Loss Of Blood Pressure Control Research Articles

Abstract 12210: Repeated Systolic Blood Pressure Measures During Intensive Treatment Show a Loss Of Protective Effect Over Time. A Secondary Analysis of the SPRINT Trial

Introduction: The SPRINT trial showed a 25% reduction in the primary outcome with SBP intensive treatment using Cox proportional risk analysis. A recent secondary analysis by the SPRINT group assessed the post-trial maintenance of this protection by considering repeated SBP measurements and using a mixed linear regression model. They found that the intervention lost its protective effect post-trial, possibly due to the loss of intensive blood pressure control. Could this loss of protective effect also be found during the clinical trial, when considering repeated measurements of systolic blood pressure in the analysis? Methods: Secondary analysis of the SPRINT study database included 9,068 patients with repeated measures of SBP and complete baseline information. Cox proportional hazards and mixed linear models were used to analyze the primary endpoint and repeated SBP measures, respectively. A Cumulative Joint Model Analysis was conducted to combine the direct and indirect effects of the intervention on the primary outcome. R Studio V12.0 software was used for the analyses. Results: The protective effect is lost during the trial, both in the total population (3.4 years) as well as in subgroups such as women (1.1 years), patients with CVD (1.3 years), CKD (1.3 years), black patients (1.8 years), younger than 75 years (2.1 years) and in patients who present serious adverse events (3.4 years) compared to those who do not present SAEs (4.2 years). Beyond the loss of blood pressure control, other factors such as cumulative BP, adverse events, and the increase in SBP variability could be considered. Conclusions: Including repeated measures of SBP revealed a loss of protective effect in the intervention during the trial and generated Simpson's paradox. This highlights the need to consider alternative statistical methods in clinical trial analysis beyond Cox proportional hazard analysis for a comprehensive perspective on intervention efficacy.

Клинический случай COVID-19 у пациентки с артериальной гипертензией и туберкулезом легких в анамнезе

The patients suffering from cardiovascular disorders [arterial hypertension, coronary artery disease (angina pectoris)] are at high risk of severe course or adverse outcome of COVID-19. The development of two disorders in one patient suggests the probability of mutual aggravation, thus requiring extra effort of the physician to prevent decompensation of both existing conditions. The paper reports the case of dynamic supervision of the female patient with arterial hypertension, the history of tuberculosis, and COVID-19. The development of acute viral infection results in the loss of blood pressure control, which requires mandatory adjustment of antihypertensive therapy for prevention of disability and all-cause mortality.

Circadian rhythms and the kidney

Numerous physiological functions exhibit substantial circadian oscillations. In the kidneys, renal plasma flow, the glomerular filtration rate and tubular reabsorption and/or secretion processes have been shown to peak during the active phase and decline during the inactive phase. These functional rhythms are driven, at least in part, by a self-sustaining cellular mechanism termed the circadian clock. The circadian clock controls different cellular functions, including transcription, translation and protein post-translational modifications (such as phosphorylation, acetylation and ubiquitylation) and degradation. Disruption of the circadian clock in animal models results in the loss of blood pressure control and substantial changes in the circadian pattern of water and electrolyte excretion in the urine. Kidney-specific suppression of the circadian clock in animals implicates both the intrinsic renal and the extrarenal circadian clocks in these pathologies. Alterations in the circadian rhythm of renal functions are associated with the development of hypertension, chronic kidney disease, renal fibrosis and kidney stones. Furthermore, renal circadian clocks might interfere with the pharmacokinetics and/or pharmacodynamics of various drugs and are therefore an important consideration in the treatment of some renal diseases or disorders.

HIPERTENSIUNEA ARTERIALĂ SECUNDARĂ ENDOCRINĂ

The need to evaluate patients for secondary hypertension is common in clinical practice. Suspicion of endocrine hypertension occurs when the disease starts suddenly at young age, in cases with loss of blood pressure control in a patient with previously well-controlled blood pressure or labile blood pressure cases. Careful medical history and physical examination are very important to rule out other factors responsible for these patterns of hypertension (certain medications, alcohol, lack of compliance to treatment or dietary salt restriction, panic attacks etc). Pheochromocytoma and Cushing syndrome – the major endocrine diseases associated with secondary hypertension – are rare in clinical practice. Instead, primary hyperaldosteronism is becoming more frequently identified. It can go unnoticed because of nonspecific clinical presentation and of the fact that hypokalaemia, classically described, is actually rare in practice.

