Abstract
We investigated the prognostic value of morning surge (MS) of blood pressure (BP) in middle‐aged treated hypertensive patients. The occurrence of a composite end point (coronary events, stroke, and heart failure requiring hospitalization) was evaluated in 1073 middle‐aged treated hypertensive patients (mean age 49 years). Patients with preawakening MS of BP above the 90th percentile (27/20.5 mm Hg for systolic/diastolic BP) were defined as having high MS of BP. During the follow‐up (mean 10.9 years), 131 cardiovascular events occurred. After adjustment for various covariates, including known risk markers and ambulatory BP parameters, patients with high MS of systolic BP (hazard ratio 1.81, 95% confidence interval 1.10‐2.96) and those with high MS of diastolic BP (hazard ratio 1.98, 95% confidence interval 1.19‐3.28) were at higher cardiovascular risk than those with normal MS. In middle‐aged treated hypertensive patients, high MS of systolic and diastolic BP is independently associated with increased cardiovascular risk.
Keywords: ambulatory blood pressure, cardiovascular risk, hypertension, morning surge
1. INTRODUCTION
Various studies have detected a circadian variation in the onset of cardiovascular events characterized by a higher incidence in the morning.1, 2, 3, 4 Ambulatory blood pressure (BP) monitoring has revealed that BP exhibits a similar diurnal variation, attaining the highest values during the morning in the majority of individuals. This discovery suggested that a high morning surge (MS) of BP might be involved in the occurrence of cardiovascular complications.
Some investigators assessed the association between MS of BP and future cardiovascular events, both in hypertensive patients5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and in general populations.15, 16, 17, 18, 19, 20 The available evidence, however, is not homogeneous.5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 In hypertensive patients, as well as in general populations, some studies6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 17 observed a negative prognostic impact of MS, whereas others5, 8, 18, 19, 20 did not. These discrepancies may be related to the characteristics of the studied population, that is, normotensive or hypertensive, young or old, untreated or treated, and to ethnic differences, methodological issues, and the confounding relationship of MS with other features of 24‐hour BP profile, such as nighttime BP pattern.5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24
Studies evaluating hypertensive patients included middle‐aged and old untreated patients,7, 8 middle‐aged and old untreated and treated patients,9, 11 old untreated and treated individuals,5, 6 and old treated patients.10, 12, 13, 14 Thus, no study specifically assessed the impact of MS in middle‐aged treated hypertensive patients.
The aim of this study was to evaluate the prognostic value of MS of BP in middle‐aged treated hypertensive patients.
2. METHODS
2.1. Patients
We built two prospective databases of our initially untreated or initially treated hypertensive patients, since 1992, to evaluate the prognostic value of ambulatory BP parameters and other risk markers. This study is one of those conducted with the database of initially treated patients. We studied 1073 sequential treated hypertensive patients aged 30‐59 years prospectively recruited from December 1992 to December 2012. Patients were referred to our hospital outpatient clinic for evaluation of BP control. Forty‐one patients were lost during follow‐up. Patients with secondary hypertension were excluded. All the individuals underwent clinical evaluation, electrocardiogram, routine laboratory tests, echocardiographic examination, and noninvasive ambulatory BP monitoring. Study population came from the same geographical area (Chieti and Pescara, Abruzzo, Italy). The study was in accordance with the Second Declaration of Helsinki and was approved by the institutional review committee. Patients gave informed consent.
2.2. Clinic BP measurement
Clinic BP was recorded by a physician using a mercury sphygmomanometer and appropriate‐sized cuffs. Measurements were performed in triplicate, 2 minutes apart, and the mean value was used as the BP for the visit. Clinic systolic and diastolic BP were defined as normal when they were <140 and <90 mm Hg.
