Vicente Pallarés, Antonio Sarría, Pedro Aranda and Luis M. Ruilope
Gorostidi, Juan J. de la Cruz, Javier Sobrino, José L. Llisterri, Javier Alonso, Ernest Vinyoles,
Alejandro de la Sierra, Josep Redon, José R. Banegas, Julián Segura, Gianfranco Parati, Manuel
Hypertensive Patients
Prevalence and Factors Associated With Circadian Blood Pressure Patterns in
Print ISSN: 0194-911X. Online ISSN: 1524-4563
Copyright © 2009 American Heart Association, Inc. All rights reserved.
is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Hypertension
doi: 10.1161/HYPERTENSIONAHA.108.124008
2009;53:466-472; originally published online January 26, 2009;
Hypertension.
http://hyper.ahajournals.org/content/53/3/466
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Pressure Patterns in Hypertensive Patients
Alejandro de la Sierra, Josep Redon, Jose´ R. Banegas, Julia´n Segura, Gianfranco Parati,
Manuel Gorostidi, Juan J. de la Cruz, Javier Sobrino, Jose´ L. Llisterri, Javier Alonso, Ernest Vinyoles,
Vicente Pallare´s, Antonio Sarría, Pedro Aranda, Luis M. Ruilope; on behalf of the Spanish Society of
Hypertension Ambulatory Blood Pressure Monitoring Registry Investigators
Abstract—Ambulatory blood pressure (BP) monitoring has become useful in the diagnosis and management of hypertensive individuals. In addition to 24-hour values, the circadian variation of BP adds prognostic significance in predicting cardiovascular outcome. However, the magnitude of circadian BP patterns in large studies has hardly been noticed. Our aims were to determine the prevalence of circadian BP patterns and to assess clinical conditions associated with the nondipping status in groups of both treated and untreated hypertensive subjects, studied separately. Clinical data and 24-hour ambulatory BP monitoring were obtained from 42 947 hypertensive patients included in the Spanish Society of Hypertension Ambulatory Blood Pressure Monitoring Registry. They were 8384 previously untreated and 34 563 treated hypertensives. Twenty-four-hour ambulatory BP monitoring was performed with an oscillometric device (SpaceLabs 90207). A nondipping pattern was defined when nocturnal systolic BP dip was⬍10% of daytime systolic BP. The prevalence of nondipping was 41% in the untreated group and 53% in treated patients. In both groups, advanced age, obesity, diabetes mellitus, and overt cardiovascular or renal disease were associated with a blunted nocturnal BP decline (P⬍0.001). In treated patients, nondipping was associated with the use of a higher number of antihypertensive drugs but not with the time of the day at which antihypertensive drugs were administered. In conclusion, a blunted nocturnal BP dip (the nondipping pattern) is common in hypertensive patients. A clinical pattern of high cardiovascular risk is associated with nondipping, suggesting that the blunted nocturnal BP dip may be merely a marker of high cardiovascular risk. (Hypertension. 2009;53:466-472.)
Key Words:circadian blood pressure pattern 䡲 nocturnal blood pressure dip 䡲 cardiovascular risk factors
䡲ambulatory blood pressure monitoring 䡲 hypertension
C
linic (office) blood pressure (BP) measurement has been the basis for the established relationship between ele-vated BP and cardiovascular morbidity and mortality.1–3Clinic BP, however, may not necessarily represent an indi-vidual’s usual BP level. Ambulatory BP monitoring (ABPM) has become an efficacious instrument aiding therapeutic decisions in hypertensive patients and other subjects at risk of cardiovascular disease. Moreover, ABPM offers more accu-rate prognostic information of cardiovascular outcomes than office readings. This has been demonstrated clearly in population-based surveys4,5 and in both treated6 – 8 and
un-treated7,9,10hypertensive subjects.
