Michele Beevers

Atenolol and Fetal Growth in Pregnancies Complicated by Hypertension

Atenolol use may be associated with growth retardation when given in pregnancy, although the relationship to trimester of initiation, duration of treatment, and its use as monotherapy is still uncertain. To compare the obstetric and fetal outcome between women receiving atenolol (as monotherapy) and other antihypertensive drug monotherapies, and also to investigate the effect of duration of treatment on fetal growth, we performed a retrospective cohort study of 312 pregnancies in 223 women attending an Antenatal Hypertension Clinic. Atenolol (as monotherapy) was given in 78 pregnancies (25.0%), other types of antihypertensive drugs as monotherapy were given in 53 pregnancies (17.0%), and multiple drug combinations were given in 90 pregnancies (28.8%). In 91 pregnancies (29.2%) no antihypertensive drugs were given. Atenolol was found to be associated with lower birth weight and ponderal index values, with a trend toward a higher prevalence of preterm (<37 weeks) delivery and small-for-gestational-age babies when compared to other antihypertensive drugs as monotherapy, or to no treatment. The adverse effect of atenolol was more pronounced in women receiving the drug earlier in their pregnancy, and continuing the drug for a longer duration. In conclusion, atenolol should be avoided in the early stages of pregnancy and given with caution at the later stages, as it is associated with fetal growth retardation, which is related to duration of treatment.

Inter-arm differences in blood pressure: when are they clinically significant?

Objective To determine whether there is significant disparity in blood pressure between the two arms. Design Prospective, observational study. Setting One general hospital in Birmingham, England. Participants Four hundred participants [age 56.3 ± 19.7 years (mean ± SD), 50% male] were recruited from staff and patients. Simultaneous bilateral blood pressure measurements were obtained using Omron HEM-705CP automated oscillatory devices; with two measurements taken in each arm. Main outcome measures Mean inter-arm blood pressure differences and frequency of clinically important disparities. Results Mean ± SD inter-arm differences in systolic and diastolic blood pressure were 1.81 ± 8.6 mmHg and −0.23 ± 8.3 mmHg, respectively. The analogous figures for mean ± SD absolute differences were 6.32 ± 6.12 mmHg and 5.06 ± 6.57 mmHg, respectively. Significant differences were present between the mean right and left arm systolic blood pressure [t (399) = 4.20, P < 0.0001], and the mean absolute difference for both systolic [t (399) = 20.65;P < 0.0001] and diastolic [t (399) = 15.39;P < 0.0001] blood pressure. The variation in mean inter-arm blood pressure was unrelated to age, sex, ethnicity, arm circumference, handedness, being hypertensive, diabetic, or previous history of cardiovascular disease. Clinically significant inter-arm differences in systolic blood pressure of > 10 and > 20 mmHg were found in 20 and 3.5%, respectively; diastolic differences of > 10 and > 20 mmHg were present in 11 and 3.5%, respectively. Age was the only significant predictor of clinically significant variations in inter-arm blood pressures and mean absolute blood pressure differences. Conclusions Significant differences in mean inter-arm systolic blood pressure, and mean absolute inter-arm systolic and diastolic blood pressure are present. This emphasizes the importance of measuring blood pressure in both arms initially to prevent this misdiagnosis of hypertension, due to normal differences in blood pressure between the arms.

Effect of atenolol on birth weight

To investigate the possible harmful effects of early antihypertensive drug therapy with atenolol versus other therapies on pregnancy outcome, we reviewed the records of 398 women referred to our antenatal hypertension clinic between 1980 and 1995. Babies born to women taking atenolol were significantly lighter than babies born to women taking other beta blockers, other antihypertensive drugs, or no therapy, suggesting that atenolol might be detrimental in early pregnancy.

Hormone replacement therapy and arterial blood pressure in postmenopausal women with hypertension.

Background. Data on the effect of hormone replacement therapy (HRT) on blood pressure (BP) in hypertensive menopausal women are limited. Objective. To investigate the association between HRT and longitudinal changes in BP in hypertensive menopausal women. Patients and methods. We recruited a total of 161 hypertensive menopausal women (mean age = 52.2±6.6 years) attending the hypertension clinic in our hospital that required HRT to attenuate the effect of menopause symptoms. These women were followed for up to 36 months, being evaluated every 6 months with measurements of their BP, weight and the number of drugs needed to control their BP. We also measured serum cholesterol levels before and after the initiation of HRT. Results. The systolic BP remained unaffected throughout the whole follow‐up period, whereas the diastolic BP was slightly reduced at 6, 24 and 36 months. This decrease was accompanied by an increased need for antihypertensive medication throughout the entire follow‐up period, while the body weight also increased at 18, 24 and 36 months. No particular differences were noted with respect to ethnicity, history of pre‐eclampsia or surgical menopause, before and after the initiation of HRT. Serum cholesterol levels remained unchanged during the evaluation period. Oestrogen–progestogen combination therapy use was associated with a lower diastolic BP and a smaller number of antihypertensive drugs compared to other forms of HRT. Conclusion. HRT use does not have an adverse gross effect on BP in hypertensive menopausal women who need it, although there may be an increased need for antihypertensive therapy during the 36‐month follow‐up period of our study.