2.3. Ambulatory BP monitoring
Ambulatory BP monitoring was performed by using a portable noninvasive recorder (SpaceLabs 90207) on a typical day, within 1 week from clinic visit. Each time a reading was taken, patients were instructed to remain motionless and to report their activity on a diary sheet. Technical aspects have been previously reported.25 Ambulatory BP readings were obtained at 15‐minute intervals from 6 am to midnight, and at 30‐minute intervals from midnight to 6 am. We evaluated the following ambulatory BP parameters: daytime (awake period as reported in the diary), nighttime (asleep period as reported in the diary) and 24‐hour systolic and diastolic BP, the extent of BP reduction from day to night (those with BP fall <10% were defined as nondippers and those with BP fall ≥10% as dippers), and preawakening MS of BP defined as the difference between the mean BP during the 2 hours after waking and the mean BP during the 2 hours before waking.6, 10, 12, 13, 14 Patients with MS values above the 90th percentile (27/20.5 mm Hg for systolic/diastolic BP) were defined as having high MS of BP. Recordings were automatically edited (ie, excluded) if systolic BP was >260 or <70 mm Hg or if diastolic BP was >150 or <40 mm Hg and pulse pressure was >150 or <20 mm Hg. All the patients had recordings of good quality (at least 70% of valid readings during the 24‐hour period, at least 20 valid readings while awake with at least two valid readings per hour and at least seven valid readings while asleep with at least one valid reading per hour), in line with minimum requirement suggested by the European Society of Hypertension.26
2.4. Echocardiography
Left atrial (LA) and left ventricular (LV) measurements and calculation of LV mass were performed according to standardized methods.27 LA diameter (cm) was indexed by body surface area (m2), and LA enlargement was defined as LA diameter/body surface area ≥2.4 cm/m2.27 LV mass was indexed by height2.7, and LV hypertrophy was defined as LV mass/height2.7 >50 g/m2.7 in men and >47 g/m2.7 in women.28 LV ejection fraction was estimated using the Teichholz formula or the Simpson rule and defined as low when it was <50%.27
2.5. Follow‐up
Patients were followed up in our hospital outpatient clinic or by their family doctors.
The occurrence of cardiovascular events was recorded during follow‐up visits or by telephone interview of the patient followed by a clinical visit. Later, medical records were obtained to confirm the events. Data were collected by the authors of this study. Those reviewing the end points were blinded to other patients’ data. In this report, we evaluated a combined end point including coronary events (sudden death, fatal and nonfatal myocardial infarction, and coronary revascularization), fatal and nonfatal stroke, and heart failure requiring hospitalization. Outcomes were defined according to standard criteria as previously reported.10, 12, 13, 14
2.6. Statistical analysis
Standard descriptive statistics were used. Study groups were compared by using unpaired t test and chi‐square or Fisher's exact test, where appropriate. Event rates are expressed as the number of events per 100 patient‐years based on the ratio of the observed number of events to the total number of patient‐years of exposure up to the terminating event or censor. Survival curves were estimated using the Kaplan‐Meier product‐limit method and compared by the log‐rank test. Cox regression analysis was used to estimate univariate and multivariate association of factors with outcome. First, we evaluated univariate association between cardiovascular events and age, gender, body mass index, smoking habit, family history of cardiovascular disease (FHCVD), previous events, diabetes, estimated glomerular filtration rate, low‐density lipoprotein (LDL) cholesterol, LV hypertrophy, asymptomatic LV systolic dysfunction at baseline, LA enlargement, clinic, daytime, nighttime, and 24‐hour systolic and diastolic BP, dipping status, high vs normal MS, antihypertensive, antiplatelet and statin therapy at baseline, and atrial fibrillation. Then, multiple regression analysis was performed reporting in the final model variables that were significantly (P < 0.05) associated with outcome in univariate analysis. The forced entry model was used. Statistical significance was defined as P < 0.05. Analyses were made with the SPSS 21 software package (SPSS Inc). Graphs were made with GraphPad Prism 5 (GraphPad software Inc).
