Is resistant hypertension really resistant?

BACKGROUND: Managing resistant hypertension is difficult and mostly involves expensive testing seeking an underlying secondary cause. This study was undertaken to determine 1) the extent of the white-coat phenomenon in patients with resistant hypertension, and 2) whether 24-h ambulatory blood pressure (BP) monitoring (ABPM) or having BP recorded by a nurse instead of the referring doctor could clarify how many apparently resistant hypertensives actually have controlled BP. METHODS: This study involved 611 patients with BP > or = 140/90 mm Hg who were referred for 24-h ABPM by their specialist or general practitioner, including 277 patients who were taking no antihypertensives (group 1), 216 taking one or two antihypertensive drugs (group 2), and 118 taking at least three antihypertensives in combination (group 3). Each had BP recorded by one of two nurses before 24-h ABPM. Controlled BP was defined as awake ambulatory BP <135/85 mm Hg and the white-coat effect was the difference between the BP recorded by the referring doctor or nurse and the average awake ambulatory BP. RESULTS: Those with resistant hypertension (group 3) were older (61 years (12) v group 1: 46 years (14) and group 2: 56 (14) years; P < .001), but were of similar weight, height, and arm circumference to the other groups. Referral systolic, but not diastolic BP was higher in resistant hypertensives (mean 171/95 v 154/95 mm Hg and 164/94 mm Hg, respectively, P < .001 for systolic BP only). Twenty-eight percent of resistant hypertensives and 32% of those taking no antihypertensive drugs had normal awake ambulatory BP and the white-coat effect attributable to the referring doctor was always greater than that due to the nurse (range 16 to 26/12 to 14 mm Hg v 9 to 17/4 mm Hg, P < .001). Nurse recorded BP was highly sensitive (97%) in identifying awake hypertension but lacked specificity (57%) to replace ABPM. CONCLUSION: Our results show that approximately one in four patients with apparent resistant hypertension referred for ABPM have controlled BP and one-third of patients referred for initial evaluation of office or clinic hypertension have normal BP using ABPM, ie, white-coat hypertension. Twenty-four-hour ABPM appears an appropriate initial step before further investigating or treating patients with apparently resistant hypertension.

Does gestational hypertension become pre-eclampsia?

OBJECTIVE: To determine the likelihood of progression from gestational hypertension (GH) to pre-eclampsia (PE) in hypertensive pregnant women and whether this change can be identified in advance by available clinical and laboratory measures. DESIGN: A retrospective analysis and a prospective study. SETTING: St George Hospital, Sydney, a teaching hospital of the University of New South Wales delivering 2500 women per year. POPULATION: Eight hundred and forty-five women with new hypertension in the second half of pregnancy, managed by a uniform protocol (661 in the retrospective analysis, 184 in the prospective study). METHODS: Clinical and laboratory data at initial presentation were compared among women with GH who developed PE and those who remained with a diagnosis of GH until delivery. Data predictive for progression from GH to PE were analysed by logistic regression analysis. MAIN OUTCOME MEASURED: Progression from GH to PE. RESULTS: In the retrospective analysis, 416 women initially presented as having GH and 62 (15%) progressed to PE. In the prospective study, 112 women initially presented with GH and 29 (26%) progressed to PE, giving an overall progression of 17%. In both studies, women who developed PE from GH presented earlier than those who remained with GH until delivery. In multiple logistic regression analyses prior miscarriage and early gestation at presentation were associated with increased likelihood of progressing from GH to PE. CONCLUSION: Approximately 15-25% of women initially diagnosed with GH will develop PE and this is more likely with earlier presentation or if the woman has had a prior miscarriage. Women with gestational hypertension diagnosed after 36 weeks of gestation have only about 10% risk of developing PE. These data should help stratify the risks of mildly hypertensive pregnant women being managed as outpatients in their third trimester.

Accuracy of automated blood pressure recorders in pregnancy.

