Comparative antihypertensive effects of hydrochlorothiazide and chlorthalidone on ambulatory and office blood pressure

Low-dose thiazide-type diuretics are recommended as initial therapy for most hypertensive patients. Chlorthalidone has significantly reduced stroke and cardiovascular end points in several landmark trials; however, hydrochlorothiazide remains favored in practice. Most clinicians assume that the drugs are interchangeable, but their antihypertensive effects at lower doses have not been directly compared. We conducted a randomized, single-blinded, 8-week active treatment, crossover study comparing chlorthalidone 12.5 mg/day (force-titrated to 25 mg/day) and hydrochlorothiazide 25 mg/day (force-titrated to 50 mg/day) in untreated hypertensive patients. The main outcome, 24-hour ambulatory blood pressure (BP) monitoring, was assessed at baseline and week 8, along with standard office BP readings every 2 weeks. Thirty patients completed the first active treatment period, whereas 24 patients completed both. An order-drug-time interaction was observed with chlorthalidone; therefore, data from only the first active treatment period was considered. Week 8 ambulatory BPs indicated a greater reduction from baseline in systolic BP with chlorthalidone 25 mg/day compared with hydrochlorothiazide 50 mg/day (24-hour mean = -12.4+/-1.8 mm Hg versus -7.4+/-1.7 mm Hg; P=0.054; nighttime mean = -13.5+/-1.9 mm Hg versus -6.4+/-1.8 mm Hg; P=0.009). Office systolic BP reduction was lower at week 2 for chlorthalidone 12.5 mg/day versus hydrochlorothiazide 25 mg/day (-15.7+/-2.2 mm Hg versus -4.5+/-2.1 mm Hg; P=0.001); however, by week 8, reductions were statistically similar (-17.1+/-3.7 versus -10.8+/-3.5; P=0.84). Within recommended doses, chlorthalidone is more effective in lowering systolic BPs than hydrochlorothiazide, as evidenced by 24-hour ambulatory BPs. These differences were not apparent with office BP measurements.     

Interchangeability of ambulatory and office blood pressure: limitations of reproducibility and agreement

A possible equivalence of office (Off) patient-recorded blood pressure (BP) and ambulatory (Amb) BP was evaluated. The criteria were the between-visits reproducibility (R) of oscillometrically measured supine office (Off), seated Off, and 24-h Amb BP and the agreement between Off and Amb data. Randomly ordered sessions were completed within 4 months in 59 untreated patients with Amb 24-h BP 136/87 (SD 14/10) mmHg and HR 72 (SD 9). R improves as SD of differences between sessions decreases with the number (n) of values included in the average so that SDD = a n(-b), where a and b are constants for each method, data sampling strategy, and group. R of a few steady Off data is better than R of a few Amb data. As n of the averaged values increases, R of Off and Amb methods converges and with n approximately 24 becomes identical. Only further increase in n of Amb data makes R of the Amb method superior than the Off method. The variably elevated initial Off BP distorts R and agreement. After approximately 6 readings, Off BP stabilizes at a lower "steady" level. "Steady" data averaged over visits are close to the Amb 24-h average from two sessions. Supine Off "steady" level is close to supine levels before sleep. The Off versus Amb method agreement improves by averaging "steady" BP from one up to four Off sessions, up to 7 "steady" Off readings over a session, and BP in both arms. At best the SBP agreement is within +/- 7.6 mmHg in 90% of cases with 24-h Amb S/D BP ranging 115-155/75-105 mmHg. The casually elevated BP can be evaluated only by the demonstrated between-visits reproducible 24-h Amb average or by the nearly equivalent average of multiple "steady" data from two to four Off visits.     