3. RESULTS
Characteristics of study groups according to MS of systolic BP are reported in Table 1. Clinic and daytime systolic and diastolic BP and 24‐hour systolic BP were significantly higher in patients with high MS. Nighttime systolic and diastolic BP were significantly lower in patients with high MS. Prevalence of nondippers was significantly higher in patients with normal MS, and very few nondippers had high MS. In patients with high MS, body mass index and beta‐blocker use tended to be lower and prevalence of LV hypertrophy and angiotensin receptor blocker use tended to be higher.
Table 1.
Characteristics of study groups by morning surge of systolic blood pressure
| Parameter | Normal MS (n = 967) | High MS (n = 106) | P |
|---|---|---|---|
| Age, y | 49 ± 7 | 50 ± 6 | 0.13 |
| Men, n (%) | 485 (50) | 56 (53) | 0.60 |
| Body mass index, kg/m2 | 28.4 ± 4.6 | 27.6 ± 4.2 | 0.05 |
| Smokers, n (%) | 236 (24) | 29 (27) | 0.50 |
| FHCVD, n (%) | 142 (15) | 15 (14) | 0.88 |
| Previous events, n (%) | 35 (4) | 2 (2) | 0.57 |
| Diabetes, n (%) | 49 (5) | 3 (3) | 0.47 |
| IFG, n (%) | 186 (19) | 26 (24) | 0.19 |
| eGFR, mL/min/1.73 m2 | 85.8 ± 20 | 84.6 ± 22 | 0.59 |
| Total cholesterol, mg/dL | 207 ± 36 | 212 ± 39 | 0.11 |
| HDL cholesterol, mg/dL | 50 ± 12 | 51 ± 13 | 0.35 |
| Triglycerides, mg/dL | 138 ± 71 | 146 ± 89 | 0.32 |
| LDL cholesterol, mg/dL | 129 ± 30 | 132 ± 31 | 0.31 |
| LV hypertrophy, n (%) | 233 (24) | 34 (32) | 0.07 |
| LA enlargement, n (%) | 96 (10) | 6 (6) | 0.15 |
| ALVSD, n (%) | 10 (1) | 1 (1) | 0.95 |
| Atrial fibrillation, n (%) | 21 (2) | 0 (0) | 0.25 |
| Clinic SBP, mm Hg | 144 ± 15 | 153 ± 15 | 0.0001 |
| Clinic DBP, mm Hg | 92 ± 10 | 95 ± 9 | 0.0001 |
| Daytime SBP, mm Hg | 133 ± 13 | 142 ± 14 | 0.0001 |
| Daytime DBP, mm Hg | 84 ± 9 | 87 ± 10 | 0.01 |
| Nighttime SBP, mm Hg | 118 ± 14 | 115 ± 15 | 0.03 |
| Nighttime DBP, mm Hg | 72 ± 9 | 69 ± 9 | 0.005 |
| 24‐h SBP, mm Hg | 129 ± 13 | 134 ± 14 | 0.0001 |
| 24‐h DBP, mm Hg | 81 ± 9 | 82 ± 9 | 0.26 |
| MS SBP, mm Hg | 12 ± 9 | 33 ± 5 | 0.0001 |
| Nondippers SBP, n (%) | 416 (43) | 6 (6) | 0.0001 |
| Diuretic, n (%) | 486 (50) | 59 (56) | 0.53 |
| Beta‐blocker, n (%) | 359 (37) | 30 (28) | 0.07 |
| Calcium antagonist, n (%) | 319 (33) | 36 (34) | 0.84 |
| ACE‐inhibitor, n (%) | 436 (45) | 45 (42) | 0.60 |
| AR‐blocker, n (%) | 194 (20) | 29 (27) | 0.08 |
| Alpha‐blocker, n (%) | 125 (13) | 9 (8) | 0.19 |
Abbreviations: ACE, angiotensin converting enzyme; ALVSD, asymptomatic left ventricular systolic dysfunction; AR, angiotensin receptor; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; FHCVD, family history of cardiovascular disease; HDL, high‐density lipoprotein; IFG, impaired fasting glucose (100‐125 mg/dL); LA, left atrial; LDL, low‐density lipoprotein; LV, left ventricular; MS, morning surge; SBP, systolic blood pressure.