Automated blood pressure recorders are used with increasing frequency by pregnant women, mostly without proper evaluation of their accuracy. We compared blood pressures (BP) recorded by 2 automated noninvasive devices, the Spacelabs 90207 ambulatory blood pressure monitor and the OMRON HEM 705 CP portable self-initiated device, with blood pressures recorded by routine sphygmomanometry in 79 pregnant women either considered 'at risk' for preeclampsia or with mild hypertension in pregnancy. The Spacelabs device tended to overestimate systolic BP by a mean 11 (SD=8) mmHg and diastolic BP by 5 (SD=7) mmHg for phase 5 pressure (p<0.001) but was similar to routine BPs for diastolic phase 4 pressures. The OMRON device tended to underestimate diastolic (phase 4) pressure by 4 (SD=6) mmHg (p<0.001) but gave similar systolic and diastolic (phase 5) pressures to routine sphygmomanometry. However, for both devices there was considerable individual patient variability in accuracy. When using these devices to record a limited number of blood pressure recordings, as in this study, we suggest that individual comparison with mercury sphygmomanometry be made in each pregnant woman before accepting the validity of these recordings.

Randomised trial of management of hypertensive pregnancies by Korotkoff phase IV or phase V.

BACKGROUND: There is debate about whether diastolic blood pressure should be recorded as the fourth (muffling, K4) or fifth (disappearance, K5) Korotkoff sound in pregnancy. We compared maternal and fetal outcomes and the likelihood that episodes of severe hypertension would be recorded when hypertensive pregnancies were managed according to either K4 or K5. METHODS: 220 pregnant women with diastolic hypertension (K4 > or =90 mm Hg) after the 20th week of gestation were enrolled in a prospective randomised study at two obstetric units in Australia; they were randomly assigned management with K4 (n=103) or K5 (n=117) for the remainder of the pregnancy. Clinical management was according to a uniform department protocol. Analysis was by intention to treat. All the women completed the trial. FINDINGS: An episode of severe hypertension (systolic > or =170 mm Hg, diastolic > or =110 mm Hg, or both) was more likely to be recorded with use of K4 than with use of K5 (39 [38%] vs 30 [26%] women, p=0.051), mainly because of a greater likelihood that severe diastolic hypertension would be recorded (34 [33%] vs 20 [17%], p=0.006). The frequency of severe systolic hypertension and simultaneous severe systolic and diastolic hypertension did not differ between groups. Pregnancy was prolonged by an average of 2 weeks in both groups, and there were no significant differences between the groups in laboratory data, requirements for antihypertensive treatment, birthweight, fetal growth retardation, or perinatal mortality. There was no eclampsia or significant maternal morbidity in either group. INTERPRETATION: A change from use of K4 to K5 would mean that one fewer case of severe diastolic hypertension would be recorded for every six hypertensive pregnancies, but all other episodes of severe hypertension would be recorded with similar frequency. Since the K4/K5 difference is smaller in hypertensive than in normotensive pregnant women and since K5 is closer to the actual intra-arterial pressure and more reliably detected, universal adoption of K5 to record diastolic blood pressure in hypertensive pregnancy should be considered.

Ambulatory blood pressure monitoring in pregnancy: what is normal?