Automated office blood pressure is in agreement with awake and mean 24‐hour ambulatory blood pressure at the lower blood pressure range

Automated office blood pressure measurement eliminates the white coat effect and is associated with awake ambulatory blood pressure. This study examined whether automated office blood pressure values at lower limits were comparable to those of awake and mean 24‐hour ambulatory blood pressure. A total of 552 patients were included in the study, involving 293 (53.1%) men and 259 (46.9%) women, with a mean age 55.0 ± 12.5, of whom 36% were treated for hypertension. Both systolic and diastolic automated office blood pressures exhibited lower values compared to awake ambulatory blood pressure among 254 individuals with systolic automated office blood pressure <130 mm Hg (119 ± 8 mm Hg vs 125 ± 11 mm Hg, P < .0001 and 75 ± 9 mm Hg vs 79 ± 9 mm Hg, P < .0001 for systolic and diastolic BPs, respectively). Furthermore, the comparison of systolic automated office blood pressure to the mean 24‐hour ambulatory blood pressure levels also showed lower values (119 ± 8 vs 121 ± 10, P = .007), whereas the diastolic automated office blood pressure measurements were similar to 24‐hour ambulatory blood pressure values. Our findings show that when automated office blood pressure readings express values <130/80 mm Hg in repeated office visits, further investigation should be performed only when masked hypertension is suspected; otherwise, higher automated office blood pressure values could be used for the diagnosis of uncontrolled hypertension, especially in individuals with organ damage.     

Blood pressure response to antihypertensive therapy: ambulatory versus office blood pressure readings

Blood pressure readings obtained by the physician in his office and ambulatory blood pressures recorded with the semi-automatic Remler device, were compared during a controlled antihypertensive drug trial. Either timolol or methyldopa was administered in in double-blind fashion to 30 patients with uncomplicated essential hypertension. All exhibited a diastolic office blood pressure greater than 95 mmHg at the end of a four-week placebo period. All patients then received a combination of hydrochlorothiazide (25 mg/day) and amiloride (2.5 mg/day). After four weeks of diuretic therapy, timolol (10 mg/day, n = 14) or methyldopa (250 mg/day, n = 16) were added randomly for six weeks. The dose of all antihypertensive agents was doubled after two weeks of therapy with diuretics combined with timolol (n = 7) or methyldopa (n = 16) because of the persistence of diastolic blood pressure levels greater than 90 mmHg at the office. When assessed in the office, the antihypertensive effect of timolol and methyldopa was similar. During ambulatory blood pressure monitoring, however, pressure levels were lower in the patients given timolol (P less than 0.05 for the diastolic). With both regimens, the blood pressure response measured outside the clinic during usual daily activities could not be predicted from that observed with office blood pressure readings. Furthermore the magnitude of the drug induced blood pressure decrease was more reproducible in time when determined outside the clinic. These data suggest that ambulatory blood pressure monitoring is more precise in evaluating the efficacy of antihypertensive therapy than office blood pressure measurement.     

Role of ambulatory blood pressure monitoring in hypertensive patients having controlled office blood pressure

Background and objectivesAmbulatory blood pressure (BP) monitoring has become useful in the diagnosis and management of hypertensive individuals. In this study we tried to know the role of office and ambulatory BP in treated hypertensive patients.Methods and patientsProspective cohort of 561 treated hypertensive patients were enrolled in the study. Hypertension definitions were according to JNC 8 classification. Office BP and ambulatory BP monitoring was done according to defined protocol.ResultsFrom a subgroup of 158 treated hypertensive patients, 91(16.2%) patients were having white coat hypertension (p value 0.00 by Pearson chi square test). In a subset of 403 patients who were having controlled BP on the day of enrolment as well as on the day of attaching ambulatory BP monitor; 98 (17.4%) patients were having masked uncontrolled hypertension (MUCH). In addition there was very significant percentage of non-dippers and reverse dippers. In our study we found that office BP has a moderate to low specificity and sensitivity and low negative predictive value for overall control in treated hypertensive patients.ConclusionAmbulatory BP monitoring should be included in the management protocol of treated hypertensive patients, for the optimal BP control.     