Variables associated with change in blood pressure control status after 1-year follow up in primary care: a retrospective analysis: the TAPAS study

This 1-year, retrospective, observational study assessed factors associated with changes in hypertension control status and differences in blood pressure (BP) management among general practitioners in Spain. In 2009, 307 investigators from 260 primary care centres in Spain recruited the first four consecutive patients with hypertension that fit into one of four predefined cohorts: (1) uncontrolled BP at baseline and at a 1-year follow-up visit; (2) uncontrolled BP at baseline and good BP control at the 1-year follow-up visit; (3) good BP control at baseline and loss of BP control at the 1-year follow-up visit; and (4) good BP control at baseline and at the 1-year follow-up visit. A total of 1385 patients were included. Patients with poor BP and patients that lost BP control exhibited more cardiovascular risk factors. Although antihypertensive treatment was increased more markedly in these patients, this was not sufficient to attain/remain BP goals. Predictors for attaining BP control were no smoking, absence of diabetes, reduction in cholesterol, low baseline cholesterol, and no weight gain. Predictors for failing to maintain BP goals were weight gain, high baseline LDL cholesterol, and no reduction in fasting glucose. NSAID prescriptions increased markedly in patients that lost BP control compared to those that maintained BP control. Antihypertensive therapy should be intensified and healthy lifestyle changes should be emphasized, particularly weight control to improve BP control. Drugs that may increase BP levels, such as NSAIDs, should also be avoided.

Dysglycemia induces abnormal circadian blood pressure variability

BackgroundPrediabetes (PreDM) in asymptomatic adults is associated with abnormal circadian blood pressure variability (abnormal CBPV).HypothesisSystemic inflammation and glycemia influence circadian blood pressure variability.MethodsDahl salt-sensitive (S) rats (n = 19) after weaning were fed either an American (AD) or a standard (SD) diet. The AD (high-glycemic-index, high-fat) simulated customary human diet, provided daily overabundant calories which over time lead to body weight gain. The SD (low-glycemic-index, low-fat) mirrored desirable balanced human diet for maintaining body weight. Body weight and serum concentrations for fasting glucose (FG), adipokines (leptin and adiponectin), and proinflammatory cytokines [monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α)] were measured. Rats were surgically implanted with C40 transmitters and blood pressure (BP-both systolic; SBP and diastolic; DBP) and heart rate (HR) were recorded by telemetry every 5 minutes during both sleep (day) and active (night) periods. Pulse pressure (PP) was calculated (PP = SBP-DBP).Results[mean(SEM)]: The AD fed group displayed significant increase in body weight (after 90 days; p < 0.01). Fasting glucose, adipokine (leptin and adiponectin) concentrations significantly increased (at 90 and 172 days; all p < 0.05), along with a trend for increased concentrations of systemic pro-inflammatory cytokines (MCP-1 and TNF-α) on day 90. The AD fed group, with significantly higher FG, also exhibited significantly elevated circadian (24-hour) overall mean SBP, DBP, PP and HR (all p < 0.05).ConclusionThese data validate our stated hypothesis that systemic inflammation and glycemia influence circadian blood pressure variability. This study, for the first time, demonstrates a cause and effect relationship between caloric excess, enhanced systemic inflammation, dysglycemia, loss of blood pressure control and abnormal CBPV. Our results provide the fundamental basis for examining the relationship between dysglycemia and perturbation of the underlying mechanisms (adipose tissue dysfunction induced local and systemic inflammation, insulin resistance and alteration of adipose tissue precursors for the renin-aldosterone-angiotensin system) which generate abnormal CBPV.

Benefits of once-daily therapies in the treatment of hypertension

In patients with hypertension, 24-hour blood pressure control is the major therapeutic goal. The number of daily doses is one characteristic of an antihypertensive agent that may affect the adequacy of 24-hour control. One measure of therapeutic coverage is the 24-hour trough-to-peak ratio, which determines the suitability of an agent for once-daily administration. The closer an agent is to a 100% trough-to-peak ratio, the more uniform the 24-hour coverage and therefore blood pressure control. High trough-to-peak ratio, long-acting antihypertensive medications lower blood pressure more gradually, which reduces the likelihood of adverse events attributable to abrupt drug action that occurs with shorter-acting agents. In hypertension, the natural diurnal variation of blood pressure may be altered, including elevated nighttime pressures. An optimal once-daily hypertension therapy would not only lower blood pressure but also normalize any blunted circadian variations in blood pressure. The benefits of once-daily agents with sustained therapeutic coverage may also be explained, in part, by increased patient adherence to simpler regimens as well as lower loss of blood pressure control during virtually inevitable intermittent noncompliance. Studies have demonstrated that once-daily antihypertensive agents have the highest adherence compared with twice-daily or multiple daily doses, including greater adherence to the prescribed timing of doses.