In addition to the mean 24-hour BP level, variation in the day-night BP pattern (the dipping status) has also been claimed as an important predictor of both target-organ dam-age and cardiovascular events.5,10 –12 On average, each 5%
attenuation in the decline in nocturnal systolic BP (SBP)/di-astolic BP (DBP) conferred an ⬇20% rise in the risk of cardiovascular mortality.11–13 Subjects with a blunted BP
decrease (⬍10%) or even an increase in BP during the night were those to exhibit a worse cardiovascular prognosis.9,13–15
However, the magnitude of the proportion of different circadian BP patterns has not been noticed previously in large studies carried out in daily practice. This may have not only
Continuing medical education (CME) credit is available for this article. Go to http://cme.ahajournals.org to take the quiz. Received October 1, 2008; first decision October 17, 2008; revision accepted December 24, 2008.
From the Hypertension Unit (A.d.l.S.), Hospital Clínic, University of Barcelona, Barcelona, Spain; Hypertension Unit, Hospital Clínico (J.R.), University of Valencia and Centro de Investigacio´n Biome´dica au Red (CIBER) of Obesity and Nutritional Disorders, Valencia, Spain; Department of Preventive Medicine and Public Health (J.R.B., J.J.d.l.C.), Autonomous University and CIBER of Epidemiology and Public Health, Madrid, Spain; Hypertension Unit (J.Segura, L.M.R.), Hospital 12 de Octubre, Madrid, Spain; Instituto Auxolo´gico (G.P.), Hospital San Genaro, Milan, Italy; Department of Nephrology (M.G.), Hospital San Agustín, Avile´s, Spain; Department of Medicine (J.Sobrino), Hospital de L’Espirit Sant, Santa Coloma de Gramanet, Spain; Centro de Salud Ingeniero Benlloch (J.L.L.), Valencia, Spain; Centro de Salud Sillería (J.A.), Toledo, Spain; Centre d’Atencio´ Primaria La Mina (E.V.), Barcelona, Spain; Unidad de Vigilancia de la Salud (V.P.), Unio´n de Mutuas, Castello´n, Spain; Instituto de Salud Carlos III (A.S.), Madrid, Spain; and Hypertension Unit (P.A.), Hospital Carlos Haya, Ma´laga, Spain.
Correspondence to Alejandro de la Sierra, Hypertension Unit, Department of Internal Medicine, Hospital Clínic, Villarroel 170, E-08036 Barcelona, Spain. E-mail asierra@clinic.ub.es
© 2009 American Heart Association, Inc.
Hypertensionis available at http://hyper.ahajournals.org DOI: 10.1161/HYPERTENSIONAHA.108.124008
clinical but also public health care relevance. Thus, the objectives of the present study were to determine the preva-lence of circadian BP patterns and to assess clinical condi-tions associated with the nondipping status in groups of both treated and untreated hypertensive subjects, studied sepa-rately. For all of the above purposes, we used the Spanish Society of Hypertension ABMP Registry, which is an ongo-ing nationwide project based on a large-scale network of primary care physicians trained in ABPM.
Patients and Methods
Study DesignThe Spanish Society of Hypertension ABPM Registry was devel-oped to promote the use of ABPM in clinical practice. The ABPM Registry is based on the distribution of ⬎900 ambulatory BP monitors, SpaceLabs 90207 (SpaceLabs Inc), for routine use by physicians from primary care centers and specialized units spread across the 17 autonomous communities covered by the public national health care system in Spain. Details of physician recruitment and characteristics of the registry have been reported previously.16 –20
Briefly, physicians and nurses received specific training about the technique of ABPM and used the internet-based platform that receives ABPM registries together with their corresponding medical charts. Physicians then obtained a result report on real time, and registries were stored in a database from an external clinical research organization. The protocol was approved by a series of institutional review boards from the different autonomous communities of Spain, and patients gave informed consent. The registry is continuously growing, with the reception of data of⬇1500 patients per month, with the first patient recruited in June 2004. For the purpose of the present study, 42 947 hypertensive patients (34 563 treated and 8384 untreated), recruited by 1126 physicians between June 2004 and December 2006, were selected.
