Donate Help Contact The AHA Sign In Home
American Heart Association
Hypertension
Search: search_blue_button Advanced Search
« Previous Article | Table of Contents | Next Article »
Hypertension. 1995;26:1093-1099

This Article
Right arrow Abstract Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Puig, J. G.
Right arrow Articles by Ortega, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Puig, J. G.
Right arrow Articles by Ortega, R.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*BENAZEPRIL HYDROCHLORIDE
Medline Plus Health Information
*Diabetes
*High Blood Pressure

(Hypertension. 1995;26:1093-1099.)
© 1995 American Heart Association, Inc.

Articles

Antihypertensive Treatment Efficacy in Type II Diabetes Mellitus

Dissociation Between Casual and 24-Hour Ambulatory Blood Pressure

Juan G. Puig; Luis M. Ruilope; Rafael Ortega; on behalf of the Spanish Multicenter Study Group

From the Division of Internal Medicine, "La Paz" University Hospital (J.G.P.); the Division of Nephrology, "Doce de Octubre" University Hospital (L.M.R.); and the Medical Department of SmithKline Beecham Pharmaceuticals (R.O.). Other principal investigators who contributed to the study are listed in "Acknowledgments."

Correspondence to Dr Juan García Puig, Costa Brava, 23, 3° D, 28034 Madrid, Spain.


*    Abstract
up arrowTop
 *Abstract
down arrowIntroduction
 down arrowMethods
 down arrowResults
 down arrowDiscussion
 down arrowReferences
 
Abstract Whole-day ambulatory blood pressure monitoring is used to confirm the diagnosis of hypertension and assess the response to antihypertensive therapy. Neither of these has been applied to patients with type II diabetes mellitus, in whom it has been proposed that the desirable blood pressure should be lower than in nondiabetics. This multicenter study was designed to examine whether there are differences in the efficacy of a first-line antihypertensive drug when assessed by casual and ambulatory blood pressure determinations in patients with type II diabetes mellitus in whom 24-hour ambulatory monitoring confirms or fails to confirm the diagnosis of hypertension. Forty-three patients (mean age, 57.7 years) with stable type II diabetes mellitus and mild hypertension (casual diastolic pressure, 90 to 104 mm Hg on at least two visits) were treated with an angiotensin-converting enzyme inhibitor (benazepril, 10 to 20 mg, once a day) for 8 weeks. Antihypertensive drug efficacy was assessed by casual (trough) and 24-hour ambulatory blood pressure monitoring. Diabetic patients were classified as nonconfirmed hypertensive if the mean 24-hour ambulatory diastolic pressure was below 85 mm Hg. Antihypertensive treatment significantly decreased both systolic and diastolic pressures when determined by either casual measurement (from a mean of 162.7/98.0 to 153.9/89.2 mm Hg; P<.001) or ambulatory monitoring (from a mean of 143.1/84.4 to 137.0/81.5 mm Hg; P<.05). Twenty-one patients (49%) were classified as confirmed hypertensive and 22 as nonconfirmed hypertensive. In confirmed hypertensive patients benazepril significantly reduced systolic and diastolic pressures when assessed by either casual or 24-hour ambulatory monitoring. In contrast, in nonconfirmed hypertensive patients benazepril significantly decreased casual diastolic pressure (mean decrease, 10.0 mm Hg) but did not substantially modify 24-hour ambulatory diastolic pressure (mean decrease, 1.3 mm Hg; P<.001). At the end of antihypertensive therapy the number of patients with diastolic pressure equal to, above, or below 90 mm Hg was remarkably different when assessed by casual versus 24-hour ambulatory determinations ({kappa}, 0.348; 95% confidence interval, -0.020 to 0.716; P>.1). The results indicate that whole-day ambulatory blood pressure monitoring identifies a substantial number of type II diabetic patients with nonconfirmed hypertension. In these patients the discrepancy in diastolic pressure reduction between casual and 24-hour ambulatory monitoring suggests that the method of blood pressure assessment is important when evaluating antihypertensive drug efficacy.


Key Words: hypertension, arterial • diabetes mellitus • angiotensin-converting enzyme inhibitors • blood pressure monitoring, ambulatory


*    Introduction
up arrowTop
 up arrowAbstract
 *Introduction
down arrowMethods
 down arrowResults
 down arrowDiscussion
 down arrowReferences
 