Endocrine Causes of Secondary Hypertension

Secondary hypertension is common in clinical practice if a broad definition is applied. Various patterns of hypertension exist in the patient with an endocrine source of their disease, including new-onset hypertension in a previously normotensive individual, a loss of blood pressure control in a patient with previously well-controlled blood pressure, and/or labile blood pressure in the setting of either of these 2 patterns. A thorough history and physical exam, which can rule out concomitant medications, alcohol intake, and over-the-counter medication use, is an important prerequisite to the workup for endocrine causes of hypertension. Endocrine forms of secondary hypertension, such as pheochromocytoma and Cushing's disease, are extremely uncommon. Conversely, primary aldosteronism now occurs with sufficient frequency so as to be considered "top of the list" for secondary endocrine causes in otherwise difficult-to-treat or resistant hypertension. Primary aldosteronism can be insidious in its presentation since a supposed hallmark finding, hypokalemia, may be variable in its presentation. It is important to identify secondary causes of hypertension that are endocrine in nature because surgical intervention may result in correction or substantial improvement of the hypertension.

Self-Measurement of Blood Pressure at Home Reduces the Need for Antihypertensive Drugs

It is still uncertain whether one can safely base treatment decisions on self-measurement of blood pressure. In the present study, we investigated whether antihypertensive treatment based on self-measurement of blood pressure leads to the use of less medication without the loss of blood pressure control. We randomly assigned 430 hypertensive patients to receive treatment either on the basis of self-measured pressures (n=216) or office pressures (OPs; n=214). During 1-year follow-up, blood pressure was measured by office measurement (10 visits), ambulatory monitoring (start and end), and self-measurement (8 times, self-pressure group only). In addition, drug use, associated costs, and degree of target organ damage (echocardiography and microalbuminuria) were assessed. The self-pressure group used less medication than the OP group (1.47 versus 2.48 drug steps; P<0.001) with lower costs ($3222 versus $4420 per 100 patients per month; P<0.001) but without significant differences in systolic and diastolic OP values (1.6/1.0 mm Hg; P=0.25/0.20), in changes in left ventricular mass index (-6.5 g/m(2) versus -5.6 g/m(2); P=0.72), or in median urinary microalbumin concentration (-1.7 versus -1.5 mg per 24 hours; P=0.87). Nevertheless, 24-hour ambulatory blood pressure values at the end of the trial were higher in the self-pressure than in the OP group: 125.9 versus 123.8 mm Hg (P<0.05) for systolic and 77.2 versus 76.1 mm Hg (P<0.05) for diastolic blood pressure. These data show that self-measurement leads to less medication use than office blood pressure measurement without leading to significant differences in OP values or target organ damage. Ambulatory values, however, remain slightly elevated for the self-pressure group.

Review of resistant hypertension

Despite the prevalence of hypertension, blood pressure (BP) can be controlled with effective therapy in most patients. However, in a small percentage of the hypertensive population, BP remains refractory to therapeutic measures. In such patients who have so-called "resistant" hypertension, proper evaluation and assessment have to be undertaken to improve the BP control. There are some situations or factors that may make hypertension control difficult in some patients. Therefore, it is necessary to identify possible reasons for the loss of BP control and rectify them to achieve normotension. In addition to indicated work-up for secondary causes, aggressive treatment (nonpharmacologic and pharmacologic) of hypertension is required to prevent excessive morbidity and mortality in this special population.