OBJECTIVE: Noninvasive 24-hour ambulatory blood pressure monitoring holds great promise as a useful tool in the management of hypertensive pregnancies and pregnancies considered "at risk" for development of preeclampsia. The purpose of this study was to define ambulatory blood pressure monitoring parameters throughout normal pregnancy, including women considered at risk for development of hypertension who continued to have a completely normal pregnancy. STUDY DESIGN: Two hundred seventy-six 24-hour ambulatory blood pressure monitoring studies were made cross-sectionally with use of a Spacelabs 90207 device (validated for use in pregnancy), at one or more of 9 to 17, 18 to 22, 26 to 30, and >30 weeks' gestation. Upper limits of normal were defined as the mean plus 2 SDs for awake and sleep ambulatory blood pressure monitoring results at each stage. RESULTS: Average awake upper limits of normal were 130/77, 132/79, 133/81, and 135/86 mm Hg at the four stages of pregnancy, respectively. Systolic blood pressure fell significantly by 12% to 14% (p < 0.0001) and diastolic blood pressure by 18% to 19% (p < 0.0001) during sleep at all stages of pregnancy. Awake ambulatory blood pressure monitoring systolic measurements were 11 to 12 mm Hg higher than "clinic" measurements (p < 0.001) and diastolic measurements were 5 to 11 mm Hg higher (p < 0.0001) throughout pregnancy. Maximum blood pressure variability ranged from 8 to 13 mm Hg. CONCLUSIONS: The upper limits of normal ambulatory blood pressure monitoring-derived measurements rise slightly as pregnancy progresses. Awake measurements are higher than "clinic" measurements recorded under relaxed conditions by a clinical researcher. The diurnal blood pressure fall and variabilities are similar during pregnancy to those seen in nonpregnant subjects. These data should provide valuable references for further studies of ambulatory blood pressure monitoring in high risk pregnancies.

Ambulatory blood pressure monitoring (ABPM) in the normal menstrual cycle and in women using oral contraceptives. Comparison with conventional blood pressure measurement.

This study was undertaken to determine if blood pressures (BP) assessed by routine sphygmomanometry and 24 h ambulatory monitoring (ABPM) alter throughout the normal menstrual cycle or in the cycle of women using oral contraceptive pills (OCP), and the interrelationships between urinary sodium (Na) and potassium (K) excretion and ABPM throughout the menstrual cycle. Eleven women with a normal ovulatory cycle (ovulatory) and ten age-matched women taking an oral contraceptive pill (OCP) were studied three times in random order during their menstrual cycle, within days 1 to 5, 13 to 16, and 25 to 28. Twenty-four hour urine Na, K, and creatinine (Cr) excretion and serum Na, K, Cr, cortisol, estradiol, progesterone and plasma renin, angiotensinogen, and aldosterone concentrations were measured. BP was measured by a mercury sphygmomanometer and by 24 h BP (Accutracker II). On days 1 to 5, daytime systolic BP was higher in OCP [mean: 123 mm Hg, 95% confidence interval: 117, 128] than ovulatory women [114 mm Hg (109, 118); P = .011] though daytime diastolic BPs were similar [OCP: 71 (68, 75), ovulatory: 69 (66, 72)]. This difference in daytime systolic BP between groups was also apparent at both of the other stages of the menstrual cycle. Nighttime systolic BPs were significantly higher in OCP users on days 13 to 16 (P < .05) and days 25 to 28 (P < .01). In women taking OCPs, daytime ABPM for days 1 to 5 were higher than their office readings by 15 (7,23)/11 (7,15) mm Hg (P = .001), whereas office and ABPM readings were similar in ovulatory women. This pattern was evident at all three stages. There was no significant change in BP throughout the menstrual cycle within either group, and no correlation between urine Na or K and BP. Systolic BPs are higher throughout the menstrual cycle in women who take OCPs than in ovulatory women but this difference is only detected when ambulatory blood pressure is assessed. Blood pressure does not change subsequently in either ovulatory or OCP-taking women throughout the menstrual cycle.

Hypertension in pregnancy: maternal and fetal outcomes according to laboratory and clinical features.