Characteristics of study groups according to MS of diastolic BP are reported in Table 2. Clinic diastolic BP, daytime systolic and diastolic BP, and 24‐hour diastolic BP were higher in patients with high MS. Nighttime systolic BP was significantly lower in patients with high MS. Prevalence of nondippers was significantly higher in patients with normal MS, and very few nondippers had high MS. Prevalence of men and FHCVD were significantly higher in patients with high MS Clinic systolic BP tended to be higher in patients with high MS.
Table 2.
Characteristics of study groups by morning surge of diastolic blood pressure
| Parameter | Normal MS (n = 967) | High MS (n = 106) | P |
|---|---|---|---|
| Age, y | 49 ± 7 | 49 ± 6 | 0.89 |
| Men, n (%) | 475 (49) | 66 (62) | 0.01 |
| Body mass index, kg/m2 | 28.4 ± 4.6 | 27.8 ± 4.2 | 0.13 |
| Smokers, n (%) | 237 (24) | 28 (26) | 0.67 |
| FHCVD, n (%) | 133 (14) | 24 (23) | 0.01 |
| Previous events, n (%) | 34 (4) | 3 (3) | 0.71 |
| Diabetes, n (%) | 48 (5) | 4 (4) | 0.59 |
| IFG, n (%) | 190 (20) | 22 (21) | 0.79 |
| eGFR, mL/min/1.73 m2 | 85.4 ± 19 | 88.2 ± 26 | 0.29 |
| Total cholesterol, mg/dL | 207 ± 36 | 208 ± 34 | 0.85 |
| HDL cholesterol, mg/dL | 50 ± 12 | 49 ± 12 | 0.37 |
| Triglycerides, mg/dL | 138 ± 73 | 146 ± 72 | 0.33 |
| LDL cholesterol, mg/dL | 129 ± 30 | 129 ± 31 | 0.92 |
| LV hypertrophy, n (%) | 236 (24) | 31 (29) | 0.27 |
| LA enlargement, n (%) | 94 (10) | 8 (8) | 0.47 |
| ALVSD, n (%) | 11 (1) | 0 (0) | 0.61 |
| Atrial fibrillation, n (%) | 20 (2) | 1 (1) | 0.71 |
| Clinic SBP, mm Hg | 144 ± 15 | 147 ± 15 | 0.053 |
| Clinic DBP, mm Hg | 92 ± 10 | 96 ± 10 | 0.0001 |
| Daytime SBP, mm Hg | 133 ± 13 | 137 ± 14 | 0.02 |
| Daytime DBP, mm Hg | 84 ± 9 | 89 ± 10 | 0.0001 |
| Nighttime SBP, mm Hg | 118 ± 14 | 114 ± 15 | 0.01 |
| Nighttime DBP, mm Hg | 71 ± 9 | 70 ± 10 | 0.14 |
| 24‐h SBP, mm Hg | 129 ± 13 | 130 ± 14 | 0.36 |
| 24‐h DBP, mm Hg | 80 ± 8 | 83 ± 9 | 0.003 |
| MS DBH, mm Hg | 9 ± 6 | 24 ± 4 | 0.0001 |
| Nondippers DBH, n (%) | 236 (24) | 2 (2) | 0.0001 |
| Diuretic, n (%) | 490 (51) | 55 (51) | 0.95 |
| Beta‐blocker, n (%) | 356 (37) | 33 (31) | 0.25 |
| Calcium antagonist, n (%) | 316 (33) | 39 (37) | 0.39 |
| ACE‐inhibitor, n (%) | 432 (45) | 49 (46) | 0.76 |
| AR‐blocker, n (%) | 200 (21) | 23 (22) | 0.81 |
| Alpha‐blocker, n (%) | 123 (13) | 11 (10) | 0.49 |
Abbreviations: ACE, angiotensin converting enzyme; ALVSD, asymptomatic left ventricular systolic dysfunction; AR, angiotensin receptor; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; FHCVD, family history of cardiovascular disease; HDL, high‐density lipoprotein; IFG, impaired fasting glucose (100‐125 mg/dL); LA, left atrial; LDL, low‐density lipoprotein; LV, left ventricular; MS, morning surge; SBP, systolic blood pressure.
