White coat hypertension is a cardiovascular risk factor: a 10-year follow-up study.

The objective of this paper was to evaluate the cardiovascular risk in white coat hypertension (WCH). WCH is a well-known clinical entity defined by persistently elevated blood pressure (BP) in the doctor's office, whereas BP in other conditions is normal. The prognosis of WCH is unsettled, although two prospective studies that include normal control groups imply that the condition is benign. This study is a 10-year follow-up study on 420 patients with grade I-II hypertension newly diagnosed by their general practitioner and 146 normal controls (NTs). Ambulatory blood pressure (ABP) monitoring was performed at baseline. With our protocollated cutoff value of daytime-ABP <135/90 mmHg, 76 (18.1%) of the 420 hypertensives were white coat hypertensives (WCHs) and 344 were established hypertensives (EHs). With a lower cutoff of 135/85 mmHg, 40 (9.5%) were WCHs. Complete follow-up data were obtained for all 566 subjects. The mean duration of follow-up was 10.2 years (range 9.0-12.5). In the WCH group, 14 first events were recorded (18.4%) consisting of two cardiovascular deaths and 12 nonfatal cardiovascular events. In the EH group, the corresponding number of events were 56 first events (16.3%), 12 cardiovascular deaths and 44 nonfatal cardiovascular events, and in the NT group 10 first events (6.8%), two cardiovascular deaths and eight nonfatal cardiovascular events. The event rate was similar in the WCH group and the EH group and significantly lower in the NT group (P<0.05). When corrected for daytime-ABP, age and other confounders, the difference remained statistically significant. When using the lower cutoff of 135/85 mmHg, WCH was still associated with a significantly higher cardiovascular event rate. In conclusion, the main finding of this 10-year follow-up study is an increased cardiovascular risk in WCH compared to normotensive controls.

No impact of blood pressure variability on microalbuminuria and left ventricular geometry: analysis of daytime variation, diurnal variation and 'white coat' effect.

OBJECTIVE: To investigate the influence of blood pressure variability on target organ involvement. METHODS: Using a cross-sectional study of a hypertension clinic at a district general hospital, 420 patients with newly diagnosed untreated essential hypertension referred on a consecutive basis from general practice and 146 normal subjects drawn at random from the Danish National Register underwent a variety of measurements which included: echocardiography with determination of left ventricular mass index and relative wall thickness and early morning urine albumin/creatinine ratio. Mean, standard deviation and coefficient of variation of automated clinic values; daytime, night-time and full 24-h period were extracted from 24-h ambulatory blood pressure (ABP) monitoring. 'White coat' effect and dip were calculated. Hypertensives were classified into subjects with high or low variability, into 'white coat' hypertensives or established hypertensives and into dippers or non-dippers. RESULTS: Standard deviation of daytime blood pressure (BP) was positively associated with target organ damage and BP level, which was not the case when variability was expressed as a coefficient of variation. Patients with high variability exhibited no more significant target organ damage than patients with low variability, but patients with established hypertension had significantly more target organ damage than the 'white coat' hypertensives. The 'white coat' effect as such was not associated with increased target organ involvement. Non-dippers had significantly more cardiac target organ damage than dippers, but the difference disappeared after correction for different 24-h BP level. CONCLUSION: BP variability data obtained by non-invasive ABP monitoring does not seem to improve the information inherent in the BP level.

White coat hypertension and blood pressure variability.

The objective of this cross-sectional study was to investigate blood pressure variability and pulse pressure in white coat hypertensives in comparison to established hypertensives and normal subjects. Four hundred and twenty patients were referred consecutively from general practice with newly diagnosed untreated essential hypertension. One hundred and forty-six control subjects were drawn at random from the Danish national register. Seventy-six patients from the former group were considered white coat hypertensive using a normalcy cutoff level of 135/90 mm Hg. Mean, standard deviation, and coefficient of variation of the blood pressures from the automated clinic readings, daytime, nighttime, and full 24-h periods were extracted from 24-h ambulatory blood pressure monitorings. Mean arterial pressure, pulse pressure, white coat effect, and dip were calculated in all three groups of subjects. The main findings were that white coat hypertensives did not differ significantly from normotensives regarding variability data except for the white coat effect. However, the white coat hypertensives had a significantly lower pulse pressure than the established hypertensives, according to clinic blood pressure and ambulatory readings. We conclude that white coat hypertension evaluated with indirect ambulatory blood pressure monitoring is not a state with a generally higher blood pressure variability than normotension or established hypertension. The patients with white coat hypertension have pulse pressure at the same level as normal controls, but significantly lower than established hypertensives.