Estudo "LOTHAR": avaliação de eficácia e tolerabilidade da combinação fixa de anlodipino e losartana no tratamento da hipertensão arterial primária

The LOTHAR study evaluated medium and long term (one year) efficacy, tolerability and metabolic effects of the fixed combination of amlodipine and losartan compared to amlodipine or losartan alone. Brazilian multicenter, randomized, double-blind and comparative trial performed with 198 patients in stage 1 and 2 essential hypertension. The fixed combination has a high antihypertensive efficacy that is sustained in the long term with very low percentage of loss of blood pressure control. This percentage is incidentally lower than that of the two monotherapy comparative regimens. In the long term, more than 60% of the patients treated with the fixed combination remained with DBP < or = 85 mmHg, and the antihypertensive effect, when assessed by ABPM persisted for 24 hours with a trough-to-peak ratio of 76.7%. The frequency of adverse events was quite low in this group, and the long-term incidence of leg edema was approximately four-fold lower than that observed with amlodipine alone. The fixed combination did not change glucose and lipid metabolism in the medium or in the long term. Based on these results, we can say that the combination of amlodipine and losartan--the first fixed combination of a calcium channel blocker and an angiotensin II receptor blocker available in the pharmaceutical market, is an excellent option for the treatment of a wide range of hypertensive patients.

Ten lessons to be learned from the withdrawal of Vioxx� (rofecoxib)

NSAIDs are one of the most ubiquitous class of drugs, with different compounds being sold as over the-counter drugs for a wide range of minor and major conditions. As a group, they rank first among causes of adverse drug reactions (ADRs) [1]. Severe gastrointestinal (GI) toxicity (i.e. upper GI bleeding, ulcers and perforation) due to aspirin and NSAIDs is probably the main cause of iatrogenic admission to hospitals [2], with important quantitative risk differ ences among NSAIDs [3-7] and with an overall attributable incidence of 150 cases/million/year [8]. In 1991, two COX-isozymes of prostaglandin G/H synthase (cyclooxigenase) were first characterized and named COX-1 (the constitutive form) and COX-2 (the inducible form). Inhibition of COX-2 was proved to be most directly implicated in reducing inflam mation, whereas inhibition of COX-1 has been re lated to significant adverse events in the GI tract [9]. This knowledge opened the door to a new class of compounds, the selective COX-2 inhibitors, which, if proved to be safer upon the GI tract that classical NSAIDs, could be potentially important 'blockbust ers' [9]. However, some words of caution are in order. First, selectivity inhibition should be regarded as a relative, rather than an absolute concept; the in vitro COX-1/COX-2 ratio differs from compound to compound (among classical as well as newer drugs); it is also critically dependent on the methodology used as well as on the concentration of the drug [9]. Secondly, NSAIDs as a group have potentially deleterious effects on the cardiovascular system; prostaglandins can counterbalance the vasoconstric tor effects of other mediators as angiotensin II, nor epinephrine or vasopressin on the kidney. They can also induce the appearance of oedemas and fluid retention, cause loss of blood pressure control and increase the risk of congestive heart failure. Thirdly, regarding its effect on platelet function, many physiopathological features of the COX-1/ COX-2 equation are still evolving. The well known antiplatelet effect of aspirin is achieved by irreversible acetylation of a serine residue at position 529 in COX-1, the only isoform of the enzyme expressed in platelets, inhibiting its main metabolite (thrombox ane A2), which has proaggregant properties. Prosta glandin I2, the predominant COX product in endothelium, has opposed effects: it inhibits platelet aggregation, causes vasodilatation and prevents the proliferation of vascular smooth-muscles. The inhi bition of these effects, previously thought to be mediated by COX-1, later has been proved to be COX-2 related [10]. If this is so, strong inhibition of COX-2 dependent prostaglandin I2 in endothelium could lead to cardiovascular damage. In 1999, the two first anti-inflammatory drugs based upon the concept of COX-2 selectivity, the so called 'coxibs' (rofecoxib and celecoxib) were intro duced into the American market. The success was impressive, and worldwide sales of rofecoxib reached US$ 2.5 billion in 2003 [11]. However, some aspects of the process were unusual. The pivotal randomised clinical trial (RCT) was only published over a year later than the commercial approval of the drug had been granted [12]. The VIGOR trial compared ro fecoxib (50 mg/od) with naproxen (1.000 mg/od) in 8.076 patients with rheumatoid arthritis. The trial showed an increased number of acute myocardial infarctions (AMI) (0.4% vs. 0.1%) in patients taking rofecoxib. Concerns about the cardiovascular safety profile of the drug were initially overcome by inter preting that the results of the trial revealed more an allegedly cardioprotective effect of naproxen rather than a cardiotoxic effect of rofecoxib [12]. This hypothesis has been repeatedly questioned be cause, in fact, epidemiological as well as 'in vitro' data on the effect on platelet aggregation and other mech anisms related to cardiovascular safety of NSAIDs (other than aspirin) are very scarce. Regulatory authorities in USA and EU reacted by including a precautionary sentence in the labelling of marketed coxibs, reflecting the findings from the VIGOR trial. Subsequently, the coxibs 'me-too' saga increased sub stantially: valdecoxib, parecoxib, etoricoxib, lumirac oxib... New results from a RCT comparing lumiracoxib vs. naproxen raised more concern about an excess risk of AMI of another coxib [13]. Meanwhile, a Merck-sponsored meta-analysis of randomised trials of rofecoxib [14] and some obser vational studies [15-17] appeared to support the an tiaggregant effect of naproxen, while other studies suggested that the increased cardiovascular risk of