Inclusion criteria were men and women agedⱖ18 years of age with either an office BPⱖ140 and/or 90 mm Hg obtained inⱖ2 measurements without receiving any antihypertensive agent (un-treated group; N⫽8384) or a documented diagnosis of essential hypertension, independent of office BP, under treatment withⱖ1 antihypertensive drug stable for ⱖ2 months (treated group; N⫽34 563). Moreover, for the inclusion in the study, it was necessary to obtain valid ABPM information and reliable, complete data on all of the variables required for the intended analysis. The diagnosis of hypertension was obtained following the Spanish Society of Hypertension guidelines,21 which, for diagnosis and
classification purposes, adopt the recommendations of the European Society of Hypertension/European Society of Cardiology.22 The
practice guidelines of the European Society of Hypertension for BP measurement were used to establish indications for ABPM.23
Exclu-sion criteria were extreme obesity with an arm circumference⬎42 cm and atrial fibrillation or other cardiac arrhythmias, which may interfere with ambulatory BP measurements.
BP Measurements
BP was measured at the office with a calibrated mercury sphygmo-manometer or a validated semiautomatic oscillometric device, after 5-minute rest in a sitting position. BP values were estimated as the mean of 2 readings. Thereafter, 24-hour ABPM was performed using the SpaceLabs 90207 automated noninvasive oscillometric device, programmed to register BP at 20-minute intervals for the 24-hour period. The majority of registries were performed on working days, and the patients were instructed to maintain their usual activities, return the following morning for device removal, and keep the arm extended and immobile at the time of each cuff inflation. Valid registries had to fulfill a series of preestablished criteria, including
ⱖ80% of SBP and DBP successful recordings during the daytime and nighttime periods, 24-hour duration, andⱖ1 BP measurement per hour. Daytime and nighttime periods were defined individually according to the patient self-reported data of going-to-bed and
getting-up times. Nocturnal BP decline and circadian patterns were defined by calculating the percentage of decline in both SBP and DBP during the night, using the following formula: (daytime BP⫺nighttime BP)/daytime BP.
Definition of Circadian Patterns
A normal dipping pattern (dipper) was diagnosed when the reduction in the average SBP during the night period was⬎10% of mean SBP during the day. When this proportion was⬎20%, the patient was classified as an extreme dipper. An abnormal dipper pattern (non-dipper) was diagnosed when the night average SBP reduction was
⬍10% with respect to day values. When the mean night SBP was higher than the day one, the patient was classified as a riser.
Study Variables
Variables collected for each patient based on the interviews and physical examination at the time of visit and on data drawn from clinical records were defined and measured in accordance with national and international guidelines.21,22These included age,
gen-der, weight, height, body mass index (BMI), duration of hyperten-sion, known cardiovascular risk factors (eg, smoking habit, dyslip-idemia, and diabetes mellitus), and clinical cardiovascular or renal disease (coronary heart disease, congestive heart failure, peripheral artery disease, cerebrovascular disease, or chronic renal failure). Details about antihypertensive treatment (generic name of drugs, and dosing time in a 3-category scheme: breakfast, lunch, and dinner) were collected in the group of treated patients.
Statistical Analysis
Data are presented as frequencies and percentages for qualitative variables and as means⫾SDs for quantitative variables. Differences in study variables between dipping and nondipping groups were assessed with the Pearson 2 for qualitative variables and the
Student’sttest for quantitative data. The following variables were considered: age (⬍60 orⱖ60 years); gender (male or female); time of day of clinical BP measurement (morning: 7:00AMto 12:00PMor evening: 12:00PMon); duration of hypertension (in years); number of antihypertensive drugs used (1 orⱖ2); time of day of antihyper-tensive drug administration (morning, evening, or morning and evening); obesity (BMI⬍30 orⱖ30 kg/m2); tobacco smoking (yes
or no); dyslipidemia (yes or no); diabetes mellitus (yes or no); and personal history of clinical cardiovascular disease or renal disease (yes or no). Associations are expressed as odds ratios with 95% CIs. Statistical significance was set atP⬍0.05. The relationships between relative nocturnal BP decline and study variables were assessed by multiple linear regression analysis. Variables significantly associated with nondipping status in the univariate analyses were subjected to multivariate analysis with a logistic regression procedure and for-ward stepwise selection ifPvalue was⬍0.20 after univariate testing. The SPSS for Windows 13.0 software (SPSS Inc) was used for statistical analysis.