White coat hypertension and target organ involvement: the impact of different cut-off levels on albuminuria and left ventricular mass and geometry.

The aim of this cross-sectional study which took place in a hypertension clinic at a district general hospital in Denmark was to make a pragmatic definition of white coat hypertension. A total of 420 patients were referred consecutively from general practice with newly diagnosed untreated essential hypertension and 146 normal subjects were drawn at random from the Danish national register. The following measurements were taken: office blood pressure; 24-h ambulatory blood pressure (BP) monitoring; echocardiography with determination of left ventricular mass index and relative wall thickness; and early morning urine albumin/creatinine ratios. Four different cut-off levels were studied. An ambulatory daytime BP of 135.6/90.4 mm Hg was found to correspond to an office BP of 140/90 mm Hg in normal controls; used as a cut-off level in patients with newly diagnosed hypertension it separated 19% as white coat hypertensives. The end-organ involvement of these white coat hypertensives differed significantly from those with established hypertension but not from the normal controls. Lower cut-off levels were less efficient in this respect, as was the case when the systolic BP was not taken into account. In conclusion a pragmatic definition of white coat hypertension should--apart from well-established hypertensive office measurements--include a cut-off level close to 135/90 mm Hg ambulatory daytime BP.

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.

Smoking related to 24-h ambulatory blood pressure and heart rate: a study in 352 normotensive Danish subjects.

This study shows the association between smoking and both office and ambulatory blood pressure. By means of stratification, a uniform number of subjects of both sexes and spanning 6 decades (aged 20 to 79 years) were recruited randomly from the local community register. A total of 352 subjects participated, including 161 smokers. Smokers (both sexes and all age groups summed), as compared with nonsmokers had statistically significant lower office blood pressure as follows (mean systolic +/- SED/mean diastolic +/- SED): (systolic and diastolic, -6.8 +/- 2.1/-3.9 +/- 1.3); day ambulatory blood pressure (diastolic, /-2.8 +/- 1.0); and night ambulatory blood pressure (systolic and diastolic, -4.2 +/- 1.8/-3.9 +/- 1.1). The intraperson variability of the day ambulatory blood pressure (as measured every 15 min) was identical for the smokers and the nonsmokers. Smokers were found to have a diminished "white coat" effect; this diminished white coat effect has not previously been described. The major white coat effect was seen in the older nonsmokers, whereas the diminished white coat effect was most pronounced in the older male smokers and in the younger female smokers. Smokers seem to have a diminished white coat effect, as well as a lower ambulatory blood pressure throughout the day (diastolic) and at night (systolic and diastolic). The similar intraperson variability found in the smokers' and nonsmokers' blood pressure further speaks for a consistently lower blood pressure in smokers as compared with nonsmokers.

[Round-the-clock blood pressure measurements in 352 persons--a reference material]. / 24 timers ambulant blodtryk hos 352 personer--et referencemateriale.

The aim of this study was to establish reference values for 24-hour ambulatory blood pressure in a Danish population stratified for gender and age in the decades from 20 to 79 years of age. A sample of 352 persons, 179 men and 173 women randomly selected from the local community register, age 20-79 years underwent 24-h ambulatory blood pressure monitoring. For men age < 50 daytime ambulatory blood pressure (median) was 125/79 mmHg and night time was 106/65 mmHg, for women the respective pressures were 113/77 mmHg and 97/64 mmHg. For men age > or = 50 daytime ambulatory blood pressure was 133/83 mmHg and night time was 124/86 mmHg, for women the respective pressures were 122/83 mmHg and 105/65 mmHg. Presently, we can only relate cardiovascular risk to clinic blood pressure. Therefore we have calculated corresponding ambulatory blood pressure values to WHO's upper limit 160/90 mmHg for normal blood pressure in the clinic and found 154/87 mmHg for daytime and 134/74 mmHg at night. For a clinic pressure of 95 mmHg the corresponding daytime value was 91 mmHg, for 100 mmHg it was 95 mmHg.

The effect of antihypertensive treatment with dihydropyridine calcium antagonists on white-coat hypertension.