Heritability of ambulatory and office blood pressure phenotypes in Swedish families

OBJECTIVE: The aim of this study was to estimate the heritability of 24-h ambulatory blood pressure and office blood pressure phenotypes in Swedish families. METHODS: We measured ambulatory and office blood pressure in 260 siblings without antihypertensive treatment from 118 families. Blood pressure heritability was estimated using standard quantitative genetic variance component analysis implemented in the 'SOLAR' software package after adjustment for significant covariates. RESULTS: Heritability values were significant for night-time systolic (37%), diastolic (32%) and mean (32%) ambulatory blood pressure (P < 0.05 for all). During daytime, systolic ambulatory blood pressure was significantly heritable (33%, P < 0.05). Twenty-four-hour systolic (30%) and diastolic (29%) ambulatory blood pressure also had significant values of heritability (P < 0.05). Pulse pressure ambulatory blood pressure was significantly heritable over 24 h (63%, P < 0.01), during daytime (53%, P < 0.01) and at night (34%, P < 0.05). None of the office blood pressure phenotypes had a significant heritability. CONCLUSIONS: We conclude that ambulatory blood pressure, in particular at night, seems better than office blood pressure to capture the heritable part of blood pressure, suggesting that ambulatory blood pressure may be a more exact estimate of an individual's true blood pressure. Genetic studies using ambulatory blood pressure as the phenotype are likely to be more powerful than those using office blood pressure. The high heritability of pulse pressure ambulatory blood pressure indicates that variation in arterial stiffness in subjects free from antihypertensive medication is strongly affected by genetic factors.     

Prognostic value of office and ambulatory blood pressure measurements in pregnancy

With the objective to assess the prognostic value of office values as compared with ambulatory monitoring in pregnancy, we analyzed 2430 blood pressure series systematically sampled from 403 untreated pregnant women for 48 consecutive hours every 4 weeks from the first visit to the hospital until delivery. Women were divided into 5 groups: "detected" gestational hypertension, women with office blood pressures >140/90 mm Hg after 20 weeks of gestation and hyperbaric index (area of blood pressure excess above the upper limit of a time-specified tolerance interval) consistently above the threshold for diagnosing hypertension in pregnancy; "undetected" gestational hypertension, office values <140/90 mm Hg but hyperbaric index above the threshold for diagnosis; normotension, both office values and hyperbaric index below the thresholds for diagnosis; white coat hypertension, women with recorded diagnosis of gestational hypertension but hyperbaric index consistently below the threshold for diagnosis; and preeclampsia, defined as gestational hypertension and proteinuria. Results indicate small and nonsignificant differences in 24-hour mean of ambulatory pressures between "detected" and "undetected" gestational hypertension at all stages of pregnancy, in contrast with highly significant differences between these two groups and normotensive pregnancies. Average office blood pressure values were similar for preeclampsia, "detected," and "undetected" gestational hypertension. The hyperbaric index was, however, significantly higher for women with preeclampsia after 20 weeks of gestation as compared with all other groups and higher for women with either "detected" or "undetected" gestational hypertension as compared with normotensive pregnant women. The incidence of preterm delivery and intrauterine growth retardation were similar for "detected" and "undetected" gestational hypertension but significantly lower for normotensive women. In pregnancy, the hyperbaric index derived from ambulatory monitoring is markedly superior to office measurements for diagnosis of what should be truly considered gestational hypertension, as well as for prediction of the outcome of pregnancy.     

How good are standardized blood pressure recordings for diagnosing hypertension? A comparison between office and ambulatory blood pressure.

Ambulatory blood pressure monitoring was compared with office blood pressure in 48 normotensive, 81 borderline hypertensives and 35 untreated hypertensives. The studied groups were chosen from a geographically defined population of middle-aged men in southern Sweden. The mean 24-h ambulatory blood pressure values for the normotensives, borderline hypertensives and untreated hypertensives were 120/76, 127/82 and 140/92 mmHg, respectively. The diurnal mean ambulatory blood pressure in the three groups was 126/80, 134/86 and 146/96 mmHg, respectively. The percentage of 24-h diastolic blood pressure peaks greater than or equal to 95 mmHg in the groups were 7%, 22% and 53%, respectively. The corresponding values greater than or equal to 90 mmHg were 16%, 38% and 69%, respectively. In the untreated hypertensive group, there was a more pronounced (P less than 0.05) systolic blood pressure increase during the morning hours (0600-1000 h) than in the normotensive and borderline hypertensive groups. Fourteen per cent of the hypertensives showed normal blood pressure values during 24-h blood pressure monitoring. Fifteen per cent of the borderline hypertensives were normotensive during ambulatory blood pressure monitoring despite repeated office diastolic blood pressure greater than or equal to 90 mmHg. The opposite (increased blood pressure during ambulatory blood pressure monitoring and at screening but normal office blood pressure) was seen in 14% of the borderline hypertensives. Normotensives were characterized by lower mean blood pressure values, fewer blood pressure peaks and a lower systolic blood pressure increase during the morning hours than hypertensives in this study of middle-aged men. The established way of diagnosing hypertension, borderline hypertension and normotension correlated well with the results of ambulatory blood pressure monitoring.     