Arterial hypertension is about twice as common in patients with type II diabetes mellitus as in nondiabetic individuals.1 Hypertension accelerates both macrovascular and microvascular complications of diabetes.2 3 4 Macrovascular disease, manifested as coronary heart disease, peripheral vascular disease, and cerebrovascular disease, is the major cause of morbidity in type II diabetes mellitus and accounts for 49% to 75% of the mortality in these patients.5 Thus, it has been recommended that hypertension in diabetic patients should be recognized and treated early and aggressively.6 However, since BP is a highly variable parameter,7 the optimal technique for establishing the diagnosis of hypertension remains controversial. According to present guidelines8 9 10 the decision to institute antihypertensive drug therapy is based on conventional measurements, usually in the physician's office (casual BP). Several studies have indicated that between 21% and 34% of patients with essential hypertension diagnosed in the physician's office have normal BP values when measured at home11 or determined by ABPM12 13 14 15 16 (called white coat, office, or nonconfirmed hypertension). ABPM may be particularly useful in diabetic subjects to reduce the potential of overtreating those who exhibit elevated casual BP values. Moreover, compared with casual BP readings, ABPM seems to better document antihypertensive drug efficacy.17 The prevalence of white coat hypertension may be higher among diabetic patients than in subjects with essential hypertension because of a greater BP variability in the former,6 but to the best of our knowledge no studies have addressed this issue. In addition, it is unknown whether the efficacy of antihypertensive therapy, as assessed by casual BP measurements and ABPM, is different in diabetic patients, in whom whole-day BP monitoring confirms or fails to confirm the diagnosis of hypertension. This multicenter study was designed to prospectively compare the antihypertensive effect of pharmacological treatment in confirmed and nonconfirmed hypertensive patients with type II diabetes mellitus.


*    Methods
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 *Methods
down arrowResults
 down arrowDiscussion
 down arrowReferences
 
Patients
This prospective, multicenter (one primary care center and six University hospitals), open trial was performed in Spain from October 1993 through June 1994. Candidates for participation in the study were patients aged 18 to 65 years who had type II diabetes mellitus according to established criteria,18 had seated diastolic BP between 90 and 104 mm Hg on at least two clinic visits, had World Health Organization stage I or II,19 and accepted to participate in the study. Patients were not included if they were pregnant, lactating, or not following a reliable contraceptive method; had seated systolic BP above 200 mm Hg, renal insufficiency (creatinine clearance <30 mL/min [0.50 mL/s]), hyperkalemia (serum potassium >5.5 mmol/L), mitral or aortic stenosis, systemic lupus erythematosus or scleroderma, symptomatic orthostatic hypotension, or clinically suspected serious drug reactions to ACE inhibitors; was being treated with lithium; had received an investigational drug 30 days before the start of the study; or had a clinical condition that in the opinion of the investigator made the patient unable to participate in the study. Patients were withdrawn from the study because of serious adverse events as evaluated by the investigators, lack of compliance (intake of the prescribed tablets <80% or >120% or failure to attend scheduled visits), systolic BP above 200 mm Hg at any stage of the study, or any other reason that in the opinion of the investigator indicated exclusion from the study.

Protocol
The protocol was approved by the local Ethics Committees; the study was performed in accordance with institutional guidelines. Informed consent was obtained from all patients. Once eligibility was established, patients provided a medical history and underwent a physical examination including fundal evaluation and laboratory analyses for assessment of renal function. The study lasted 8 weeks (treatment period) and was preceded by a 2-week washout/run-in period during which no antihypertensive medications were allowed. At the end of this period patients with seated diastolic BP between 90 and 104 mm Hg entered the active treatment phase. Immediately before entering this phase, patients were subjected to 24-hour ABPM. They then were given 10 mg benazepril, to be taken daily between 7 and 10 AM. Patients returned for a clinic visit at 28±4 days, and if the casual diastolic BP remained at or above 90 mm Hg, the dose of benazepril could be either doubled (ie, 20 mg/d) or kept at the same level (10 mg/d) with the addition of another first-line antihypertensive drug. On day 56±4 after the start of the treatment period, a second 24-hour ABPM was performed. At the end of this study casual BP and pulse rate were determined.

Efficacy
Antihypertensive efficacy was assessed by two methods: conventional BP measurement (trough) and 24-hour ABPM. All clinical decisions were based on casual BP readings. Casual BP was determined according to the recommendations of the British Society of Hypertension,20 with the use of a mercury sphygmomanometer and the first and fifth Korotkoff sounds for systolic and diastolic BPs, respectively. Each value was the average of three readings taken 1 minute apart. Pulse rate was measured by palpation of the radial artery for 30 seconds, after BP determinations. Each patient who was evaluated had two 24-hour ABPMs (baseline and treatment). Readings were obtained with the SpaceLabs 90202 and 90207 portable automated oscillometric devices on working days of average activity. BP readings were obtained every 20 minutes from 6 AM to midnight and every 30 minutes from 12:01 to 5:59 AM. All ambulatory BP recordings were truncated so that their total duration did not exceed 24 hours. For elimination of the transition periods between daytime and sleep and vice versa, during which BP often changes rapidly, daytime was defined as 8 AM to 10 PM and nighttime as midnight to 6 AM.21 These periods adequately reflect the habits of the average Spanish population. The first dose of benazepril was given at the end of the first 24-hour ABPM and the last dose before the second 24-hour ABPM. Each 24-hour report was immediately edited and reduced to 24 consecutive 1-hour averages, as previously described.22 An ABPM study was considered adequate for evaluation when the number of valid readings was greater than or equal to 75% of those programmed. If 2 or more hours contained nonvalid readings, the ABPM study was considered inadequate.