OBJECTIVE: To investigate the interrelations between blood pressure variables and treatment effects in white-coat and established hypertensive patients. DESIGN: A substudy on data from a randomized clinical trial on two dihydropyridine calcium antagonists, in which treatment intensity relied on office blood pressure, but with ambulatory blood pressure recordings performed before and after treatment. PATIENTS: Ninety-two hypertensive patients from general practices. RESULTS: Office and ambulatory blood pressures were only poorly correlated (r = 0.27-0.49). There was no significant correlation between treatment effects evaluated in terms of office and ambulatory blood pressures. Seventeen patients were classified as white-coat hypertensives; these differed in that their office blood pressure declined more with placebo, but similarly when administered active treatment, whereas their ambulatory blood pressure was not affected. An initial ambulatory blood pressure amounting to 127.4/84.8 mmHg was associated with no ambulatory treatment effect on average. CONCLUSION: These findings expose the shortcomings of office blood pressure measurements and strengthen the conception that white-coat hypertensives should not be treated pharmacologically.

24-h ambulatory blood pressure in 352 normal Danish subjects, related to age and gender.

UNLABELLED: The study was conducted to determine age and sex stratified normal values for 24-h ambulatory blood pressure. A sample of 352 healthy subjects (all white) were randomly selected from the community register and stratified by sex and age groups in decades from 20 to 79 years of age. Persons with a history of hypertension, cerebral apoplexy, diabetes, myocardial or renal disease, and who were taking blood pressure-influencing medication were excluded. Ambulatory blood pressure was recorded over 24 h, with measurements taken every 15 min from 07:00 to 22:59, and every 30 min from 23:00 to 6:59. Systolic blood pressure increased only slightly with age and was significantly higher in men than in women. The diastolic blood pressure increased only slightly with age in both sexes until the 50 to 59 years age group and declined thereafter. The diastolic blood pressure was not different for the two sexes. Both systolic and diastolic blood pressure were approximately 15% lower during the night regardless of age or sex. Ambulatory blood pressure during the daytime was on an average of 5 mm Hg lower than office blood pressure, but the mean difference between the two measurements increased with age. The variability of the difference also increased with age. IN CONCLUSION: Normal values for ambulatory blood pressure are presented in a randomly selected age- and gender-stratified population. Differences between office blood pressure and ambulatory blood pressure increased with age suggesting that the previously observed higher blood pressure seen in the elderly partly might be explained by a greater impact of white coat hypertension in older people.

Office and ambulatory blood pressure: a comparison between amlodipine and felodipine ER. Danish Multicentre Group.

The anti-hypertensive efficacy and safety of extended-release (ER) felodipine (5, 10 or 20 mg) and amlodipine (5 or 10 mg) once daily were compared in patients with mild-to-moderate essential hypertension in a double-blind, double-dummy, randomised, comparative study. A total of 118 patients were allocated to a 12-week, double-blind treatment with either felodipine ER (n = 57) or amlodipine (n = 61). The anti-hypertensive effect was evaluated by measuring office blood pressure (BP) at baseline and after 4, 6, 8 and 12 weeks, together with 24 h ambulatory blood pressure monitoring (ABPM) at baseline, on day 1 of treatment and at the end of the study. The mean office BP changes from baseline to week 12 were -13.4 (+/- 15.7)/-11.8 (+/- 6.9) mmHg for felodipine ER (mean daily dose 11.2 mg) and -15.3 (+/- 17.0)/-12.9 (+/- 7.3) mm Hg for amlodipine (mean daily dose 7.4 mg). All BP reductions were significant (P < 0.01) with respect to time, but differences between treatment groups were not significant. The mean ambulatory BP changes from baseline to end of the study were -11.6 (+/- 5.2)/-10.0 (+/- 2.0) mmHg for felodipine ER and -16.3 (+/- 4.4)/-9.6 (+/- 3.0) mm Hg for amlodipine, both significant (P < 0.01). The fall in ambulatory SBP was significantly greater (P < 0.001) in the patients treated with amlodipine compared with felodipine ER whereas there was no difference between the groups with respect to ambulatory DBP. Both drgs were well tolerated with a withdrawl rate of 12% equally distributed.(ABSTRACT TRUNCATED AT 250 WORDS)

[Albuminuria in persons with real hypertension, white coat hypertension and normotension]. / Albuminuri hos personer med reel hypertension, konsultationshypertension og normotension.