Single, double, and triple antihypertensive therapies were not different between the groups (approximately 25%, 55%, and 20%, respectively, in each group for both MS of systolic and diastolic BP). Use of aspirin and statin was not significantly different between patients with high and normal MS of systolic BP (7.5% vs 7.7% and 8.5% vs 4.8%, respectively) and those with high and normal MS of diastolic BP (6.0% vs 7.9% and 6.6% vs 5.0%, respectively).
During the follow‐up (mean 10.9 years, range 1‐20 years), 131 cardiovascular events occurred. There were 91 coronary events, 34 stokes, and 6 heart failures with reduced ejection fraction. The event rate of the population was 1.15 per 100 patient‐years. There were 107 events (74 coronary events, 29 strokes, and 4 heart failures) and 24 events (17 coronary events, 5 strokes and 2 heart failures) in patients with normal and high MS of systolic BP, respectively, and 110 events (76 coronary events, 30 strokes and 4 heart failures) and 21 events (15 coronary events, 4 strokes and 2 heart failures) in patients with normal and high MS of diastolic BP, respectively. The event rate in patients with normal and high MS of systolic BP was 1.00 and 2.19 per 100 patient‐years, respectively, and that in patients with normal and high MS of diastolic BP was 1.03 and 2.08 per 100 patient‐years, respectively. Event‐free survival curves of study groups according to MS of systolic and diastolic BP are reported in Figure 1.
Figure 1.
Event‐free survival curves of study groups. DBP, diastolic blood pressure; MS, morning surge; SBP, systolic blood pressure
Univariate analysis showed that age, gender, smoking habit, FHCVD, diabetes, previous events, LDL cholesterol, LV hypertrophy, clinic, daytime, nighttime and 24‐hour BP, nondipping for diastolic BP, and high MS for systolic and diastolic BP were significantly associated with increased cardiovascular risk, and that nondipping for systolic BP tended to be associated with increased risk (Table 3).
Table 3.
Risk of cardiovascular events in univariate analysis
| Parameter | HR (95% CI) | P |
|---|---|---|
| Age (10 y) | 1.88 (1.40‐2.52) | 0.0001 |
| Gender (M vs W) | 2.44 (1.67‐3.54) | 0.0001 |
| Smoking (yes vs no) | 1.89 (1.33‐2.69) | 0.0001 |
| FHCVD (yes vs no) | 2.94 (1.85‐4.67) | 0.0001 |
| Diabetes (yes vs no) | 3.10 (1.65‐5.75) | 0.0001 |
| Previous events (yes vs no) | 3.26 (1.58‐6.73) | 0.001 |
| LDL cholesterol (10 mg/dL) | 1.08 (1.02‐1.15) | 0.006 |
| LV hypertrophy (yes vs no) | 3.10 (2.15‐4.56) | 0.0001 |
| Clinic SBP (10 mm Hg) | 1.25 (1.13‐1.37) | 0.0001 |
| Clinic DBP (10 mm Hg) | 1.26 (1.06‐1.50) | 0.008 |
| Daytime SBP (10 mm Hg) | 1.36 (1.24‐1.50) | 0.0001 |
| Daytime DBP (10 mm Hg) | 1.45 (1.21‐1.73) | 0.0001 |
| Nighttime SBP (10 mm Hg) | 1.26 (1.14‐1.39) | 0.0001 |
| Nighttime DBP (10 mm Hg) | 1.32 (1.11‐1.58) | 0.002 |
| 24‐h SBP (10 mm Hg) | 1.36 (1.24‐1.50) | 0.0001 |
| 24‐h DBP (10 mm Hg) | 1.42 (1.17‐1.73) | 0.0001 |
| Nondippers vs Dippers SBP | 1.39 (0.99‐1.96) | 0.06 |
| Nondippers vs Dippers DBP | 1.53 (1.06‐2.19) | 0.02 |
| High vs Normal MS SBP | 2.23 (1.43‐3.47) | 0.0001 |
| High vs Normal MS DBP | 2.31 (1.44‐3.70) | 0.001 |
Abbreviations: CI, confidence interval; DBP, diastolic blood pressure; FHCVD, family history of cardiovascular disease; HR, hazard ratio; LDL, low‐density lipoprotein; LV, left ventricular; M, men; MS, morning surge; SBP, systolic blood pressure; W, women.