Data Analysis
Nonconfirmed or white coat hypertension was defined on the basis of an average 24-hour ambulatory diastolic BP value below 85 mm Hg.23 24 The study required 32 assessed patients in order to have an 80% power at the 5% level (two-tailed) to detect a 5 mm Hg difference between diastolic BP determined by conventional methods compared with ABPM. To achieve this objective, 46 patients (estimated patient loss, 30%) had to be recruited into the study. The variables measured during the run-in period before the first 24-hour ABPM study were taken as baseline values. The variables measured at the end of the second 24-hour ABPM study were taken as treatment values. Mean differences between conventional BP and 24-hour ABPM values were examined by Student's two-tailed paired t test or Wilcoxon rank sum test for nonnormal data. Repeated-measures ANOVA was used to test for treatment effects. Only data from patients who completed the 8-week study period were included for these comparisons. Relationships among selected variables were assessed by the Pearson method. Fisher's exact test was used to compare proportions. To deal with the imprecision of mean values, 95% CI values were calculated.25 Statistical analysis was performed with the SAS package (SAS Institute Inc), version 6.08. Results are given as mean±SD. Significance was taken at a value of P<.05 (two-tailed).


*    Results
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 up arrowMethods
 *Results
down arrowDiscussion
 down arrowReferences
 
Patient Characteristics
Fifty-three patients were included in the study. Each of the seven participating centers included between 6 and 12 patients. Ten patients were excluded from the study (7 because of inadequate ABPM, 2 because of adverse events, and 1 because of protocol violation; withdrawal rate, 19%); therefore, 43 patients (16 men, 27 women; mean age, 57.7 years; range, 28 to 65 years) completed the study. Of these patients, 25 (58%) had received previous antihypertensive drugs (12 patients received ACE inhibitors, 5 diuretics, 3 calcium antagonists, and 5 a combination of these drugs). Concomitant medications allowed during the study included insulin (7 patients), hypoglycemic agents (27 patients), hypouricemic drugs (4 patients), and nonesteroidal anti-inflammatory drugs (3 patients). Patient compliance was excellent as judged by an intake of more than 80% and less than 120% of the prescribed benazepril tablets. The mean dose of benazepril was 14.7 mg/d. At week 4, 23 (53.5%) patients had a casual diastolic BP below 90 mm Hg, and 20 (46.5%) patients had a casual diastolic BP equal to or above 90 mm Hg; the dose of benazepril was doubled (20 mg/d) in the latter patients.

Comparison of Casual BP Measurements and ABPM
Baseline and treatment systolic and diastolic BP values were significantly lower when determined by 24-hour ABPM compared with casual BP measurement (Table 1). This could be attributed to the diluting effect of the lower nighttime BP readings. However, baseline and treatment daytime systolic and diastolic BP values were also significantly lower than casual BP measurements. The discrepancy between both methods of BP determination is emphasized by the weak correlation between baseline casual diastolic BP and 24-hour ambulatory diastolic BP (r=.368, P>.1).


View this table:
[in this window]
[in a new window]
  		Table 1. Pulse Rate and BP Determined by Conventional Methods and ABPM at Baseline and After 8 Weeks of Benazepril Treatment in Diabetic Patients

Benazepril treatment was associated with a significant reduction in both systolic and diastolic BP values when assessed by either conventional measurement or 24-hour ABPM (Table 1). Moreover, systolic BP was significantly decreased during the daytime and nighttime, whereas diastolic BP was significantly reduced during the daytime but not the nighttime. Pulse rate was similar when measured by conventional methods and by ABPM and was not essentially modified by ACE inhibition therapy.