A prospective comparison of office blood pressure, daytime ambulatory blood pressure and urinary albumin excretion was performed in 284 consecutive patients from general practice with newly diagnosed, untreated mild to moderate hypertension. Based on daytime ambulatory blood pressure 173 were classified as established hypertensives and 111 as white coat hypertensives. A sample of 127 subjects drawn from the Danish national register served as a normotensive control group. It was found that urinary albumin/creatinine ratio differed significantly between the three groups; the difference remained significant after correction for covariables. Early morning urine albumin/creatinine ratio was weakly but significantly correlated to blood pressure. Early morning urine albumin/creatinine ratio was as reproducible a measure as 24-hour albumin excretion. It is concluded that white coat hypertensive patients have less renal involvement than patients with established hypertension, but more than a normotensive control group.

Comparative effects of amlodipine and felodipine ER on office and ambulatory blood pressure in patients with mild to moderate hypertension. Danish Multicentre Group.

The anti-hypertensive efficacy and safety of extended-release (ER) felodipine (5, 10 or 20 mg) and amlodipine (5 or 10 mg) once daily were compared in patients with mild to moderate essential hypertension in a double-blind, double-dummy, randomised, comparative study. One hundred and eighteen patients were randomised to receive either felodipine ER (n = 57) or amlodipine (n = 61) for 12 weeks. Efficacy was assessed by measuring office blood pressure (BP) at baseline and after 4, 6, 8 and 12 weeks, together with 24h ambulatory blood pressure monitoring (ABPM) at baseline, on day 1 of treatment and at the end of the study. The mean office BP changes from baseline to week 12 were -13.4/-11.8 mmHg for felodipine ER (mean daily dose 11.2 mg) and -15.3/-12.9 mm Hg for amlodipine (mean daily dose 7.4 mg). Changes in office BP between treatment groups were not significant. The mean 24h ambulatory BP changes from baseline to end of the study were -11.6/-10.0 mm Hg for felodipine ER and -16.3/-9.6 mm Hg for amlodipine, both significant (P < 0.01). The fall in systolic ambulatory BP was significantly greater (P < 0.001) in the amlodipine-compared with felodipine ER-treated patients but there was no difference between the groups with respect to diastolic ambulatory BP. Both drugs were well tolerated with only seven patients withdrawing because of side-effects, equally distributed between treatment groups. Headache and flushing were significantly (P < 0.05) more frequent in the felodipine ER group. Amlodipine appears to be more potent on a milligram to milligram basis and induces fewer side-effects than does felodipine ER.

Microalbuminuria in 411 untreated individuals with established hypertension, white coat hypertension, and normotension.

We compared urinary albumin excretion in normotensive subjects and patients with white coat and established hypertension. The study involved prospective comparison of office blood pressure, daytime ambulatory blood pressure, and urinary albumin excretion in consecutive patients (n = 284) who were selected from general practice with newly diagnosed mild to moderate hypertension before the institution of pharmacologic antihypertensive therapy. All patients had a diastolic office blood pressure above 90 mm Hg; 173 had a consistently elevated diastolic blood pressure (established hypertension), and 111 had an average daytime ambulatory blood pressure below 90 mm Hg (white coat hypertension). A sample of 127 subjects drawn from the Danish national register served as a normotensive control group. The main outcome measure was the ratio of early morning urinary albumin to creatinine. This ratio differed significantly among the three groups, being (on a molar basis) 21 +/- 69 x 10(-6) in the normotensive subjects, 22 +/- 39 x 10(-6) in the white coat hypertensive patients, and 51 +/- 177 x 10(-6) in patients with established hypertension. The difference remained significant after correction for covariables. The ratio of early morning urinary albumin to creatinine was weakly but significantly correlated to blood pressure, was more pronounced for ambulatory than for office measurements, was more pronounced for systolic than for diastolic pressure, and was more pronounced for hypertensive than for normotensive individuals. The ratio was as reproducible a measure as 24-hour albumin excretion. We conclude that white coat hypertensive patients have less renal involvement than patients with established hypertension but more than a normotensive control group.

The prevalence of myocardial ischemia six months after thrombolytic treatment of acute coronary episodes. A subset of a placebo controlled, randomised trial, the ASSET Study.