Lack of evidence of low ionized calcium levels in systemic hypertension.

An epidemiologic screening survey was conducted in 325 male industrial workers to investigate the relation between serum total and ionized calcium concentrations and blood pressure. No relation was found. Previous reports of lower serum ionized calcium levels in hypertensive patients may be related to methodologic deficiencies both in the selection of subjects and in ionized calcium measurement. These data do not support the concept that increased blood pressure levels are related to calcium deficiency or to abnormal plasma calcium homeostasis.

Serum urate is associated with baseline renal dysfunction but not survival or deterioration in renal function in malignant phase hypertension.

Background There has been speculation whether serum uric acid levels are an independent prognostic factor in patients with hypertension. Objective To investigate the clinical associations and prognostic value of serum urate in patients with malignant phase hypertension (MHT), by comparing clinical features in patients with serum urate levels above and below the median levels for this population, and secondly, by performing a survival analysis in these patients. Patients and methods Review of the data on 153 patients (98 males; mean age 50.3 years, SD 13.5) with MHT on the west Birmingham MHT register. Median uric acid levels in this population was 0.41 mmol/l (6.9 mg/dl), with an interquartile range of 0.34–0.50 mmol/l (5.7–8.4 mg/dl). Clinical characteristics of patients with a serum urate < 0.41mmol/l (group 1) were compared to those with levels above the median (0.41 mmol/l, group 2). Results Mean duration of follow-up was similar in both groups. The mean diastolic blood pressure at presentation and both mean systolic and diastolic blood pressures at follow-up were significantly higher in group 2 (that is, those with high serum urate levels) (unpaired t test, P = 0.039). There was also more renal dysfunction in group 2 patients with MHT, with higher mean serum urea and creatinine levels, both at presentation and at follow-up (unpaired t test, P < 0.01). The commonest causes of death were myocardial infarction (n = 7), heart failure(n = 4), stroke (n = 10) and renal failure (n = 5). There was no difference in mean survival duration between groups 1 and 2 (Kaplan–Meier, 64.6 versus 66.8 months; log-rank test, P = 0.519). Serum urate levels also did not predict the rise in serum creatinine levels (log-rank test, P = 0.84) or urea (P = 0.4033) amongst these patients. Using a multivariate Cox proportional hazards analysis, the only independent predictors of outcomes (death or the need for dialysis) were age (P = 0.007) and serum creatinine levels at presentation (P = 0.0046). Conclusion Our analysis of a large series of patients with MHT shows that those with high urate levels had higher diastolic blood pressures and greater renal impairment at baseline. At follow-up, patients with median serum urate > 0.41mmol/l showed a greater deterioration in renal function and higher blood pressures, but no significant difference in survival. Serum urate levels also do not appear to be predictive of the deterioration in renal function or overall survival in patients with MHT.

Do patients with de novo hypertension differ from patients with previously known hypertension when malignant phase hypertension occurs

Malignant phase hypertension (MHT) represents the most severe form of hypertension, and many consider that this condition only occurs in poorly managed patients with previously known hypertension. To investigate this further, we studied 350 patients with MHT on the West Birmingham MHT database: 195 (55.7%) of these presented de novo, without any known past history of hypertension (Group 1), and 146 (41.7%) were previously known hypertensives (Group 2), of whom 86 were receiving antihypertensive therapy; in 9 patients, the status was uncertain. Median duration of clinical followup was similar in both groups (36.0 v 37.5 months, Mann-Whitney test P = .795). Patients presenting de novo with MHT (Group 1) were younger, with a predominance of whites and men. Nevertheless, the clinical features, blood pressures, and renal function at presentation were similar to MHT patients with previously known hypertension. Renal function at follow-up was also similar in both groups. There was an excess of women and nonwhites in MHT patients with previously known hypertension (Group 2), who also had higher mean follow-up blood pressures. On univariate life-table analysis, there was no statistically significant difference in survival time between Groups 1 and 2 (mean 57.5 v 63.5 months, median 36.0 v 37.0 months; log-rank test, P = .456). Using a multivariate Cox analysis of baseline variables, the independent predictors of outcome (death or dialysis) were age at presentation (P = .0019), diastolic blood pressure (P = .0466), serum urea (P = .006), and serum creatinine (P < .001). Whether the patient had presented de novo, without any known history of hypertension (Group 1) or had previously known hypertension (Group 2) did not independently predict outcome (P = .6549). We suggest that MHT can occur de novo in patients without previously known hypertension, and the clinical characteristics and prognosis in such patients were similar to MHT patients with previously known hypertension.