Results
General Characteristics of Patients Included
In the cohort of 8384 untreated patients, 55.6% were men, with a mean age of 53.2⫾13.8 years. Office SBP/DBP was 152.1⫾14.2/92.7⫾9.9 mm Hg, and 24-hour ambulatory BP
was 132.0⫾12.7/80.8⫾9.6 mm Hg. Mean BMI was
28.1⫾4.4 kg/m2. Cardiovascular risk factors included dyslip-idemia in 27.5% of cases, diabetes mellitus in 9.3%, and current smoking in 21.1%. History of cardiovascular clinical conditions included coronary heart disease in 1.6%, stroke in 1.5%, congestive heart failure in 0.5%, and chronic renal disease in 0.3%.
In the cohort of 34 563 treated patients, 53% were men, and the mean age was 60.0⫾13.8 years. Office SBP/DBP was 149.5⫾19.3/87.8⫾11.7 mm Hg, and 24-hour ambulatory BP
was 130.6⫾14.6/77.0⫾19.3 mm Hg. Approximately 57% of patients were on monotherapy, and 79% took their
medica-tion in the morning. Mean BMI was 29.0⫾4.7 kg/m2.
Cardiovascular risk factors included dyslipidemia in 37.5% of cases, diabetes mellitus in 18.7%, and current smoking in 17.2%. History of cardiovascular clinical conditions included coronary heart disease in 6.3%, stroke in 4.1%, congestive heart failure in 2.2%, and chronic renal disease in 1.7%.
Prevalence of Different Circadian Patterns
In the cohort of untreated patients, dippers accounted for 50.2% (n⫽4208) of the study population, extreme dippers for 8.8% (n⫽740), nondippers for 35.0% (n⫽2934), and risers for 6.0% (n⫽502). The prevalence of dipping (dippers/ extreme dippers) and nondipping (nondippers/risers) patterns was 59% and 41%, respectively (Figure, left).
In the cohort of patients receiving antihypertensive treat-ment, dippers accounted for 39.9% (n⫽13 800), extreme
dippers for 7.2% (n⫽2499), nondippers for 39.4%
(n⫽13 594), and risers for 13.5% (n⫽4670). The prevalence of dipping (dippers/extreme dippers) and nondipping (non-dippers/risers) patterns was 47.2% and 52.8%, respectively (Figure, right).
Clinical Characteristics Associated With Dipping Status
The main characteristics of the study sample according to dipping status are shown in Table 1. Dippers and nondippers showed statistically significant differences in most of the study variables, and these differences were consistent in both groups of untreated and treated patients. Those with a nondipping profile were older, more frequently women and obese, and had a longer duration of hypertension. They also more frequently had a previous diagnosis of dyslipidemia, type 2 diabetes mellitus, or cardiovascular disease. Con-versely, the proportion of smokers was slightly lower in those with a nondipping pattern, in both treated and untreated patients.
Dipping status was not associated with the presence of isolated clinical hypertension (“white coat”) in untreated patients or with isolated office resistance in the treated group, because the proportion of patients with 24-hour BP ⬍130/ 80 mm Hg was similar in dippers and nondippers. In the cohort of patients receiving antihypertensive therapy, nondip-ping status was associated with the use of a greater number of
drugs (P⬍0.001) but not with the time of the day when treatment was administered (P⫽0.352).
