical trial.

The international database of self-recorded blood pressures in normotensive and untreated hypertensive subjects.

OBJECTIVES: To pool data from individual subjects in an attempt to determine an operational threshold for making clinical decisions based on the self-recorded blood pressure (SRBP) and to examine how many hypertensive subjects, diagnosed by conventional blood pressure (CBP) measurement, would have a self-recorded blood pressure within the normotensive range if the proposed thresholds were applied. DATA SOURCES: Thirteen research groups studied 4668 untreated subjects. RESULTS: In total 2401 subjects were normotensive, 494 were borderline hypertensive and 1773 were definitely hypertensive. Hypertension had been diagnosed from the mean of 1-6 (median 3) CBP measurements obtained during 1-3 (median 1) visits. The reference values for SRBP measurements determined from the 95th percentiles of the distributions for normotensive subjects were 137 mmHg systolic and 85 mmHg diastolic. Of the subjects with systolic hypertension, 16% had systolic SRBP

Once-daily antihypertensive treatment with calcium antagonists: utopia or reality?

Although a large number of antihypertensive drugs have been approved for once- or twice-daily dosing, no standardized set of evidence is required to demonstrate that the blood pressure reduction is sustained for 24 h. The recent literature on calcium antagonists was therefore searched for the arguments usually put forward to objectify a long duration of action. Most studies relied on ambulatory blood pressure monitoring. However, several published reports were difficult to interpret for a variety of reasons, such as: (1) a non-blinded non-randomized study design; (2) a statistical analysis, which was discordant with the study design; (3) analyses confined to the 24 h, day-time and night-time pressure means; (4) the absence of a baseline adjustment and/or formal statistical testing; (5) the "post hoc" subdivision of patients into responders and non-responders; and (6) the absence of a well-specified time-frame linking drug intake to the observed antihypertensive effects. According to the authors' interpretation, amlodipine, diltiazem SR (modified release), felodipine SR, isradipine SR, nifedipine SR, nitrendipine and verapamil SR have all been confirmed to reduce both the conventional and the 24 h blood pressure. Some studies went beyond the 24 h blood pressure means and also presented separate results for the day-time (or awake) and night-time (or sleeping) periods, or investigated the blood pressure reduction at the end of the dosing interval, or compared the diurnal blood pressure profiles on different treatments.(ABSTRACT TRUNCATED AT 250 WORDS)

The older hypertensive. Assessment and treatment.

A meta-analysis is presented of 8 therapeutic trials in elderly hypertensive patients. In an intention-to-treat analysis, cardiovascular mortality was decreased on average by 22% (95% confidence interval ranging from -32% to -10%). This decrease was explained by both a reduction in coronary mortality by 26% (-40% to -9%) and in cerebrovascular mortality by 33% (-50% to -9%). The effectiveness of therapy in terms of reducing cardiovascular mortality is not established with confidence in those trials where the diastolic blood pressure at randomization is below 95 mmHg or in the patients above 75 years of age. A goal blood pressure is not definitively established, but a reduction of the systolic blood pressure to about 150 mmHg may be optimal. Extrapolation of the trial results to the elderly population with systolo-diastolic hypertension at large seems acceptable for the western population, but may be premature for the Asian and African elderly. Beta-blockers and especially diuretics are recommended as first-line drugs in elderly patients with symptomless, uncomplicated hypertension, since the effectiveness of other drugs in reducing morbidity and mortality is not yet established. Recommendation for treatment of symptomless patients with isolated systolic hypertension may be premature. The ongoing Syst-Eur and Syst-Chin trials may provide further information.

Trials in elderly patients with isolated systolic hypertension.

The hypothesis that antihypertensive drugs should be prescribed to elderly patients with isolated systolic hypertension is being addressed in at least 3 trials: the Systolic Hypertension in the Elderly Program (SHEP) in the United States, a trial in China, and the Syst-Eur study in Europe. The SHEP trial has recently reported its final morbidity and mortality results. This article summarizes the protocol of the European study. To be eligible for the Syst-Eur trial, patients must be at least 60 years old and have a systolic blood pressure averaging 160-219 mmHg with a diastolic pressure less than 95 mmHg. Patients must give their informed consent and be free of major cardiovascular and non-cardiovascular diseases at entry. The patients are randomized into active treatment or placebo. Active treatment consists of nitrendipine (10-40 mg/d), combined with enalapril (5-20 mg/d) and hydrochlorothiazide (12.5-25 mg/d), as necessary. The control group received matching placebos. The drugs (or matching placebos) are stepwise titrated and combined in order to reduce systolic blood pressure by 20 mmHg at least to a level below 150 mmHg. Morbidity and mortality are monitored to enable an intention-to-treat and per protocol comparison of the outcome in the two treatment groups.

Efficacy of antihypertensive drugs given once a day: the calcium antagonists revisited.

BACKGROUND: A large number of antihypertensive drugs have been approved for administration once or twice a day, but no standardized evidence is required to demonstrate that the reduction in blood pressure is sustained over 24 h. AIM: To test the validity of claims of a long duration of action for second-generation calcium antagonists. METHOD: Literature search. FLAWS IN REPORTED STUDIES: Most studies relied on ambulatory blood pressure monitoring. However, several reports were difficult to interpret because (1) the study was not blinded or random; (2) the statistical analysis was inappropriate for the study design; (3) analyses were confined to the means of 24-h, daytime and night-time blood pressure; (4) there was no baseline adjustment or formal statistical testing; (5) patients were subdivided into responders and non-responders after treatment; (6) there was no specified time frame linking drug intake to the observed antihypertensive effects. CLAIMS NOT SUBSTANTIATED: The authors of the articles reviewed concluded that amlodipine, nitrendipine and modified (slow-release) formulations of diltiazem, isradipine, nifedipine and verapamil reduced both conventional (clinic) and the 24-h blood pressure levels. In some studies separate results were presented for the daytime (awake) and night-time (sleeping) periods; some investigated the reduction in blood pressure at the end of the dose interval; and some compared the diurnal blood pressure profiles with different drug treatments. However, these reports gave discrepant results, suggesting that at least under certain study conditions the effect of nitrendipine and of slow-release diltiazem, isradipine and nifedipine did not give full 24-h cover with a single daily dose. CONCLUSIONS: We conclude that the interpretation of studies on long-acting antihypertensive agents using ambulatory blood pressure monitoring would be easier if the same standards were applied as required in clinical studies using conventional blood pressure measurements.

Methods for describing the diurnal blood pressure curve.

Ambulatory blood pressure recordings supply information on the blood pressure variation during habitual daily activities and sleep. Whether the circadian blood pressure curve is modulated by an endogenous clock or whether the diurnal fluctuations in blood pressure are mainly or exclusively determined by the pattern of activity remains disputed. Whatever the underlying mechanism, most experts agree that it still remains to be ascertained whether the blood pressure profile can help in unraveling the pathophysiology of hypertension and determining a subject's cardiovascular risk. The methods for parametrizing the diurnal blood pressure curve in individual subjects, summarized in this article, may provide summary statistics for larger groups of individuals or for the population at large.