Home blood pressure monitoring (HBPM) is well accepted among patients [
There are diurnal variations in HBPM averages, and current guidelines recommend the BP measurements to be performed at least in the morning and in the evening [
The diurnal HBPM rhythm may provide important prognostic information. For instance, studies have highlighted the stand-alone predictive ability of morning over evening BP for subclinical target organ damage [
The home-based morning/evening BP difference (MEdiff) is a potentially useful index for the management of treated hypertensive patients, which is calculated as morning minus evening home BP. It is already known to be a significant predictor of left ventricular hypertrophy [
In this study we attempted to clarify the determinants of home MEdiff in a standardized fashion in Argentine medicated patients referred to an institution for BP control.
This was a cross-sectional study where medical records were reviewed retrospectively to extract data from hypertensive outpatients aged ≥18 years referred for an HBPM by their treating physicians to the Hypertension Section, Department of Internal Medicine,
We used the hospital’s electronic medical database in order to obtain information on medical history, intake of medications, and smoking habits of each participant. Hypertension was classified as a conventional BP of at least 140 mmHg systolic or 90 mmHg diastolic and an average home BP of at least 135 mmHg systolic or 85 mmHg diastolic according to internationally accepted limits [
According to a protocol already published by our group [
All data are expressed as mean ± SD or percentage. For comparison of means and proportions, we applied
In total, there were 376 patients included in the study, of which 9 were discarded due to lack of morning or evening measurements. Of the remaining 367 subjects who were finally included for analysis, 365 (99.5%) were Caucasians, 242 (65.9%) were women, and 43 (11.7%) were current smokers. All of the patients were taking one or more blood pressure-lowering drugs (mean ± SD: 2.2 ± 1.0): calcium-channel blockers (204, 55.6%), diuretics (136, 37.1%), ACE inhibitors (132, 36.0%), angiotensin receptor blockers (148, 40.3%), beta blockers (142, 38.7%), alpha blockers (15, 4.1%), and other drug groups (13, 3.5%). Age ranged from 25 to 91 years (mean ± SD: 66.2 ± 14.5). The number of total self-recorded BP measurements ranged from 16 to 28 (mean ± SD: 24.7 ± 2.9). Hyperlipidemia and diabetes mellitus were observed in 71.1% and 10.6% of patients, respectively (Table
Characteristics of the study population.
Characteristic | Total |
---|---|
Number of subjects (%) | 367 |
Women | 242 (65.9) |
Caucasians | 365 (99.5) |
Smokers | 43 (11.7) |
Uncontrolled hypertension | 133 (36.2) |
Diabetes mellitus | 39 (10.6) |
Previous cardiovascular disease | 42 (11.4) |
Previous cerebrovascular disease | 24 (6.5) |
Mean (±SD) characteristic | |
Age, y | 66.2 (14.5) |
Body mass index, kg/m2 | 28.1 (4.5) |
Conventional BP, mmHg | |
Systolic | 140.3 (17.5) |
Diastolic | 79.6 (10.7) |
Self-recorded systolic BP, mmHg | |
All measurements | 131.5 (14.1) |
Morning | 133.1 (16.5) |
Evening | 132.0 (15.7) |
Morning-evening difference | 1.1 (12.5) |
Self-recorded diastolic BP, mmHg | |
All measurements | 73.8 (7.6) |
Morning | 75.8 (8.4) |
Evening | 73.5 (8.2) |
Morning-evening difference | 2.3 (6.1) |
Self-recorded pulse rate, beats/min | |
All measurements | 71.3 (10.9) |
Morning | 69.4 (11.2) |
Evening | 72.0 (11.6) |
Number of self-recorded BP measurements | 24.7 (2.9) |
Number of antihypertensive drugs | 2.2 (1.0) |
Serum cholesterol, mmol/L | 4.89 (1.0) |
Uncontrolled hypertension was a home blood pressure of at least 135 mmHg systolic or 85 mmHg diastolic. Diabetes mellitus was a self-reported diagnosis, a fasting or random blood glucose level of 7.0 mmol/L (126 mg/dL) or 11.1 mmol/L (200 mg/dL) or higher, or a use of antidiabetic drugs. Smoking was daily use of tobacco products. Previous cardiovascular disease included ischemic heart disease, atrial fibrillation, or congestive heart failure. Previous cerebrovascular disease included transient ischemic attack or stroke.
Mean conventional BP was 140.3 ± 17.5/79.6 ± 10.7 mmHg. Mean total self-recorded BP was 131.5 ± 14.1/73.8 ± 7.6 mmHg. Morning and evening home BPs were 133.1 ± 16.5/75.8 ± 8.4 and 132.0 ± 15.7/73.5 ± 8.2 mmHg, respectively. Uncontrolled hypertension on conventional BP measurements was observed in 208 (56.7%) patients and on home-based BP measurements in 133 (36.2%) patients, according to clinic and home BP cutoff levels suggested in hypertension guidelines [
The MEdiff ranged from −56.7 to 56.5 mmHg systolic (mean ± SD: 1.1 ± 12.5,
In smokers, MEdiff was −
After excluding smokers in the analysis, overall MEdiff reached statistical significance for both systolic (
In univariate analyses, the variables analyzed were age, gender, ethnicity, smoking habit, office systolic and diastolic, BMI, diabetes, history of cardiovascular and cerebrovascular disease, number and class of antihypertensive drugs, and total cholesterol. Of these, the significantly predictive variables which were later incorporated to the multivariable linear regression model were age (
In the multivariable analysis of our study, the independent determinants of elevated systolic MEdiff were age and smoking and of diastolic MEdiff were age, smoking, total cholesterol, and calcium-channel blockers. These determinants explained 6.2% and 8.5% of the variance in systolic and diastolic morning-evening home BP difference (Table
Multivariable linear regression model for morning-evening blood pressure difference.