We performed two multivariate analyses including age, gender, smoking habit, FHCVD, diabetes, previous events, LDL cholesterol, LV hypertrophy, 24‐hour systolic or diastolic BP, nondipping for systolic or diastolic BP, and high vs normal MS of systolic or diastolic BP. Results of multivariate analyses are reported in Figure 2. After adjustment for the aforesaid covariates, the risk of cardiovascular events remained significantly higher in patients with high MS of systolic and diastolic BP. Other variables that remained significantly associated with outcome were age, gender, smoking habit, FHCVD, diabetes, LDL cholesterol, LV hypertrophy, 24‐hour systolic or diastolic BP, and nondipping for diastolic BP; nondipping for systolic BP approached statistical significance.
Figure 2.
Risk of cardiovascular events in patients with high morning surge (MS) of systolic and diastolic blood pressure (SBP and DBP, respectively) compared to patients with normal MS. Data are adjusted for age, gender, smoking habit, FHCVD, diabetes, previous events, LDL cholesterol, LV hypertrophy, 24‐h systolic or diastolic BP, and dipping status for systolic or diastolic BP. Hazard ratio (HR) and 95% confidence interval (CI) values are 1.81 (1.10‐2.96) in patients with high MS of SBP and 1.98 (1.19‐3.28) in patients with high MS of DBP
4. DISCUSSION
This study shows that, in middle‐aged treated hypertensive patients, a high MS of systolic and diastolic BP is associated with increased cardiovascular risk, independently of other ambulatory BP parameters and risk markers.
There are few studies in the literature assessing the impact of MS in treated hypertensive patients. Moreover, previous studies evaluated middle‐aged and old untreated and treated patients,9, 11 old untreated and treated individuals,5, 6 and old treated patients.10, 12, 13, 14
This is the first study to report an independent association between high MS of BP and cardiovascular risk in middle‐aged treated hypertensive patients. Moreover, this is the first study to show an adverse prognostic impact of high MS of diastolic BP in middle‐aged patients.