OBJECTIVES: To determine the predictive value of clinical and laboratory parameters for maternal and fetal complications in pregnant women with hypertension. DESIGN: Prospective data collection. SETTING: Two primary referral hospitals in the southern suburbs of Sydney between March 1987 and July 1994. SUBJECTS: 1183 pregnant women with hypertension managed conjointly by a physician and obstetrician. INTERVENTION: Uniform management protocol, plus antihypertensive medications if systolic blood pressure was persistently > or = 160 mmHg and/or diastolic blood pressure > or = 90 mmHg. MAIN OUTCOME MEASURES: Maternal and fetal complications, as defined by the Australasian Society for the Study of Hypertension in Pregnancy Consensus Statement. RESULTS: Of 825 women with pre-eclampsia (502 mild; 323 severe), univariate analysis showed that hyperuricaemia, proteinuria and severe hypertension were significantly associated with a higher rate of maternal and fetal complications. In multivariate analyses without confounders, only primiparity, low serum albumin levels and absence of diabetes were significantly associated with severe pre-eclampsia. Severe pre-eclampsia, high haemoglobin levels and low platelet count were associated with higher rates of small-for-gestational-age babies, but only low serum albumin levels were associated with increased perinatal mortality rates. Low birthweight was associated with severe hypertension and severe pre-eclampsia. CONCLUSIONS: Simple clinical and laboratory parameters are useful predictors for maternal and fetal outcomes in pregnancies complicated by hypertension.

Inadequacy of dipstick proteinuria in hypertensive pregnancy.

The objective of this study was to determine the accuracy of ward urinalysis and the sensitivity of dipstick testing in the assessment of proteinuria in hypertensive pregnant women. Subjects were 230 consecutive hypertensive pregnant women who were admitted to hospital over a 2-year period. Routine ward urinalyses for protein, obtained on a mid-stream sample before and after a 24-hour urine collection for quantitating proteinuria, were compared with the 24-hour urine protein excretion. As a control for dipstick accuracy, urinalysis was also performed on a mixed aliquot of each of the 24-hour samples by a single observer experienced in urinalysis. True proteinuria was considered as > 300 mg/day. The positive predictive value for urinalysis ranged from 38% (for the precollection test) to 60% (for tests on the aliquot). Negative predictive values were 86-88%. The false negative rates at 'nil' or 'trace' proteinuria ranged from 8-18%. The false positive rates at '3+' (3 g/L) or '4+' (> or = 20 g/L) ranged from 0-17%, at '2+' (1 g/L) from 18-50% and at '1+' (0.3 g/L) from 67-83%. Best results for urinalysis were obtained on the aliquot testing but even under these ideal circumstances there was a high false positive rate (67%) at '1+' (0.3 g/L) urinalysis level. These studies show that in routine clinical practice 'nil' or 'trace' proteinuria will miss significant proteinuria in approximately 1 out of 8 hypertensive pregnant women while '3+' (3 g/L) or '4+' ( > or = 20 g/L) will rarely be a false positive. At urinalysis of '1+' or '2+' a 24-hour urine collection is required to be certain about the presence or absence of proteinuria. Research studies should demand 24-hour urine protein quantitation and not rely solely upon urinalysis results.

Ambulatory blood pressure in pregnancy: comparison of the Spacelabs 90207 and Accutracker II monitors with intraarterial recordings.

OBJECTIVE: Our purpose was to compare systolic and diastolic blood pressures obtained with the Spacelabs 90207 (Spacelabs Medical Products, Dee Why, Australia) or Accutracker II (Suntech Medical Instruments, Melbourne, Australia) ambulatory blood pressure monitoring devices with intraarterial blood pressures in pregnant women. STUDY DESIGN: Direct (intraarterial) and resting blood pressures with the ambulatory blood pressure monitoring device were compared in 39 pregnant women (14 Accutracker II and 25 Spacelabs 90207). RESULTS: The Accutracker II device underestimated direct systolic pressure by -9 (-13, -3) mm Hg (median, interquartile range) (p = 0.028) but gave similar diastolic pressure. The Spacelabs 90207 device gave similar systolic pressures but overestimated direct diastolic pressure by 7 (2, 12) mm Hg (p < 0.001). Variability for systolic and diastolic blood pressures within subjects was similar with the two devices. Both received poor gradings by standards of the British Hypertension Society and did not meet criteria of the Association for the Advancement of Medical Instrumentation, with intraarterial recordings used as the reference. CONCLUSIONS: The Accutracker II device significantly underestimated resting direct systolic pressure, whereas the Spacelabs 90207 device significantly overestimated resting direct diastolic pressure in pregnant women. Although poor gradings were achieved for both devices when intraarterial pressures were used as the reference, this is similar to comparisons of routine mercury sphygmomanometry with intraarterial recordings and does not mean these devices are unsuitable for use in pregnancy.