When the relative nocturnal BP decline was analyzed as a continuous variable, again, older patients, obese, nonsmokers, diabetics, and those with previous cardiovascular disease had a blunted SBP and DBP decline during the night (Tables S1 and S2, please see the online data supplement at http:// hyper.ahajournals.org). Moreover, in the group of treated patients, BP decline was less pronounced in those treated with
⬎1 agent but minimally influenced by the time of drug administration (Tables S1 and S2).
We performed a multiple linear regression analysis and found that blunted nocturnal SBP (Table 2) and DBP (Table S3) decline were associated with most of the variables that were statistically significant in the bivariate analysis, includ-ing age, gender, BMI, diabetes mellitus, and previous cardio-vascular disease. Relationships were consistent in both treated and untreated patients, as well as in the entire cohort and for both SBP and DBP dip. The exceptions were female gender, which for diastolic dipping was only significant in the treated cohort, and nonsmoking, which was only significant for systolic dipping in treated patients.
Furthermore, the inclusion of the type of treatment (major classes of drugs, all possible combinations of 2 drugs and the combination of ⱖ3 drugs) did not significantly affect the variables associated with the nocturnal BP decline (data not shown). In the whole group and in those treated, a blunted nocturnal BP decline was also associated with a greater number of antihypertensive drugs (Table 2 and Table S3).
Finally, the results of the multiple logistic analysis also revealed a very close pattern of variables associated with the dipping status in both treated and untreated subjects, as well as in the entire cohort (Table 3). After adjusting for 24-hour SBP and DBP, age⬎60 years, and BMI⬎30 kg/m2, diabetes mellitus and overt cardiovascular or renal disease were associated with the nondipping status. Moreover, in the group of treated patients, treatment with⬎1 antihypertensive agent was also associated with nondipping.
Discussion
The present study, carried out in a large population of both treated and untreated hypertensive outpatients attended in routine conditions of daily practice, showed that ⬇50% of hypertensives presented a blunted nocturnal BP decline. The proportion was lower in untreated patients (41%) and higher Untreated group (N=8384)
740
4208 502
2934
Extreme dipper Dipper
Non-dipper Riser
Treated group (N=34563) 2499
13800
13594 4670
Extreme dipper Dipper
Non-dipper Riser
in the treated group (53%). Factors associated with a nondip-ping status, however, were consistently similar in both untreated and treated patients and related to an older age, other cardiovascular risk factors (eg, obesity and diabetes), and overt cardiovascular or renal disease. As a consequence of the blunted BP nocturnal fall, nocturnal BP values were significantly higher in nondipping hypertensives as compared with the dippers, even when no differences were present during the awake period.
In addition, some relevant information emerged from the group of patients receiving antihypertensive therapy. Despite the fact that antihypertensive treatment increased the proba-bility of a nondipping pattern, whatever the time at which the medication is given, a blunted nocturnal BP decline was associated with the need for more antihypertensive drugs used for BP control.