Comparative Changes After Antihypertensive Therapy in ABPM-Defined Hypertensive and Normotensive Patients
Analysis of baseline 24-hour ambulatory BP values revealed that 21 diabetic patients (49%) were confirmed hypertensive, based on the criterion of an average whole-day diastolic BP equal to or above 85 mm Hg, and 22 patients (51%) had a mean 24-hour diastolic BP below 85 mm Hg and thus were classified as nonconfirmed hypertensive. The antihypertensive effect of benazepril depended not only on the method of BP determination but also on the subgroup analyzed. Baseline and treatment 24-hour ABPM values were significantly lower than casual BP values in both the confirmed and nonconfirmed hypertensive groups (Table 2). Not unexpectedly, the differences between casual and ambulatory BP values were more pronounced in nonconfirmed hypertensive patients. The mean baseline diastolic BP difference between casual and 24-hour ABPM in the confirmed hypertensive group was 7.6 mm Hg (95% CI, 1.1 to 14.1) and was 19.4 mm Hg (95% CI, 10.7 to 28.1) in the nonconfirmed hypertensive group (P<.001). In confirmed hypertensive patients ACE inhibition therapy was associated with a significant reduction of casual systolic and diastolic BP values, but only casual diastolic BP decreased significantly in nonconfirmed hypertensive patients (Table 2). The reduction of both systolic and diastolic 24-hour ABPM values was also significant in confirmed hypertensive patients. In contrast, antihypertensive treatment did not significantly decrease systolic and diastolic ABPM values in nonconfirmed hypertensive patients. In these patients the mean benazepril-induced decrease in casual diastolic BP was 10.0 mm Hg and when assessed by ABPM was 1.3 mm Hg (difference, 8.7 mm Hg; 95% CI, 3.6 to 13.8; P<.001). The difference between both groups in the response to antihypertensive therapy was also evident when daytime BP variations were compared. Benazepril therapy significantly reduced daytime systolic and diastolic BP values in confirmed hypertensive patients but did not substantially modify daytime systolic and diastolic BP values in nonconfirmed hypertensive diabetic patients. Further differences between confirmed and nonconfirmed hypertensive diabetic patients were apparent when the BP response assessed by ABPM was viewed on an hourly basis over 24 hours (Fig 1). Compared with baseline 24-hour ABPM values, antihypertensive therapy significantly reduced diastolic BP during the whole day in confirmed hypertensive diabetic patients (Fig 1A) but not in nonconfirmed hypertensive patients (Fig 1B). The observed reduction in 24-hour ambulatory systolic and diastolic BP values in confirmed hypertensive patients was due to a decrease in daytime BP because nighttime systolic and diastolic BP values were not significantly modified. Despite a significant correlation between casual and 24-hour ambulatory diastolic BP at the end of drug treatment (r=.652, P<.001), the discrepancy between the two methods of BP measurement is manifested by the low concordance observed in the number of patients with a diastolic BP above or below 90 mm Hg with ACE inhibition therapy ({kappa}, 0.348; 95% CI, -0.020 to 0.716; P>.1). Of the 22 patients with nonconfirmed hypertension, all showed 24-hour ambulatory diastolic BP below 90 mm Hg, but only 15 (68%) had casual diastolic BP on treatment below 90 mm Hg (Fig 2). Similarly, of the 21 patients with confirmed hypertension, 11 achieved goal diastolic BP (casual diastolic BP <90 mm Hg) and 10 did not. Of the former only 8 patients (73%) showed 24-hour ambulatory diastolic BP below 90 mm Hg, and among the latter, 4 patients had ambulatory diastolic BP above 90 mm Hg. Pulse rate was similar in both groups and not significantly modified by benazepril treatment (data not shown).


View this table:
[in this window]
[in a new window]
  		Table 2. Effect of 8 Weeks of Benazepril Treatment on BP Determined by Conventional Methods and ABPM in Confirmed and Nonconfirmed Hypertensive Patients



View larger version (39K):
[in this window]
[in a new window]
  		Figure 1. Line graphs show mean hourly diastolic BP before (open symbols) and during (closed symbols) antihypertensive treatment with benazepril (10 to 20 mg/d) in 43 patients with type II diabetes mellitus and mean 24-hour ambulatory diastolic BP equal to or above 85 mm Hg (confirmed hypertensive patients, n=21) (A) or below 85 mm Hg (nonconfirmed hypertensive patients, n=22) (B). *P<.05 with respect to baseline diastolic BP.



View larger version (23K):
[in this window]
[in a new window]
  		Figure 2. Scatterplot shows relationship between diastolic BP at the end of drug therapy (benazepril, 10 to 20 mg/d) assessed by conventional methods (clinic determinations) and ABPM in 43 patients with type II diabetes mellitus and mean 24-hour ambulatory diastolic BP equal to or above 85 mm Hg (confirmed hypertensive patients, closed symbols) or below 85 mm Hg (nonconfirmed hypertensive patients, open symbols).

Adverse Events
Thirteen patients (24.5%) among those who had taken at least one dose of the studied medication (n=53) reported a total of 19 adverse events. Only 5 of these events (epigastric pain, cough [3 patients], dry mouth), occurring in 4 patients, were thought to be related or possibly related to benazepril therapy. These related adverse events were of moderate intensity and led to discontinuation of the drug in 2 patients, both reporting cough.


*    Discussion
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 up arrowMethods
 up arrowResults
 *Discussion
down arrowReferences
 