Patient-specific differences between blood pressure estimated from 24 h ambulatory measurements and serial office self-recordings

The long-term true blood pressure, estimated in terms of the repeatable 24 h ambulatory mean (24 hAmb) pressure, is probably best related to progressive cardiovascular deterioration and is vital for clinical decision-making. Serial self-measurements (SELF) under quiet conditions may reflect this level, but with an annoying uncertainty in individual patients. This uncertainty is characterized by analyzing differences between the SELF readings of seated/supine patients on their own and the reference 24 hAmb values based on 72 recordings. From at-random replicated sessions of 59 subjects, the sources of uncertainty can be separated into three components: a systematic (non-random) variable difference in level from person to person, a mean systematic difference in level between methods, and random variability determining repeatability between sessions. An unstable alerting reaction distorts about six initial self-recordings and increases the random variability. The following 7-12 or 13-24 'steady-state' values show a comparable random variability but reflect the 24 hAmb level only when compared as the average of all patients. The standard deviation for repeatability is about 50-100% higher for SELF than for 24 hAmb. The patient-specific difference between methods contributes more than +/-10 mmHg to the uncertainty interval of the SELF results. These patient-specific differences recur at repeat sessions and thus cannot be reduced by averaging the results of sequential SELF sessions. In contrast, two 24 hAmb results provide a 95% uncertainty interval of +/-5 mm Hg. Thus, the averaged results of multiple SELF sessions can be used to detect major changes in blood pressure but are, as a result of patient-specific differences, too unreliable when the value to be estimated (the true value) is the expected long-term value of 24 hAmb results.     

Comparison between office and ambulatory blood pressure in young and elderly subjects with isolated systolic hypertension

BACKGROUND: It has been claimed that isolated systolic hypertension (ISH) in the elderly is not a sustained condition but a short-lasting increase in office systolic blood pressure magnified by arterial stiffness. DESIGN: Office and ambulatory blood pressures werecompared at baseline and after 3 months of observation of young and elderly subjects with ISH. METHODS: The study was carried out in 39 young (mean age 27.1+/-9.8 years) and 37 elderly patients (mean age 72.5+/-5.7 years). Office blood pressure was defined as the mean of six readings. All subjects underwent two non-invasive 24 h blood pressure monitorings performed 3 months apart and echocardiography (n = 50). RESULTS: The difference between office and mean 24 h systolic/diastolic blood pressure was 27.9/8.2 mmHg in the young and 18.9/6.9 mmHg in the elderly patients (P < 0.01 for systolic blood pressure). Twenty-four-hour (P < 0.001), daytime (P = 0.001) and night-time (P < 0.001) systolic blood pressures were higher in the elderly and the difference between daytime and night-time systolic blood pressure was greater in the young (P < 0.05). Office and ambulatory heart rates were significantly higher in the young subjects. The elderly patients showed a greater left ventricular wall thickness ( P = 0.005 for posterior wall; P < 0.005 for septum), relative wall thickness (P = 0.01) and left ventricular mass index (P = 0.001) and impaired left ventricular filling rate ( P = 0.05), whereas systolic performance and stroke volume were no different in the two groups. Due to the higher heart rate, cardiac output was greater in the young (P = 0.03). CONCLUSION: These data show that larger differences between office and ambulatory systolic blood pressure are not unique to elderly patients with ISH. Increased ambulatory blood pressure levels and a decreased nocturnal blood pressure fall were associated with left ventricular structural and functional abnormalities in the elderly subjects.     

Predictors of controlled ambulatory blood pressure in treated hypertensive patients with uncontrolled office blood pressure.