Measuring blood pressure in pregnant women: a comparison of direct and indirect methods.

OBJECTIVES: Our goals were to determine (1) whether Korotkoff phase IV or V sound was a more accurate measure of diastolic blood pressure in pregnancy and (2) interobserver variability of mercury sphygmomanometry of pregnant women. STUDY DESIGN: Direct (intraarterial) and indirect (mercury sphygmomanometry) blood pressures were compared in 28 pregnant women. Interobserver variability was assessed in a separate study of 86 pregnant women using four highly trained observers. RESULTS: (1) Routine sphygmomanometry underestimated direct systolic pressure by 11 (3, 18) mm Hg, p < 0.001 (median, interquartile range of differences). Phase IV Korotkoff sound overestimated direct diastolic pressure by 9 (2, 12) mm Hg (p < 0.001) and phase V by 4 (2, 7) mm Hg (p = 0.04). Phase V-recorded diastolic pressure was closer to direct diastolic pressure significantly more often (75%) than was phase IV-recorded diastolic pressure (21%) (p = 0.003). Mean arterial pressures did not differ significantly according to the method used. (2) Median blood pressures did not differ among the four observers for systolic, diastolic phase IV, or phase V recordings. Maximum difference for blood pressure recording among observers was 4 (2, 6) mm Hg. CONCLUSIONS: Auscultatory sphygmomanometry in pregnant women underestimates systolic and overestimates diastolic blood pressure, but the phase V Korotkoff sound is more likely to represent the true diastolic pressure than is the phase IV sound.

Endothelin excretion in hypertensive pregnancy. Relationship to glomerular filtration rate, blood pressure, and sodium excretion.

The objective of this study was to determine whether urinary endothelin (ET) excretion is altered in pregnant women with preeclampsia or essential hypertension compared with normal pregnant and nonpregnant women, and whether urinary ET excretion is significantly related to glomerular filtration rate (GFR), blood pressure, or sodium excretion in hypertensive pregnant women. Subjects included 85 hypertensive women in their third trimester (32 with severe preeclampsia, 37 with mild preeclampsia [some of whom may be classified as having "transient (gestational) hypertension" by other classifications], and 16 with essential hypertension), 42 normal third-trimester pregnant women, and 26 normal nonpregnant women. Twenty-four-hour urine ET and creatinine excretion were measured in all women. ET was extracted from urine and measured by radioimmunoassay. Plasma creatinine, serum uric acid and albumin concentrations, and urine protein and sodium excretion were also measured. Twenty-four-hour ET excretion was significantly higher (P < .01) in normal pregnant women (14.7 [9.1 to 20.1] pmol/day; median [interquartile range]) than in nonpregnant women (8.4 [6.4 to 15.2] pmol/day) and was reduced significantly (P < .01) in hypertensive pregnant women (severe preeclampsia: 9.0 [5.5 to 12.4] pmol/day; mild preeclampsia: 7.2 [5.7 to 9.9] pmol/day; essential hypertension: 7.5 [6.4 to 9.4] pmol/day) compared to values for normal pregnant women. Twenty-four-hour urine ET excretion in hypertensive pregnant women was correlated positively but weakly with both creatinine clearance (r = 0.31, P < .01) and urine sodium excretion (r = 0.34, P < .01). Urinary ET excretion is increased in normal pregnancy and reduced from these values in pregnancies complicated with preeclampsia or essential hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumin excretory rate in normal and hypertensive pregnancy.