There is no doubt regarding the importance of ABPM in the diagnosis and management of hypertension, as stated in international guidelines.22,23 Twenty-four-hour BP provides
refined prognostic information regarding future cardiovascu-lar outcomes in comparison with office or clinic BP4 –10and
also helps in making therapeutic decisions in patients who exhibit discordance between clinic and ambulatory BP values (isolated office hypertension or resistance and masked
hyper-tension).24 The Spanish Society of Hypertension ABPM
Registry has contributed by extending the use of ABPM in primary practice. Furthermore, the large number of patients included in the registry has aided to collect relevant informa-tion about several ABPM-related parameters, as reflected in previous reports.16 –20
The relative prognostic importance of nocturnal BP decline has generated a great scientific interest.5,9,10 –15,25 A blunted
Table 1. Characteristics of Untreated and Treated Hypertensive Patients According to Dipping (Dippers/Extreme Dippers) and Nondipping (Nondippers/Risers) Status
Variable
Untreated Patients Treated Patients
Dipping (n⫽4948)
Nondipping
(n⫽3436) P
Dipping (n⫽16 299)
Nondipping
(n⫽18 264) P
Sex, % women 42.7 46.9 0.001 45.5 48.5 ⬍0.001
Age, y 51.1⫾13.1 56.3⫾14.1 ⬍0.001 55.7⫾13.5 61.9⫾13.3 ⬍0.001
Ageⱖ60 y, % 25.7 42.4 ⬍0.001 39.8 59.8 ⬍0.001
SBP, mm Hg
Clinic 151.9⫾13.8 152.4⫾14.8 0.117 149.1⫾18.4 149.8⫾20.0 0.003
24-h 131.1⫾11.8 133.3⫾13.8 ⬍0.001 129.3⫾13.1 131.7⫾15.7 ⬍0.001
Daytime 136.6⫾12.3 135.0⫾14.0 ⬍0.001 134.7⫾13.7 132.8⫾15.7 ⬍0.001
Nighttime 115.0⫾11.2 128.5⫾14.4 ⬍0.001 113.6⫾12.3 128.6⫾16.8 ⬍0.001
% Nocturnal decline in BP, mm Hg 15.7⫾4.1 4.7⫾4.9 ⬍0.001 15.6⫾4.2 3.1⫾6.1 ⬍0.001
DBP, mm Hg
Clinic 93.0⫾9.6 92.2⫾10.4 ⬍0.001 89.0⫾11.1 86.6⫾12.1 ⬍0.001
24-h 81.2⫾9.1 80.2⫾10.2 ⬍0.001 78.2⫾9.7 76.2⫾10.6 ⬍0.001
Daytime 85.6⫾9.5 82.2⫾10.4 ⬍0.001 82.3⫾10.1 77.8⫾10.9 ⬍0.001
Nighttime 68.2⫾8.7 74.5⫾10.3 ⬍0.001 65.7⫾9.1 71.6⫾10.7 ⬍0.001
% Nocturnal decline in BP, mm Hg 20.4⫾5.6 9.1⫾6.4 ⬍0.001 20.2⫾5.7 7.8⫾7.1 ⬍0.001
24 h BP⬍130/80 mm Hg, % 31.9 31.3 0.604 42.5 41.5 0.057
Office BP measured in the morning, % 78.8 79.2 0.635 77.9 79.0 0.010
Duration of hypertension, y 1.3⫾2.9 1.8⫾4.0 ⬍0.001 4.9⫾6.4 6.9⫾7.5 ⬍0.001
Proportion of patients treated withⱖ2 antihypertensive agents, %
NA NA 35.3 49.7 ⬍0.001
Proportion of patients receiving all or part of their antihypertensive medication at night, %
NA NA 20.5 21.2 0.352
BMI, kg/m2 27.8⫾4.2 28.4⫾4.6 ⬍0.001 28.6⫾4.5 29.3⫾4.8 ⬍0.001
BMIⱖ30 kg/m2, % 25.8 31.0 ⬍0.001 32.7 39.6 ⬍0.001
Current smoking, % 22.5 19.7 0.002 19.5 15.1 ⬍0.001
Dyslipidemia, % 27.6 29.5 0.056 35.2 39.5 ⬍0.001
Diabetes mellitus, % 7.3 12.4 ⬍0.001 14.5 22.4 ⬍0.001
History of cardiovascular disease, %
Congestive heart failure 0.4 0.6 0.401 1.5 2.8 ⬍0.001
Cerebrovascular disease 1.1 2.0 0.001 2.9 5.2 ⬍0.001
Coronary heart disease 1.0 2.3 ⬍0.001 4.1 8.3 ⬍0.001
Chronic renal disease 0.2 0.4 0.188 1.0 2.3 ⬍0.001
NA indicates not applicable.
nighttime BP decline is also regarded as a prognostic marker of cardiovascular events, both in hypertensive subjects7,9,11,15
and in the general population.12,13 Using a large cohort of
patients from the ABPM Spanish database, we have observed that the amount of nocturnal BP decline was closely related to the level of risk. Nondipping was associated with advanced age, obesity, and diabetes mellitus, conditions that increase cardiovascular risk. Moreover, a history of previous cardio-vascular or renal disease was more common in nondippers than in dippers.