Although some treated hypertensive patients have controlled 24-h ambulatory blood pressure (ABP) despite their uncontrolled office blood pressure (BP), the factors relating to the control of 24-h ABP remain unknown. We conducted a study to assess 24-h ABP and its association with other cardiovascular risk factors, including echocardiographic left ventricular hypertrophy (LVH), in elderly hypertensive patients (n =41) with uncontrolled office BP (>140/90 mmHg) during long-term medication. Although a majority of the patients had isolated elevation of office systolic BP (SBP), there was no significant relationship between office SBP and 24-h SBP, and about half of the patients had controlled 24-h ABP (125+/-8/69+/-6 mmHg). Patients with controlled 24-h ABP (125+/-8/69+/-6 mmHg) had similar office BP (150+/-6/77+/-5 vs. 150+/-7/79+/-7 mmHg), but lower left ventricular mass index (LVMI) (123+/-34 vs. 156+/-34 g/m(2)) and body mass index (BMI) (24.4+/-2.1 vs. 26.4+/-3.6 kg/m(2)) compared with those with uncontrolled 24-h ABP (149+/-13/78+/-7 mmHg). Multivariate analysis showed that LVMI and BMI were independently associated with controlled 24-h ABP, and the control status of 24-h ABP was highly dependent on the presence of LVH and obesity. Therefore, absence of LVH and obesity may be useful for predicting the level of control of 24-h ABP in treated patients whose office BP is uncontrolled without ABP measurements.     

Reproducibility of blood pressure response to hydrochlorothiazide

Few studies have investigated the reproducibility of responses to antihypertensive therapies. The purpose of this study was to assess the reproducibility of the blood pressure response to a thiazide diuretic, a preferred initial treatment for hypertension. Twenty-two subjects who underwent monotherapy with hydrochlorothiazide as part of a study to identify predictors of blood pressure response agreed to undergo the same protocol a second time, 26.6+/-11.8 (range, 4-52) months after their first participation. The mean systolic and diastolic blood pressure responses to hydrochlorothiazide did not differ significantly between the first and second participation (systolic response, -14.2+/-16.4 mm Hg vs. -16.0+/-16.5 mm Hg; diastolic response, -7.1+/-11.8 mm Hg vs. -6.6+/-8.6 mm Hg), and these responses were significantly correlated between the two trials (systolic response, r=0.61 and p<0.01; diastolic response, r=0.64 and p<0.01). However, both the direction and magnitude of responses for individual subjects varied considerably, with the limits of agreement between the first and second participations (i.e., 2 standard deviations above and below the mean difference between responses) ranging from 27.4 mm Hg to -23.8 mm Hg for systolic blood pressure response and from 17.4 mm Hg to -18.4 mm Hg for diastolic blood pressure response. These results show that the average systolic and diastolic blood pressure responses to hydrochlorothiazide for a group of subjects are reproducible; however, the responses for individual subjects are unpredictable.     

Association of office and ambulatory blood pressure with blood lead in workers before occupational exposure

In view of decreasing lead exposure and guidelines endorsing ambulatory above office blood pressure (BP) measurement, we reassessed association of BP with blood lead (BL) in 236 newly employed men (mean age, 28.6 years) without previous lead exposure not treated for hypertension. Office BP was the mean of five auscultatory readings at one visit. Twenty-four-hour BP was recorded at 15- and 30-minute intervals during wakefulness and sleep. BL was determined by inductively coupled plasma mass spectrometry. Systolic/diastolic office BP averaged 120.0/80.7 mm Hg, and the 24-hour, awake, and asleep BP 125.5/73.6, 129.3/77.9, and 117.6/65.0 mm Hg, respectively. The geometric mean of blood lead was 4.5 μg/dL (interquartile range, 2.60–9.15 μg/dL). In multivariable-adjusted analyses, effect sizes associated with BL doubling were 0.79/0.87 mm Hg (P = .11/.043) for office BP and 0.29/?0.25, 0.60/?0.10, and ?0.40/?0.43 mm Hg for 24-hour, awake, and asleep BP (P ≥ .33). Neither office nor 24-hour ambulatory hypertension was related to BL (P ≥ .14). A clinically relevant white coat effect (WCE; office minus awake BP, ≥20/≥10 mm Hg) was attributable to exceeding the systolic or diastolic threshold in 1 and 45 workers, respectively. With BL doubling, the systolic/diastolic WCE increased by 0.20/0.97 mm Hg (P = .57/.046). Accounting for the presence of a diastolic WCE, reduced the association size of office diastolic BP with BL to 0.39 mm Hg (95% confidence interval, ?0.20 to 1.33; P = .15). In conclusion, a cross-sectional analysis of newly hired workers before lead exposure identified the WCE as confounder of the association between office BP and BL and did not reveal any association between ambulatory BP and BL.     