1. The purpose of this study was to determine whether the 24 h urinary albumin excretory rate was increased in the third trimester of normal pregnancy or in pregnant women with hypertension who had 24 h urinary total protein excretion within the normal range. 2. Twenty-four hour urinary creatinine and albumin excretions were determined prospectively in 26 non-pregnant and 115 pregnant women in their third trimester (40 in normal pregnancy, 38 with mild pre-eclampsia, 20 with severe pre-eclampsia, 17 with essential hypertension) in whom urinary total protein excretion was normal. Both the urinary albumin excretion rate and the urinary albumin/creatinine ratio were compared among the groups. The clearance of albumin relative to that of creatinine was also calculated in the hypertensive women and in 14 of the non-pregnant women and nine of the normal pregnant women. 3. The twenty-four hour urinary albumin excretion rate was similar in non-pregnant [8(5-10) mg/day; median (interquartile range)] and normal pregnant [7(6-10) mg/day] women. Women with essential hypertension [6(4-16) mg/day] and mild pre-eclampsia [7(4-10) mg/day] had a urinary albumin excretion rate similar to that of normal pregnant women. Women with severe pre-eclampsia had an urinary albumin excretion rate increased [13(7-32) mg/day] compared with other groups (P < 0.05). The clearance of albumin relative to that of creatinine was elevated significantly only in women with severe pre-eclampsia compared with normal pregnant women (0.00054 versus 0.00012; P < 0.05). Blood pressures were similar among all hypertensive groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulatory blood pressure monitoring during pregnancy. Comparison with mercury sphygmomanometry.

There is little information concerning the relationship between blood pressures obtained by standard mercury sphygmomanometry and ambulatory blood pressure monitoring (ABPM) in pregnancy. We compared readings obtained with these two methods using an Hawksley random zero mercury sphygmomanometer and an Accutracker II ABPM device. Blood pressures were compared over 90 min with the pregnant woman seated and, in a separate study, over 30 min during standing and ambulation. When pregnant women were seated, the ABPM overestimated the systolic blood pressure (BP) by 5 (3,6) mm Hg (mean, 95% confidence limits) (P < .001) and underestimated diastolic phase IV readings by 7 (-9, -6) mm Hg (P < .001) and phase V readings by 3 (-5, -1) mm Hg (P < .01). Eighty-three percent of systolic readings agreed within 10 mm Hg. Seventy-six percent of diastolic phase V (but only 45% of phase IV) readings agreed within 6 mm Hg. When pregnant women were ambulatory, the ABPM overestimated systolic BP by 7 (4,10) mm Hg (P < .001) and underestimated diastolic phase IV readings by 6 (-8, -4) mm Hg (P < .001) and phase V readings by 4 (-6, -2) mm Hg (P < .01). Eighty percent of systolic readings agreed within 10 mm Hg. Fifty-five percent of diastolic phase V and 50% of diastolic phase IV readings agreed within 6 mm Hg. The Accutracker II blood pressure readings are reasonably comparable to those of mercury sphygmomanometry in pregnant women, particularly when assessing group data.(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement of blood pressure during pregnancy: evaluation of the 'TriCUFF'.

Previous surveys have revealed that a major source of error in measuring blood pressure in pregnant women is failure to use a large cuff when necessary. We have tested the hypothesis that this problem could be overcome by using a single cuff containing automatically selected inflation bladders of appropriate size, the TriCUFF. We compared readings obtained with the TriCUFF with those obtained using standard adult or large (obese) cuffs in 51 pregnant women. Thirty nine had normal upper arm circumferences (< 34 cm) and 12 increased arm circumferences (> or = 34 cm). The TriCUFF overestimated standard cuff systolic and diastolic (phase IV) readings by 2 (0-4) mmHg (mean, 95% confidence limits) (p < 0.05). There was no difference between readings for women with large arms. Agreement between readings by both methods was acceptable for clinical practice in most cases. Use of the TriCUFF could significantly improve the accuracy of blood pressure recording in pregnant women.