It has been claimed that categorization of patients into dippers and nondippers is poorly reproducible26,27and leads
to some confusion when its relationship with potential clini-cal associated factors is examined. In the present study, however, the results obtained by categorization of patients into dippers and nondippers or by regarding the relative nocturnal BP decline as a continuous variable were essen-tially the same, thus enhancing the consistency of the observation.
Equally important is that clinical variables associated with a nondipping pattern were present in both treated and
un-treated patients. The multivariate analysis performed in the present study (the multiple linear regression using relative nocturnal BP decline as the dependent variable and the logistic regression of the variables associated with the dip-ping status) yielded similar results. In fact, most of the variables included in the analysis maintained their statistical significance, and the results were similar in treated and untreated patients, as well as in the entire cohort.
The proportion of nondipping status was higher and the relative nocturnal BP decline was blunted in the cohort of treated patients compared with the untreated one. This has been attributed to the use of antihypertensive treatment, which is commonly administered in the morning and lowers BP, especially during daytime.7,12With the data of the present
study, it seems to be an inaccurate assumption. When patients taking medication in the morning, in the evening, or twice a day were compared, no differences in the relative nocturnal BP decline were observed. Moreover, the proportion of patients receiving all or a part of their medication at night was not different between dippers and nondippers. Consequently,
Table 2. Results of Multiple Linear Regression Analysis of Independent Variables Associated With the Relative Nocturnal SBP Decline
Variable
Untreated Patients Treated Patients All Patients
Coefficient(95% CI) P Coefficient(95% CI) P Coefficient(95% CI) P Age, y ⫺0.089 (⫺0.098 to⫺0.079) ⬍0.001 ⫺0.139 (⫺0.148 to⫺0.130) ⬍0.001 ⫺0.119 (⫺0.126 to⫺0.113) ⬍0.001
Female gender ⫺0.314 (⫺0.580 to⫺0.048) 0.021 ⫺0.228 (⫺0.442 to⫺0.014) 0.037 ⫺0.274 (⫺0.443 to⫺0.106) 0.001
BMI, kg/m2 ⫺0.093 (⫺0.123 to⫺0.063) ⬍0.001 ⫺0.092 (⫺0.114 to⫺0.069) ⬍0.001 ⫺0.088 (⫺0.106 to⫺0.070) ⬍0.001
Smoking NS 0.343 (0.045 to 0.641) 0.024 0.352 (0.128 to 0.576) 0.002
Diabetes mellitus ⫺1.141 (⫺1.852 to⫺0.969) ⬍0.001 ⫺0.894 (⫺1.149 to⫺0.640) ⬍0.001 ⫺1.033 (⫺1.252 to⫺0.815) ⬍0.001
Ischemic heart disease ⫺2.076 (⫺3.043 to⫺1.109) ⬍0.001 ⫺2.183 (⫺2.565 to⫺1.801) ⬍0.001 ⫺2.211 (⫺2.557 to⫺1.866) ⬍0.001
Chronic kidney disease ⫺2.622 (⫺4.958 to⫺0.287) 0.028 ⫺1.339 (⫺2.030 to⫺0.646) ⬍0.001 ⫺1.469 (⫺2.110 to⫺0.827) ⬍0.001
Cerebrovascular disease ⫺1.465 (⫺3.345 to⫺0.176) 0.005 ⫺1.487 (⫺1.954 to⫺1.019) ⬍0.001 ⫺1.524 (⫺1.940 to⫺1.108) ⬍0.001
Congestive heart failure NS ⫺1.339 (⫺2.032 to⫺0.646) ⬍0.001 ⫺1.523 (⫺2.087 to⫺0.960) ⬍0.001
No. of antihypertensive drugs* NA ⫺0.683 (⫺0.785 to⫺0.581) ⬍0.001 ⫺0.663 (⫺0.733 to⫺0.593) ⬍0.001
NS indicates not significant; NA, not applicable.