The results of this study show that a substantial number of hypertensive patients with type II diabetes mellitus show normal BP when determined by 24-hour ABPM and that treatment with benazepril significantly reduced ambulatory BP in confirmed hypertensive patients but did not significantly modify whole-day BP in nonconfirmed hypertensive diabetics (white coat hypertension). Previous studies in patients with essential hypertension have documented that between 21% and 34% of subjects with persistently elevated casual BP have normal daytime ambulatory BP.11 12 13 14 15 16 These prevalences are markedly lower compared with the result of a 51% prevalence of white coat hypertension among type II diabetics. Although our study was not designed to address this specific issue, the finding of a higher prevalence of white coat hypertension in type II diabetics could be attributed to selection bias or to some of the factors contributing to the white coat effect,26 such as a predominance of female patients or increased BP lability or reactivity in type II diabetes. We are unaware of previous studies that have assessed the usefulness of ABPM in diabetic patients, but the increased BP variability in this condition has led to the proposal that a higher number of BP measurements may be helpful for establishing the diagnosis of hypertension.6 It is debatable whether patients with white coat hypertension should receive antihypertensive therapy. Previous reports have concluded that white coat hypertensive patients can be regarded as normotensive.12 13 27 28 However, in recent years several studies have indicated that white coat hypertension may not be a benign condition but a variant of hypertension, because these patients evidenced metabolic,24 neuroendocrine,24 cardiac,24 29 and renal30 abnormalities that were intermediate between the findings in normotensive subjects and patients with established hypertension. Guidelines for the management of essential hypertension advise starting antihypertensive treatment when casual diastolic BP remains at 95 mm Hg or above.8 9 10 Although we do not yet know the optimal BP reduction that should be attained in hypertensive patients, both the increased cardiovascular risk of diabetic patients31 32 33 and the report that cardiovascular events in subjects with glucose intolerance occurred at a lower level of diastolic BP compared with nondiabetic subjects34 substantiates the recommendation that the desirable goal BP be lower (<130/85 mm Hg) in diabetic than in nondiabetic patients.6 Thus, it is conceivable that sporadic elevations of BP in daily life (white coat hypertension) may impose a number of detrimental effects in patients with diabetes. Until the results are available of long-term prospective studies35 designed to determine the efficacy of intensive versus moderate antihypertensive control on the outcome of diabetic complications in type II diabetic patients with casual diastolic BP equal to or above 80 mm Hg, the BP threshold at which antihypertensive treatment should be initiated is uncertain.

Some studies have assessed the effect of drug treatment on ambulatory BP in nondiabetic patients with elevated casual BP who were classified as confirmed and nonconfirmed hypertensive according to 24-hour ABPM.36 37 38 39 A common finding of these studies was that antihypertensive drugs did not significantly reduce ambulatory BP in nonconfirmed essential hypertensive patients. A feature of the present work that differentiates it from previous antihypertensive drug studies is that we have examined type II diabetic patients. This may be of particular interest because diabetic patients are prone to orthostatic hypotension,40 and lowering BP below the autoregulatory range may lead to reduced heart perfusion,41 among other harmful effects.42 The results of the present study show that BP measured in the clinic responded differently to benazepril than ambulatory BP, particularly in diabetic patients with a mean 24-hour ambulatory diastolic BP below 85 mm Hg. In fact, benazepril treatment significantly reduced casual systolic and diastolic BP values in confirmed hypertensive diabetic patients, and this BP reduction was also evident when assessed by ABPM. In contrast, benazepril therapy significantly decreased casual diastolic BP in nonconfirmed hypertensive patients, but this decrease was not evident when BP was assessed by 24-hour ABPM. The arbitrary 24-hour ambulatory diastolic BP limit of 85 mm Hg was chosen because it has been used as the cutoff value to differentiate confirmed and nonconfirmed essential hypertensive patients in most recent studies24 43 44 45 and has also been recommended in the International Society of Hypertension consensus document.23 In addition, the results of this study emphasize the importance of ABPM over the entire 24-hour period for adequate assessment of the magnitude and duration of the antihypertensive effect.35 46 47 Benazepril treatment significantly reduced daytime systolic and diastolic ambulatory BP values in confirmed hypertensive patients, whereas no significant daytime antihypertensive effect was seen among diabetic patients with nonconfirmed hypertension. Taken together, these data suggest that the efficacy of antihypertensive drugs may depend on the method of BP assessment; despite a significant reduction in casual diastolic BP, ambulatory BP did not significantly decrease in diabetic patients with a baseline ambulatory diastolic BP below 85 mm Hg.

A cautionary note seems appropriate. Since this study was designed to assess differences in antihypertensive drug efficacy depending on the method of BP measurement, a placebo-treated group was not included. Thus, it cannot be established whether the observed benazepril-mediated casual BP reduction in nonconfirmed hypertensive patients could be attributed to a true antihypertensive effect, regression to the mean phenomenon, BP reduction being limited to the clinic setting, and/or patient selection on the basis of casual BP. In addition, the results of this study cannot be generalized to other first-line antihypertensive drugs and/or other hypertensive nondiabetic populations.