Some hypotheses could be formulated about the mechanisms by which high MS of BP acts as a predictor of cardiovascular events. A high MS of BP might cause injuries to the arterial wall, such as endothelial damage, disorganization of the muscular layers, and fracture of the elastin fibers, and to plaque rupture.29 In this context, it could be argued that both high MS of systolic and diastolic BP might have predisposed to cerebrovascular events in our middle‐aged population. Concerning coronary events, high MS of systolic and diastolic BP could have predisposed to this outcome in relation to age.30 Indeed, in the Framingham Heart Study, it has been shown that diastolic BP is a stronger predictor of coronary events in patients aged <50 years and that systolic and diastolic BP equally predict risk in those aged 50‐59 years.30 In patients aged ≥60 years, systolic BP is a stronger predictor of coronary artery disease risk.30 Moreover, we have previously reported that treated overdipper (or extreme dipper) hypertensive patients, that is, those with the lowest nighttime BP who also show the highest MS in BP, have more nighttime ischemic episodes.31 Whether this aspect may be implicated in the occurrence of type 2 myocardial infarction32 or predisposes to the occurrence of coronary events in the context of a successive high MS in BP or has no relevance independently of high MS in BP or whether high MS of BP and low nighttime BP may act differently in stimulating the atherosclerotic process and prompting cardiovascular events remains to be elucidated.12 In the same context, it has been described that overdipper hypertensive patients show greater odds for the presence of coronary artery calcium, a subclinical indicator of coronary atherosclerosis.33
In addition, a high MS is associated with other factors that could contribute to explain increased cardiovascular risk. Indeed, it has been reported that a high MS in BP is associated with coronary microvascular dysfunction,34 sympathetic overactivity and QTc dispersion,35 increased oxidative stress,36 unstable plaques related to enhanced ubiquitin‐proteasome activity,37 increased circulating inflammatory markers,38 increased platelet aggregation,3, 39 and impaired hemostatic activity.3, 40 All the above mentioned factors could contribute to the occurrence of cerebral and coronary events in patients with high MS of BP by promoting the atherosclerotic process and by triggering its complications that lead to cardiovascular events. Finally, we have recently reported that high MS is independently associated with increased risk of heart failure with reduced ejection fraction.13
In our previous manuscripts dealing with older patients,10, 12, 13, 14 we used a cutoff of 23 mm Hg (upper tertile of MS of systolic BP in dippers) to define high MS. In these middle‐aged patients, who generally show higher vascular elasticity, we hypothesized that a higher BP increase would be necessary to trigger cardiovascular events. In this context, we selected the 90th percentile of MS of BP, which has been frequently used in the literature, to define high MS.
This study has some limitations. First, we studied only Caucasian patients and our results cannot be applied to other ethnic groups. Second, our data were obtained in middle‐aged treated hypertensive patients and cannot be extrapolated to other patients. Third, it remains unclear whether higher MS of BP reflects an intrinsic characteristic of some patients or uncontrolled BP because of treatment features (dosage or timing of drug therapy); these aspects however do not lessen our findings. Fourth, the lack of association of cardiovascular risk with treatment strategy does not mean lack of efficacy of therapy because all patients were treated with antihypertensive therapy, most of whom received multiple therapy, and patients were not randomized to antihypertensive or antiplatelet or statin therapy. Fifth, like in other prospective studies published by various study groups around the world, either with untreated or treated hypertensive patients at baseline, adherence to therapy, or changes of therapy during follow‐up could not be completely evaluated.
In conclusion, in middle‐aged treated hypertensive patients, MS of systolic and diastolic BP is associated with higher cardiovascular risk independently of other ambulatory BP parameters and risk markers.
CONFLICT OF INTEREST
No conflict of interest to disclose.
AUTHOR CONTRIBUTIONS
Francesca Coccina wrote the paper, revised the manuscript critically for important intellectual content, and gave final approval of the version to be submitted and of the revised version. Anna M. Pierdomenico performed statistical analysis, revised the manuscript critically for important intellectual content, and gave final approval of the version to be submitted and of the revised version. Chiara Cuccurullo, Piergiusto Vitulli, and Jacopo Pizzicannella collected the data, revised the manuscript critically for important intellectual content, and gave final approval of the version to be submitted and of the revised version. Francesco Cipollone designed the study, revised the manuscript critically for important intellectual content, and gave final approval of the version to be submitted and of the revised version. Sante D. Pierdomenico collected the data, designed the study, contributed to the writing of the paper, revised the manuscript critically for important intellectual content, and gave final approval of the version to be submitted and of the revised version.
Coccina F, Pierdomenico AM, Cuccurullo C, et al. Prognostic value of morning surge of blood pressure in middle‐aged treated hypertensive patients. J Clin Hypertens. 2019;21:904–910. 10.1111/jch.13600
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