*Data are from 1 drug onward in treated patients and from 0 drugs onward in the entire group.
Table 3. Logistic Regression Analysis
Variable Reference
Untreated Patients Treated Patients All Patients
Odds Ratio (95% CI) P Odds Ratio (95% CI) P Odds Ratio (95% CI) P
Age,ⱖ60 y ⬍60 y 1.83 (1.66 to 2.02) ⬍0.001 1.57 (1.47 to 1.67) ⬍0.001 1.64 (1.56 to 1.73) ⬍0.001
Female gender Male 1.10 (1.01 to 1.19) 0.028 NS NS
BMI,ⱖ30 kg/m2 ⬍30 kg/m2 1.23 (1.12 to 1.35) ⬍0.001 1.20 (1.13 to 1.26) ⬍0.001 1.19 (1.14 to 1.25) ⬍0.001
Current smoker Non smoker NS NS NS
Dyslipidemia, present Absent NS 1.09 (1.04 to 1.14) 0.018 1.05 (1.01 to 1.10) 0.035
Diabetes mellitus, present Absent 1.42 (1.24 to 1.62) ⬍0.001 1.14 (1.06 to 1.22) ⬍0.001 1.19 (1.12 to 1.27) ⬍0.001
Overt cardiovascular or renal disease
Absent 1.63 (1.34 to 2.00) ⬍0.001 1.52 (1.41 to 1.64) ⬍0.001 1.52 (1.42 to 1.64) ⬍0.001
No. of antihypertensive drugs
ⱖ1 No treatment NA NA 1.25 (1.18 to 1.33) ⬍0.001
the level of risk with higher proportions of elderly subjects, diabetics, and those with a history of cardiovascular or renal disease, in comparison with the untreated cohort, can explain the presence of nondipping. The need for more antihyperten-sive drugs in the nondipping group could also reflect the severity and the difficulty in treating elevated BP.
The present findings should be interpreted taking into account some limitations of the study, including the cross-sectional design, which precludes conclusions about causal relationships, and the classification of dippers and nondippers with a single 24-hour ABPM. The poor reproducibility over time of the classification of hypertensive patients into dippers and nondippers based on single ABPM has already been mentioned,26,27but the concordance of the results obtained by
looking at the night:day ratio as a continuous variable adds scientific validity to the results obtained. Furthermore, the large number of patients included in the analysis adds also strength to the observation of a high prevalence of a nondip-ping pattern and the identification of independent variables significantly associated with blunted BP decrease during the night.
Perspectives
The findings of the present study have implications in clinical practice. The circadian pattern was analyzed in the greatest cohort of patients with ABMP data obtained until now. In hypertensives, treated and nontreated, a worse cardiovascular risk profile, including advanced age, other risk factors, and diseases are the main factors associated with a blunted nocturnal BP decrease or a nondipping pattern. In this sense, this circadian pattern could be seen as a marker of high cardiovascular risk, helping to achieve more refined prognos-tic information.28 Although treated patients are more often
nondippers, our results suggest that the level of risk could be the main responsibility of nondipping and not the treatment itself.
Acknowledgments
We thank all of those members of the Spanish Society of Hyperten-sion Ambulatory Blood Pressure Monitoring Registry who partici-pated in the study. The names of all of the participating practitio-ners have been published previously and are available at http:// www.cardiorisc.com. We thank Marta Pulido, MD, for editing the article and for editorial assistance.
Source of Funding
The main funding for the study was obtained from Lacer Spain, SA, through an unrestricted educational grant.
Disclosures
None.References
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