The findings that a substantial proportion of type II diabetic patients thought to be hypertensive in fact have white coat hypertension and that antihypertensive treatment did not reduce ambulatory BP in these patients have specific implications. First, they provide a solid basis for the recommendation that a higher number of BP readings than usually needed should be obtained in diabetic patients before the diagnosis of confirmed hypertension is established.6 This is in accordance with the finding that multiple BP readings obtained semiautomatically in the outpatient clinic result in a value similar to that obtained by 24-hour ABPM in mild essential hypertensive patients.48 Second, ABPM could provide a more realistic evaluation than casual BP determinations in type II diabetics and thus may have important clinical implications in terms of both diagnosis and treatment of hypertension. This is further supported by the observation of a low concordance value in the number of patients with diastolic BP above or below 90 mm Hg at the end of drug therapy when measured by casual versus 24-hour ABPM. Thus, antihypertensive therapy in patients with elevated casual BP but normal ambulatory BP could result in no real gain in BP control. Studies designed to assess the optimal technique for diagnosis and management of hypertension may ultimately lead to the adoption of new strategies to avoid unnecessary or excessive medication, changes in lifestyle, and the psychological effects of being labeled hypertensive.10 Finally, since ACE inhibitors have demonstrated a renal protective effect in normotensive type II diabetic patients,49 50 51 the excellent tolerability of benazepril shown in the present study suggests that type II diabetic patients with white coat hypertension may also benefit from receiving ACE inhibition therapy. Longitudinal observations, however, are required to characterize the natural history of patients with type II diabetes and white coat hypertension and to determine the optimal BP level associated with a lower incidence of diabetic end-organ complications.


*    Selected Abbreviations and Acronyms
 
ABPM = ambulatory blood pressure monitoring
ACE = angiotensin-converting enzyme
BP = blood pressure
CI = confidence interval


*    Acknowledgments
 
We gratefully acknowledge the grant, technical assistance, and generous supply of the study medication by SmithKline Beecham Pharmaceuticals, Madrid, Spain. The statistical analysis was performed by CIBEST, Madrid, Spain. Erik Lundin provided help in the preparation of the manuscript. The following principal investigators and institutions contributed to the study: J. Abellán (Centro de Salud Molina de Segura, Murcia), P. Aranda (Hospital Carlos Haya, Málaga), C. Calvo (Hospital Xeral de Galicia, Santiago de Compostela), J. Redón (Hospital de Sagunto, Sagunto), and D. Sanz Guajardo (Hospital Puerta de Hierro, Madrid).

Received June 18, 1995; first decision September 10, 1995; accepted October 3, 1995.


*    References
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 up arrowMethods
 up arrowResults
 up arrowDiscussion
 *References
 