Combination ACE inhibitors and angiotensin II receptor blockers for hypertension.

To review data concerning combined angiotensin-converting enzyme (ACE) inhibitor and angiotensin II receptor blocker (ARB) therapy for hypertension. MEDLINE (1966-April 2003), IPA (1970-April 2003), and EMBASE (1974-April 2003) with search terms of ACE inhibitor, angiotensin receptor blocker, essential hypertension, and combination therapy. ACE inhibitors provide incomplete blockade of the renin-angiotensin system, sometimes leading to loss of blood pressure control. Addition of ARBs may in theory further reduce blood pressure. Studies of combined ACE inhibitor and ARB therapy for managing hypertension were evaluated. While studies have shown statistically significant blood pressure reductions with ACE/ARB combination therapy, clinical significance is lacking. Further trials are needed before routine use of the combination can be recommended.

Loss of blood pressure control and rates of edema in older treated hypertensive patients following administration of the COX-2 specific inhibitors celecoxib vs. Rofecoxib William B. White, Andrew Whelton, Alfonso E. Bello, John G. Fort, University of Connecticut School of Medicine, Farmington, CT, UCRC, Inc., and Johns Hopkins University School of Medicine, Baltimore, MD

Loss of blood pressure control and rates of edema in older treated hypertensive patients following administration of the COX-2 specific inhibitors celecoxib vs. Rofecoxib William B. White, Andrew Whelton, Alfonso E. Bello, John G. Fort, University of Connecticut School of Medicine, Farmington, CT, UCRC, Inc., and Johns Hopkins University School of Medicine, Baltimore, MD

Practical relevance of the 24-hour trough: peak ratio of antihypertensive drugs.

INTRODUCTION OF THE TROUGH:PEAK RATIO: The mean antihypertensive effect of a drug, measured just before the next dose in a multiple-dose regimen, is generally used as a criterion for approval by regulatory agencies. However, for many short-acting drugs very high doses may be required to maintain some antihypertensive activity at the end of the dosing interval. This may lead to an excessive reduction in blood pressure at the time of peak drug effect. In order to avoid unnecessarily large doses, regulatory agencies have introduced a new standard, the trough:peak ratio, which may be 50-60% but should should ideally be higher. BENEFITS OF HIGH TROUGH:PEAK RATIO: A high trough:peak ratio indicates a long duration of action. This may provide a better risk:benefit ratio compared to shorter acting antihypertensive agents by giving optimal therapeutic coverage for 24 h or even longer. Greater benefit may be gained from better control of overnight blood pressure, especially in the early morning hours when both a steep rise in blood pressure and a higher rate of cardiovascular events have been observed. Large swings in blood pressure may occur when the peak is too high in relation to the trough, increasing blood pressure variability, which may in turn increase target organ damage. A high trough:peak ratio may protect the patient against drug-induced blood pressure fluctuations. It may also produce fewer adverse effects as the blood pressure may fall further and the onset of action may be more gradual. This, together with an effective single daily dose, may increase patient compliance. Furthermore, an antihypertensive effect that lasts more than 24 h protects the patient against a rapid loss of blood pressure control when a dose is omitted or delayed. TROUGH:PEAK RATIO OF AVAILABLE ANTIHYPERTENSIVE DRUGS: We performed a literature survey to evaluate the practical relevance of the trough:peak ratio and to determine how it might help in the choice of antihypertensive agents. The results suggested that not all single daily doses of angiotensin converting enzyme inhibitors or calcium antagonists had a trough:peak ratio of > 50%. We conclude that specially designed, prospective clinical trials should be conducted to address this issue.