The purpose of this prospectively conducted study was to determine the prevalence of transient myocardial ischemia, evaluated from 24 h continuous ECG monitoring and exercise test, 6 months after inclusion in the Anglo Scandinavian Study of Early Thrombolysis (the ASSET trial, a randomised, placebo controlled study of alteplase for survival in patients with suspected acute myocardial infarction (AMI)), and to relate these findings to development of cardiac events. Of the 58 consecutively studied patients ischemic responses were found in 13 (45%) of 29 patients initially treated with placebo, and in 21 (72%) of 29 alteplase treated patients (P = 0.03). After another 6 months, i.e. 12 months after the acute event, two patients were dead, two had non-fatal reinfarctions and three had coronary artery by-pass surgery in the group with ischemic response; no events were recorded in patients without ischemia (P < 0.05). Alteplase treated patients more often had late myocardial ischemia, and cardiac events were found in patients with ischemia. Since the ASSET trial has demonstrated significantly higher short- and long-term survival rate in the alteplase treated group, it was indicated (1) that alteplase treated patients were better positioned for sustaining subsequent ischemia and thus cardiac events due to preservation of viable myocardial tissue, and (2) that late ischemia in the setting of initial alteplase treatment may convey other information than ischemia occurring in placebo treated patients.

Left ventricular mass and geometry in patients with established hypertension and white coat hypertension.

This study was designed to compare the cardiac mass and geometry in white coat hypertensive patients and established hypertensive patients through the prospective comparison of office blood pressure, daytime ambulatory blood pressure, and echocardiographically determined left ventricular mass and cardiac geometry in consecutive patients. We studied 143 patients from general practice in an outpatient hypertension unit. The patients had newly diagnosed mild-to-moderate hypertension prior to the institution of pharmacological anti-hypertensive therapy. All patients had a diastolic office blood pressure above 90 mm Hg; 90 had a consistently elevated diastolic blood pressure (established hypertension), whereas 53 had an average daytime ambulatory blood pressure below 90 mm Hg (white coat hypertension). Left ventricular mass index was significantly higher in the group with established hypertension, 102.4 +/- 26.6 g/m2 (mean +/- SD) v 93.6 +/- 23.5 (P = .045). Relative wall thickness was likewise significantly higher, 0.36 +/- 0.07 v 0.33 +/- 0.06 (P = .004). There was no significant difference in left atrial dimension. In a multiple regression model the ambulatory measurements and not the office measurements were statistically significantly associated with the extent of cardiac hypertrophy. Further, 44/53 (83%) of the patients with white coat hypertension had normal left ventricular dimensions, versus only 55/90 (61%) of the patients with established hypertension (P = .033). Thus, white coat hypertensive patients display less cardiac involvement than patients with established hypertension, indicating that they should rather be treated as normotensives than as hypertensives, ie, not with pharmacological antihypertensive therapy.

[What do we know about consultation hypertension?]. / Hvad ved vi om konsultationshypertension?

This review article examines the essential literature concerning "white coat" hypertension. It is stated that "white coat" hypertension is present in approximately 20% of patients with diagnosed mild to moderate hypertension. It is concluded that the pathophysiology of "white coat" hypertension is incompletely investigated; that the prognosis for untreated "white coat" hypertension seems fair; medical treatment being scarcely required. It is concluded further that more accurate diagnosis of mild to moderate hypertension, including the use of ambulatory blood pressure monitoring, will reduce the overall expenses by approximately million Danish crowns annually (approximately 2,000,000 pounds).

Clinical evaluation of the Takeda Medical (A & D) TM 2420 ambulatory blood pressure monitor. Practical experience and comparison with direct and indirect measurements.

Takeda Medical (A & D) TM 2420 is an automatic ambulatory blood pressure monitoring system employing the auscultatory technique. The device was used under stable conditions and compared to readings from the Hawksley random-zero sphygmomanometer using a double headset stethoscope and a Y-connection. We tested 85 subjects (aged 13-89 years, systolic blood pressure 85-212 mmHg, diastolic blood pressure 40-116 mmHg) and found a difference amounting to 1.6 +/- 6.7 mmHg (mean +/- SD) for systolic and 2.1 +/- 4.5 mmHg for diastolic readings (Hawksley-TM 2420). In 62 subjects a comparison with simultaneous measurement on the opposite arm with the Hawksley manometer showed similar results. When comparing intra-arterial readings from 10 subjects, a difference (intra-arterial-TM 2420) of -1.9 +/- 12.1 mmHg was found for systolic pressures, while the diastolic difference was -10.7 +/- 8.7 mmHg. Twenty-four hour monitoring was performed on 80 subjects; 70 of these yielded usable tracings. The proportion of successful recordings was acceptable, but the device was not suitable for bicycle stress testing. The quality of the accessories provided with the equipment could be improved, but in spite of this the monitoring system was found to be recommendable for clinical use.