  1. Feher MD. Hypertension in non-insulin dependent diabetes mellitus and its management. Postgrad Med J. 1991;67:938-946. [Medline] [Order article via Infotrieve]
  2. Sowers JR, Khoury S. Diabetes and hypertension: a review. Prim Care. 1991;18:509-524. [Medline] [Order article via Infotrieve]
  3. Klein R, Klein BEK, Moss SE, Davis MD, DeMets DL. Is blood pressure a predictor of the incidence or progression of diabetic retinopathy? Arch Intern Med. 1989;149:2427-2432. [Abstract]
  4. Selby JV, FitzSimmons SC, Newman JM, Katz PP, Sepe S, Showstack J. The natural history and epidemiology of diabetic nephropathy: implications for prevention and control. JAMA. 1990;263:1954-1960. [Medline] [Order article via Infotrieve]
  5. Panzram G. Mortality and survival in type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia. 1987;30:123-131. [Medline] [Order article via Infotrieve]
  6. The National High Blood Pressure Education Program Working Group. National High Blood Pressure Education Program Working Group report on hypertension in diabetes. Hypertension. 1994;23:145-158. [Abstract/Free Full Text]
  7. Waeber B, Rutschmann B, Nüssberger J, Brunner HR. Evaluation of antihypertensive therapy: discrepancies between office and ambulatory recorded blood pressure. J Hypertens. 1991;9(suppl 3):S53-S56.
  8. Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The Fifth Report of the Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure (JNC V). Arch Intern Med. 1993;153:154-183. [Medline] [Order article via Infotrieve]
  9. The Guidelines Subcommittee of the WHO/ISH Mild Hypertension Liaison Committee. 1993 Guidelines for the management of mild hypertension: memorandum from a World Health Organization/International Society of Hypertension meeting. Hypertension. 1993;22:392-403. [Free Full Text]
  10. American College of Physicians. Automated ambulatory blood pressure and self-measured blood pressure monitoring devices: their role in the diagnosis and management of hypertension. Ann Intern Med. 1993;118:889-892. [Abstract/Free Full Text]
  11. Gaudemaris R, Chau NP, Mallion J-M. Home blood pressure: variability, comparison with office readings and proposal for reference values. J Hypertens. 1994;12:831-838. [Medline] [Order article via Infotrieve]
  12. Drayer JIM, Weber MA, Nakamura DK. Automated ambulatory blood pressure monitoring: a study in age-matched normotensive and hypertensive men. Am Heart J. 1985;109:1334-1338. [Medline] [Order article via Infotrieve]
  13. White WB. Assessment of patients with office hypertension by 24-hour noninvasive ambulatory blood pressure monitoring. Arch Intern Med. 1986;146:2196-2199. [Abstract]
  14. Pickering TG, James GD, Boddie C, Harshfield GA, Blank S, Laragh JH. How common is white coat hypertension? JAMA. 1988;259:225-228. [Abstract]
  15. Hoegholm A, Kristensen KS, Madsen NH, Svendsen TL. White coat hypertension diagnosed by 24-h ambulatory monitoring: examination of 159 newly diagnosed hypertensive patients. Am J Hypertens. 1992;5:64-70. [Medline] [Order article via Infotrieve]
  16. Khoury S, Yarows SA, O'Brien TK, Sowers JR. Ambulatory blood pressure monitoring in a nonacademic setting: effects of age and sex. Am J Hypertens. 1992;5:616-623. [Medline] [Order article via Infotrieve]
  17. Canter DA, Texter MJ, McLain RW. Short report: ambulatory blood pressure monitoring can play an integral role in patient selection, dosage adjustment and efficacy assessment in clinical trials of antihypertensive agents. J Hypertens. 1994;12:491-494. [Medline] [Order article via Infotrieve]
  18. National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes. 1979;28:1039-1057. [Medline] [Order article via Infotrieve]
  19. WHO Expert Committee. Arterial Hypertension. Geneva, Switzerland: World Health Organization; 1978. Technical Report Series No. 628.
  20. Petrie JC, O'Brien ET, Littler WA, de Swiet M. Recommendations on blood pressure measurement. BMJ Clin Res Ed. 1986;293:611-615.
  21. Sateesen J, O'Brien ET, Atkins N, Amery AK, on behalf of the ad-hoc working group. Short report: ambulatory blood pressure in normotensive compared with hypertensive subjects. J Hypertens. 1993;11:1289-1297. [Medline] [Order article via Infotrieve]
  22. Neutel JM, Smith DHG, Ram CVS, Kaplan NM, Papademetriou V, Fagan TC, Lefkowitz MP, Kazempour MK, Weber MA. Application of ambulatory blood pressure monitoring in differentiating between antihypertensive agents. Am J Med. 1993;94:181-187. [Medline] [Order article via Infotrieve]
  23. ISH Scientific Committee of The International Society of Hypertension's Consensus Conference on Indirect Ambulatory Blood Pressure Monitoring. Consensus document on non-invasive ambulatory blood pressure monitoring. J Hypertens. 1990;8(suppl 6):S135-S140.
  24. Weber MA, Neutel JM, Smith DHG, Graettinger WF. Diagnosis of mild hypertension by ambulatory blood pressure monitoring. Circulation. 1994;90:2291-2298. [Abstract/Free Full Text]
  25. Gardner MJ, Altman DG. Confidence intervals rather than P values: estimation rather than hypothesis testing. BMJ. 1986;292:746-750.
  26. Pickering TG. Clinic measurement of blood pressure and the white coat effect. In: Pickering TG, ed. Ambulatory Monitoring and Blood Pressure Variability. London, UK: Science Press; 1991:7.1-7.14.
  27. The National High Blood Pressure Education Program Coordinating Committee. National High Blood Pressure Education Program Working Group report on ambulatory blood pressure monitoring. Arch Intern Med. 1990;150:2270-2280. [Abstract]
  28. Verdecchia P, Porcellati C, Schillaci G, Borgioni C, Ciucci A, Battistelli M, Guerrieri M, Gatteschi C, Zampi I, Santucci A, Santucci C, Reboldi G. Ambulatory blood pressure: an independent predictor of prognosis in essential hypertension. Hypertension. 1994;24:793-801. [Abstract/Free Full Text]