Benazepril versus felodipine as supplement to bendroflumethiazide: evaluation by office and ambulatory blood pressure

OBJECTIVE: To compare a combination of a thiazide diuretic and an angiotensin converting enzyme inhibitor with a thiazide diuretic and a calcium antagonist. DESIGN: A double-blind randomized trial with subjects in two parallel groups administered either 10-20 mg benazepril once daily or 5-10 mg extended-release felodipine once daily, both titrated according to diastolic office blood pressure. During run-in and all 12 weeks of the study members of both groups were administered 2.5 mg bendroflumethiazide once daily. We measured 24 h ambulatory blood pressure with thiazide alone and after 12 weeks of combination therapy. SETTING: General practices. PATIENTS: We studied 96 hypertensive patients (50 women and 46 men), aged 25-75 years, whose blood pressures were insufficiently regulated (i.e. office diastolic blood pressure >/= 95 mmHg) despite treatment with a thiazide diuretic for at least 3 months. RESULTS: The responses of office blood pressure after 12 weeks of treatment did not differ between the groups and neither did the proportions of responders. The ambulatory recordings revealed, after 12 weeks of treatment, a fall in daytime blood pressure of 16.3/10.3 mmHg in members of the benazepril group compared with a fall of 8.5/5.2 mmHg in members of the felodipine group (P < 0.001/<0.001). Analysis of variance showed that the systolic but not the diastolic office blood pressure in members of the benazepril group was significantly lower during the 12-week study period. When evaluating rising single quote, left (low)white-coat-positive' patients separately, there was a tendency for there to be a more pronounced reduction of their (normal) blood pressure with benazepril therapy. There was a significant reduction in weight of patients in the benazepril group (by 0.9 kg), but not of patients in the felodipine group. We observed no difference in side effects between the two treatment groups.CONCLUSION: Add-on therapies both with benazepril and with felodipine are effective and both drug regimens are well tolerated, but ambulatory blood pressure monitoring yielded differing results.     

Determination of ambulatory blood pressure control in treated patients with controlled office blood pressures

Office blood pressure measurement is the standard for assessing blood pressure control. Many patients, however, take their antihypertensive medication in the morning, so they are likely to have their office blood pressure measured during the maximal antihypertensive effect. It is therefore unknown whether patients deemed by office blood pressure to be controlled do in fact have 24h blood pressure control. The objectives of this study were to determine blood pressure control, including blood pressure control while the patients were awake and during the first 6 hours after awakening, by ambulatory blood pressure monitoring (ABPM) in treated hypertensive patients deemed by office blood pressure measurements to be controlled. A total of 103 patients on a stable antihypertensive regimen and deemed to be controlled in terms of office blood pressure values (mean office blood pressure <140/90mmHg) were enrolled. Patients were stratified by cardiovascular risk status and the number of antihypertensive medications that they were taking. Seventy-eight out of 103 participants successfully completed ABPM. The mean ambulatory blood pressure was greater than 135/85mmHg and 140/90mmHg while awake for 37% (95% confidence interval [CI] 26-48%) and 23% (95% CI 14-32%) of all patients respectively. Forty-eight per cent (95% CI 33-63%) of patients taking monotherapy versus 25% (95% CI 11-39%) of patients on multiple antihypertensive medications were uncontrolled (P=0.039) using 135/85mmHg as the reference value. Thirty-one per cent (95% CI, 17-44%) of patients on monotherapy versus 14% (95% CI 3-25%) of patients on multiple antihypertensive medication were uncontrolled (P=0.064) using 140/90mmHg instead. These results demonstrate that a high number of patients deemed by office blood pressure to be under control do not have adequate blood pressure control based on ABPM.