Drug Interactions in Hypertensive Patients

Antihypertensive treatment has proven benefits, and the number of patients being treated with these drugs is significant. Hypertensive patients may have other medical illnesses for which they receive medications, and interactions between antihypertensive agents and other drugs is likely. Some of these interactions may lead to undesirable effects or even loss of blood pressure control. However, drug interactions can also be beneficial when 2 antihypertensive drugs with different pharmacological actions are prescribed in combination and with a clear therapeutic objective in mind. Clinicians should be aware of the mechanisms and the consequences of the different types of interaction in hypertensive patients, so that a desired pharmacological response can be achieved with the fewest side effects in the patients.

Placebo-controlled Trial of Atenolol in Treatment of Pregnancy-associated Hypertension

Atenolol was compared with placebo in a randomised and double-blind prospective study of 120 women with mild to moderate pregnancy-associated hypertension who were also initially managed conventionally by bed rest. Atenolol given once daily significantly reduced blood-pressure, prevented proteinuria, and reduced the number of hospital admissions. Loss of blood-pressure control leading to withdrawal from the study was commoner among the placebo group, whose babies had a high morbidity. Respiratory distress syndrome occurred only in the placebo group. Intrauterine growth retardation, neonatal hypoglycaemia, and hyperbilirubinaemia occurred with the same frequency in the two groups. Neonatal bradycardia was more common after atenolol but the systolic blood-pressure of the babies was the same in both groups. There was no difference between the groups in maternal symptoms which could have been attributed to beta-blocker therapy. Thus atenolol is more effective than conventional obstetric management in this form of hypertension and does not adversely affect mother or baby.

Pharmacokinetics and Pharmacodynamics of Clonidine in Varying States of Renal Function

Previous studies have reported a therapeutic window of 0.8 to 2.0 ng/ml within which clonidine exerts its antihypertensive effect. This study was designed to investigate whether there was any loss of blood pressure control when plasma clonidine concentrations exceeded this window owing to its accumulation in renal insufficiency. The results indicate that clonidine concentrations of up to 30 ng/ml in patients with end-stage renal disease (ESRD) can be associated with a maintenance of blood pressure control. It remains to be learned whether this phenomenon of high concentrations and control of blood pressure in our ESRD patient population may be related to altered (decreased) peripheral α-receptor sensitivity and inability to develop vasoconstriction. There is precedence for autonomic imbalance and altered tissue sensitivity in ESRD.

Pharmacokinetics and Pharmacodynamics of Clonidine in Varying States of Renal Function

Previous studies have reported a therapeutic window of 0.8 to 2.0 ng/ml within which clonidine exerts its antihypertensive effect. This study was designed to investigate whether there was any loss of blood pressure control when plasma clonidine concentrations exceeded this window owing to its accumulation in renal insufficiency. The results indicate that clonidine concentrations of up to 30 ng/ml in patients with end-stage renal disease (ESRD) can be associated with a maintenance of blood pressure control. It remains to be learned whether this phenomenon of high concentrations and control of blood pressure in our ESRD patient population may be related to altered (decreased) peripheral alpha-receptor sensitivity and inability to develop vasoconstriction. There is precedence for autonomic imbalance and altered tissue sensitivity in ESRD.

PLACEBO-CONTROLLED TRIAL OF ATENOLOL IN TREATMENT OF PREGNANCY-ASSOCIATED HYPERTENSION

Atenolol was compared with placebo in a randomised and double-blind prospective study of 120 women with mild to moderate pregnancy-associated hypertension who were also initially managed conventionally by bed rest. Atenolol given once daily significantly reduced blood-pressure, prevented proteinuria, and reduced the number of hospital admissions. Loss of blood-pressure control leading to withdrawal from the study was commoner among the placebo group, whose babies had a high morbidity. Respiratory distress syndrome occurred only in the placebo group. Intrauterine growth retardation, neonatal hypoglycaemia, and hyperbilirubinaemia occurred with the same frequency in the two groups. Neonatal bradycardia was more common after atenolol but the systolic blood-pressure of the babies was the same in both groups. There was no difference between the groups in maternal symptoms which could have been attributed to beta-blocker therapy. Thus atenolol is more effective than conventional obstetric management in this form of hypertension and does not adversely affect mother or baby.