  29. Kuwajima I, Suzuki Y, Fujisawa A, Kuramoto K. Is white coat hypertension innocent? Structure and function of the heart in the elderly. Hypertension. 1993;22:826-831. [Abstract/Free Full Text]
  30. Hoegholm A, Bang LE, Kristensen KS, Nielsen JW, Holm J. Microalbuminuria in 411 untreated individuals with established hypertension, white coat hypertension, and normotension. Hypertension. 1994;24:101-105. [Abstract/Free Full Text]
  31. Kannel WB, McGee DL. Diabetes and cardiovascular risk factors: the Framingham study. Circulation. 1979;59:8-13. [Abstract/Free Full Text]
  32. Dupree EA, Meyer MB. Role of risk factors in complications of diabetes mellitus. Am J Epidemiol. 1980;112:100-112. [Abstract/Free Full Text]
  33. Fuller JH. Coronary-heart disease risk and impaired glucose tolerance: the Whitehall study. Lancet. 1980;1:1373-1376. [Medline] [Order article via Infotrieve]
  34. Dodson PM, Horton RC. The hypertension of diabetes mellitus: mechanisms and implications. J Hum Hypertens. 1988;1:249-258. [Medline] [Order article via Infotrieve]
  35. Savage S, Johnson Nagel N, Estacio RO, Feig PU, MacCarthy EP, Lukken NJ, Ziegler R, Schrier RW. The ABCD (Appropriate Blood Pressure Control in Diabetes) trial: rationale and design of a trial of hypertension control (moderate or intensive) in type II diabetes. Online J Curr Clin Trials. 24 November 1993; Doc No. 104.
  36. Weber MA, Cheung DG, Graettinger WF, Lipson JL. Characterization of antihypertensive therapy by whole-day blood pressure monitoring. JAMA. 1988;259:3281-3285. [Abstract]
  37. Lacourcière Y, Poirier L, Dion D, Provencher P. Antihypertensive effect of isradipine administered once or twice daily on ambulatory blood pressure. Am J Cardiol. 1990;65:467-472. [Medline] [Order article via Infotrieve]
  38. Ashida T, Abe H, Kawano Y, Yoshida K, Kimura G, Kojima S, Yoshimi H, Kawamura M, Imanishi M, Sanai T, Kuramochi M, Omae T. Effects of nifedipine SR and enalapril on office, home and ambulatory blood pressure in `white-coat' systemic hypertension. Am J Cardiol. 1990;66:498-501. [Medline] [Order article via Infotrieve]
  39. Fagard R, Bielen E, Staessen J, Thijs L, Amery A. Response of ambulatory blood pressure to antihypertensive therapy guided by clinic pressure. Am J Hypertens. 1993;6:648-653. [Medline] [Order article via Infotrieve]
  40. Stein PP, Black HR. Drug treatment of hypertension in patients with diabetes mellitus. Eur J Clin Pharmacol. 1992;42:569-576. [Medline] [Order article via Infotrieve]
  41. Strandgaard S, Haunso S. Why does antihypertensive treatment prevent stroke but not myocardial infarction? Lancet. 1987;2:658-660. [Medline] [Order article via Infotrieve]
  42. Sowers JR, Levy J, Zemel MB. Hypertension and diabetes. Med Clin North Am. 1988;72:1399-1414. [Medline] [Order article via Infotrieve]
  43. Weber MA. Evaluating the diagnosis and prognosis of hypertension by automated blood pressure monitoring. Am Heart J. 1988;116:1118-1123. [Medline] [Order article via Infotrieve]
  44. Krakoff LR, Eison H, Phillips RH, Leiman SJ, Lev S. Effect of ambulatory blood pressure monitoring on the diagnosis and cost of treatment for mild hypertension. Am Heart J. 1988;116:1152-1154. [Medline] [Order article via Infotrieve]
  45. Staessen J, Fagard R, Lijnen P, Thijs L, van Hoof R, Amery A. Reference values for ambulatory blood pressure: a meta-analysis. J Hypertens. 1990;8(suppl 6):S57-S64.
  46. Waeber B, Petrillo A, Nussberger J, Hofstetter J-R, Scherrer U, Bidiville J, Waeber G, Brunner HR. Are some hypertensive patients overtreated? A prospective study of ambulatory blood pressure recording. Lancet. 1987;2:732-734. [Medline] [Order article via Infotrieve]
  47. Weisser B, Mengden T, Vetter W. Ambulatory twenty-four-hour blood pressure measurement in pharmacological studies. J Hypertens. 1991;8(suppl 6):S87-S92.
  48. Mancia G, Ulian L, Parati G, Trazzi S. Increase in blood pressure reproducibility by repeated semi-automatic blood pressure measurements in the clinic environment. J Hypertens. 1994;12:469-473. [Medline] [Order article via Infotrieve]
  49. Ravid M, Savin H, Jutrin I, Bental T, Katz B, Lishner M. Long-term stabilizing effect of angiotensin-converting enzyme inhibition on plasma creatinine and on proteinuria in normotensive type II diabetic patients. Ann Intern Med. 1993;118:577-581. [Abstract/Free Full Text]
  50. American Diabetes Association. National Kidney Foundation. Consensus development conference on the diagnosis and management of nephropathy in patients with diabetes mellitus. Diabetes Care. 1994;17:1357-1361. [Medline] [Order article via Infotrieve]
  51. Clark CM, Lee DA. Prevention and treatment of the complications of diabetes mellitus. N Engl J Med. 1995;332:1210-1217.[Free Full Text]



This article has been cited by other articles:


Home page
 Diabetes CareHome page
K. Kamoi, M. Miyakoshi, S. Soda, S. Kaneko, and O. Nakagawa
Usefulness of Home Blood Pressure Measurement in the Morning in Type 2 Diabetic Patients
Diabetes Care, December 1, 2002; 25(12): 2218 - 2223.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Puig, J. G.
Right arrow Articles by Ortega, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Puig, J. G.
Right arrow Articles by Ortega, R.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*BENAZEPRIL HYDROCHLORIDE
Medline Plus Health Information
*Diabetes
*High Blood Pressure

Hypertension Home | Subscriptions | Archives | Feedback | Authors | Help | AHA Journals Home | Search
Copyright © 1995 American Heart Association, Inc. All rights reserved. Unauthorized use prohibited.