Variable | Beta-coefficient |
|
---|---|---|
Systolic morning-evening home BP difference | ||
Age | 0.12 (0.03–0.21) | 0.007 |
Smoking habit | −7.52 (−11.44–[−3.61]) | <0.0001 |
Diastolic morning-evening home BP difference | ||
Age | 0.07 (0.03–0.12) | 0.001 |
Total cholesterol | 0.99 (0.38–1.6) | 0.002 |
CCB use | 1.44 (0.21–2.66) | 0.02 |
Smoking habit | −2.91 (−4.81–[−1.02]) | 0.003 |
Adjusted
The purpose of our study was to evaluate the determinants of home-based MEdiff in Argentine patients who were referred to the Hypertension Section of our hospital to perform an HBPM. Our main finding in 367 subjects was that older age, smoking, total cholesterol, and use of calcium-channel blockers were independent determinants of the home-based MEdiff. To the best of our knowledge, these are the first data of the kind gathered from a South American group, mainly comprising Caucasian urban middle-class individuals, predominantly females.
In the subjects of our study we found that, with the exception of smokers, in which home BP had a higher evening profile, home diastolic BP was significantly higher in the morning than in the evening and after excluding smokers from our cohort both systolic and diastolic BPs were significantly higher in the morning. These findings are similar to those studies performed in Northeast Asia [
Ethnic variations have been explained before partly by the difference in evening BP measuring times: for instance, the Japanese guidelines [
In our study, patients were instructed to take the measurements before supper, in order to prevent a postprandial effect on evening BP measurements, which has already been characterized with HBPM after lunch [
Since taking a night-time shower or drinking alcohol are very uncommon in our setting, we would assume that there was not an association between evening BP decreases and these circumstances in our cohort of patients. However, since our results were more similar to the Japanese, it may be well expected that other factors may have played a role in decreasing evening home BP or increasing morning home BP other than the aforementioned lifestyle habits and the HBPM schedule.
One of the most likely relevant factors influencing the circadian home BP pattern in this study may have been the fact that all the subjects were under medication. The type, dosage, timing, and pharmacokinetic profiles of the antihypertensive drugs used may partly explain these BP differences, especially since subjects were instructed to measure morning home BP before the intake of medication. These drugs and time-related features may have also exaggerated the MEdiff in those studies which showed a similar morning-higher-than-evening pattern, such as the Japanese study of Ishikawa et al. [
Typically, medications are taken once a day, mostly in the morning, and the peak of the antihypertensive effect is observed in the evening. However, none of the studies has specified timing of medication nor associations with simple versus long-acting agents nor treatment scheduling.
In our study, CCBs appeared as the only group of drugs to independently determine home-based diastolic MEdiff.
The evidence on the effect of antihypertensive drugs by group on self-measured MEdiff is very limited. In previous studies, Ikeda et al. [
On the other hand, Ishikawa et al. [
In day-by-day home BP variability, the evidence is also rather limited and shows a favourable effect of CCBs (amlodipine, in particular) but not of
Our data are in contradiction with these favourable effects of CCBs on home BP variability, which have been attributed to many intrinsic features such as their vasodilating effects on peripheral muscular arteries, decreased peripheral resistance, increased baroreflex sensitivity, reduced arterial stiffness, and long elimination half-lives. They also contradict the results with
To the best of our knowledge, this is the first study to show an association between total cholesterol and home-based diastolic MEdiff. Lee et al. [
However, total cholesterol has been linked to other forms of variability such as within visit BP variability [
Older age was found to be a determinant for both systolic and diastolic MEdiff levels in this study. This is consistent with findings by other authors [
In our study, smoking was an independent determinant of both systolic and diastolic home MEdiff levels and was associated with a decrease in MEdiff levels. Home systolic BP in this group was significantly higher in the evening than in the morning.
In this respect, information from previous studies is consistent with these results. The J-MORE study [
Tobacco consumption has interindividual behavioural variations during the day because each person has different sleeping rhythms and daytime customs when it comes to lighting a cigarette. However, the evening-type smokers of both genders are more likely to be current and ever smokers due to nicotine dependence than the morning types [
Pathophysiologically, the effect may be partly explained by several mechanisms such as increased arterial stiffness and aortic wave reflection [
Due to the hospital-based nature of our study, it is difficult to generalize the present findings to the overall community. In addition, the patients affiliated to our health plan are mainly urban Argentine middle-class individuals of European descent (in the majority of cases Italian and Spanish) who may not reflect other ethnicities living in South America.
Since the information on smoking habits and intake of medications was obtained from an electronic medical registry, the number of smokers and drugs used by the patients may have been underestimated. In addition, timing of smoking and intake of medication were not controlled.
Interpretation of the results should be analyzed carefully due to the cross-sectional nature of the study which precludes cause-effect relationships and also because an exaggerated response in home MEdiff may be a reflection of two separate phenomena, an increase in morning BP and/or a decrease in evening BP.
In a general population, Asayama et al. [
In conclusion, in a cohort of Argentine medicated patients, in whom timing and dosage of treatment were not controlled, older age, smoking, total cholesterol, and use of calcium-channel blockers were independent determinants of home-based MEdiff. BP was higher in the morning except for smokers.
The authors declare that there is no conflict of interests regarding the publication of this paper.